To see the other types of publications on this topic, follow the link: Meropenem.
Dissertations / Theses on the topic 'Meropenem'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Meropenem.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Mendez, Andreas Sebastian Loureiro. "Estudo de estabilidade do antibiótico meropenem." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2007. http://hdl.handle.net/10183/28512.
Full textAbstract:
A estabilidade de medicamentos constitui um tema atual e de grande importância no meio científico. Tem sido constantemente abordada em estudos direcionados à avaliação da qualidade das preparações farmacêuticas. O meropenem, um antibiótico carbapenêmico de amplo espectro de ação, é utilizado como um importante recurso terapêutico para o tratamento de infecções graves. Por ser um agente antimicrobiano ativo e eficaz, de uso clínico em muitos países, tornase necessária a pesquisa mais aprofundada de sua estabilidade, propiciando um maior entendimento dos aspectos que podem influenciar na sua manipulação e armazenamento. O presente trabalho objetiva a avaliação da estabilidade do meropenem em condições de degradação forçada, contemplando a determinação da cinética de degradação, o isolamento e identificação de produtos de decomposição e a determinação da citotoxicidade das amostras degradadas e dos produtos isolados. Amostras de meropenem pó para solução injetável (500 mg) e solução reconstituída em água (50 mg/mL) foram submetidas à degradação térmica em diferentes temperaturas. Para a decomposição ácido-base, soluções aquosas de meropenem a 1,0 mg/mL foram preparadas em HCl 0,1 M e NaOH 0,1 M, e estocadas a 25 °C. As amostras foram analisadas por cromatografia líquida de alta eficiência, em sistema de fase reversa. Para o ensaio de determinação cinética, as amostras submetidas à maior temperatura de degradação foram também analisadas por ensaio microbiológico – método de difusão em ágar-cilindros em placas. O isolamento do produto de degradação térmica foi efetuado através da combinação das técnicas de cromatografia em coluna e cromatografia em camada delgada preparativa. Para o produto oriundo de catálise básica, a identificação foi efetuada diretamente na amostra degradada, não havendo a necessidade de prévio isolamento. A elucidação estrutural dos produtos de degradação foi realizada por ressonância magnética nuclear e espectrometria de massas. As amostras degradadas e o produto de catálise básica foram avaliados in vitro quanto ao potencial citotóxico frente a células mononucleares. Para determinação da viabilidade celular, os conteúdos celulares foram avaliados por citometria de fluxo. Os resultados dos ensaios de cinética química indicaram que o meropenem sofre decomposição térmica seguindo reação de primeira ordem. As amostras degradadas apresentaram uma acentuada redução de teor, com formação de produtos de degradação. As técnicas cromatográficas de purificação utilizadas permitiram o isolamento de um produto oriundo da degradação térmica da solução reconstituída. A identificação demonstrou que o mesmo teve uma modificação estrutural extensa, gerada a partir de reações de decomposição passíveis de ocorrer para o derivado carbapenêmico avaliado. Para o produto de degradação básica, verificou-se o rompimento do anel β-lactâmico, em reação característica destes compostos. A avaliação preliminar da citotoxicidade indicou que as amostras ensaiadas apresentam toxicidade celular in vitro após 48 horas de incubação, fornecendo indícios de necessidade de atenção para este aspecto. A totalidade dos resultados obtidos neste trabalho permite a conclusão de que a estabilidade do meropenem é um tema de grande relevância e deve ser considerada na hora da manipulação do produto, de modo a evitar problemas de qualidade oriundos de amostras degradadas e seus produtos de degradação.The stability of pharmaceuticals is a current and important subject in the scientific field. It has been frequently cited in studies related with the quality evaluation of pharmaceutical preparations. Meropenem, a carbapenemic antibiotic with broad spectrum, is used as an important therapeutic agent for the treatment of several infections. Since it is an active and effective antimicrobial, used in many countries, it is necessary the complete research about its stability, providing more knowledge about the aspects that could influence in its handle and storage. The aim of this work is the evaluation of meropenem stability in forced degradation conditions, including the determination of degradation kinetics, the isolation and identification of decomposition products and the citotoxicity evaluation of degraded samples and isolated products. Meropenem powder for injection (500 mg) and reconstituted solution in water (50 mg ml-1) were submitted to thermal degradation. For acid-basic decomposition, meropenem aqueous solution at 1.0 mg ml-1 were prepared in HCl 0.1 M and NaOH 0.1 M, and stored at 25 °C. The samples were analysed by high performance liquid chromatography, in reverse phase system. In the kinetics determination, the samples stored at 45 °C and 90 °C were also evaluated by microbiological assay, applying the cylinder-plate method. The isolation of thermal degradation product was carried out by column chromatography and preparative thin layer chromatography. For the product obtained through basic catalysis, the identification was done directly in the degraded sample, without previous isolation. The structural elucidation of degradation products was performed by nuclear magnetic ressonance and mass spectrometry. The degraded samples and basic catalysis product were evaluated with respect to citotoxic potential in vitro against mononuclear cells. The cellular viability was determined by flow citometry. The results of chemical kinetics indicated that thermal decomposition of meropenem is described by first order reaction. The degraded samples showed a significant reduction in the potency, with formation of degradation products. The chromatographic purification techniques allowed the isolation of one thermal degradation product. For the basic degradation product, it was verified the hidrolysis of β-lactam ring, in a caracterisitc reaction for these compounds. The preliminary citotoxicity evaluation indicated that samples were toxic after 48 hours. The results obtained in this work allowed to conclude that the stability of meropenem is a subject of great importance and should be considered in the handle of the product, in order to avoid quality problems from degraded samples and degradation products.
2
Abbott, Stacey, Georgina Rubal-Peace, and Jamie Natkowski. "Appropriate Use of Meropenem: A Pharmacy Intervention." The University of Arizona, 2014. http://hdl.handle.net/10150/614200.
Full textAbstract:
Class of 2014 AbstractSpecific Aims: The primary objective was to determine the effectiveness of a criteria-based antibiotic order form (CBAOF) at increasing appropriate meropenem use at University of Arizona Medical Center –South Campus (UAMCSC). The secondary objective was to assess any cost savings associated with increased appropriate meropenem use. Methods: A retrospective chart review of patients (n = 133) meeting inclusion criteria at UAMCSC during the pre and post-intervention periods was conducted. Outcomes included appropriate empiric use of meropenem, appropriate treatment of a known pathogen use of meropenem, appropriate dose and frequency of meropenem, appropriate antibiotic streamlining after culture and susceptibility report, and meropenem acquisition costs. Main Results: Appropriate empiric use of meropenem was significantly higher after the implementation of the CBAOF (100% vs. 65.8%, p = 0.002). Although not statistically significant, the post-intervention group had more patients meeting the criteria for appropriate use of meropenem for a known pathogen than the pre-intervention group (50% vs. 40%, p = 0.809). There were no differences between the pre and post-intervention groups with respect to appropriate dose of meropenem or appropriate frequency. After the implementation of the CBAOF there were significantly more patients who received antibiotic streamlining within 24 hours of culture and susceptibility reports (12.5% vs. 48.7%, p = 0.002). Drug acquisition costs for meropenem were reduced by approximately $30,000 after CBAOF implementation. Conclusion: The CBAOF was effective at increasing appropriate empiric meropenem use and decreasing meropenem acquisition costs at UAMCSC.
3
Wolken, Kathryn, and Velliyur Viswesh. "The Appropriateness of Antibiotic Therapy in Patients Initiated on Meropenem in a University-Affiliated Hospital." The University of Arizona, 2011. http://hdl.handle.net/10150/623557.
Full textAbstract:
Class of 2011 AbstractOBJECTIVES: To determine the appropriateness of antimicrobial therapy in patients initiated on empiric meropenem therapy. METHODS: Adult patients prescribed empiric meropenem therapy between January 1, 2010 and March 31, 2010 at a tertiary care, academic medical center were included. Data collected included site of infection, culture and susceptibility data, risk factors for multi-drug resistant organisms, and changes in antimicrobial therapy during the first seven days after meropenem therapy was initiated. Demographic variables included age, sex, weight, and race. RESULTS: RESULTS: A total of 89 patients were included in the study analysis. Initial culture(s) was obtained before administration of antibiotics in only 58% of patients. During the first 24 hours of admission, four or more different antibiotics were prescribed in 26% of patients often with overlapping spectrums of activity. The majority of patients received meropenem for either less than 1 day or greater than 4 days. CONCLUSION: The primary issues identified with appropriate antibiotic prescribing involved the timing of cultures, and multiple changes in antibiotic therapy without culture-driven reasoning.
4
MacKenzie, Fiona M. "Investigations of the postantibiotic effect and related antibacterial activity of meropenem." Thesis, Robert Gordon University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239961.
Full text
5
Lima, Camila Nayane de Carvalho. "Convulsant carbapenems potential of different models in experimental convulsion: benchmarking, behavioral and neurochemical." Universidade Federal do CearÃ, 2011. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=9563.
Full textAbstract:
CoordenaÃÃo de AperfeiÃoamento de NÃvel SuperiorEpilepsy is the most common neurological disorder, affecting 50 million people worldwide, 40 million of them in developed countries. People of all races, genders, socioeconomic conditions and regions are affected. The pilocarpine (P400) is a cholinergic agonist characterized by inducing seizures evolving to status epilepticus, similar to human temporal lobe epilepsy. The pentylenetetrazole (PTZ) is a GABA antagonist that mimics the small-mal seizures (absence seizure) and tonic-clonic seizures in humans. The strychnine is a potent convulsant and acts mainly as a selective antagonist of postsynaptic inhibition mediated by glycine. Its main action is to increase the excitability of the spinal reflex . The convulsant picrotoxin is an agent that blocks chloride channels activated by gamma-aminobutyric acid. Convulsant agents were administered intraperitoneally, 10 minutes after intravenous administration of carbapenÃmcios With the development of this work, we found that pretreatment with imipenem or meropenem interfere with various neurotransmitter systems when animals are subjected to seizures induced by pilocarpine at a dose of 400mg/kg, 55mg/Kg at a dose of pentylenetetrazole, strychnine and picrotoxin 10mg/Kg 2mg/kg. This has been evidenced by increasing levels of excitatory amino acids such as glutamate and on the other hand, a decrease in levels of inhibitory amino acids such as GABA reinforcing the existence of a possible modulatory pathway of these amino acids in control and development of seizure occurs when pre-treatment with imipenem or meropenem.
Epilepsia à o mais freqÃente distÃrbio neurolÃgico, atingindo 50 milhÃes de pessoas no mundo, 40 milhÃes delas em paÃses desenvolvidos. Pessoas de todas as raÃas, sexos, condiÃÃes socioeconÃmicas e regiÃes sÃo acometidas. A pilocarpina (P400) à um agonista colinÃrgico que se caracteriza por induzir convulsÃes que evoluem para status epilÃpticus, similar à epilepsia do lobo temporal humana. O pentilenotetrazol (PTZ) à um antagonista GABA que mimetiza convulsÃes do pequeno-mal (crise de ausÃncia) e do tipo tÃnico-clÃnico em humanos. A estricnina à um potente convulsivante e atua, principalmente, como antagonista competitivo seletivo da inibiÃÃo pÃs-sinÃptica mediada pela glicina. Sua principal aÃÃo à o aumento da excitabilidade reflexa da medula. A picrotoxina à um agente convulsivante que bloqueia os canais de cloro ativados pelo Ãcido gama-aminobutÃrico. Os agentes convulsivantes foram administrados intraperitonialmente, apÃs 10 minutos da administraÃÃo intravenosa dos carbapenÃmcios Com o desenvolvimento deste trabalho, podemos observar que o prÃ-tratamento com imipenem ou meropenem interfere com vÃrios sistemas de neurotransmissores quando os animais sÃo submetidos à convulsÃo induzida pela pilocarpina na dose de 400mg/kg, pentilenotetrazol na dose de 55mg/Kg, estricnina 2mg/Kg e picrotoxina 10mg/Kg. Tal efeito foi evidenciado atravÃs do aumento nos nÃveis de aminoÃcidos excitatÃrios como o glutamato e, por outro lado, uma diminuiÃÃo nos nÃveis de aminoÃcidos inibitÃrios como o GABA reforÃando a existÃncia de uma possÃvel via modulatÃria desses aminoÃcidos no controle e desenvolvimento de crises epilÃpticas quando ocorre o prÃ-tratamento com imipenem/cilastatina ou meropenem.
6
Gilcher, Thomas [Verfasser]. "Pharmakokinetik von Linezolid und Meropenem bei Intensivpatienten mit kontinuierlicher Nierenersatztherapie / Thomas Gilcher." Mainz : Universitätsbibliothek der Johannes Gutenberg-Universität Mainz, 2016. http://d-nb.info/1225685389/34.
Full text
7
MASCENA, Guilherme Veras. "Resposta terapêutica de ratos com peritonite fecal submetidos ao uso de meropenem intravenoso." Universidade Federal de Pernambuco, 2014. https://repositorio.ufpe.br/handle/123456789/17454.
Full textAbstract:
Submitted by Isaac Francisco de Souza Dias (isaac.souzadias@ufpe.br) on 2016-07-18T18:44:57Z
No. of bitstreams: 2
license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5)
TESE GUILHERME VERAS 19 OUT-MM.pdf: 2315237 bytes, checksum: dfde31585678c4be265e3df28d667cb7 (MD5)Made available in DSpace on 2016-07-18T18:44:57Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE GUILHERME VERAS 19 OUT-MM.pdf: 2315237 bytes, checksum: dfde31585678c4be265e3df28d667cb7 (MD5) Previous issue date: 2014-11-10
Objetivo: Avaliar o resultado do tratamento com meropenem intravenoso de peritonite grave em ratos com diferentes idades. Métodos: Trinta ratos Wistar estratificados em três grupos: grupo I - seis meses de idade; grupo II - 12 meses de idade; e grupo III - 18 meses de idade, submetidos à indução de peritonite autógena com suspensão de fezes a 10% (6ml/kg de rato), foram tratados com meropenem intravenoso na dose única de 40mg/Kg de rato. Os animais que sobreviveram foram acompanhados por 45 dias. Os parâmetros das variáveis quantitativas foram expressos por suas médias e pelo erro padrão da média (EPM) e p < 0,05 foi usado para rejeitar a hipótese de nulidade. O estudo foi aprovado pelo Comitê de Ética no Uso de Animais. Resultados: A mortalidade foi igual para os grupos I e II (10%). No grupo III, 4 dos 10 animais morreram nas primeiras 24 horas e mais 4 até 48 horas. De interesse, mesmo os ratos jovens que sobreviveram apresentaram abscessos residuais nas cavidades abdominal e torácica, embora tenham evoluído com vida quase normal. Com exceção de um rato do grupo I, todos os animais sobreviventes dos três grupos apresentaram hemocultura negativa. Conclusões: O tratamento da peritonite fecal autógena grave com meropenem intravenoso alcançou bons resultados em ratos com seis e doze meses de idade, mesmo considerando os abscessos residuais na cavidade abdominal e torácica. No entanto, 8 dos 10 ratos idosos (80%) não conseguiram superar o desafio infeccioso inicial, provando que o envelhecimento é um fator de risco muito importante no prejuízo da resposta imunológica. Assim, a sepse continua a ser uma situação desafiadora, especialmente em idosos.
