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Asthana, Sonal, Purva Mathur, and Vibhor Tak. "Detection of Carbapenemase Production in Gram-negative Bacteria." Journal of Laboratory Physicians 6, no. 02 (2014): 069–75. http://dx.doi.org/10.4103/0974-2727.141497.
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ABSTRACTThe greatest threat to antimicrobial treatment of infections caused by Gram-negative bacteria is the production of carbapenemases. Metallo-beta-lactamases and plasmid-mediated serine carbepenemases like Klebsiella pneumonia carbapenemase are threatening the utility of almost all currently available beta-lactams including carbapenems. Detection of organisms producing carbapenemases can be difficult, because their presence does not always produce a resistant phenotype on conventional disc diffusion or automated susceptibility testing methods. These enzymes are often associated with laboratory reports of false susceptibility to carbapenems which can be potentially fatal. Moreover, most laboratories do not attempt to detect carbapenemases. This may be due to the lack of availability of guidelines and procedures or lack of knowledge and expertise. Because routine susceptibility tests may be unreliable, special tests are required to detect the resistance mechanisms involved. This document describes the standard methodology for detection of various types of carbapenemases, which can be put to use by laboratories working on antimicrobial resistance in Gram-negative bacteria.
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Hammoudi Halat, Dalal, and Carole Ayoub Moubareck. "The Current Burden of Carbapenemases: Review of Significant Properties and Dissemination among Gram-Negative Bacteria." Antibiotics 9, no. 4 (2020): 186. http://dx.doi.org/10.3390/antibiotics9040186.
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Carbapenemases are β-lactamases belonging to different Ambler classes (A, B, D) and can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, which hydrolyze a broad variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are clinical due to compromising the activity of the last resort antibiotics used for treating serious infections, and epidemiological due to their dissemination into various bacteria across almost all geographic regions. Carbapenemase-producing Enterobacteriaceae have received more attention upon their first report in the early 1990s. Currently, there is increased awareness of the impact of nonfermenting bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, as well as other Gram-negative bacteria that are carbapenemase-producers. Outside the scope of clinical importance, carbapenemases are also detected in bacteria from environmental and zoonotic niches, which raises greater concerns over their prevalence, and the need for public health measures to control consequences of their propagation. The aims of the current review are to define and categorize the different families of carbapenemases, and to overview the main lines of their spread across different bacterial groups.
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Ageevets, V. A., O. S. Sulian, A. A. Avdeeva та ін. "Comparative Activity of Carbapenem Antibiotics Against Gram-Negative Carbapenemase Producers of Different Groups". Antibiotics and Chemotherapy 67, № 1-2 (2022): 9–15. http://dx.doi.org/10.37489/0235-2990-2022-67-1-2-9-15.
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The rapid spread of gram-negative bacteria resistance to carbapenems due to the production of carbapenemases requires new treatment options. The activity of carbapenem antibiotic biapenem, recently registered in Russia, against producers of various carbapenemases was studied in comparison with other antibiotics of this group. Among NDM-type carbapenemase producers, 77.8% demonstrated clinical susceptibility to biapenem; 50.3% and 21.1% of isolates were susceptible to meropenem and imipenem, respectively. Among the producers of OXA-48-type carbapenemases, 82,6%, 60,9%, and 65,2% of isolates demonstrated susceptibility to biapenem, imipenem, and meropenem, respectively.Producers of KPC-type carbapenemases were 100% resistant to all carbapenems. The introduction of biapenem will significantly expand the possibilities of treating severe infections caused by carbapenemase producers.
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Das, Parijat, Kumar Anand Shrutiraaj, Manish Ranjan, and Sourav Sen. "Prevalence of Carbapenem Resistance and their Genotypic Profile among Gram-Negative Bacteria in a Tertiary Care Hospital in Western India." Annals of Pathology and Laboratory Medicine 8, no. 5 (2021): A116–123. http://dx.doi.org/10.21276/apalm.3053.
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Background: Resistance to carbapenems due to carbapenemases has been increasingly noticed worldwide. Detection of carbapenemases among Gram‑negative bacteria (GNB) is important for
 both clinicians and infection control practitioners. Both phenotypic and molecular methods can be used for detection of Carbapenemases production. Molecular methods although the gold standard for detection of carbapenemases are not used routinely as they might not be immediately available coupled with expertise required, cost and infrastructure incurred and limited by the number of targets detected.
 Methods: Consecutive non-repeat gram negative isolates isolated from various clinical specimens from intensive care unit (ICU) were included in the study. Antimicrobial susceptibility testing was done on Mueller Hinton’s agar by Kirby Bauer Disc diffusion method as per the Clinical and Laboratory Standards Institute (CLSI) guidelines. Isolates resistant to Meropenem were further screened for carbapenemase producing genes using multiplex polymerase chain reaction (PCR). The results were statistically analysed.
 Result: A total of 350 gram negative bacteria were screened for carbapenem resistance. Carbapenem resistance was found in 109 GNB. The metallo‑ β‑lactamases were most common carbapenemases followed by KPC.
 Conclusion: Carbapenemase producing bacteria are a major threat of the 21st century. Preventing emergence and spread of these pathogens through strict infection control practices, judicious use of antibiotics and early and timely detection will contribute in preserving carbapenems, the last resort antibiotics.
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Karn, Sitesh, Narayan Dutt Pant, Sanjeev Neupane, Saroj Khatiwada, Shaila Basnyat, and Basudha Shrestha. "Prevalence of carbapenem resistant bacterial strains isolated from different clinical samples: study from a tertiary care hospital in Kathmandu, Nepal." Journal of Biomedical Sciences 3, no. 1 (2017): 11–15. http://dx.doi.org/10.3126/jbs.v3i1.16846.