Purpose: To evaluate the treatment outcome of severe peritonitis treated with intravenous meropenem in rats with increasing age. Methods: Thirty Wistar rats stratified in three groups: group I – six month-old; group II – 12 month-old; and group III – 18 month-old, underwent autogenously fecal peritonitis (6 ml/kg rat), were treated with intravenous meropenem at a single dose of 40 mg/kg of rat. The survival animals were followed-up for 45 days. The parameters of the quantitative variables were expressed as means and standard error of the mean (SEM) and p <0.05 was used to reject the null hypothesis. The study was approved by the Ethics Committee on Animal Use. Results: Mortality was similar for groups I and II (10%). In group III, 4 of 10 animals died within the first 24 hours and 4 more up to 48 hours. Of interest, even young rats that survived had residual abscesses in both the abdominal and thoracic cavities, although they were living an almost normal life. Except for one rat in group I, all surviving animals of the three groups showed a negative blood culture. Conclusions: The outcome of severe autogenously peritonitis in rats treated with intravenous meropenem in rats was good in animal with ages of six and twelve months, even considering the residual abscesses in the abdominal and chest cavities. However, 8 of 10 elderly rats (80%) could not overcome the initial infectious challenge, proving that aging is an important risk factor in the loss of immune response. Thus, sepsis continues to be a challenging situation, especially in the
8
Hands, Catherine Lauren. "Relationships between zinc and meropenem resistance in the natural environment and experimental bioreactors." Thesis, University of Newcastle upon Tyne, 2016. http://hdl.handle.net/10443/3512.
Full textAbstract:
The efficacy of antibiotics is being challenged by the emergence of bacteria resistant to antibiotics (AR), both in natural and clinical settings. Antibiotics and associated AR can be transmitted and dispersed via environmental bacteria, however AR might also be conferred in situ, without antibiotic pressure. For example, release of metal-bearing wastes to natural environments can proliferate AR. An important case is the influence of zinc (Zn) contamination on environmental AR, which increased tetracycline and quinolone resistance in wastewater isolates. However, how Zn might influence AR to therapeutically critical carbapenem antibiotics, including meropenem is unknown, which fuelled this study. Here the percentage of total isolates resistant to Zn, meropenem and-or both, were compared and assessed in varied microbial communities from natural environments and bioreactors. Overall, Zn levels, and Zn and meropenem resistant isolates correlated in all settings. For example, the abundance of combined meropenem plus Zn resistant isolates was significantly higher in high Zn (South Tyne) versus low Zn (North Tyne) sediments, and correlated with soluble and total Zn levels (p-value < 0.010 and p-value < 0.050, respectively), implying that acquired Zn resistance might confer meropenem resistance to isolates. In parallel, batch reactors seeded with North and South Tyne sediments, and amended with 2.00 mg/L (low) and 100 mg/L (high) Zn (2 x 2 design), showed increased relative percent meropenem resistant isolates in reactors with high (South Tyne: 21.0%; North Tyne: 31.0%) versus low Zn (South Tyne: 17.0%; North Tyne: 14.0%), whereas, sediment source (South vs North Tyne) was not important. Further, sediment soluble Zn levels significantly correlated with meropenem resistant isolates in all reactors, suggesting that the observed meropenem resistance was a possible “side effect” of cellular defence against Zn toxicity. Similar results were seen in Zn and meropenem-amended rotating tubular reactors treating domestic wastewater. Reactors dosed with 2.00 mg/L meropenem plus 100 mg/L Zn showed combined resistance in 51.0% of reactor effluent isolates, whereas only 24.0% displayed combined resistance with amendments of 2.00 mg/L meropenem and 20.0 mg/L Zn. Overall, elevated Zn levels significantly increased Zn, meropenem and combined resistance in isolates from sediments, batch reactors and tubular reactors. Therefore, one can conclude Zn levels impact meropenem resistance, although evidence suggest meropenem resistance is most apparent when Zn is present and resistance can be lost when Zn is removed, suggesting cross resistance mechanisms.
9
Lohmeier, Stefanie [Verfasser]. "Der Einfluss einer blutspiegelgestützten Therapie mit Meropenem bei Intensivpatienten mit schweren Infektionen / Stefanie Lohmeier." Magdeburg : Universitätsbibliothek, 2018. http://d-nb.info/1171899742/34.
Full text
10
Loos, Stefanie [Verfasser]. "Etablierung und Durchführung des Therapeutischen Drug Monitorings unter kontinuierlicher Antibiotikagabe am Beispiel von Meropenem / Stefanie Loos." Ulm : Universität Ulm, 2018. http://d-nb.info/1169747124/34.
Full text
11
Leusin, Fabiane. "Farmacocinética do Meropenem infundido por 3 horas em pacientes criticamente enfermos em terapia renal substitutiva contínua." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/48990.
Full textAbstract:
A terapia renal substitutiva contínua (TRSC) é amplamente utilizada em pacientes criticamente enfermos com insuficiência renal aguda (IRA). O meropenem é um carbapenêmico usado em pacientes críticos que tem uma atividade antibacteriana dependente do tempo. O objetivo do estudo foi avaliar a farmacocinética do meropenem infundido em três horas em pacientes submetidos à TRSC. Estudamos as concentrações plasmáticas e de efluente em cinco pacientes submetidos à TRSC. As amostras foram coletadas em momentos 0, 30 min, e 1, 2, 4, 6 e 8 horas após o início de uma infusão de 3 horas. As determinações de meropenem foram feitas por cromatografia líquida de alta eficiência. Quatro pacientes do sexo masculino e um feminino, idade de 53,0 ± 19,7 (23 a 80 anos), 62,1 ± 10,6 kg, foram estudados. Parâmetros farmacocinéticos apresentados em mediana (amplitude): concentrações plasmáticas, 34.86mg / L (10,08-139,27); tempo de meia vida (t ½), 1,8 h (1,4-3,0); volume de distribuição (Vd), 8,29 L (5,8-15,3); depuração total (Dept ) 3,98 L / h (2,51-4,35); concentração máxima (Cmax) 48,5 mg/L (37,0-105,8); concentração mínima (Cmin) 20,1 mg / L (14,0-16,6); constante de eliminação (Kel), 0,38 (0,34-0,43); área sob a curva de concentração versus tempo (AUC 0 a 8 h), 251,1 mg / Lh (229,7-398,4); (AUC de 0a∞), 275,1 mg /Lh (263,8-453,6).A depuração total pela TRSC variou de 8,46 a 18,33 ml/min. No efluente as concentrações máximas foram 24,35 e 74,81 mg /L. A eliminação de meropenem por TRSC é semelhante ao que é relatado pelo rim normal, quando é infundido por 3 horas a cada 8 h. Os níveis plasmáticos foram sempre acima do MIC necessário. Podemos concluir que não houve necessidade de ajuste de dose do meropenem com a dose de TRSC prescrita.Continuous renal replacement therapy (CRRT) is widely used in critically ill patients with acute kidney injury (AKI). Meropenem is a carbapenem used in critically ill patients, which has a time dependent antibacterial activity. The aim of the study was to assess the pharmacokinetics of meropenem on a 3-hour infusion in patients undergoing CRRT due to AKI. We studied the plasmatic and effluent concentrations in five patients undergoing CRRT. The samples were collected at moments 0, 30 minutes, and 1, 2, 4, 6 and 8 hours after the beginning of the 3-hour infusion. The meropenem determinations were made through high performace efficiency liquid chromatography (HPLC). Four male patients and one female patient, with a mean age of 53,0 ± 19,7 (23 to 80 years), weighing 62,1 ± 10,6 kgs were studied. Pharmacokinetic parameters presented in medians (range): plasmatic concentrations, 34.86mg / L (10,08-139,27); half-life (t ½), 1,8 h (1,4-3,0); volume of distribution (Vd), 8,29 L (5,8-15,3); total clearance (CLT) 3,98 L / h (2,51-4,35); (Cmax) (maximum plasma concentration), 48,5 mg / L (37,0-105,8); Cmin (minimum plasma concentration)20,1 mg / L (14,0-16,6); elimination constant (Kel), 0,38 (0,34-0,43); area under the concentration versus time curve (AUC 0 a 8 h), 251,1 mg / Lh (229,7-398,4); (AUC 0 a ∞) 275,1 mg / Lh (263,8-453,6). In the effluent, the maximum concentrations varied from 24,35 to 74,81 mg/L, and the clearance from the therapy varied from 8,46 to 18,33 ml/min. The elimination of meropenem through CRRT is similar to that of a normal kidney, given a 3-hour infusion every 8 hours. Plasmatic levels were always above the necessary MICs. We can conclude there was no need for dose adjustment of meropenem with the prescribed CRRT dose.
12
Lyly, Jonathan. "PKPD models for colistin and meropenem on a wild-type and a resistant strain of Pseudomonas aeruginosa." Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-150283.
Full textAbstract:
Resistant bacteria are becoming more and more of a problem but treatment with antibiotics in combination may overcome and prevent resistance development. The combination of meropenem and colistin against Pseudomonas aeruginosa has been proposed as a promising treatment to increase the bactericidal effect and a synergistic effect has been proposed. A Pharmacokinetic-Parmacodynamic (PKPD) model that describes the dynamics of bacteria kill could be used to evaluate if the effects are additive or not. The model could later also be used to find optimal dosing for both of the antibiotics used alone or in combination with each other. The aim of the present study was to develop a PKPD model that describes the bactericidal activity of the two antibiotics, both in mono-therapy and in combination. The data were from in vitro static time kill-curve experiments that had been conducted on two strains of Pseudomonas aeruginosa; the wild-type (ATCC 27853) and the resistant-type (PL0603761). Resistance was observed in the experimental data and thus it had to be taken into account in the modelling. PKPD models were fitted to the bacterial counts in NONMEM with pharmacodynamic compartments for susceptible and resting bacteria. In the resting compartment the bacteria could not be killed. The bacteria moved into the resting compartment from the susceptible compartment when a certain concentration of bacteria was obtained. A pharmacokinetic compartment characterized changes in drug concentrations and the drug degradation during the experimental time was considered. Two different drug effects were tried on the susceptible bacteria, linear effect and Emax models.. The resistance development occurring during the experiments was described by two compartments where the parameter kon determined the rate of onset of resistance development. In the final model, kon was found to either be concentration-independent or dependent, depending on antibiotics and bacteria. The degree of resistance development produced an overall inhibitory effect on the drug effect. The growth rate was estimated to be lower and the EC50 to be higher for the resistant compared to the wild-type bacteria. The model was used to predict the expected time-kill curve if the effect of the two drugs are additive when combining the two drugs. The observed bacteria kill was lower than the model predicted for the wild-type bacteria. For the resistant bacteria the assumption of additive bacteria kill for the two drugs-seemed adequate.
13
Kulengowski, Brandon T. "IN VITRO ACTIVITY OF POLYMYXIN B AND MEROPENEM ALONE AND IN COMBINATION AGAINST CARBAPENEM-RESISTANT ENTEROBACTERIACEAE." UKnowledge, 2016. http://uknowledge.uky.edu/pharmacy_etds/57.
Full textAbstract:
Background: Infections caused by carbapenem-resistant Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae are among the most urgent threats of the infectious disease realm. The incidence of these infections has only been increasing over the years and due to very limited treatment options, mortality is estimated at about 50%.
Methods: To evaluate the in vitro activity of meropenem and polymyxin B against carbapenem-resistant Enterobacteriaceae, antimicrobial susceptibility testing and time-kill studies were performed on K. pneumoniae clinical isolates representing a wide range of meropenem resistance (MICs 4 – 128 mg/L).
Results: Regrowth was observed at clinically relevant concentrations of meropenem alone (4, 16, and 64 mg/L) or polymyxin B alone (0.25 and 1 mg/L) within 24 hours. However, meropenem and polymyxin B in combination were consistently bactericidal, achieving synergistic activity in strains with lower meropenem resistance (MICs ≤32 mg/L).
Conclusions: Our findings are in agreement with the limited available literature, but we add that the synergistic interaction between meropenem and polymyxin B is dependent on the degree of meropenem resistance in KPC-producing K. pneumoniae. This data suggests that lower level resistance to carbapenems may be amenable to antimicrobial combinations involving a carbapenem and a polymyxin.
14
Oliveira, Maura Salaroli de. "Avaliação farmacocinética e farmacodinânica de meropenem e vancomicina em pacientes submetidos à diálise estendida de baixa eficiência (SLED)." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5134/tde-14112017-154634/.
Full textAbstract:
INTRODUÇÃO: A combinação de sepse e insuficiência renal com necessidade de diálise é bastante comum nas Unidades de Terapia Intensiva e esta situação tem elevada mortalidade. Um desafio neste cenário é prescrever a dose correta dos antimicrobianos para o tratamento destas infecções. Em pacientes críticos e hemodinamicamente instáveis que necessitam de terapia renal substitutiva, um dos métodos mais utilizados é a diálise contínua, entretanto, recentemente, tem-se utilizado a diálise de baixa eficiência - conhecida como SLED, da abreviação do inglês \"sustained low-efficiency dialysis\". Esta modalidade de terapia renal substitutiva combina características da hemodiálise contínua com a intermitente, utilizando o equipamento da diálise intermitente, com menores fluxos sanguíneos e de dialisato, e com vantagem de menor custo. Apesar do fluxo mais baixo, por ser utilizado tempo mais prolongado, a SLED frequentemente resulta em maior clearance e especula-se que a remoção dos fármacos seria maior. Há escassez de estudos que avaliaram a farmacocinética e farmacodinâmica de antimicrobianos em pacientes submetidos à SLED.OBJETIVOS: Avaliar adequação farmacodinâmica de meropenem e vancomicina em pacientes submetidos a diálise estendida de baixa eficiência. Avaliar a depuração paramêtros farmacocinéticos durante a sessão de SLED. MÉTODOS: Foi realizado estudo prospectivo descritivo observacional com coleta de material biológico julho de 2012 a julho de 2014 HC-FMUSP. Foram incluídos pacientes submetidos à SLED em uso de vancomicina e/ou meropenem. Foram coletadas amostras de sangue seriadas (tempos: imediatamente antes do início da sessão de diálise, 0,5h, 1h, 2h, 4h após o início do tratamento e ao final da sessão). A quantificação dos antimicrobianos foi realizada através dos métodos analíticos de quantificação em Cromatografia Líquida de Alta Eficiência (CLAE). Os parâmetros farmacocinéticos foram calculados apenas durante a sessão de diálise utilizando-se o software WinNonlin. A área sob a curva foi determinada para a vancomicina. Para o meropenem, calculou-se o tempo acima da MIC. Resultados: Foram incluídos 24 pacientes tratados com vancomicina e 21 com meropenem eforam obtidas 170 amostras de plasma. As concentrações médias de vancomicina sérica e meropenem: antes da sessão de SLED foram 24,5 e 28,0 ?g / ml, respectivamente; e após SLED 14 e 6 ?g / ml, respectivamente. A depuração média foi de 41% para a vancomicina e 78% para o meropenem. Para vancomicina, 22 (96%), 19 (83%) e 16 (70%) pacientes teriam atingido o alvo (AUC0-24 > 400) considerando-se MIC 0,5; <= 1mg/l e <= 2 mg/l respectivamente. Para meropenem, 19 (95%), 18 (90%) e 11 (55%) pacientes teriam atingido a meta (70% de tempo acima da CIM) se infectados com isolados com MIC <= 1, <= 4 e <= 8 mg/l, respectivamente. Conclusões: Em pacientes críticos, meropenem evancomicina foram removidas durante o SLED. Entretando, a maioria dos pacientes alcançaria alvo PK-PD, excepto para CIMs mais altas. Sugerimos doses de manutenção de 1g a cada 12 ou 8 horaspara meropenem. Para a vancomicina, deve-se utilizar abordagem mais individualizada com monitorização sérica, uma vez que ensaios comerciais são disponíveisBackground: Antibiotic dosing is a challenge in critically ill patients undergoing renal replacement therapy. Our aim was to evaluate pharmacokinetics and pharmacodynamics of meropenem and vancomycin in patients undergoing SLED.Methods: ICU patients undergoing SLED, receiving meropenem and/or vancomycin, were prospectively evaluated. Blood samples were collected at the start of SLED and 0.5; 1; 2; 4 and 6 hours later. Antimicrobial levels were determined by HPLC. Noncompartimental pharmacokinetic analysis was performed. Area under the curve was determined for vancomycin. For meropenem, time above MIC was calculated. Results: 24 patients receiving vancomycin and 21 receiving meropenem were included; 170 plasma samples were obtained. Median serum vancomycin and meropenem concentrations: before SLED were 24.5 and 28.0 ?g/ml, respectively; and after SLED 14 and 6 ?g/ml, respectively. Mean removal was 41% for vancomycin and 78% for meropenem. For vancomycin, 22 (96%), 19(83%) and 16(70%) patients would have achieved the target (AUC0-24>400) considering MIC 0.5; <= 1mg/l and <= 2 mg/l, respectively. For meropenem, 19 (95%), 18 (90%) and 11(55%) patients would have achieved the target (70% of time above MIC) if infected with isolates with MIC <= 1, <= 4 and <= 8mg/l, respectively. Conclusions: In critically ill patients, meropenem and vancomycin were removed during SLED. Despite this, overall high PK/PD target attainment was obtained, except for higher MICs. We suggest maintenance doses of 1g tid or bid for meropenem. For vancomycin, more individualized approach using therapeutic drug monitoring should be used, as commercial assays are available
15
Barth, Natália. "Avaliação do sinergismo entre polimixina B com tigeciclina, imipenem e meropenem em isolados de enterobactérias produtoras de KPC." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/115024.
Full textAbstract:
Enterobactérias como Klebsiella pneumoniae e Enterobacter spp. estão entre as principais causas de infecções hospitalares e estão frequentemente associadas à produção da enzima Klebsiella pneumoniae carbapenemase (KPC). A emergência de isolados produtores desta e de outras carbapenemases é um grave problema de saúde pública uma vez que as opções terapêuticas tornam-se extremamente limitadas. As polimixinas frequentemente constituem uma das poucas opções disponíveis, porém têm sido associadas a menor eficácia clínica, maior mortalidade e toxicidade. Além disso, há descrição in vitro da emergência de subpopulações heterorresistentes de isolados expostos a esta droga. Neste contexto, muitos estudos têm avaliado a terapia combinada como alternativa e a utilização das polimixinas com outras classes de antimicrobianos tem mostrado resultados mais eficazes em comparação às monoterapias no tratamento de infecções causadas por bactérias multirresistentes, como aquelas produtoras KPC. Assim, o objetivo deste estudo foi avaliar o desempenho de combinações entre polimixina B (PMB) com a tigeciclina (TGC) e com os carbapenêmicos imipenem (IPM) e meropenem (MEM) contra enterobactérias produtoras de KPC-2 pelo método de Time Kill Curves - TKC (Curva de Tempo-Morte). Os isolados foram previamente caracterizados como produtores de KPC-2 e incluíram seis clones de três espécies distintas, sendo dois isolados de K. pneumoniae (KP), dois de Enterobacter cloacae (EC) e dois de Serratia marcescens (SM), provenientes de banco de amostras. A PMB foi testada em concentrações de 0,5, 1,0 e 2,0 μg/mL, enquanto os carbapenêmicos e TGC foram testados a uma concentração fixa de 4,0 e 1,0 μg/mL, respectivamente. Os tubos contendo o inóculo e antibióticos foram incubados a 35 °C e uma alíquota foi semeada em placa de ágar sangue nos tempos: 0, 0,25, 1, 2, 4, 8, 12 e 24 horas, para a contagem das colônias. Os resultados foram interpretados conforme as seguintes definições: i) atividade bactericida = redução ≥ 3 log10 na contagem total de unidades formadoras de colônia (UFC)/mL comparado ao inóculo inicial; ii) atividade bacteriostática = manutenção ou redução < 3 log10 na contagem total de UFC/mL comparado ao inóculo original; iii) sinergismo = diminuição ≥ 2 log10 na contagem total de UFC/mL entre a combinação de antimicrobianos e o agente mais ativo, após 24 horas de incubação. De acordo com nossos resultados, IPM, MEM e TGC não apresentaram efeito bacteriostático ou bactericida quando testados como única droga contra todos os isolados produtores de KPC-2. Todas as combinações de antibióticos mostraram sinergismo com atividade bactericida ou, pelo menos, um efeito bacteriostático para todos os isolados testados, sendo as combinações mais efetivas aquelas onde a de PMB foi usada nas concentrações de 1,0 e 2,0 μg/mL e combinada aos carbapenêmicos. Embora tenham sido observadas concentrações inibitórias mínimas elevadas para PMB contra os isolados de SM, para ambas as cepas houve sinergismo quando a PMB foi combinada a IPM e MEM. Nossos resultados confirmam a superioridade das combinações de antimicrobianos em comparação às monoterapias e sugerem que, a PMB combinada com carbapenêmicos ou TCG pode ser uma opção terapêutica eficaz para o tratamento de infecções causadas por isolados de enterobactérias produtores de KPC-2.Enterobacteria such as Klebsiella pneumoniae and Enterobacter spp. are among the leading causes of nosocomial infections and are often associated with Klebsiella pneumoniae carbapenemase (KPC) production. The emergence of KPC and other carbapenemases is a serious public health problem due to the limited therapeutic. Polymyxins often constitute one of the few options available, but it have been associated with lower clinical efficacy, toxicity and increased mortality. Moreover, several studies have demonstrated the emergence of heteroresistant subpopulations when isolates are exposed to this drug. In this context, some authors have evaluated the combined therapy as an alternative and the use of polymyxins with other classes of antibiotics have shown to be more effective compared to the monotherapies for the treatment of infections caused by multiresistant bacteria. Therefore, the aim of this study was to evaluate the performance of polymyxin B (PMB) with carbapenems imipenem (IPM) and meropenem (MEM) and tigecycline (TGC) combinations against KPC-2 producing Enterobacteriaceae by Time Kill Curves method. Isolates were previously characterized as KPC-2 producing comprising six distinct clones that included: two K. pneumoniae (KP), two Enterobacter cloacae (EC) and two Serratia marcescens (SM). PMB was tested at concentrations 0,5, 1,0 and 2,0 μg/mL, whereas carbapenems and TGC were tested at a fixed concentration of 4.0 and 1.0 μg/mL, respectively. Tubes with inoculum and antibiotics were incubated at 35 °C and an aliquot was plated on blood agar plates at times: 0, 0.25, 1, 2, 4, 8, 12 and 24 hours for counting colonies. The results were interpreted according to the following definitions: i) bactericidal activity = ≥ 3 log10 reduction in total count of colony forming units (CFU)/mL compared to the initial inoculum; ii) bacteriostatic activity = maintenance or reduction < 3 log10 in total count of CFU/mL compared to the original inoculum; iii) synergism = ≥ 2 log10 decrease in total count of CFU/ml between the combination and the most active antimicrobial agent after 24 hours of incubation. According to our results, IPM, MEM and TGC showed no bacteriostatic or bactericidal effects when tested as a single drug against all KPC-2-producing isolates. All combinations of antibiotics showed synergism with bactericidal activity or at least, a bacteriostatic effect for all the six isolates. The more effective combinations were those that PMB was used at 1,0 and 2,0 μg/mL, combined with carbapenems. Although high minimum inhibitory concentrations were observed for PMB against isolates of SM, for both strains, synergism was observed when PMB was combined with IPM and MEM. Our results confirm the superiority of antimicrobial combinations compared to monotherapies and suggest that PMB combined with carbapenem or TCG can be an effective therapeutic option for the treatment of infections caused by KPC-2-producing Enterobacteriaceae.
16
Attemalm, Christine, Jonathan Efverström, Dania Elkhalifa, Viktor Hansen, and Yasmine Sundelin Tjärnström. "An Investigation of Cefadroxil and Meropenem’s Supply Chain and Estimationof the Health Economic Consequences in Sweden due to Shortage." Thesis, Uppsala universitet, Institutionen för kemi - Ångström, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-415426.
Full textAbstract:
Sweden has been increasingly affected by drug shortage and the public healthcare system has identified a large amount of antibiotics risking shortage. Drug shortage of antibiotics is a worldwide problem with complex causes and consequences affecting many countries healthcare systems. The aim of this study is to investigate the shortage of cefadroxil and meropenem. More specifically, to investigate risk factors in the supply chain contributing to their backorders as well as possible consequences for Swedish healthcare due to shortage. To formulate the supply chain for cefadroxil and meropenem, the active pharmaceutical ingredient (API) manufacturers, final dosage form (FDF) holders and market authorization holders (MAHs)were identified. 4 active API manufactures, 18 active FDF holders and 4 MAHs were identified for cefadroxil and 4 active API manufactures, 32 FDF holders and 8 MAHs were identified for meropenem. In order to analyse the causes behind these antibiotic shortages, problems with the manufactures were researched using various sources. Since API production is the first step in thesupply chain, problems connected to the API manufactures was the sole focus in this study. Research identified several problems with the API manufacturers for both antibiotics, indicating that the shortages can in fact be explained by issues in the supply chain. In order to calculate and get an estimate of the health economic costs for society, a model based on direct and indirect costs was used. The direct costs were calculated by comparing the most suitable alternative treatment methods. For cefadroxil there were 5 alternatives in the case of shortage for the oral suspension from Mylan AB (the only product covered in this section of the report due to limited data), whereof 3 of the alternatives still were cefadroxil products. These 3 were cefadroxil dispersible tablets, cefadroxil capsules and Grüncef. The other 2 alternatives were Clindamycin and the combination antibiotic Trimethoprim/Sulfamethoxazol (Eusaprim R). Meropenem had only one identified alternative drug called imipenem. In addition to comparing alternative treatments, the cost of extra labor hours spent on dealing with shortages as well as the increased risk of AMR was also also investigated closely. The indirect costs were based on loss of production due to patient care being longer and more demanding as a result of unforeseen side effects caused by the alternative treatments. This was analyzed qualitatively, in other words no definitive cost was calculatedfor loss of production. Results showed that the exchange from Cefadroxil Mylan oral suspension to cefadroxil dispersible tablets would cost Sweden approximately +35 105 SEK/day. The exchange to cefadroxil capsules would cost -30 939 SEK/day and for Grüncef the cost would be +311 814 SEK/day. As for the other 2 antibiotics, the cost would be -23 103 SEK/day for Clindamycin and -53 084 SEK/day for Eusaprim R. When exchanging meropenem for imipenem, the direct cost was estimated to +343 299 SEK/day. Regarding the cost for extra labor hours spent on dealing with shortage, this was estimated to 1.6 MSEK per shortage, regardless of the antibiotic and shortage duration. The costscalculated for the replacement pharmaceuticals were based on worst case scenarios for when all MAHs had their products unavailable. If the calculated values are of any relevance for real life situations depends on the fragility of the supply chain. In other words, how big these health economicconsequences are for Swedish healthcare is dependant on the risk of unavailability for these antibiotics which goes back to the fragility of the supply chain. In regards to AMR, research showed that substituting cefadroxil for clindamycin and meropenem for imipenem increased the risk of AMR and as a consequence, the direct cost increased as well. The use of clindamycin to treat infections caused by Methicillin-Resistant Staphylococcus Aureus (MRSA) could lead to an additional cost of +3665 SEK/outpatient visit in the case of induced resistance against the antibiotic. Substituting meropenem for imipenem would result in an additional cost of +1160 SEK/day assuming that the bacteria behind the infection is ESBLcarba, an Enterobacteriaeac able to break down carbapenems (a class of antibiotics in which meropenem and imipenem reside). Using licensed drugs could minimize this risk but would however come at a cost for the patients health due to the extended lead time as a result of importation. This would in turn increase the indirect cost to society in the form of loss of production. Despite maybe lowering the risk of AMR, the calculated costs for shortage/day show that using licensed drugs would in fact increase the direct cost a great deal. The calculations for Grüncef and imipenem illustrate this as they proved to be much more costly than the other alternative treatments.
17
Oyola, Salcedo Delia Graciela. "Evaluación de la influencia del meropenem en la formación de piocianina y alginato en Pseudomonas aeruginosa formadora de biopelícula." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2014. https://hdl.handle.net/20.500.12672/3881.
Full textAbstract:
La presente tesis tuvo como objetivo principal evaluar la influencia del meropenem en la formación de piocianina y alginato por cepas de Pseudomonas aeruginosa formadoras de biopelículas. Se detectó un 75% (60/80) de cepas formadoras de biopelículas por el método de O'Toole - Kolter de 80 aislados provenientes de pacientes de los Hospitales Nacionales Edgardo Rebagliati Martins y Guillermo Almenara Irigoyen, de las cuales el 30.0% (18/60) evidenciaron producción de piocianina en una concentración de 6.0 ug/mL a 6.5 ug/mL y el 36.6% (22/60) se evidenció producción de alginato en concentraciones de 6 ug/mL a 10 ug/mL expresado como ácido urónico en presencia de meropenem a la concentración de 10 μg . Sin embargo en ausencia de meropenem se obtuvo una menor producción de piocianina y alginato, por lo que se comprobó que el pigmento de piocianina y la producción de alginato son mecanismos de virulencia que favorecen la supervivencia de Pseudomonas aeruginosa en presencia del antibiótico.Tesis
18
Blaß, Natalie [Verfasser]. "Bestimmung der Konzentration von Meropenem und Ertapenem im Plasma und der Peritonealflüssigkeit von Patienten mit morbider Aipositas / Natalie Blaß." Ulm : Universität Ulm, 2021. http://d-nb.info/1238147658/34.
Full text
19
Pereira, Dariane Castro. "Sistemas de efluxo MexAB-OprM e MexXY e produção de carbapenemanses em pseudomonas aeruginosa : efeito na resistência aos carbapenêmicos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/96648.