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Background Carbapenems are considered as drugs of choice for the treatment of the infections caused by drug resistant bacteria. However, in the recent years the prevalence of carbapenem resistant gram negative bacteria has increased significantly. The main objective of this study was to determine the prevalence of carbapenemase producing gram negative bacteria among all the clinical isolates.Material and methods A total of 3246 non-repeated, different clinical specimens from patients attending Kathmandu Model Hospital, from July 2013 to January 2014 were cultured and the gram negative bacterial isolates obtained were subjected to identification with the help of colony morphology, Gram’s stain and conventional biochemical tests. Kirby-Bauer disk diffusion technique was used to perform antimicrobial susceptibility testing. Phenotypic confirmation of carbapenemase and AmpC beta-lactamase production was done by combined disc method.Results 890 samples showed the growth of bacterial pathogens. Out of total 769 gram negative bacteria, 57 were found to be carbapenem resistant. Of which, highest number (47) of the isolates were found to be metallo-β lactamase (MBL) producers. Six bacterial isolates produced both (Klebsiella pneumoniae carbapenemase) KPC and MBL, whereas only one isolate was found to be positive for both MBL and AmpC. Three bacterial strains showed carbapenem resistance due to over production of AmpC β-lactamase.Conclusion Among carbapenem resistant gram negative bacteria, MBL was present as the major enzyme responsible for resisting carbapenem antibiotics.
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Montiel-Riquelme, Francisco, Elisabeth Calatrava-Hernández, Miguel Gutiérrez-Soto, Manuela Expósito-Ruiz, José María Navarro-Marí, and José Gutiérrez-Fernández. "Clinical Relevance of Antibiotic Susceptibility Profiles for Screening Gram-negative Microorganisms Resistant to Beta-Lactam Antibiotics." Microorganisms 8, no. 10 (2020): 1555. http://dx.doi.org/10.3390/microorganisms8101555.
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The increasing resistance to antibiotics is compromising the empirical treatment of infections caused by resistant bacteria. Rapid, efficient, and clinically applicable phenotypic methods are needed for their detection. This study examines the phenotypic behavior of β-lactam-resistant Gram-negative bacteria grown on ChromID ESBL medium with ertapenem, cefoxitin, and cefepime disks, reports on the coloration of colonies, and establishes a halo diameter breakpoint for the detection of carbapenemase-producing bacteria. We studied 186 β-lactam-resistant Gram-negative microorganisms (77 with extended spectrum beta lactamase (ESBL), 97 with carbapenemases, and 12 with AmpC β-lactamases (AmpC)). Susceptibility profiles of Gram-negative bacteria that produced ESBL, AmpC, and carbapenemases were similar to the expected profiles, with some differences in the response to cefepime of ESBL-producing microorganisms. Coloration values did not differ from those described by the manufacturer of ChromID ESBL medium. In the screening of carbapenemase production, inhibition halo diameter breakpoints for antibiotic resistance were 18 mm for Enterobacterales and ertapenem, 18 mm for Pseudomonas and cefepime, and 16 mm for Acinetobacter baumannii and cefepime. This innovative phenotypic approach is highly relevant to clinical laboratories, combining susceptibility profiles with detection by coloration of high-priority resistant microorganisms such as carbapenemase-producing A. baumannii, carbapenemase-producing Pseudomonas spp., and ESBL and/or carbapenemase-producing Enterobacterales.
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Bogiel, Tomasz, Mateusz Rzepka, and Eugenia Gospodarek-Komkowska. "An Application of Imipenem Discs or P. aeruginosa ATCC 27853 Reference Strain Increases Sensitivity of Carbapenem Inactivation Method for Non-Fermenting Gram-Negative Bacteria." Antibiotics 10, no. 7 (2021): 875. http://dx.doi.org/10.3390/antibiotics10070875.
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Non-fermenting Gram-negative rods are one of the most commonly isolated bacteria from human infections. These microorganisms are typically opportunistic pathogens that pose a serious threat to public health due to possibility of transmission in the human population. Resistance to beta-lactams, due to carbapenemases synthesis, is one of the most important antimicrobial resistance mechanisms amongst them. The aim of this study was to evaluate the usefulness of the Carbapenem Inactivation Method (CIM), and its modifications, for the detection of carbapenemase activity amongst non-fermenting Gram-negative rods. This research involved 81 strains of Gram-negative rods. Of the tested strains, 55 (67.9%) synthesized carbapenemases. For non-fermenting rods, 100% sensitivity and specificity was obtained in the version of the CIM test using imipenem discs and E. coli ATCC 25922 strain. The CIM test allows for differentiation of carbapenems resistance mechanisms resulting from carbapenemase synthesis from other resistance types. It is a reliable diagnostic method for the detection of carbapenemase activity amongst non-fermenting Gram-negative rods. Application of imipenem discs and P. aeruginosa ATCC 27853 reference strain increases CIM results sensitivity, while imipenem discs and E. coli ATCC 25922 strain use maintains full precision of the test for non-fermenting rods.
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Ibadin, Ephraim E., Angela Eghiomon, Nosakhare L. Idemudia, et al. "Phenotypic Distribution of Serine- and Zinc-Type Carbapenemases Among Clinical Bacterial Isolates in a Tertiary Hospital in Benin, Nigeria." International Journal of Enteric Pathogens 8, no. 1 (2020): 3–7. http://dx.doi.org/10.34172/ijep.2020.02.
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Background: Serine and zinc type carbapenemases are distributed in many genera of bacteria and are typically associated with specific regions or countries. Objectives: This study phenotypically determined the prevalence of serine and zinc-type carbapenemases among Gram-negative bacilli recovered from clinical specimens in Benin, Nigeria. Materials and Methods: Totally, 158 consecutive non-duplicate bacterial isolates (gram-negative bacilli) recovered from clinical samples were screened for serine and zinc-type carbapenemases using the simplified carbapenemase inactivation (sCIM) and ethylenediaminetetraacetic acid -double-disc synergy test methods. Results: The isolates recovered from clinical specimens included 126 Enterobacteriaceae (79.7%), 7 Acinetobacter spp (3.7%), and 28oxidase positive gram negative bacilli (17.7%). Twenty-eight isolates (17.7%) out of the 158 tested samples were carbapenemase positive. There was no significant difference in the prevalence of serine- and zinc-type carbapenemases (P=0.0748). However, the prevalence of zinc-type carbapenemase was significantly higher in Pseudomonas aeruginosa compared with other isolates (P=0.0028) while that of serinetype carbapenemase was not affected by the type of clinical isolates (P=0.7216). Finally, the prevalence of both serine- and zinc-type carbapenemases were not affected (P>0.05) by clinical specimens and the source of isolates (in-patient vs. out-patient) respectively. Conclusion: In general, the prevalence of zinc-type (12%) carbapenemases was insignificantly higher than that of serine-type (5.7%) carbapenemases. The measures to reduce infections caused by carbapenemase-producing organisms (CPOs) are advocated accordingly.
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Huynh, Tuan, and Loan Luong. "SG-APSIC1083: Prevalence and classification of carbapenemase-producing gram-negative bacilli at a medical center in Ho Chi Minh City, Vietnam." Antimicrobial Stewardship & Healthcare Epidemiology 3, S1 (2023): s27. http://dx.doi.org/10.1017/ash.2023.81.
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Objectives: The identification and classification of carbapenemases are meaningful in clinical treatment, epidemiology, and multidrug-resistant bacteria control. We sought to identify the proportion of carbapenemase-producing and carbapenemase classifications in gram-negative bacilli in our hospital. Methods: Isolates of gram-negative bacilli were extracted from sputum, blood, and urine samples in a medical center in Ho Chi Minh City. The identification of gram-negative bacilli was performed using the Phoenix M50 automated system (Becton Dickinson, Franklin Lakes, NJ). An antibiogram was conducted using the disk-diffusion method to detect meropenem-resistant gram-negative bacteria. Carbapenemase confirmation and classification of isolates resistant or intermediately resistant to meropenem were performed using the NMIC500 CPO kit on the Phoenix M50 system. Results: Among 599 isolates of gram-negative bacilli, 108 isolates were resistant or intermediately resistant to carbapenem (meropenem). Of these108 isolates, 107 (99.1%) were resistant due to the carbapenemase-producing mechanism. The proportions of resistant or intermediately resistant isolates to carbapenem were as follows: 73.8% for Acinetobacter baumannii, 26.4% for Klebsiella pneumoniae, 25.9% for Pseudomonas aeruginosa, and 2.8% for Escherichia coli. Class D carbapenemase accounted for the highest proportion, with 53 (49.5%) of 107 isolates, followed by class B with 31 isolates (29%), and class A with the lowest proportion of 2 isolates (1.9%). Also, 44.4% of Acinetobacter baumannii isolates and 74.4% of Klebsiella pneumoniae isolates produced class D carbapenemase. Conclusions: Gram-negative bacilli are resistant to carbapenem primarily due to the carbapenemase-secreting mechanism. D-class carbapenemase accounted for the highest percentage, followed by B-class type, and A-class carbapenemase in gram-negative bacilli.
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Ragueh, Ayan Ali, Mohamed Houmed Aboubaker, Sitani Idriss Mohamed, Jean-Marc Rolain, and Seydina M. Diene. "Emergence of Carbapenem-Resistant Gram-Negative Isolates in Hospital Settings in Djibouti." Antibiotics 12, no. 7 (2023): 1132. http://dx.doi.org/10.3390/antibiotics12071132.
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Introduction: The antimicrobial resistance (AMR) of bacteria is increasing rapidly against all classes of antibiotics, with the increasing detection of carbapenem-resistant isolates. However, while growing prevalence has been reported around the world, data on the prevalence of carbapenem resistance in developing countries are fairly limited. In this study, we investigated and determined the resistance rate to carbapenems among multidrug-resistant Gram-negative bacteria (MDR-GNB) isolated in Djibouti and characterized their resistance mechanisms. Results: Of the 256 isolates, 235 (91.8%) were identified as Gram-negative bacteria (GNB). Of these GNBs, 225 (95.7%) isolates exhibited a multidrug resistance phenotype, and 20 (8.5%) isolates were resistant to carbapenems, including 13 Escherichia coli, 4 Acinetobacter baumannii, 2 Klebsiella pneumoniae and 1 Proteus mirabilis. The most predominant GNB in this hospital setting were E. coli and K. pneumoniae species. Carbapenemase genes such as blaOXA-48 and blaNDM-5 were identified, respectively, in six and four E. coli isolates, whereas the carbapenemase blaNDM-1 was identified in three E. coli, two K. pneumoniae, one P. mirabilis and one A. baumannii. Moreover, three A. baumannii isolates co-hosted blaOXA-23 and blaNDM-1. Materials and Methods: A total of 256 clinical strains collected between 2019 and 2020 were identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Antibiotic susceptibility testing was performed using disk diffusion and E-test methods. Real-time polymerase chain reaction (RT-PCR), standard PCR and sequencing were used to investigate genes encoding for extended-spectrum-β-lactamases, carbapenemases and colistin resistance genes. Conclusions: We report, for the first time, the presence of MDR-GNB clinical isolates and the emergence of carbapenem-resistant isolates in Djibouti. In addition to performing antimicrobial susceptibility testing, we recommend phenotypic and molecular screening to track the spread of carbapenemase genes among clinical GNB isolates.
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Zhu, Yihua, Xinjian Cao, Fuying Chu, and Xinling Li. "Community prevalence of carbapenemase-producing Gram-negative bacteria." Tropical Journal of Pharmaceutical Research 20, no. 8 (2022): 1757–63. http://dx.doi.org/10.4314/tjpr.v20i8.29.
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Purpose: To raise awareness of carbapenemase-producing organisms, identify “at-risk” patients when admitted in a medical healthcare facility, and to outline effective infection prevention and control measures in order to halt the entry and spread of these organisms.