Full textAbstract:
Introdução. Pseudomonas aeruginosa é um patógeno clinicamente importante. Existem diversos mecanismos de resistência aos antimicrobianos em P. aeruginosa, dentre eles a produção de enzimas (β-lactamases) e sistemas de efluxo se destacam, uma vez que são capazes de conferir resistência aos carbapenêmicos. Objetivo. Avaliar os sistemas de efluxo MexAB-OprM e MexXY em isolados clínicos de P.aeruginosa de pacientes atendidos no Hospital de Clínicas de Porto Alegre-RS e relacionar a expressão destes sistemas com a CIM de meropenem em isolados produtores e não produtores de metalo-beta-lactamases (MBL). Metodologia. Um total de 86 isolados de P. aeruginosa com suscetibilidade reduzida aos carbapenêmicos foram avaliados. A hiperexpressão dos sistemas MexAB e MexXY foi determinada fenotipicamente utilizando inibidor seletivo da bomba (PAβN). MBLs foi determinada por PCR utilizando primers específicos. Resultados. O fenótipo de hiperexpressão dos sistemas de efluxo estudados foi observado em 34 (47,8%) dos 71 isolados negativos para a produção de MBL e em 14 (93.3%) dos 15 isolados MBL positivos. Na presença de PaβN, todos os isolados não produtores de MBL apresentaram uma redução da CIM para meropenem para valores na faixa de suscetibilidade. Entretanto, das 13 P. aeruginosa produtoras de MBL que diminuíram a CIM, essa redução não foi para valores dentro da faixa de sensibilidade. Conclusão. Os isolados de P. aeruginosa não produtores de MBL apresentam resistência ao meropenem devido a hiperexpressão de MexAB-OprM. Na presença de PaβN, independente de apresentarem produção de MBL, o CIM de meropenem reduziu para valores ≤ 8 mg/L. Contudo, quando isolados não apresentavam MBL, a CIM de meropenem reduziu para níveis de sensibilidade.Introduction. Bacterial efflux pump systems are resistance mechanisms which may lead to therapeutic failure of antibiotic treatment since many antimicrobial agents are substrate for these mechanisms. The aim of the study was to evaluate the expression of the MexAB, MexXY pump efflux and to determine its influence on meropenem MIC in carbapenemase producing and non-producing P. aeruginosa. Methods. A total of 86 non-repetitive clinical isolates of P. aeruginosa with reduced susceptibility to carbapenems were evaluated. Overexperession of MexAB and MexXY efflux systems were evaluated phenotypically using the PAβN selective inhibitor. Metallo-β-lactamases (MBL) were detected by PCR using specific primers. Results. The efflux pump-overexpressed phenotype was observed in 34 (47.8%) MBL-negative and in 14 (93.3%) MBL-positive isolates. In the presence of the PaβN, all non-producers of MBL presented a reduction of meropenem MICs to the range of susceptibility. In contrast, the 13 P. aeruginosa MBL-producing isolates decreased meropenem MICs at least 16-fold but this reduction did not reach the range of susceptibility. Conclusion. P. aeruginosa non-MBL-producing showed resistance to meropenem due to overexpression of MexAB-OprM. In the presence of PaβN, the isolates harboring or not MBL genes, the meropenem MICs were reduced to values ≤8 mg/L. However, when the isolates harbor MBL genes, the meropenem MIC values were reduced to the susceptibility.
20
Alves, Marcelle Duarte. "Efeito da dose de cefepime, piperacilina-tazobactam e meropenem na mortalidade de pacientes com infecção da corrente sanguínea por enterobactérias." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/61901.
Full textAbstract:
Introdução: estudos de farmacocinética/farmacodinâmica (FC/FD) observaram que a probabilidade de alcançar o alvo FC/FD é maior quando a dose do beta-lactâmico é otimizada. Porém, poucos estudos demonstraram que a otimização de dose resulta em melhores desfechos clínicos. Métodos: Fatores associados com mortalidade em 30 dias foram avaliados em 100 pacientes com bacteremia por enterobactérias tratados com cefepime, piperacilina-tazobactam ou meropenem em um estudo de coorte prospectivo. Posologia dos antibióticos foi classificada em otimizada, apropriada e potencialmente inapropriada. Resultados: Cinquenta e dois (52%) episódios foram causados por E. coli, seguidos por K. pneumoniae (10%). Dezesseis (16%) episódios foram causados por isolados resistentes à cefepime e não houve nenhum caso de resistência à carbapenêmicos. A maioria dos isolados apresentou concentrações inibitórias mínimas (CIMs) baixas para as drogas prescritas (≤0.5, ≤1.0, ≤1/4 mg/L, para meropenem, cefepime e piperacilina-tazobactam respectivamente). Cefepime foi o antimicrobiano mais frequentemente prescrito para tratamento empírico e definitivo. Terapia otimizada foi observada em 42% dos pacientes e terapia adequada em 58%. A mortalidade em 30 dias foi 37%. Escore de Pitt, Charlson e apresentação com sepse severa foram independentemente associados à mortalidade. Não houve diferença em mortalidade entre os pacientes que receberam terapia otimizada e terapia adequada. Conclusões: os resultados mostram que a otimização das doses de cefepime, piperacilina-tazobactam e meropenem não teve impacto em mortalidade Em pacientes recebendo terapia empírica apropriada para bacteremias por Enterobacteriaceae. Este achado pode ser devido aos baixos valores de CIM apresentados pelas bactéria. Comorbidades e a severidade da apresentação são fatores associados à pior evolução.Background: Pharmacokinetic/pharmacodynamic (PK/PD) studies have shown that the probability of PK/PD target attainment is higher when optimized dosage regimes of beta-lactams are employed, but few studies have shown clinical benefit of such strategy. Methods: We investigated the effect of dosage regimes in 30-day mortality in 100 patients with Enterobacteriaceae bloodstream infections (BSIs) receiving appropriate empirical therapy with cefepime, piperacillin-tazobactam or meropenem. Posology of antibiotic was classified as optimized, adequate and possibly inadequate. Results: Most isolates presented relatively low MIC for the prescribed drugs (≤0.5, ≤1.0, ≤1/4 μg/mL, for meropenem, cefepime and piperacillin-tazobactam respectively). Cefepime was the most common prescribed drug for empirical and main therapy. Optimized posology was prescribed in 42% of patients and adequate in 58%. The overall 30-day mortality was 27.0%. Charlson score, Pitt score and presentation with severe sepsis were independently associated with the 30-day mortality. Patients receiving optimized dosage regime presented no distinct 30-day mortality of those with adequate ones (25.0% versus 28.3%, P=0.89), even after inclusion in multivariate model. Conclusion: Our results suggest that dosage regime optimization of cefepime, piperacillin-tazobactam and meropenem may have no effect on mortality when infecting bacteria with low MICs for these drugs. In patients receiving appropriate empirical therapy for Enterobacteriaceae BSI, baseline comorbidity is an independent predictor of death and the severity of BSI presentation is also significantly associated with this outcome is such patients. Studies in population with higher MIC heterogeneity are required to evaluate the role of optimized doses in clinical setting.
21
König, Christina [Verfasser], and Claudia [Akademischer Betreuer] Langebrake. "Pharmakokinetik ausgewählter Antiinfektiva unter sustained low-efficiency dialysis (SLED)- am Beispiel von Meropenem und Ceftazidim / Christina König ; Betreuer: Claudia Langebrake." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2017. http://d-nb.info/1128820285/34.
Full text
22
Force, Sanmartín Enriqueta. "Estudio experimental de la eficacia de meropenem y rifampicina en el tratamiento de la meningitis neumocócica sensible y resistente a betalactámicos." Doctoral thesis, Universitat de Barcelona, 2008. http://hdl.handle.net/10803/1101.
Full textAbstract:
La meningitis neumocócica es una enfermedad grave con elevada morbimortalidad y su tratamiento constituye un problema no completamente resuelto desde la aparición en todo el mundo de resistencias a penicilina y cefalosporinas. Meropenem es un carbapenémico que tiene una buena actividad in vitro frente a los principales patógenos que causan meningitis. El clásico modelo de meningitis en el conejo puede no ser adecuado para estudiar meropenem por la facilidad en hidrolizar la Dehidropeptidasa I.El objetivo del estudio es evaluar la eficacia terapéutica de meropenem y rifampicina solos y combinados, frente a dos cepas con diferente sensibilidad a betaláctámicos, utilizando los modelos de meningitis en conejo y en cobaya, y determinar si el modelo de meningitis en conejo puede utilizarse para estudiar meropenem.
DISEÑO DEL ESTUDIO. Estudio in vitro mediante curvas de letalidad. Estudio in vivo en el modelo de meningitis en el conejo y en la cobaya. En ambos estudios se ensayan varias pautas antibióticas frente a dos cepas de neumococo, una sensible y otra resistente a penicilina y cefalosporinas. Previamente se hacen estudios de farmacocinética de los antibióticos en ambos modelos animales, para establecer las dosis y el intervalo entre las mismas.
RESULTADOS. En las curvas de letalidad meropenem es bactericida y rifampicina bacteriostático. La combinación de ambos fármacos es sinérgica o indiferente. En el modelo de la cobaya todos los tratamientos, excepto rifampicina son bactericidas desde las 6 horas. En el modelo del conejo, meropenem es bactericida a las 6 horas frente a la cepa sensible, pero con la cepa resistente se observan fracasos terapéuticos a las 6 horas, siendo bactericida a las 24 horas. La combinación de meropenem más rifampicina mejora significativamente la eficacia de meropenem en solitario en la cepa resistente.
CONCLUSIONES. La combinación de meropenem y rifampicina in vitro es sinérgica o indiferente. Meropenem ha demostrado su eficacia en el tratamiento de la meningitis neumocócica en la cobaya, frente a dos cepas con diferente sensibilidad a betalactámicos. La combinación de meropenem más rifampicina no aumenta la eficacia del meropenem en solitario.
No hay congruencia entre el modelo del conejo y de la cobaya. El retardo en la eficacia de meropenem frente a la cepa resistente en la meningitis en el conejo sugiere que este modelo no es adecuado para estudiar este antibiótico y pone de manifiesto la importancia de la correcta elección del modelo animal en el desarrollo de estudios de eficacia antibiótica.
Meropenem y la combinación de meropenem y rifampicina pueden ser considerados como una alternativa en el tratamiento de la meningitis bacteriana, y constituyen un tratamiento adecuado para las meningitis producidas por neumococos resistentes a cefalosporinas.
"Experimental study efficacy of meropenem and rifampin in the therapy of β-lactams-susceptible and -resistant pneumococcal meningitis"
TEXT:
The increasing spread of cephalosporin- resistant strains has reduced the therapeutic options for pneumococcal meningitis. Meropenem is a broad-spectrum carbapenem antibiotic which is highly active against the major bacterial pathogens causing meningitis, and penetrates well into the cerebrospinal fluid. Results with meropenem in the experimental rabbit model of penumococcal meningitis have been controversial and the possible role of renal dehydropeptidase I in meropenem efficacy has been suggested.
The aim of this study was to determine the in vitro and in vivo efficacies of meropenem alone and combined with rifampin against two Streptococcus pneumoniae strains with different susceptibility to β-lactams using the rabbit and the guinea pig meningitis models, and the possible influence of the animal model over results.
Two strains of Streptococcus pneumoniae with different susceptibility to beta-lactams have been used in a guinea pig model and the classical rabbit meningitis model.
In vitro killing curves meropenem was bactericidal and rifampin was bacteriostatic. Combinations of meropenem plus rifampin were synergic or indifferent. All treatments were bactericidal from 6 h in the guinea pig model. In the rabbit model meropenem was bactericidal at 6 h against the susceptible strain but against the resistant therapeutical failures were recorded at 6 h being bactericidal at 24 h. In the resistant strain the addition of rifampin improves the activity of meropenem alone.
In conclusion, meropenem have shown bactericidal activity in both experimental models and might be a good option in the management of pneumococcal meningitis. This work emphasises the importance of an adequate election of the animal model for the appropriate development of studies of antimicrobial efficacy.
23
Lobos, Saldías Carmen Gloria. "Análisis del consumo de antibióticos restringidos : imipenem, meropenem, cefoperazon-sulbactam, cefepime, piperacilina-tazobactam, vancomicina y linezolid en Clínica Dávila, período 2004-2005." Tesis, Universidad de Chile, 2006. http://www.repositorio.uchile.cl/handle/2250/105507.
Full textAbstract:
Unidad de práctica para optar al título de Químico FarmacéuticoNo autorizada por el autor para ser publicada a texto completo en el Portal de Tesis Electrónicas
La Farmacia Asistencial es una de las áreas en que puede desempeñarse un profesional químico farmacéutico, siendo según estudios del Centro de Estudios Farmacéuticos (CEFAR) donde trabajan más del 76% de los profesionales y puede estar inserta tanto en el área pública como privada. La práctica prolongada para optar al título de químico farmacéutico, se realizó en el Servicio de Farmacia de Clínica Dávila en dos etapas, la primera fue realizada mediante un conocimiento general de las actividades desarrolladas por un químico farmacéutico en una farmacia hospitalaria y se efectuó durante todo el período de práctica y la segunda consistió en realizar una revisión del consumo de antimicrobianos restringidos, al interior de la clínica con el fin de generar pautas, a futuro, respecto de la utilización y protocolización del uso de éstos medicamentos. Las actividades fueron destinadas a conocer y permitir familiarizarse con las labores que realiza el químico farmacéutico en el área asistencial, en donde éste profesional lleva parte importante de la gestión que realiza la institución de salud a la que pertenece. No debemos olvidar que existen muchas y diversas actividades que anteceden al momento en que el paciente recibe el medicamento prescrito y que son necesarias para el éxito de una buena dispensación. Todo esto ayuda a cumplir con la función que se realiza en la farmacia asistencial y que es responsabilidad del químico farmacéutico, velar por el uso racional de los medicamentos
24
Alves, Paola Hoff. "Atividade da polimixina B isoladamente e em combinação com tigeciclina, meropenem e ertapenem frente a isolados de Enterobacter sp. resistentes aos carbapenêmicos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/156633.
Full textAbstract:
Diante do aumento global da resistência microbiana, cada vez mais as combinações de antimicrobianos são utilizadas na tentativa de obter uma atividade sinérgica eficaz que possa ser utilizada na prática clínica. O objetivo deste trabalho foi comparar a atividade de polimixina B isoladamente e em combinação com tigeciclina e carbapenêmicos (ertapenem e meropenem), frente a isolados de Enterobacter sp. resistentes aos carbapenêmicos. Foram selecionados quatro isolados de Enterobacter sp. resistentes aos carbapenêmicos, sendo três isolados produtores de carbapenemases (KPC, NDM, OXA-48-like) e um não produtor de carbapenemases (NPC). A avaliação da atividade sinérgica antimicrobiana foi realizada por ensaio de time-kill com as seguintes concentrações de cada antimicrobiano: tigeciclina 1mg/L, meropenem 1mg/L e ertapenem 0,5mg/L, que correspondem aos pontos de corte de sensibilidade do CLSI (2016). Para polimixina B, foram utilizadas diferentes concentrações de acordo com o perfil de susceptibilidade do isolado: para os isolados sensíveis, utilizou-se 0,5x; 1x e 2x a CIM do isolado; para o isolado resistente, foram utilizados 0,5x; 1x e 2x o ponto de corte de sensibilidade do CLSI (2 mg/L). Foi considerada sinérgica a combinação com redução ≥ 2 logs do inoculo inicial em comparação ao antimicrobiano sozinho mais ativo. As combinações de polimixina B em diferentes concentrações (0,5; 1 e 2mg/L) com meropenem apresentaram atividade sinérgica para a cepa produtora de NDM (CIM polimixina B 1 mg/L; CIM meropenem 8 mg/L) As combinações de polimixina B com tigeciclina foram sinérgicas apenas na concentração de polimixina B de 0,125 mg/L para cepa produtora de OXA-48-like (CIM polimixina B 0,25 mg/L; CIM tigeciclina 2 mg/L) e na concentração de 1 mg/L para a cepa produtora de NDM. Para a cepa NPC (CIM polimixina B 0,5 mg/L; CIM tigeciclina 4 mg/L; CIM meropenem 4 mg/L), apenas a tripla combinação com polimixina B (1 mg/L), tigeciclina e meropenem apresentou atividade sinérgica. A combinação de dois carbapenêmicos não apresentou atividade sinérgica para nenhum isolado, porém, quando acrescentado tigeciclina ao esquema, observou-se sinergismo no isolado produtor de OXA-48-like, o que leva ao questionamento da efetividade da terapia “carbapenem suicida”. Para o isolado produtor de KPC e com padrão de resistência a polimixina B, nenhuma das combinações testadas apresentou sinergismo. Esta situação é bastante preocupante devido à alta prevalência de infecções por bactérias produtoras de KPC nos hospitais brasileiros, juntamente com as crescentes taxas de resistência as polimixinas.Due to the increase in microbial resistance, combinations of antimicrobials are increasingly being used to improve the therapeutic response. The objective of this study was to compare the activity of polymyxin B alone and in combination with tigecycline and carbapenem (ertapenem and meropenem) against to carbapenem-resistant Enterobacter sp isolates. Four isolates were selected, three were carbapenemase-producing (KPC, NDM, OXA-48-like) and a non-carbapenemase-producing (NCP). The evaluation of synergistic antimicrobial activity was performed by time-kill assay with the following concentrations of each antimicrobial: tigecycline 1mg/L, meropenem 1mg/L and ertapenem 0.5mg/L, which correspond to the breakpoints of CLSI (2016). For polymyxin B, different concentrations were used according to the susceptibility profile of the isolate: for susceptible isolates, it was used 0.5x; 1x and 2x the MIC of the isolate, for the resistant isolates it was used 0.5x; 1x and 2x the breakpoint of CLSI (2 mg/L). The combination with reduction ≥ 2 logs of the initial inoculum compared to the most active antimicrobial alone was considered synergies. Combinations of polymyxin B at different concentrations (0.5; 1 and 2 mg/L) with meropenem showed synergistic activity for the NDM-producing isolate (MIC polymyxin B 1 mg/L, MIC meropenem 8 mg/L) Combinations of polymyxin B with tigecycline were synergistic only at the concentration of polymyxin B of 0.125 mg/L for the OXA-48-like-producing isolate (MIC polymyxin B 0.25 mg/L, MIC tigecycline 2 mg/L) and at the concentration of 1 mg/L for the NDM-producing isolate. For the NCP isolate (MIC polymyxin B 0.5 mg/L; MIC tigecycline 4 mg/L; MIC meropenem 4 mg/L), only the triple combination of polymyxin B (1 mg/L) plus tigecycline and meropenem presented synergistic activity. The combination of two carbapenems was not synergic for the four isolates; however, when tigecycline was added to the regimen, synergies for the OXA-48-like-producing isolate were observed. Therefore, the so called, "carbapenem suicide" therapy was not effective in vitro against our isolates. For the KPC-producing isolate that it is polymyxin B resistant, none of the combinations tested showed synergies. This situation is very worrisome due to high prevalence of infections by KPC-producing in the Brazilian hospitals, associate with the increasing rates of polymyxins resistance.
25
Hoppe, Sebastian [Verfasser], Lutz [Akademischer Betreuer] Binder, Michael [Akademischer Betreuer] Oellerich, Helmut [Akademischer Betreuer] Eiffert, and Patricia [Akademischer Betreuer] Virsik-köpp. "Die Pharmakokinetik von Meropenem bei Patienten mit schweren Infektionen / Sebastian Hoppe. Gutachter: Michael Oellerich ; Helmut Eiffert ; Patricia Virsik-Köpp. Betreuer: Lutz Binder." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2010. http://d-nb.info/1042671575/34.
Full text
26
Sánchez-Ato, Luis A., Flavia A. Cuestas-Quiroz, Carla Agurto-Saldaña, and David Estela-Ayamamani. "Pregnancy-Induced Hemophagocytic Lymphohistiocytosis: A Case Report." Springer, 2020. http://hdl.handle.net/10757/655520.
Full text
27
Rissel, René [Verfasser], and Tobias [Akademischer Betreuer] Fink. "Einfluss einer antiinfektiven Therapie mit Meropenem auf flüchtige organische Verbindun-gen in der Ausatemluft während polymikrobieller Sepsis bei der Ratte / René Rissel ; Betreuer: Tobias Fink." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2017. http://d-nb.info/117316314X/34.
Full text
28
LIMA, Fernanda Cristina Gomes de. "Análise da ação do meropenem e Polimixina E com a IgG humana frente isolados de Pseudomonas aeruginosa provenientes de infecções relacionadas à Assistência à Saúde." reponame:Repositório Institucional da UFPE, 2015. https://repositorio.ufpe.br/handle/123456789/14079.
Full textAbstract:
Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2015-05-26T17:40:43Z
No. of bitstreams: 2
license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5)
Dissertação_de_mestrado FERNANDA correção após apresentação FINALIZADA DIGITAL.pdf: 1967282 bytes, checksum: 8e1bd13e2a7cb2f2b493bb443c3db0f9 (MD5)Made available in DSpace on 2015-05-26T17:40:43Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação_de_mestrado FERNANDA correção após apresentação FINALIZADA DIGITAL.pdf: 1967282 bytes, checksum: 8e1bd13e2a7cb2f2b493bb443c3db0f9 (MD5) Previous issue date: 2015-02-23
Pseudomonas aeruginosa é uma importante causa de infecções apresentando, no Brasil, altas taxas de morbidade e mortalidade. Os principais mecanismos de resistência utilizados por P. aeruginosa são a produção de β-lactamases e a expressão de bombas de efluxo. O uso de IgG e antibióticos para tratamento destas infecções tem apresentado resultados bem sucedidos, o que motiva a realização de estudos quanto a atividade in vitro da IgG humana com antibióticos frente a isolados de P. aeruginosa. O objetivo deste estudo foi detectar a presença dos genes de resistência, a relação clonal, o tempo de morte em isolados de P. aeruginosa provenientes de Infecções relacionadas à saúde (IrAS) de hospitais públicos do Recife-PE, em 2014, e verificar in vitro a taxa de fagocitose e a produção de oxido nítrico (NO) por monócitos humanos quando infectados por P. aeruginosa tratada com IgG humana em associação a Meropenem e Polimixina E. Foram avaliados 32 isolados para a detecção de genes de resistência por PCR, e para a avaliação de similaridade genética por ERIC-PCR. Destes, foram selecionados os 5 isolados apresentando maior número de genes de resistência e menor similaridade genética. Esses cinco isolados foram submetidos às associações dos sub-CIMs destes antibióticos com a IgG humana, para a determinação do tempo de morte, da taxa de fagocitose de células bacterianas e para a dosagem de NO por monócitos humanos. Foi detectado a presença do gene blaKPC em dois isolados de P. aeruginosa. Todos os isolados possuem os genes mexR, mexB, mexE e rpsL, apenas um isolado foi negativo para os genes mexA e mexF. Foram detectados 30 perfis genéticos distintos entre os isolados bacterianos. O tempo de morte dos isolados revelou que os tratamentos combinados com antibióticos, principalmente Polimixina E, são mais letais para as células bacterianas. A taxa de fagocitose por monócitos humanos revelou que quando infectados com bactéria tratada com IgG mais antibiótico, os monócitos ficam mais ativos à fagocitose e reduz drasticamente a quantidade de células bacterianas. Houve diferença significativa na produção de NO naqueles tratados com Meropenem e IgG. Com o presente estudo concluiu-se que a combinação de IgG mais antibiótico pode ser uma alternativa para o tratamento dessas infecções, pois a bactéria estará em número reduzido facilitando a fagocitose.
29
Ulldemolins, Gómez Marta. "Optimization of meropenem and piperacillin dosing in critically ill patients with septic shock and acute kidney injury requiring continuous renal replacement therapy: a pharmacokinetic and pharmacodynamic study." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/585924.
Full textAbstract:
BACKGROUND:
Early and appropriate antibiotic administration has been shown to be the most effective intervention for reducing mortality in critically ill patients with septic shock and multiple organ dysfunction syndrome (MODS). However, despite its relevance, antibiotic dosing in those patients with MODS including acute kidney injury (AKI) that require continuous renal replacement therapy (CRRT) still represents a major challenge for clinicians. In our environment, the broad[spectrum beta[lactams meropenem and piperacillin (in combination with tazobactam) are the antibiotics most frequently prescribed to these patients with very high levels of sickness severity. The impact of septic shock, AKI and CRRT on these antibiotics’ dose requirements is vital, as medical interventions and the disease itself are likely to produce significant variations in their pharmacokinetics (PK), which may lead to alterations in drug concentrations over time and hence compromise the achievement of drug concentrations within the therapeutic range. However, it is still very complex to individualize piperacillin and meropenem dosing in patients with septic shock and AKI necessitating CRRT.
HYPOTHESIS:
Meropenem and piperacillin dosing is not optimal in critically ill patients with septic shock and AKI requiring CRRT due to disease and medical[driven variations in antibiotic PK and, therefore, in dose requirements, which may lead to failure in the achievement of therapeutic concentrations.
AIMS:
1. To evaluate the suitability of current meropenem and piperacillin dosing recommendations in critically ill patients with septic shock and AKI necessitating CRRT;
2. To identify the sources of variability that compromise optimal drug dosing in this patient population; and
3. To develop new recommendations that allow dose individualization considering these variability sources.
METHODS:
Three studies have been developed under the study hypothesis and aims.
Study 1: Literature review. A systematic literature review and critical evaluation of the available evidence on meropenem and piperacillin dosing in critically ill patients with septic shock and AKI necessitating CRRT has been performed.
Studies 2 and 3: Characterization of the PK of meropenem and piperacillin in critically ill patients with septic shock and AKI necessitating CRRT. Two observational, prospective, multicenter, open[label pharmacokinetic studies have been performed in the Intensive Care Units from three Spanish tertiary hospitals. Thirty patients with septic shock and CRRT receiving meropenem and 19 patients receiving piperacillin have been enrolled. Two population PK models have been developed and subsequently validated with data from these patients, and Monte Carlo simulations have been undertaken using NONMEM v.7.3®.
RESULTS:
The main finding of study 1 is that present “oneTsizeTfitsTall” dosing recommendations for meropenem and piperacillin in critically ill patients with septic shock and AKI requiring CRRT are based on studies with some drawbacks, such as: 1) different sickness severities and levels of renal function, 2) different admission diagnostics (medical versus surgical versus trauma), 3) different clinical managements mainly CRRT settings, 4) heterogeneous PK methodologies, and 5) different PD targets for dosing recommendations. This scenario limits extrapolation of their conclusions to our patient population.
Later on, studies 2 and 3 have identified important sources of meropenem and piperacillin PK variability that may assist in dose individualization. For meropenem, the main finding of the population PK analysis is the relationship existing between the 24h urine output and meropenem total clearance (CL). Patients with conserved diuresis (>500mL/24h) exhibit at least a 30% increase in meropenem total CL compared to those patients who are anuric (<100mL/24h), increase that is directly proportional to urine volume. Following Monte Carlo simulations based on this population PK model have shown that for maintaining unbound concentrations of meropenem above the minimum inhibitory concentration (MIC) of the bacteria for a 100% of the dosing interval (100%
FuT>MIC), oligoanuric patients (residual diuresis 0[500mL/24h) require 500mg/q8h over 30min for the treatment of susceptible bacteria (MIC<2mg/L), while patients with preserved diuresis (>500 mL/24h) require the same dose over a 3h[infusion. If bacteria with MIC close to the resistance breakpoint (2[4mg/L) are to be treated with meropenem, a dose of 500mg/q6h is necessary: over a 30min[bolus for oligoanuric patients and over a 3h[infusion for patients with preserved diuresis. For the attainment of more conservative PD targets (40% FuT>MIC), 500mg/q8h over a 30min[bolus is sufficient regardless of residual diuresis
With regards to piperacillin, the main finding of the population PK analysis is the relationship existing among the type of membrane used for CVVHDF, the patient’s weight and piperacillin total CL; for a body weight of 80kg, piperacillin total CL is doubled when a 1.5m2 AN69 acrylonitrile and sodium methallyl sulfonate copolymer filter pre[ coated with heparin and polyethyleneimine (AN69ST) is used compared to the CL for a 0.9m2 AN69 filter. Subsequent Monte Carlo simulations have shown that for a PD target of 100% FuT>MIC, patients receiving CVVHDF with 1.5m2 AN69ST membranes require doses of 4000mg/q8h for the treatment of bacteria with a susceptibility to piperacillin close to the clinical breakpoint (MIC = 8[16mg/L). In contrast, 2000mg/q8h are sufficient for patients with CVVHDF using 0.9m2AN69 membranes. For the treatment of bacteria with high susceptibility to piperacillin (MIC ≤ 4mg/L) or for the attainment of a more conservative PD target (50% FuT>MIC), 2000mg/q8h are sufficient in all cases.
CONCLUSIONS:
Due to data heterogeneity, current meropenem and piperacillin dosing recommendations for patients with septic shock and CRRT follow a one[size[fits[all fashion, which often translates into a best[guess dosing at the bedside. In this context, we have shown that identification and consideration of clinical and demographic parameters that influence meropenem and piperacillin PK, such as 24h urine output, patient’s weight and type of CRRT membrane, is advantageous for dose titration. As they are characteristics easy to be measured at the bedside, the implementation of our research findings in the real clinical setting is easy and may be helpful in the complex process of optimization of antibiotic use in the Intensive Care Unit.L’administració precoç d’antibioteràpia apropiada ha demostrat ser la intervenció més eficaç per reduir la mortalitat en pacients crítics amb xoc sèptic i síndrome de disfunció multiorgànica (SDMO). Malgrat la seva rellevància, però, la dosificació antibiòtica en els pacients amb SDMO incloent insuficiència renal aguda (IRA) que requereixen teràpia continua de suport renal (TCSR) encara representa un repte diari pels professionals de la salut. Al nostre medi, els antibiòtics beta[lactàmics d’ampli espectre meropenem i piperacilelina (en combinació amb tazobactam) són els antibiòtics més prescrits a aquests pacients d’altíssima complexitat i gravetat. L'impacte del xoc sèptic, la IRA i la TCSR en els requeriments de dosis d'aquests fàrmacs és vital, ja que tant la pròpia malaltia com les intervencions mèdiques produeixen alteracions significatives en la seva farmacocinètica (FC), que duen a variacions en els perfils concentració[temps i, conseqüentment, comprometen l'assoliment de concentracions del fàrmac dins del rang terapèutic. No obstant això, individualitzar la dosificació de meropenem i piperacilelina en pacients amb xoc sèptic, IRA i requeriment de TCSR és encara molt complex. HIPÒTESI: La dosificació de meropenem i piperacilelina en pacients crítics amb xoc sèptic i IRA que requereixen TCSR és sub[òptima degut a les variacions en el comportament FC dels fàrmacs produïdes tant per la malaltia com pel maneig mèdic d’aquesta. Aquestes variacions FC poden comprometre l'assoliment de concentracions terapèutiques. OBJECTIUS: 1. Avaluar la idoneïtat de les recomanacions actuals sobre dosificació de meropenem i piperacilelina en pacients crítics amb xoc sèptic i IRA que requereixen TCSR; 2. Identificar les fonts de variabilitat que comprometen l’exposició òptima a aquests antibiòtics en la nostra població de pacients; i 3. Desenvolupar noves recomanacions per individualitzar la dosificació d’aquests antibiòtics tenint en compte aquestes fonts de variabilitat. METODOLOGIA: En base a la hipòtesi i els objectius, s’han desenvolupat els tres estudis següents: Estudi 1: Revisió de la literatura. S’ha realitzat una revisió sistemàtica i avaluació crítica de l'evidència disponible sobre la dosificació de meropenem i piperacilelina en pacients crítics amb xoc sèptic, IRA i requeriment de TCSR. Estudis 2 i 3: Caracterització de la FC de meropenem i piperacilelina en pacients crítics amb xoc sèptic i IRA que requereixen TCSR. S’han realitzat dos estudis farmacocinètics multicèntrics, oberts, prospectius observacionals, a les Unitats de Medicina Intensiva de tres hospitals espanyols de tercer nivell. S’han inclòs a l’estudi 30 pacients amb xoc sèptic, IRA i TCSR que rebien meropenem i 19 pacients que rebien piperacilelina. Amb les dades procedents d’aquests pacients, s’han desenvolupat i validat dos models FC poblacionals, a partir dels quals s’han realitzat simulacions de Monte Carlo de diferents esquemes terapèutics (mitjançant el software NONMEM v.7.3®). RESULTATS: La principal troballa de l'estudi 1 és que les recomanacions actuals de dosificació de meropenem i piperacilelina en pacients crítics amb xoc sèptic i IRA que requereixen TCSR es basen en estudis amb algunes limitacions, com ara: 1) diferents nivells de gravetat de la malaltia i de disfunció renal, 2) diferents diagnòstics d’ingrés (mèdic versus quirúrgic versus trauma), 3) diferents maneigs clínics, principalment referent a les característiques de la TCSR, 4) metodologies heterogènies d’anàlisi FC, i 5) diferents objectius farmacodinàmics (FD) en base als quals es fan les recomanacions de dosificació. Això compromet l'extrapolació dels resultats d’aquests estudis a la nostra població de pacients. Posteriorment, els estudis 2 i 3 han identificat importants fonts de variabilitat en la FC de meropenem i piperacilelina, que si es consideren en el moment de la dosificació poden ser útils per individualitzar el tractament antibiòtic. Pel que fa a meropenem, la principal conclusió de l'anàlisi FC poblacional és la relació existent entre la diüresi acumulada de 24h i l’aclariment total de meropenem (CL). Els pacients amb diüresi conservada (>500ml/24h) presenten un increment d’almenys el 30% sobre el CL total de meropenem en comparació amb aquells pacients anúrics (<100mL/24h), sent aquest augment en el CL del fàrmac directament proporcional al volum d'orina. Posteriorment, les simulacions de Monte Carlo basades en aquest model FC poblacional han demostrat que per tal de mantenir les concentracions de meropenem per damunt de la concentració mínima inhibitòria (CMI) dels bacteris durant un 100% de l'interval de dosificació (100% FuT>CMI), els pacients oligo[anúrics (diüresi residual de 0[500mL/24h) requereixen 500mg/q8h administrats en un bolus de 30 minuts per al tractament de microorganismes susceptibles (CMI <2 mg/L), mentre que els pacients amb diüresi conservada (>500mL/24h) requereixen la mateixa dosi administrada mitjançant una perfusió de 3h. Pel tractament de microorganismes amb una CMI propera al límit de susceptibilitat (2[ 4mg/L) és necessària una dosi de 500mg/q6h: administrada en un bolus de 30 minuts de en pacients oligo[anúrics i mitjançant una perfusió de 3h en pacients amb una diüresi conservada. Si s’escull un objectiu FD més conservador, (40% FuT>CMI), una dosi de 500mg/q8h administrada en un bolus de 30 minuts és suficient amb independència de la diüresi residual. Pel que fa a la piperacilelina, la principal conclusió de l'anàlisi FC poblacional és la relació existent entre el tipus de membrana utilitzada per la TCSR, el pes del pacient i el CL total de piperacilelina; per a un pes de 80 kg, el CL total de piperacilelina es duplica quan es fa servir una membrana d’1,5m2 de copolímer d’acrilonitril i sulfat sòdic de metalelil amb un recobriment d’heparina i polietilenimina (AN69ST) en comparació amb el CL total observat quan es fa servir un filtre AN69 convencional de 0,9m2. Posteriors simulacions de Monte Carlo han demostrat que per a un objectiu FD de 100% FuT>CMI, els pacients que reben TCSR amb membranes AN69ST d’1,5m2 requereixen dosis de 4000mg/q8h per al tractament de microorganismes amb CMI properes al límit de susceptibilitat (CMI = 8[ 16mg/L). Per contra, 2000mg/q8h són suficients per als pacients que reben TCSR amb membranes AN69 de 0,9 m2. Per al tractament de soques d’alta susceptibilitat a la piperacilelina (CMI ≤ 4mg/L), o per l’assoliment d'un objectiu FD més conservador (50% FuT>CMI), 2000mg/q8h són suficients en tots els casos.