 Methods: A total of 1043 un-duplicated urine specimens of healthy volunteers who had no travel history or history of hospitalization were screened. The carbapenemase genotype of each imipenem-resistant strain was determined. Molecular typing and homology analysis of the main carbapenemase-producing strains were used to reveal the mode of transmission of resistance genes. Through transfer joint experiments, the potential risk of spread of carbapenemase genes was assessed.
 Results: A total of 19 carbapenemase-producing strains from 1,043 non-duplicated healthy volunteers (1.82 %) were identified. The main carbapenemase-producing organism was E. coli (42.1 %, 8/19). The main carbapenemase genotype of E. coli was blaKPC-2 (7 strains). Results from multi-locus sequence typing (MLST) indicated that 7 E. coli isolates belonged to ST-10, ST-101, ST-131, ST-405, ST-410 and ST-1193 and ST-2562. Homologous cluster analysis revealed that the sequence types among the 7 E. coli were high in diversity. The blaKPC-2 gene was successfully transferred from these isolates to 10.22-14 via conjugation. All recipient cells showed marked decreases in carbapenem sensitivity to imipenem (p < 0.05)). The degrees of conjugation were 2.10±0.12 ×10-4, 1.96±0.14×10-4, 2.72±0.18 ×10-4, 3.15±0.20 × 10-4, 2.92±0.23 ×10-4, 3.50±0.20 ×10-4 and 4.12±0.24 ×10-4 in recipient cells of TC7.23-51, TC8.9-42, TC8.15-11, TC8.23-59-3, TC8.23-83, TC9.08-47 and TC10.13-15, respectively.
 Conclusion: The findings demonstrate the pattern and features of carbapenemase-insensitive E. coli. The blaKPC-2 was the main community-prevalent gene of carbapenem-resistant E. coli. In view of increasing incidence of resistance to multi-drug therapy, surveillance of insensitivity to antibiotics is vital, especially urinary system infection due to carbapenem-insensitive E. coli.
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Dortet, Laurent, Laurent Poirel, and Patrice Nordmann. "Worldwide Dissemination of the NDM-Type Carbapenemases in Gram-Negative Bacteria." BioMed Research International 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/249856.
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The emergence of one of the most recently described carbapenemases, namely, the New Delhi metallo-lactamase (NDM-1), constitutes a critical and growingly important medical issue. This resistance trait compromises the efficacy of almost all lactams (except aztreonam), including the last resort carbapenems. Therapeutical options may remain limited mostly to colistin, tigecycline, and fosfomycin. The main known reservoir of NDM producers is the Indian subcontinent whereas a secondary reservoir seems to have established the Balkans regions and the Middle East. Although the spread ofblaNDM-like genes (several variants) is derived mostly by conjugative plasmids in Enterobacteriaceae, this carbapenemase has also been identified inP. aeruginosaandAcinetobacterspp.Acinetobactersp. may play a pivotal role for spreadingblaNDMgenes for its natural reservoir to Enterobacteriaceae. Rapid diagnostic techniques (Carba NP test) and screening of carriers are the cornerstone to try to contain this outbreak which threatens the efficacy of the modern medicine.
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Ahmed, Heshu Jalal, and Aryan R. Ganjo. "Detection of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli Recovered from Clinical Specimens in Erbil City Kurdistan Region of Iraq." Al-Mustansiriyah Journal of Science 30, no. 2 (2019): 10. http://dx.doi.org/10.23851/mjs.v30i2.612.
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Background: Carbapenems are usually the choice of antimicrobial agents in infections produced by Enterobacteriaceae bacteria-producing ESBL (extended spectrum β-lactamases). Carbapenemase production among clinical isolates of Enterobacteriaceae has been widely reported and Resistance to carbapenems group is generally due to production of Carbapenemases. Phenotypic determination and distinction of Carbapenemases in drug-resistant gram-negative is crucial for appropriate infection control. Materials and Methods: Carbapenemase production among Enterobacteriaceae isolates was identified phenotypically using a commercially available EDTA-combined disc diffusion test containing inhibitors to the various carbapenemase classes and Modified Hodge test (MHT). Results: A total of 98 Enterobacteriaceae isolates were included, 42(42.8%) were Multi-drug resistant (MDR), 27(27.5%) were XDR while 8(8.2%) exhibited pan-drug resistance (PDR). Of the 74 isolates of Escherichia coli and 24 Klebsiella pneumoniae that were positive for carbapenemase production, 12 (16.2%) and 9 (37.5%) were Metallo beta-lactamase (MBL) producers respectively, Hence, the overall prevalence of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in this study were 47.3% and 87.5%. Conclusion: Carbapenemase-producing Enterobacteriaceae was indeed recognized in our hospitals. The EDTA-combination disk test was a rapid, cost-effective and suitable method which will be able to identify and distinguish the carbapenem-resistant bacterial isolates within the hospitals especially when molecular detection techniques are not available.
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Rudresh, Shoorashetty Manohara, Giriyapur Siddappa Ravi, Lakshminarayanappa Sunitha, Sadiya Noor Hajira, Ellappan Kalaiarasan, and Belgode Narasimha Harish. "Simple, rapid, and cost-effective modified Carba NP test for carbapenemase detection among Gram-negative bacteria." Journal of Laboratory Physicians 9, no. 04 (2017): 303–7. http://dx.doi.org/10.4103/jlp.jlp_138_16.