30
Jakob, André [Verfasser], Matthias [Akademischer Betreuer] Gründling, Matthias [Gutachter] Gründling, and Alexander [Gutachter] Brinkmann. "Etablierung eines Routine-Therapeutischen-Drug-Monitorings (TDM) für Meropenem bei Patienten mit schwerer Sepsis oder septischem Schock / André Jakob ; Gutachter: Matthias Gründling, Alexander Brinkmann ; Betreuer: Matthias Gründling." Greifswald : Ernst-Moritz-Arndt-Universität, 2018. http://d-nb.info/1166315134/34.
Full text
31
Jakob, André Verfasser], Matthias [Akademischer Betreuer] [Gründling, Matthias [Gutachter] Gründling, and Alexander [Gutachter] Brinkmann. "Etablierung eines Routine-Therapeutischen-Drug-Monitorings (TDM) für Meropenem bei Patienten mit schwerer Sepsis oder septischem Schock / André Jakob ; Gutachter: Matthias Gründling, Alexander Brinkmann ; Betreuer: Matthias Gründling." Greifswald : Ernst-Moritz-Arndt-Universität, 2018. http://nbn-resolving.de/urn:nbn:de:gbv:9-opus-22832.
Full text
32
Lindman, Elin. "A spectrophotometric method to analyze antibiotics in plasma: A validation study." Thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-355556.
Full textAbstract:
Antibiotic resistance is one of the most serious medical problems in the world. To counteract the increase in antibiotic resistance, new rapid and effective analytical methods are needed. To effectively treat infections in critically ill patients, optimal antibiotic dosages are required. DrugLog® is an instrument that uses a spectrophotometric method to analyze antibiotics in plasma in the wavelength range 200-800 nm. The aim of this study was to do a method validation of the instrument DrugLog®. The study material that was used was whole blood from healthy donor and routine citrate plasma samples from the laboratory. The precision of the method and stability of plasma, the best way to filtrate lipids from plasma and four antibiotics (meropenem, cefotaxime, vancomycin, piperacillin/tazobactam) were investigated. The precision of the method, measured as CV% was less than 0.62 and stability plasma showed a CV% of 135.74 after 24 h in room temperature. The stability for the different antibiotics after 24 h in room temperature showed a CV% of 8.11 for meropenem, 40.80 for vancomycin, 16.55 for cefotaxime and 2.92 for the combination antibiotic piperacillin/tazobactam. It was also determined that bacterial filter was the best way to remove lipids from plasma. In conclusion DrugLog® is a suitable instrument to analyze concentration of antibiotics in patients during antibiotic treatment, however further validations are needed.
33
Syed, Mohamed Ami Fazlin. "Pharmacokinetic and Pharmacodynamic Modeling of Antibiotics and Bacterial Drug Resistance." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-188306.
Full textAbstract:
Exposure to antibiotics is an important factor influencing the development of bacterial resistance. In an era where very few new antibiotics are being developed, a strategy for the development of optimal dosing regimen and combination treatment that reduces the rate of resistance development and overcome existing resistance is of utmost importance. In addition, the optimal dosing in subpopulations is often not fully elucidated. The aim of this thesis was to develop pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PKPD) models that characterize the interaction of antibiotics with bacterial growth, killing and resistance over time, and can be applied to guide optimization of dosing regimens that enhance the efficacy of mono- and combination antibiotic therapy. A mechanism-based PKPD model that incorporates the growth, killing kinetics and adaptive resistance development in Escherichia coli against gentamicin was developed based on in vitro time-kill curve data. After some adaptations, the model was successfully applied for similar data on colistin and meropenem alone, and in combination, on one wild type and one meropenem-resistant strain of Pseudomonas aeruginosa. The developed population PK model for colistin and its prodrug colistin methanesulfonate (CMS) in combination with the PKPD model showed the benefits for applying a loading dose for this drug. Simulations predicted the variability in bacteria kill to be larger between dosing occasions than between patients. A flat-fixed loading dose followed by an 8 or 12 hourly maintenance dose with infusion duration of up to 2 hours was shown to result in satisfactory bacterial kill under these conditions. Pharmacometric models that characterize the time-course of drug concentrations, bacterial growth, antibacterial killing and resistance development were successfully developed. Predictions illustrated how PKPD models based on in vitro data can be utilized to guide development of antibiotic dosing, with examples advocating regimens that (i) promote bacterial killing and reduce risk for toxicity in preterm and term newborn infants receiving gentamicin, (ii) achieve a fast initial bacterial killing and reduced resistance development of colistin in critically ill patients by application of a loading dose, and (iii) overcome existing meropenem resistance by combining colistin and meropenem
34
Gallo, Stephanie Wagner. "Avalia??o do fen?tipo de persist?ncia em isolados nasocomiais de Acinetobacter calcoaceticus-baumannii." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2017. http://tede2.pucrs.br/tede2/handle/tede/7566.
Full textAbstract:
Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-07-04T17:46:23Z
No. of bitstreams: 1
TES_STEPHANIE_WAGNER_GALLO_PARCIAL.pdf: 790698 bytes, checksum: 760c735fb69bbd136bd69c8c9ddfb82d (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-07-04T17:46:32Z (GMT) No. of bitstreams: 1 TES_STEPHANIE_WAGNER_GALLO_PARCIAL.pdf: 790698 bytes, checksum: 760c735fb69bbd136bd69c8c9ddfb82d (MD5)
Made available in DSpace on 2017-07-04T17:46:40Z (GMT). No. of bitstreams: 1 TES_STEPHANIE_WAGNER_GALLO_PARCIAL.pdf: 790698 bytes, checksum: 760c735fb69bbd136bd69c8c9ddfb82d (MD5) Previous issue date: 2017-03-27
Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Funda??o de Amparo ? Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
Acinetobacter calcoaceticus-baumannii (ACB) complex comprises opportunistic and emerging pathogens that are responsible for several diseases, mainly affecting immunocompromised patients and those hospitalized in intensive care units. Therapeutic options for ACB infections are restricted, since these microorganisms are often resistant to most antimicrobials. In addition, these bacteria may also form persister cells, which constitute a small population of susceptible cells able to survive lethal concentrations of bactericidal antimicrobials and other stressors. This phenotype is associated with failure in antimicrobial therapy, especially in chronic and recurrent infections. Therefore, the aim of this study was to evaluate the presence of persister cells from ACB complex isolates exposed to meropenem and/or polymyxin B, in biofilm and planktonic cells, as well as to analyze these cells regarding their morphology and identify expression patterns of proteins possibly involved in the formation and maintenance of persistence. For this, 20 clinical isolates were characterized for the ability to form biofilm on polystyrene surface, and for meropenem and polymyxin B susceptibility, by the assessment of Minimum Inhibitory Concentration (MIC). All isolates were exposed to meropenem at different concentrations above the MIC, while five isolates were exposed to polymyxin B for the assessment of the persisters presence. For all experiments, in order to estimate the fraction of remaining cells, aliquots were removed at determined time points, followed by serial decimal dilutions and drop plating technique on nutrient agar. All isolates presented persisters at different proportions, in both culture conditions when exposed to meropenem or polymyxin B after 48 h. The higher fractions were verified in biofilm for both antimicrobials in comparison with planktonic cultures. Meropenem concentrations did not influence persisters levels. However, after polymyxin B exposure, persister cells fractions were dependent on the concentration employed. After 24 h polymyxin B exposure, a growth resumption of surviving cells was observed. These cells were again evaluated for susceptibility to this antimicrobial, remaining susceptible with MIC of 1 ?g/ mL. Moreover, integrity of polymyxin B in the supernatant of the cultures was verified by chromatographic assay, demonstrating that polymyxin B is not significantly degraded after 48 h exposure. On the other hand, when meropenem and polymyxin B were associated at different concentrations, no resumption of cell growth was observed, as well as this combination was able to eradicate persister cells from A. baumannii (Acb-1) cultured in late exponential phase. Furthermore, Nano-Liquid Chromatography Coupled to Tandem Mass Spectrometry was employed for the identification and relative quantification of proteins possibly associated with persistence in A. baumannii, after exposure to meropenem. Different patterns of expression were identified between persister cells present in planktonic and biofilm cultures, suggesting that persistence may be regulated by different mechanisms. Proteins involved in the cell division and DNA replication were overexpressed in planktonic persisters, in agreement with the electron scanning microscopy images that presented dividing cells in this culture condition. Overexpression of glucose dehydrogenase (GDH), NADH dehydrogenase 1 (NDH-1), succinate dehydrogenase and ATP synthase indicates the electron transfer from the GDH-catalyzed reaction to the electron transport chain as a possible energy source for persisters, supporting the presence of cell division observed in planktonic culture. Conversely, proteins involved in amino acid metabolism, as well as major elongation factors were underexpressed in Acb-1 persister cells, suggesting that protein synthesis is reduced, even though many proteins were overproduced. Increased expression of several membrane-related proteins has also been observed, indicating possible changes in its composition and function, although proteins related to lipid metabolism were underexpressed. Overall, proteomic analysis of the persister cells showed that these cells could be physiologically distinct when cultured under different conditions, as well as overtime in the same condition. Therefore, considering the different behaviors of Acb-1 when exposed alone to meropenem or polymyxin B, as well as when exposed to these drugs in combination, it was concluded that each antimicrobial might act as a different stressor, possibly leading and/or selecting distinct tolerance mechanisms among persisters, which enabled their eradication when the drugs were combined.