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Abstract PURPOSE: Detection of carbapenemases among Gram-negative bacteria (GNB) is important for both clinicians and infection control practitioners. The Clinical and Laboratory Standards Institute recommends Carba NP (CNP) as confirmatory test for carbapenemase production. The reagents required for CNP test are costly and hence the test cannot be performed on a routine basis. The present study evaluates modifications of CNP test for rapid detection of carbapenemases among GNB. MATERIALS AND METHODS: The GNB were screened for carbapenemase production using CNP, CarbAcineto NP (CANP), and modified CNP (mCNP) test. A multiplex polymerase chain reaction (PCR) was performed on all the carbapenem-resistant bacteria for carbapenemase genes. The results of three phenotypic tests were compared with PCR. RESULTS: A total of 765 gram negative bacteria were screened for carbapenem resistance. Carbapenem resistance was found in 144 GNB. The metallo-β-lactamases were most common carbapenemases followed by OXA-48-like enzymes. The CANP test was most sensitive (80.6%) for carbapenemases detection. The mCNP test was 62.1% sensitive for detection of carbapenemases. The mCNP, CNP, and CANP tests were equally sensitive (95%) for detection of NDM enzymes among Enterobacteriaceae. The mCNP test had poor sensitivity for detection of OXA-48-like enzymes. CONCLUSION: The mCNP test was rapid, cost-effective, and easily adoptable on routine basis. The early detection of carbapenemases using mCNP test will help in preventing the spread of multidrug-resistant organisms in the hospital settings.
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Moussa, Diawara, Coulibaly Modibo, Samaké Dramane, et al. "Antimicrobial resistant in Gram-negative bacilli: Enterobacteriaceae and non-fermenting bacilli isolated at Sominé DOLO Hospital of Mopti, Mali." GSC Biological and Pharmaceutical Sciences 18, no. 1 (2022): 008–13. https://doi.org/10.5281/zenodo.5919584.
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<strong>Background</strong>: β-lactams and carbapenems are the major antibiotics used to treat gram-negative bacteria and non-fermenting bacilli. However, the increasing production of β-lactamase and carbapenemase limits the therapeutic options. Our study aims to determine the resistant phenotypes of these bacteria while describing their epidemiological aspect. <strong>Material and Methods</strong>: This was a cross-sectional study by consecutive enrollment from January 2018 to December 2019 at Sominé DOLO Hospital of Mopti, Mali. We performed manual method for bacteria culture, identification and antibiotics sensitivity testing. The antibiotics sensitivity testing was accessed by the diffusion method according to CA-SFM/EUCAST (“Comité de l’Antibiogramme de la Société Française de Microbiologie” / European Committee on Antimicrobial Susceptibility Testing) recommendations V1.0 february 2018 and V2.0 may 2019 2019 V.2.0. May recommendation released in 2019. Data were analyzed by software R 4.0.3 GUI 1.73 Catalina build (7892). <strong>Results</strong>: At all 904 samples were included in this study. Out of the 904 cultures, 297 sample (32.85%) were positive. The rates of enzymes production were as follow: Extended-spectrum ß-lactamase (ESBL) 56.42% (101/179), cepholosporinase hyperproduction (HCASE) 15.64% (28/179), cephalosporinase production (CASE) 6.14% (11/179), penicillinase hyperproduction (HP) 5.58% (10/179), carbapenemase production (CP) 6.14% (11/179) and savage strains 10.05% (18/179). <strong>Conclusion</strong>: Our data showed a high prevalence of resistance to β-lactamins and carbapenemes in gram-negative bacteria and non-fermenting bacillus bacilli. The A high level of β-lactamase and carbapenemase production by gram negative bacillius were also reported by others authors calls for the rational use of antibiotic in hospital setting.
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Moussa Diawara, Modibo Coulibaly, Dramane Samaké, et al. "Antimicrobial resistant in Gram-negative bacilli: Enterobacteriaceae and non-fermenting bacilli isolated at Sominé DOLO Hospital of Mopti, Mali." GSC Biological and Pharmaceutical Sciences 18, no. 1 (2022): 008–13. http://dx.doi.org/10.30574/gscbps.2022.18.1.0021.
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Background: β-lactams and carbapenems are the major antibiotics used to treat gram-negative bacteria and non-fermenting bacilli. However, the increasing production of β-lactamase and carbapenemase limits the therapeutic options. Our study aims to determine the resistant phenotypes of these bacteria while describing their epidemiological aspect. Material and Methods: This was a cross-sectional study by consecutive enrollment from January 2018 to December 2019 at Sominé DOLO Hospital of Mopti, Mali. We performed manual method for bacteria culture, identification and antibiotics sensitivity testing. The antibiotics sensitivity testing was accessed by the diffusion method according to CA-SFM/EUCAST (“Comité de l’Antibiogramme de la Société Française de Microbiologie” / European Committee on Antimicrobial Susceptibility Testing) recommendations V1.0 february 2018 and V2.0 may 2019 2019 V.2.0. May recommendation released in 2019. Data were analyzed by software R 4.0.3 GUI 1.73 Catalina build (7892). Results: At all 904 samples were included in this study. Out of the 904 cultures, 297 sample (32.85%) were positive. The rates of enzymes production were as follow: Extended-spectrum ß-lactamase (ESBL) 56.42% (101/179), cepholosporinase hyperproduction (HCASE) 15.64% (28/179), cephalosporinase production (CASE) 6.14% (11/179), penicillinase hyperproduction (HP) 5.58% (10/179), carbapenemase production (CP) 6.14% (11/179) and savage strains 10.05% (18/179). Conclusion: Our data showed a high prevalence of resistance to β-lactamins and carbapenemes in gram-negative bacteria and non-fermenting bacillus bacilli. The A high level of β-lactamase and carbapenemase production by gram negative bacillius were also reported by others authors calls for the rational use of antibiotic in hospital setting.
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Devkota, Surya Prasad, Ashmita Paudel, Dharm Raj Bhatta, and Krishna Gurung. "Carbapenemase among Clinical Bacterial Isolates in Nepal." Journal of Nepal Health Research Council 18, no. 2 (2020): 159–65. http://dx.doi.org/10.33314/jnhrc.v18i2.2039.
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Gram-negative isolates producing carbapenemase enzymes is a great public health problem in developing countries and their control is challenging task due to the involvement of multiple factors including the practice of self-medication, use of antibiotics on animal farms, poor hospital hygiene, etc. During this study, we searched various databases for relevant publication on carbapenemase-producing isolates in Nepal.
 Various classes of carbapenemases had been reported in Nepal. Most frequent was the New Delhi Metallo beta lactamase with many variants where NDM-1 was most prevalent. Similarly, Oxacillinase and Klebsiella pneumoniae carbapenemase producers were also prevalent in Nepal. While other carbapenemases like VIM, IPM, and DIM also detected. The isolates producing carbapenemases were extremely drug-resistant as they also co-produced various other carbapenemases, beta-lactamases, 16S rRNA methylase. Most isolates were resistant to many members of carbapenem, cephalosporin, quinolone, penicillin, aminoglycoside group of antibiotics. Such isolates had very few treatment options as only last line drugs like colistin, fosfomycin, and tigecycline was effective against most of these isolates. Carbapenemase production by almost all major human pathogens including E. coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter. Citrobacter, Proteus, Providencia is a matter of concern because some of these enzymes are located on plasmids and pose rapid dissemination among various gram-negative pathogens. Timely surveillance for carbapenemase producers throughout the nation, their proper treatment, and proper hospital hygiene to prevent nosocomial infections by carbapenemase producers, controlled use of carbapenems, educating health care workers, students and the general public about the adverse effects of antimicrobial resistance is imminent.
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Beshah, Daniel, Adey Feleke Desta, Gurja Belay Woldemichael, et al. "High burden of ESBL and carbapenemase-producing gram-negative bacteria in bloodstream infection patients at a tertiary care hospital in Addis Ababa, Ethiopia." PLOS ONE 18, no. 6 (2023): e0287453. http://dx.doi.org/10.1371/journal.pone.0287453.
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Background Bloodstream infection due to beta-lactamase and carbapenemase-producing gram-negative bacteria poses a substantial challenge to the effectiveness of antimicrobial treatments. Therefore, this study aimed to investigate the magnitude of beta-lactamase, carbapenemase-producing gram-negative bacteria, and associated risk factors of bloodstream infections in patients at a tertiary care hospital, in Addis Ababa, Ethiopia. Methods An institutional-based cross-sectional study was conducted with convenience sampling techniques from September 2018 to March 2019. Blood cultures were analyzed from 1486 bloodstream infection suspected patients across all age groups. The blood sample was collected using two BacT/ALERT blood culture bottles for each patient. Gram stain, colony characteristics, and conventional biochemical tests were used to classify the gram-negative bacteria at the species level. Antimicrobial susceptibility testing was carried out to screen beta-lactam and carbapenem drug-resistant bacteria. The E-test was conducted for extended-spectrum-beta-lactamase and AmpC-beta-lactamase-producers. A modified and EDTA-modified carbapenem inactivation method was conducted for carbapenemase and metallo-beta-lactamases producers. Data collected using structured questionnaires and medical records were reviewed, encoded, and cleaned using EpiData V3.1. software. The cleaned data were exported and analyzed using SPSS version 24 software. Descriptive statistics and multivariate logistic registration models were used to describe and assess factors associated with acquiring drug-resistant bacteria infection. A p-value <0.05 was considered statistically significant. Result Among 1486 samples, 231 gram-negative bacteria were identified; of these, 195(84.4%) produce drug-hydrolyzing enzymes, and 31(13.4%) produce more than one drug-hydrolyzing enzyme. We found 54.0% and 25.7% of the gram-negative bacteria to be extended-spectrum-beta-lactamase and carbapenemase-producing, respectively. The extended-spectrum-beta-lactamase plus AmpC-beta-lactamase-producing bacteria account for 6.9%. Among the different isolates Klebsiella pneumonia 83(36.7%) was the highest drug-hydrolyzing enzyme-producing bacteria. Acinetobacter spp 25(53.2%) was the most carbapenemase producer. Extended-spectrum-beta-lactamase and carbapenemase-producing bacteria were high in this study. A significant association between age groups and extended-spectrum-beta-lactamase producer bacterial infection was seen, with a high prevalence in neonates (p = <0.001). Carbapenemase showed a significant association with patients admitted to the intensive care unit (p = 0.008), general surgery (p = 0.001), and surgical intensive care unit (p = 0.007) departments. Delivery of neonates by caesarean section, and insertion of medical instruments into the body were exposing factors for carbapenem-resistant bacterial infection. Chronic illnesses were associated with an extended-spectrum-beta-lactamase-producing bacterial infection. Klebsiella pneumonia and Acinetobacter species showed the greatest rates of extensively drug-resistant (37.3%) and pan-drug-resistance (76.5%), respectively. According to the results of this study, the pan-drug-resistance prevalence was found to be alarming. Conclusion Gram-negative bacteria were the main pathogens responsible for drug-resistant bloodstream infections. A high percentage of extended-spectrum-beta-lactamase and carbapenemase-producer bacteria were found in this study. Neonates were more susceptible to extended-spectrum-beta-lactamase and AmpC-beta-lactamase-producer bacteria. Patients in general surgery, caesarean section delivery, and intensive care unit were more susceptible to carbapenemase-producer bacteria. The suction machines, intravenous lines, and drainage tubes play an important role in the transmission of carbapenemase and metallo-beta-lactamase-producing bacteria. The hospital management and other stakeholders should work on infection prevention protocol implementation. Moreover, special attention should be given to all types of Klebsiella pneumoniae and pan-drug resistance Acinetobacter spp transmission dynamics, drug resistance genes, and virulence factors.
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Mushi, Martha F., Stephen E. Mshana, Can Imirzalioglu, and Freddie Bwanga. "Carbapenemase Genes among Multidrug Resistant Gram Negative Clinical Isolates from a Tertiary Hospital in Mwanza, Tanzania." BioMed Research International 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/303104.