Os pat?genos pertencentes ao complexo Acinetobacter calcoaceticus-baumannii (ACB) s?o considerados oportunistas e emergentes, respons?veis por ocasionar diversas enfermidades, acometendo principalmente pacientes imunocomprometidos e internados em unidades de tratamento intensivo. As op??es terap?uticas para o tratamento de infec??es ocasionadas por estes pat?genos s?o restritas, uma vez que estes apresentam frequentemente resist?ncia ? maioria dos antimicrobianos. Al?m disso, essas bact?rias podem ainda formar c?lulas persisters, que constituem uma pequena popula??o de c?lulas suscet?veis capazes de tolerar concentra??es letais de antimicrobianos bactericidas e outros agentes estressores. Este fen?tipo est? associado a falhas na terapia antimicrobiana, especialmente nas infec??es cr?nicas e recorrentes. Desta forma, o objetivo deste trabalho foi avaliar a presen?a de c?lulas persisters formadas por isolados do complexo ACB frente ? exposi??o ao meropenem e/ou ? polimixina B, na condi??o de biofilme e em cultivo planct?nico, assim como analisar estas c?lulas morfologicamente e identificar padr?es de express?o de prote?nas que pudessem estar envolvidos na forma??o e manuten??o da persist?ncia. Para tanto, 20 isolados cl?nicos foram caracterizados quanto ? capacidade em formar biofilme em superf?cie de poliestireno, e ? suscetibilidade ao meropenem e ? polimixina B, que foi avaliada por meio da determina??o da Concentra??o Inibit?ria M?nima (CIM) a estes f?rmacos. Todos os isolados foram submetidos ? exposi??o ao meropenem em diferentes concentra??es acima da CIM, enquanto que cinco foram expostos ? polimixina B para a avalia??o da presen?a de c?lulas persisters. Para todos os experimentos, a fim de estimar a fra??o de c?lulas remanescentes, al?quotas foram removidas em tempos determinados, efetuando-se dilui??es decimais seriadas e semeadura pela t?cnica da gota em ?gar nutriente. C?lulas persisters, em diferentes fra??es, foram encontradas nos cultivos de todos os isolados, tanto em biofilmes como na condi??o planct?nica, ap?s a exposi??o por 48 h ao meropenem e ? polimixina B, sendo as fra??es mais elevadas encontradas na condi??o de biofilme para ambos os antimicrobianos. As diferentes concentra??es de meropenem avaliadas n?o influenciaram os n?veis de c?lulas persisters; entretanto, frente ? exposi??o ? polimixina B, a fra??o de c?lulas mostrou-se dependente da concentra??o empregada. Ap?s exposi??o ? polimixina B por 24 h, foi observada retomada de crescimento das c?lulas sobreviventes, que foram avaliadas novamente quanto ? suscetibilidade a este antimicrobiano, mantendo-se suscet?veis com CIM de 1 ?g/mL, bem como foi verificada a integridade do antimicrobiano no sobrenadante destes cultivos por ensaios cromatogr?ficos, demonstrando que o mesmo n?o sofre degrada??o ap?s 48 h de exposi??o. Entretanto, quando se associou meropenem ? polimixina B em diferentes concentra??es, al?m de n?o ter sido observada a retomada de crescimento das c?lulas remanescentes, ocorreu a erradica??o das c?lulas persisters de um isolado de A. baumannii (Acb-1) cultivado em fase exponencial tardia. Al?m disso, a t?cnica de Nano-Cromatografia L?quida acoplada ? Espectrometria de Massas em Tandem foi empregada para a identifica??o e quantifica??o relativa de prote?nas possivelmente associadas ? persist?ncia em A. baumannii, ap?s a exposi??o ao meropenem. Diferentes padr?es de express?o foram identificados entre as c?lulas persisters presentes em cultivo planct?nico e em biofilme, sugerindo que a regula??o da persist?ncia possa ser realizada por mecanismos diferentes. Observou-se express?o aumentada de prote?nas envolvidas nos processos de divis?o celular e replica??o de DNA, especialmente no cultivo planct?nico, em concord?ncia com a presen?a de divis?o celular observada nas imagens obtidas a partir da microscopia eletr?nica de varredura nesta condi??o de cultivo. O aumento de express?o da glicose desidrogenase (GDH), NADH desidrogenase (NDH-1), succinato desidrogenase e ATP sintase indicam a transfer?ncia de el?trons a partir da rea??o catalisada por GDH para a cadeia de transporte de el?trons como uma poss?vel fonte de energ?tica para as persisters, corroborando a observa??o da presen?a de divis?o celular observada no cultivo planct?nico. Em contraste, prote?nas envolvidas no metabolismo de amino?cidos, bem como os principais fatores de elonga??o apresentaram express?o diminu?da em c?lulas persisters de Acb-1, sugerindo que a s?ntese proteica esteja reduzida, mesmo que muitas prote?nas tenham sido identificadas com express?o aumentada. Muitas prote?nas relacionadas ? membrana apresentaram a sua express?o aumentada, indicando poss?veis altera??es em sua composi??o e fun??o, embora prote?nas relacionadas ao metabolismo de lip?deos tenham apresentado express?o diminu?da. A an?lise prote?mica das c?lulas persisters, sobretudo, mostrou que estas c?lulas podem ser fisiologicamente distintas quando cultivadas em condi??es diferentes, bem como ao longo do tempo em uma mesma condi??o. Desta forma, considerando os distintos comportamentos do Acb-1 quando exposto isoladamente ao meropenem ou ? polimixina B, bem como quando exposto a estes f?rmacos ao mesmo tempo, pode-se concluir que cada antimicrobiano pode ter atuado como um diferente estressor, possivelmente, levando a e/ou selecionando mecanismos de toler?ncia diferentes entre as persisters, o que possibilitou a sua erradica??o quando os f?rmacos foram combinados.
35
Salinas, Herrera Darlen Alejandra. "Estudio de consumo y elaboración de manual de utilización racional de antibióticos de uso restringido : vancomicina, linezolid, imipenem-cilastatino, meropenem, cefepima, anfotericina B, cefoperazona-sulbactam, ertapenem, colistina y piperacilina-tazobactam." Tesis, Universidad de Chile, 2007. http://repositorio.uchile.cl/handle/2250/105656.
Full textAbstract:
Unidad de práctica para optar al título de Químico FarmacéuticoNo autorizada por el autor para ser publicada a texto completo en el Portal de Tesis Electrónicas
El profesional químico farmacéutico está apto para desempeñarse en un amplio campo laboral, ya que posee una rigurosa formación en distintos ámbitos de la ciencia, pudiendo hacerlo tanto en el área pública como privada, así también como entregador de servicio o fiscalizador. Una de las áreas en que puede desempeñarse es en la Farmacia Asistencial, ya sea pública o privada y, dentro de la misma, en distintas subáreas. La práctica prolongada para optar al título de químico farmacéutico se realizó en el Servicio de Farmacia de Clínica Dávila y se dividió en dos etapas: a) La primera de ellas, estuvo destinada a conocer el quehacer profesional en todo lo que abarca la farmacia propiamente tal, a saber, compras y gestión con proveedores, recepción e ingreso de compras de medicamentos y otros, recepción y dispensación de medicamentos a los servicios, elaboración de papelillos y dosis unitaria, dilución de drogas oncológicas y preparación de nutriciones parenterales y, finalmente, asistencia al comité de farmacia de la clínica. b) La segunda, se centró en analizar el consumo de antimicrobianos en el período enerodiciembre del año 2006 y elaborar un manual de utilización racional de antibióticos de uso restringido, de acuerdo a los fármacos seleccionados por los infectólogos de la clínica. El manual de utilización racional de antibióticos de uso restringido abarcó diez agentes antimicrobianos: anfotericina B, cefepima, cefoperazona-sulbactam, colistina, ertapenem, imipenem-cilastatina, linezolid, meropenem, piperacilina-tazobactam y vancomicina. El estudio de consumo y la elaboración del manual, se realizó con el objetivo de entregar información farmacológica a los profesionales de la salud y la posibilidad de generar pautas, a futuro, respecto de una mejor utilización de estos agentes y disminuir la aparición de resistencia bacteriana
36
Fürstenberg, Hannes Martin Lothar [Verfasser], Matthias [Akademischer Betreuer] Gründling, Matthias [Gutachter] Gründling, and Frank [Gutachter] Bloos. "Untersuchungen zur primär kalkulierten antiinfektiven Therapie von Patienten mit schwerer Sepsis und septischem Schock unter besonderer Berücksichtigung des Antibiotikums Meropenem / Hannes Martin Lothar Fürstenberg ; Gutachter: Matthias Gründling, Frank Bloos ; Betreuer: Matthias Gründling." Greifswald : Ernst-Moritz-Arndt-Universität, 2018. http://d-nb.info/1166315177/34.
Full text
37
Fürstenberg, Hannes Martin Lothar Verfasser], Matthias [Akademischer Betreuer] [Gründling, Matthias Gutachter] Gründling, and Frank [Gutachter] [Bloos. "Untersuchungen zur primär kalkulierten antiinfektiven Therapie von Patienten mit schwerer Sepsis und septischem Schock unter besonderer Berücksichtigung des Antibiotikums Meropenem / Hannes Martin Lothar Fürstenberg ; Gutachter: Matthias Gründling, Frank Bloos ; Betreuer: Matthias Gründling." Greifswald : Ernst-Moritz-Arndt-Universität, 2018. http://nbn-resolving.de/urn:nbn:de:gbv:9-opus-22875.
Full text
38
Kristoffersson, Anders. "Study Design and Dose Regimen Evaluation of Antibiotics based on Pharmacokinetic and Pharmacodynamic Modelling." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-264798.
Full textAbstract:
Current excessive use and abuse of antibiotics has resulted in increasing bacterial resistance to common treatment options which is threatening to deprive us of a pillar of modern medicine. In this work methods to optimize the use of existing antibiotics and to help development of new antibiotics were developed and applied. Semi-mechanistic pharmacokinetic-pharmacodynamic (PKPD) models were developed to describe the time course of the dynamic effect and interaction of combinations of antibiotics. The models were applied to illustrate that colistin combined with a high dose of meropenem may overcome meropenem-resistant P. aeruginosa infections. The results from an in vivo dose finding study of meropenem was successfully predicted by the meropenem PKPD model in combination with a murine PK model, which supports model based dosage selection. However, the traditional PK/PD index based dose selection was predicted to have poor extrapolation properties from pre-clinical to clinical settings, and across patient populations. The precision of the model parameters, and hence the model predictions, is dependent on the experimental design. A limited study design is dictated by cost and, for in vivo studies, ethical reasons. In this work optimal design (OD) was demonstrated to be able to reduce the experimental effort in time-kill curve experiments and was utilized to suggest the experimental design for identification and estimation of an interaction between antibiotics. OD methods to handle inter occasion variability (IOV) in optimization of individual PK parameter estimates were proposed. The strategy was applied in the design of a sparse sampling schedule that aim to estimate individual exposures of colistin in a multi-centre clinical study. Plasma concentration samples from the first 100 patients have been analysed and indicate that the performance of the design is close to the predicted. The methods described in this thesis holds promise to facilitate the development of new antibiotics and to improve the use of existing antibiotics.
39
Söderhäll, Thomas. "Antibiotic combination therapies against carbapenamse producing Klebsiella pneumoniae." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-452424.
Full textAbstract:
The treatment options for multidrug resistant bacteria are dwindling and it is an important issue of research in medicine to solve. One of the more problematic bacterial species is Klebsiella pneumoniae, it can cause infections with high morbidity that are difficult to treat. Common antibiotics for treatment of these infections are carbapenems but K. pneumoniae can produce enzymes called carbapenemases that can hydrolyze carbapenems and most other beta-lactam antibiotics. In this study carbapenemase genes were introduced chromosomally to a previously susceptible K. pneumoniae strain using λ-Red recombineering. Further constructs were made with non-functional porins to examine how they affect combination treatment with carbapenems. Antibiotic combination therapy was evaluated against constructed carbapenemase- (KPC-2, NDM-1 and OXA-48) producing K. pneumoniae strains. Screening was done using time-lapse microscopy (oCelloScope), and combinations with better effect than treatment with a single antibiotic were chosen for time-kill assays. The results shows that a triple combination of colistin, meropenem and the beta-lactamase inhibitor avibactam gives an improved effect, up to twice the effect compared to monotherapy and up to 1.8 times increased effect compared to double combination. The synergistic effect was greater when adding colistin to treat the strains with non-functional porins, indicating that colistin can increase the permeability for other antibiotics into the cell. This is an interesting finding that need to be researched further.
40
Moritz, Janina [Verfasser], Richard [Akademischer Betreuer] Strauß, and Richard [Gutachter] Strauß. "Entwicklung einer Methode zur Analyse der Plasmakonzentrationen von Piperacillin, Ceftazidim und Meropenem. Prüfung auf die Notwendigkeit eines Therapeutischen Drug Monitorings bei deren Einsatz bei kritisch Kranken mit organersetzenden Verfahren. / Janina Moritz ; Gutachter: Richard Strauß ; Betreuer: Richard Strauß." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2020. http://d-nb.info/1221370340/34.
Full text
41
Donamore, Bruna Kern. "Influ?ncia de condi??es de cultivo na forma??o de c?lulas persisters em Acinetobacter calcoaceticus-baumanni." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2016. http://tede2.pucrs.br/tede2/handle/tede/7540.
Full textAbstract:
Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T18:34:28Z
No. of bitstreams: 1
DIS_BRUNA_KERN_DONAMORE_PARCIAL.pdf: 256997 bytes, checksum: a87e4fb183ebf7c784b824c77b71092c (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T18:34:34Z (GMT) No. of bitstreams: 1 DIS_BRUNA_KERN_DONAMORE_PARCIAL.pdf: 256997 bytes, checksum: a87e4fb183ebf7c784b824c77b71092c (MD5)
Made available in DSpace on 2017-06-30T18:34:43Z (GMT). No. of bitstreams: 1 DIS_BRUNA_KERN_DONAMORE_PARCIAL.pdf: 256997 bytes, checksum: a87e4fb183ebf7c784b824c77b71092c (MD5) Previous issue date: 2016-03-31
Acinetobacter calcoaceticus-baumannii complex opportunistic human pathogens are responsible for several diseases affecting specially intensive care units and immunocompromised patients. These bacteria may also present the persistence phenotype, where a small population of susceptible bacteria survives after a high antimicrobial concentration treatment ? which the fraction of surviving cells may be affected by environmental conditions present in the medium. Thus, the aim of this study was to evaluate the influence of oxygen availability and galactose, sodium citrate and sheep blood presence in the formation of these cells upon meropenem and tobramycin exposure. For this, 10 clinical isolates, sent by the Clinical Pathology Laboratory of S?o Lucas Hospital, had their susceptibility characterized regarding the minimum inhibitory concentration (MIC) to tobramycin and meropenem. The influence of different environmental conditions was analyzed by exposing late exponential-phase cultures to meropenem and tobramycin for 48 h in the presence of sodium citrate, galactose and sheep blood; or in aerated or static condition. For all evaluations, aliquots were removed at determined time points, followed by serial decimal dilutions and drop plating technique on nutrient agar, to estimate the fraction of surviving cells. Aerated condition promoted a reduction of persister cells fraction ? independent of antimicrobial used ?, and, in addition, concentrations of tobramycin higher than 10X MIC provided even lower levels of these cells after 48 h of treatment. Regarding the presence of different sources of nutrients, it was observed that sodium citrate presence in 48 h of meropenem treatment promoted lower fraction of surviving cells when compared to this same antibiotic associated with galactose; whereas tobramycin exposure in the presence of galactose provided a reduced formation of persister cells in the first 6 h of treatment. Sheep blood, however, did not affect the fraction of surviving cells after 48 h of treatment, independently of the antimicrobial used. A remarkable heterogeneity in the behavior of all 10 isolates used in the study was present, regardless the conditions that have been exposed. Thus, it is possible that the conditions imposed in the experiments have influenced in the formation of persister cells by enhanced production of reactive oxygen species, and through the availability of more targets for antibiotic action by the bacterial growth stimulation.
Os pat?genos oportunistas do complexo Acinetobacter calcoaceticus-baumannii s?o respons?veis por diversas enfermidades, acometendo principalmente pacientes de unidades de tratamento intensivo e imunocomprometidos. Estas bact?rias podem ainda apresentar o fen?tipo de persist?ncia, onde uma pequena popula??o de bact?rias suscet?veis sobrevive ap?s o tratamento com elevadas concentra??es de antimicrobianos - podendo essa fra??o de c?lulas sobreviventes ser afetada pelas condi??es ambientais presentes no meio. Desta forma, o objetivo deste trabalho foi avaliar a influ?ncia da disponibilidade de oxig?nio e da presen?a de galactose, citrato de s?dio e sangue de carneiro na forma??o destas c?lulas frente ? exposi??o ao meropenem e ? tobramicina. Para isto, 10 isolados cl?nicos, cedidos pelo Laborat?rio de Patologia Cl?nica do Hospital S?o Lucas da PUCRS, tiveram sua suscetibilidade caracterizada quanto ? concentra??o inibit?ria m?nima (CIM) de tobramicina e de meropenem. A influ?ncia das diferentes condi??es ambientais foi analisada ao expor culturas de fase exponencial tardia ao meropenem e ? tobramicina por 48 h na presen?a de citrato de s?dio, galactose ou sangue de carneiro; ou em uma condi??o aerada ou est?tica. Para todas as observa??es, al?quotas foram removidas em tempos determinados, seguidas de dilui??es decimais seriadas e semeadura pela t?cnica da gota em ?gar nutriente, para estimar a fra??o de c?lulas sobreviventes. A condi??o aerada promoveu uma diminui??o na fra??o de c?lulas persisters - independente do antimicrobiano utilizado -, e tamb?m verificarmos que concentra??es superiores a 10X a CIM de tobramicina proporcionaram n?veis ainda menores destas c?lulas ap?s 48 h de tratamento. Quanto ? presen?a de diferentes fontes de nutrientes, foi observado que a presen?a de citrato de s?dio no tratamento de 48 h com meropenem proporcionou uma menor fra??o de c?lulas sobreviventes comparado a quando este mesmo antimicrobiano estava associado ? galactose; enquanto a exposi??o ? tobramicina na presen?a de galactose promoveu uma menor forma??o de c?lulas persisters nas primeiras 6 h de tratamento. O sangue de carneiro, entretanto, n?o afetou a fra??o de c?lulas sobreviventes ap?s 48 h de tratamento, independente do antimicrobiano utilizado. P?de-se ainda constatar uma not?vel heterogeneidade no comportamento de todos os 10 isolados utilizados no estudo, independente das condi??es as quais foram expostos. Desta forma, ? poss?vel que as condi??es avaliadas nos experimentos tenham influenciado a forma??o c?lulas persisters atrav?s da maior produ??o de esp?cies reativas de oxig?nio, e por disponibilizar mais alvos para a a??o dos antimicrobianos ao estimular o crescimento bacteriano.