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The burden of antimicrobial resistance (AMR) is rapidly growing across antibiotic classes, with increased detection of isolates resistant to carbapenems. Data on the prevalence of carbapenem resistance in developing countries is limited; therefore, in this study, we determined the prevalence of carbapenemase genes among multidrug resistant gram negative bacteria (MDR-GNB) isolated from clinical specimens in a tertiary hospital in Mwanza, Tanzania. A total of 227 MDR-GNB isolates were analyzed for carbapenem resistance genes. For each isolate, five different PCR assays were performed, allowing for the detection of the major carbapenemase genes, including those encoding the VIM-, IMP-, and NDM-type metallo-beta-lactamases, the class A KPC-type carbapenemases, and the class D OXA-48 enzyme. Of 227 isolates, 80 (35%) were positive for one or more carbapenemase gene. IMP-types were the most predominant gene followed by VIM, in 49 (21.59%) and 28 (12%) isolates, respectively. Carbapenemase genes were most detected inK. pneumoniae24 (11%), followed byP. aeruginosa23 (10%), andE. coliwith 19 isolates (8%). We have demonstrated for the first time a high prevalence of MDR-GNB clinical isolates having carbapenem resistance genes in Tanzania. We recommend routine testing for carbapenem resistance among the MDR-GNB particularly in systemic infections.
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Dahab, R. A., Alamin Mohamed Ibrahim, and Hisham N. Altayb. "Phenotypic and genotypic detection of carbapenemase enzymes producing gram-negative bacilli isolated from patients in Khartoum State." F1000Research 6 (September 7, 2017): 1656. http://dx.doi.org/10.12688/f1000research.12432.1.
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Background: Carbapenems are used as antibiotics of last resort for treating infections due to multidrug-resistant Gram-negative bacilli, but emergence of Carbapenem resistant Gram-negative bacilli have been reported due to the production of Carbapenemase enzymes that significantly limits treatment options for life-threatening infections. Objective: This study aimed to detect Carbapenem resistant Gram-negative bacilli from patients attended to different hospitals in Khartoum state and to detect Carbapenemase enzymes production by phenotypic and genotypic methods. Methods: A hospital based cross sectional study was conducted in Khartoum state in the period from February to August 2016. Hundred and forty nine Gram-negative bacilli bacteria were isolated from different clinical specimens. Blood agar, Chromogenic agar media, MacConkey agar, XLD mediaandstandard biochemical tests were used for isolation and identification of Gram-negative bacilli from different samples. Standard antimicrobial susceptibility testing to Carbapenem antibiotic was performed for all isolates, then detection of Carbapenemase enzymes production for the resistant isolates was performed using Modified Hodge Test and PCR. Results: Hundred and forty nine Gram-negative bacilli were isolated from 147 different clinical specimens. The most predominant Gram-negative bacilli isolates was E.coli (54.4%), followed by Klebsiella species (29.5%). More than fifty percent of the isolates were Carbapenem resistant. Fifty six percent of the resistant isolates were positive by Modified Hodge Test. By using PCR, 17.3% of resistant organisms were harbored blaOXA48 gene, and 6.7% harbored blaIMP gene. E.coli was the most bacteria that harbored the blaoxa48 followed by Klebsiella species. blaIMP gene was harbored only by E.coli. Conclusion: The percentage of resistance to Carbapenems due to production of Carbapenemase enzymes is very high in Sudan.BlaOXA48 gene is more predominant than blaIMP in this study.
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Abdeta, Abera, Adane Bitew, Surafel Fentaw, et al. "Phenotypic characterization of carbapenem non-susceptible gram-negative bacilli isolated from clinical specimens." PLOS ONE 16, no. 12 (2021): e0256556. http://dx.doi.org/10.1371/journal.pone.0256556.
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Background Multidrug resistant, extremely drug-resistant, pan-drug resistant, carbapenem-resistant, and carbapenemase-producing gram-negative bacteria are becoming more common in health care settings and are posing a growing threat to public health. Objective The study was aimed to detect and phenotypically characterize carbapenem no- susceptible gram-negative bacilli at the Ethiopian Public Health Institute. Materials and methods A prospective cross-sectional study was conducted from June 30, 2019, to May 30, 2020, at the national reference laboratory of the Ethiopian Public Health Institute. Clinical samples were collected, inoculated, and incubated for each sample in accordance with standard protocol. Antimicrobial susceptibility testing was conducted using Kirby-Bauer disk diffusion method. Identification was done using the traditional biochemical method. Multidrug-resistant and extensively drug-resistant isolates were classified using a standardized definition established by the European Centre for Disease Prevention and Control and the United States Centers for Disease Prevention and Control. Gram-negative organisms with reduced susceptibility to carbapenem antibiotics were considered candidate carbapenemase producers and subjected to modified carbapenem inactivation and simplified carbapenem inactivation methods. Meropenem with EDTA was used to differentiate metallo-β-lactamase (MBL) from serine carbapenemase. Meropenem (MRP)/meropenem + phenylboronic acid (MBO) were used to differentiate Klebsiella pneumoniae carbapenemase (KPC) from other serine carbapenemase producing gram-negative organisms. Results A total of 1,337 clinical specimens were analyzed, of which 429 gram-negative bacterial isolates were recovered. Out of 429 isolates, 319, 74, and 36 were Enterobacterales, Acinetobacter species, and Pseudomonas aeruginosa respectively. In our study, the prevalence of multidrug-resistant, extensively drug-resistant, carbapenemase-producing, and carbapenem nonsusceptible gram-negative bacilli were 45.2%, 7.7%, 5.4%, and 15.4% respectively. Out of 429 isolates, 66 demonstrated reduced susceptibility to the antibiotics meropenem and imipenem. These isolates were tested for carbapenemase production of which 34.8% (23/66) were carbapenemase producers. Out of 23 carbapenemase positive gram-negative bacteria, ten (10) and thirteen (13) were metallo-beta-lactamase and serine carbapenemase respectively. Three of 13 serine carbapenemase positive organisms were Klebsiella pneumoniae carbapenemase. Conclusion This study revealed an alarming level of antimicrobial resistance (AMR), with a high prevalence of multidrug-resistant (MDR) and extremely drug-resistant, carbapenemase-producing gram-negative bacteria, particularly among intensive care unit patients at the health facility level. These findings point to a scenario in which clinical management of infected patients becomes increasingly difficult and necessitates the use of “last-resort” antimicrobials likely exacerbating the magnitude of the global AMR crisis. This mandates robust AMR monitoring and an infection prevention and control program.