42
Elkhaili, Hassan. "Pharmacocinétique in vivo et pharmacodynamie in vitro / ex vivo chez le microporc yucatan du céfépime, du cefpirome et du méropénème face à des bactéries multirésistantes." Strasbourg 1, 1997. http://www.theses.fr/1997STR15036.
Full text
43
Matta, Roula. "Infections nosocomiales et résistance aux antibiotiques chez les bacilles à GRAM négatifs : étude de cohorte multicentrique dans les hôpitaux libanais." Electronic Thesis or Diss., Bordeaux, 2023. http://www.theses.fr/2023BORD0485.
Full textAbstract:
Les infections nosocomiales et la résistance bactérienne aux antibiotiques sont répandues au niveau mondial avec une prévalence plus élevée dans les pays en développement aux ressources limitées dont le Liban. Au Liban, les données épidémiologiques sur la résistance chez les bactéries à Gram négatif aux antibiotiques de dernier recours dans les hôpitaux et sur les infections nosocomiales sont rares. Objectifs : Nous avons conduit trois travaux visant à répondre aux objectifs suivants : une première étude pour identifier et comparer les différentes bactéries identifiées dans les infections communautaires et les infections nosocomiales, en mettant l'accent sur les comorbidités et les facteurs sociodémographiques associés. Puis deux études ciblant la résistance aux antibiotiques de dernier recours chez les bacilles à Gram négatif afin d’en décrire l’épidémiologie et d’identifier les caractéristiques des patients associées à cette résistance. La mortalité chez les patients porteurs d’un bacille à Gram négatif résistant aux carbapénèmes a été analysée. Méthodes. Le premier travail a consisté en une étude de cohorte rétrospective, multicentrique, menée dans cinq hôpitaux. Les données ont été recueillies à l'aide d'une fiche standardisée (données démographiques : genre et âge, maladies sous-jacentes et type d’infection acquise). Les deux autres études ont reposé sur une étude de cohorte prospective à partir d’une base de données constituée dans neuf hôpitaux libanais entre 2016-2017 (caractéristiques des patients, variables liées à l’hospitalisation et variables liées aux caractéristiques de l’infection). Les données ont été collectées et traitées avec Statistical Package for the Social Sciences SPSS, version 24. Des régressions logistiques ont été utilisées pour définir le profil des patients pour chaque type de résistance (céphalosporines de 3° génération- C3G, fluoroquinolones, aminosides, carbapénémes) observées chez les bacilles à Gram négatif (entérobactérales, Pseudomonas aeruginosa et Acinetobacter baumannii). Une analyse de sensibilité basée sur les résultats extrêmes des valeurs manquantes relatives à la sensibilité des bactéries a permis de prendre en compte les données manquantes et de fournir des résultats robustes. Résultats. La première étude a montré l’importance des bacilles à Gram négatif résistants aux antibiotiques au sein des infections nosocomiales mais aussi des infections communautaires avec deux facteurs indépendants de l’acquisition d’une infection nosocomiale : âge avancé et état d'immunosuppression. Les deux autres études ont montré des pourcentages de résistances élevées chez les bacilles à Gram négatif ciblés et ont permis d’établir différents profils de patients pour chaque type de résistance. Par exemple, pour Escherichia coli, la résistance aux C3G était associée à une admission antérieure à l’hôpital et à la présence d’une sonde urinaire. De la même façon, la résistance aux carbapénèmes chez les bacilles à Gram négatif était associée aux patients chirurgicaux, à la présence d’une sonde urinaire ainsi qu’à une infection pulmonaire ou du site opératoire. Concernant la mortalité globale, le modèle proportionnel de Cox a montré que la résistance aux carbapénèmes était associée à une différence significative en termes de survie hospitalière chez les patients porteurs de bacilles à Gram négatif non fermentants par rapport aux bactéries sensibles. Conclusions. Nous avons rapporté la résistance aux antibiotiques de derniers recours chez les entérobactérales (E. coli et entérobactérales non- E. coli) et les bacilles à Gram négatif non fermentants identifiées dans des hôpitaux libanais où les données épidémiologiques sont rares. La description des profils de patients porteurs de ces souches bactériennes résistantes permettra aux cliniciens de prescrire une antibiothérapie probabiliste adaptéeHospital-acquired infections and bacterial resistance to antibiotics are widespread worldwide, with a higher prevalence in developing countries with limited resources, including Lebanon. In Lebanon, epidemiological data on resistance among Gram-negative bacteria to antibiotics of last resort in hospitals and on nosocomial infections are scarce. Aims: We conducted three studies to meet the following objectives: a first study to identify and compare the different bacteria identified in communityacquired infections and nosocomial infections, focusing on associated co-morbidities and sociodemographic factors. This was followed by two studies targeting resistance to last-resort antibiotics in Gram-negative bacilli, in order to describe the epidemiology and identify patient characteristics associated with this resistance. Mortality in patients with Gram-negative bacilli resistant to carbapenems was analyzed. Methods. The first study was a retrospective, multicenter cohort study conducted in five hospitals. Data were collected using a standardized form (demographic data: gender and age, underlying diseases and type of acquired infection). The other two studies were based on a prospective cohort study using a database compiled in nine Lebanese hospitals between 2016 and 2017 (patient characteristics, variables related to hospitalization and variables related to the characteristics of the infection). Data were collected and processed using Statistical Package for the Social Sciences SPSS version 24. Logistic regressions were used to define the profile of patients for each type of resistance (3rd generation cephalosporins-3GC, fluoroquinolones, aminoglycosides, carbapenem) observed in Gram-negative bacilli (Enterobacteria, Pseudomonas aeruginosa and Acinetobacter baumannii). A sensitivity analysis based on the extreme results of the missing values for bacterial sensitivity was used to take account of the missing data and provide robust results. Results. The first study showed the importance of Gram-negative bacilli resistant to antibiotics in both hospital and community-acquired infections, with two independent factors in the acquisition of a nosocomial infection: advanced age and immunosuppression. The other two studies showed high percentages of resistance in the targeted Gram-negative bacilli and established different patient profiles for each type of resistance. For example, in Escherichia coli, resistance to 3GC was associated with previous hospital admission and the presence of a urinary catheter. Similarly, resistance to carbapenems in Gram-negative bacilli was associated with surgical patients, the presence of a urinary catheter, and pulmonary or surgical site infection. In terms of overall mortality, the Cox proportional model showed that carbapenem resistance was associated with a significant difference in hospital survival in patients with nonfermenting gram-negative bacilli compared with susceptible bacteria. Conclusions. We report on resistance to antibiotics of last resort in enterobacteria (E. coli and Non-E. coli enterobacterales) and non-fermenting Gram-negative bacilli identified in Lebanese hospitals, where epidemiological data are scarce. Describing the profiles of patients carrying these resistant bacterial strains will enable clinicians to prescribe appropriate probabilistic antibiotic therapy
44
Hoppe, Sebastian. "Die Pharmakokinetic von Meropenem bei Patienten mit schweren Infektionen." Doctoral thesis, 2010. http://hdl.handle.net/11858/00-1735-0000-0006-AFAC-F.
Full text
45
Kuo, Pei-chun, and 郭姵君. "1.Pharmacokinetic studies on Meropenem 2.Bioequivalence studies on Gentamycin." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/20690560099117886465.
Full text
46
Pei-Hua, Yang, and 楊佩樺. "1.Bioequivalence Studies on Trazodone 2. Pharmacokinetic Studies on Meropenem." Thesis, 2001. http://ndltd.ncl.edu.tw/handle/97725138412904036566.
Full textAbstract:
碩士國立臺灣大學
藥學研究所
89
1.1.Bioequivalence Studies on Trazodone Trazodone is a triazolopyridine derivative with antidepressant activity that is chemically unrelated to other currently available antidepressants. Its pharmacological properties differ from those of most other antidepressants. Trazodone exhibits antiserotonin activity, but its mechanism of action in depressive illness in humans is not clear. Comparative plasma levels of trazodone after oral dosing of two formulations, Mesyrel and Torlex, were investigated. A randomized two-way crossover study with 16 healthy male volunteers was carried out. Owing to the strong drowsiness occurred in one subject, only 15 subjects completed the study. A 50mg single dose was administrated to each subject after overnight fasting. Blood samples were collected and analyzed by high performance liquid chromatography (HPLC). The methods for sample refrigeration, pretreatment and analysis were validated before study. The pharmacokinetic parameters includeing AUC, Cmax, Tmax were determined by WinNonlin noncompartmental analysis. Following ANOVA and 90% CI evaluations, there was no statistically significant defferences between the two formulations. The results showed that Torlex and Mesyrel were bioequivalent. 2.Pharmacokinetic Studies on Meropenem Meropenem is a novel carbapenem antibiotics, similar to imipenem, with high activity in vitro against a broad spectrum of bacteria, effective therapy for a variety of experimental infections and moderate to severe infection in humans. It is active against almost all clinically significant aerobes and anaerobes, particularly the three most common causes of community-acquired bacterial meningitis, Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. Meropenem and imipenem are both widely distributed in body tissues and fluids, including cerebrospinal fluid. The wider clinical use of imipenem for the treatment of meningitis has been limited by high incidence of seizures. The use of meropenem appears the similar bacteriological and clinical efficacy to imipenem and there is no significant propensity to cause seizures. This study is undertaken to determine the concentrations of meropenem in the cerebrospinal fluid (CSF) and plasma of patients with inflamed meningitis following a single iv dose. Patients eligible for inclusion in this study were 28 males and females with bacterial meningitis who were already receiving antibiotics treatment. A single iv dose of meropenem was administrated as a 30-min infusion. CSF and Blood samples were obtained from each patient at 2 hours after the infusion. Meropenem concentrations in CSF and plasma were analyzed by reversed phase high-performance liquid chromatography (HPLC). Very small amount of drug was found in the brain and CSF, however, the meropenem concentration in CSF was in excess of the reported MIC90 for most of the pathogens associated with this disease. The CSF / Plasma drug concentration ratio was between 1-29%, which is similar to some research.
47
張敬馨. "Pharmacokinetics of meropenem in patients with biliary diseases and in rats." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/61306407502563470481.
Full textAbstract:
碩士高雄醫學大學
藥學研究所
88
Meropenem is a carbapenem antibiotic with broad-spectrum activity against many common pathogens and appears to be widely distributed to most tissues with adequate concentration. The aim of this study was to assess the pharmacokinetics of meropenem in plasma and bile of patients with biliary tract diseases and to compare the parameters in patients with various renal functions in different age groups. Twenty-nine patients with biliary tract diseases received one dose of 1000 mg meropenem by intravenous infusion over 30 minutes. Blood and bile samples were collected initially to five hours after dosing and were analyzed by high-performance liquid chromatography. Patients were grouped by creatinine clearance less than 30, 30-50, and greater than 50 ml/min as group I, II, and III as well as age younger and older than 65 years old as group A and B. Pharmacokinetic parameters were calculated as a two-compartment open model. The peak plasma concentration, volume of distribution at steady state, elimination half-life, and total clearance of twenty-nine patients were 38.90 g/ml, 26.60 L, 105.71 minutes and 424.23 ml/min, respectively. The elimination half-life increased and total clearance decreased by impaired renal function, advanced age and various diseases. Therefore, adjustment of dosage and dosing interval might be considered individually. The accumulated amount in bile was 0.1﹪of dose and the concentration in bile ranged from 0.50 to 46.26 g/ml within five hours after dosing. Meropenem concentration in bile was high enough to inhibit most pathogens resulted in biliary tract infections. In microdialysis study of rats, meropenem demonstrated linear pharmacokinetic properties within dose from 50 to 150 mg/kg（r = 0.80）. The elimination half-life, total clearance and volume of distribution at steady state were 7.72 minutes, 213.20 ml/min/kg and 1.22 l/kg, respectively. The correlation between meropenem plasma and bile concentration was not found in patients. However, the correlation between the ratio of meropenem bile concentration to plasma concentration and time within 10-45 minutes after dosing was found in rats（r = -0.55）. It might be required advanced study to investigate this issue in the future. Key words: Meropenem, Pharmacokinetics, Biliary tract diseases, Microdialysis
48
Wang, Yi-Ting, and 王怡婷. "Comparative proteomic studies on the meropenem causing death of Pseudomonas aeruginosa." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/7284a2.
Full text
49
Hartmann, Claudia. "Meropenem versus Ceftazidim als initiale Monotherapie bei febriler Neutropenie immunsupprimierter Kinder und Jugendlicher /." 2004. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=012848236&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Full text
50
Hung, Yi-Chun, and 洪宜君. "The Impact of Meropenem Infusion Time on Resistant Strains Selection in Anus and Throat." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/41441225607354931669.
Full textAbstract:
碩士中國醫藥大學
醫學研究所碩士班
95
Background Meropenem, a broad-spectrum antibiotic of carbapenem, is active against both gram-positive and negative organisms. There were postulate that the way of administration may influence effect of the pharmacodynamics in bactericidal activity (%T＞MIC). However , the bactericidal activity is coherent between the high dosage (2000 mg) and low dosage (500 mg). In the view of cost effectiveness goal, choice the low dose 500 mg meropenem with correct administration way may a best priority of strategy. Objectives The aims of this study was to differentiated the pharmacodynamics between 3 hours infusion and 30 minutes infusion of 500 mg meropenem. Materials and methods This was open-randomized study, adults with ventilation in the intensive care had infection required antimicrobial agent treatment were randomized to receive 500 mg of meropenem every 6 hours by 3 hours or 30 minutes infusion for 2 weeks. Throat and anus swab cultures were obtained at baseline and at the end of study therapy and take culture to compare the change of throat and gut flora. Endpoints： Observations and comparison the change of throat and gut flora. Result： One hundred and four patients were randomized to receive 30 minutes (n=55) or 3 hours (n=49) infusion of meropenem. Throat and anus swab cultures of these patients were done before and after meropenem administration. The throat culture results of 30 minutes infusion group before and after meropenem use were Enterobacteriaceae (27/3)、ESBL-producing Enterobacteriaceae (12/0) and glucose-non-ferment gram-negative bacilli (GNFGNB) (30/31); 3 hours group were Enterobacteriaceae (23/0)、ESBL-producing Enterobacteriaceae (8/0) and GNFGNB (39/37). The anus culture results of 30 minutes infusion group before and after meropenem use were Enterobacteriaceae (53/48)、ESBL-producing Enterobacteriaceae (42/28) and GNFGNB (15/27); 3 hours group were Enterobacteriaceae (46/32)、ESBL-producing Enterobacteriaceae (38/16) and GNFGNB (12/20). Conclusion： 3 hours infusion of meropenem 500 mg every 6 hours has more decreasing the colonization of Enterobacteriaceae, ESBL– producing Enterobacteriaceae strains and Amp C inducible strains in throat and anus than 30 minutes infusion.