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Vamsi, K. Sreeja, S. Rama Moorthy, T. S. Murali, et al. "Phenotypic Methods for the Detection of Metallo-Beta-Lactamase Production by Gram-negative Bacterial Isolates from Hospitalized Patients in A Tertiary Care Hospital in India." Journal of Pure and Applied Microbiology 15, no. 4 (2021): 2019–26. http://dx.doi.org/10.22207/jpam.15.4.23.
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Drug-resistant bacteria are a global health concern owing to the high morbidity and mortality they can cause, especially in countries such as India. Gram-negative bacteria, including Enterobacteriaceae, Pseudomonas, and Acinetobacter, are primarily responsible for expanding the scope of drug resistance. These antibiotic-resistant pathogens are particularly associated with serious infections in hospitals. The production of carbapenemase by gram-negative bacteria appears to be the major reason for their resistance to carbapenems. The study was a prospective study done from March 2018 to December 2020. All the carbapenem-resistant isolates from various clinical samples were further tested for the production of carbapenemases/metallo-beta-lactamases production by various phenotypic tests like carbaNp, Imipenem–EDTA combined disc synergy test, Double-disc synergy test and E-test methods. Of all carbapenem-resistant gram-negative bacteria isolated from patients in a hospital in India, 237 (88.1%) carbapenemase producers were identified, among which 217 (91.5%) were metallo-beta-lactamase (MBL) producers. Therefore, the detection of MBL producers is important for preventing their infectious spread. The present study revealed that most MBL producers were isolated from patients of 0–9 to years of age (63.9%). The double-disc synergy test (DDST) and E-test MBL strips were more sensitive than the combined disc test in detecting MBLs. Because the DDST was the simplest and most effective method, it can be used for the routine laboratory screening of MBL producers in hospitals.
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Kutsevalova, Olga Yu, Yu Yu Kozel, D. A. Rozenko, D. V. Martynov, and O. V. Korshunkova. "Antimicrobial resistance of gram-negative pathogens isolated from hospitalized patients in Rostov region." Clinical Microbiology and Antimicrobial Chemotherapy 22, no. 2 (2020): 143–48. http://dx.doi.org/10.36488/cmac.2020.2.143-148.
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Objective. To evaluate resistance rates to carbapenems and III–IV generation cephalosporins among gramnegative bacteria, including production of carbapenemases and extended-spectrum beta-lactamases (ESBL). Materials and Methods. A total of 460 gram-negative bacteria isolated from hospitalized patients aged 1 to 85 years from 8 medical institutions of Rostov-on-Don and the region from April 2018 to December 2019 were tested by conventional microbiological methods. The most common acquired carbapenemases genes were determined by real-time PCR using commercial kits (Central Research Institute of Epidemiology, Russia). Results. The tested isolates included 180 (39.1%) isolates of K. pneumoniae, 87 (18.9%) – E. coli, 101 (22.0%) – A. baumannii and 92 (20.0%) – P. aeruginosa. K. pneumoniae and E. coli isolates exhibited the high resistance rates to cefotaxime – 96.7% and 71.2%, to ceftazidime – 95.5% and 54.0%, and to cefepime – 95.5% and 54.0%, respectively. ESBL production was detected in 35.0% and 78.2% of K. pneumoniae and E.coli isolates, respectively. K. pneumoniae and E. coli isolates were resistant to imipenem, meropenem, and ertapenem: 57.8% and 3.4%; 55.0% and 2.3%; 60.0% and 4.6%, respectively. Carbapenemase production was detected in 27.8% of K. pneumoniae and 4.6% of E. coli isolates. The most common beta-lactamases were metallo-beta-lactamases (NDM) and serine carbapenemases (OXA-48). A. baumannii isolates showed the high resistance rates to imipenem and meropenem (87.1% and 85.1%). The most common beta-lactamases were metallo-beta-lactamases (NDM) and serine carbapenemases (OXA-24⁄40 and OXA-23). P. aeruginosa isolates also showed the high resistance to carbapenems – imipenem (61.9%) and meropenem (58.7%). The most common betalactamases were metallo-beta-lactamases (VIM) and GES-5. Conclusions. The results of this microbiological study indicate the extremely high prevalence of aerobic gram-negative bacteria in different infections. A. baumannii, P. aeruginosa, K. pneumoniae and E. coli isolates being resistant to third- and fourth-generation cephalosporins and carbapenems are particularly dangerous, especially due to production of ESBL and carbapenemases. The most clinically important are OXA and NDM beta-lactamases.
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Novikova, I. E., Z. Z. Sadeeva, R. A. Shakirzyanova, et al. "The using of the polymerase chain reaction for the detection of resistance genes in gram-negative bacteria in routine practice in a pediatric hospital." Russian Clinical Laboratory Diagnostics 67, no. 3 (2022): 180–85. http://dx.doi.org/10.51620/0869-2084-2022-67-3-180-185.
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Objective - assessment of RT-PCR for the detection of carbapenem-resistance genes in gram-negative bacteria. A total, 499 strains of gram-negative microorganisms isolated in two pediatric hospitals in 2019-2020 were studied. Species identification was performed using MALDI-ToF mass-spectrometry (Bruker Daltonics, Germany). Meropenem and imipenem minimal inhibitory concentration (MIC) was determined by E-test method (BioMerieux, France). The presence of acquired carbapenemase genes of IMP, NDM, VIM, KPC, OXA-48, OXA-23, OXA-40, OXA-58-groups was determined by RT-PCR. Klebsiella pneumoniae (34%), Escherichia coli (4%), Serratia marcescens (6%) and other members of Enterobacterales (6%), also gram-negative non-glucose-fermenting bacteria Acinetobacter baumannii (14%), Pseudomonas aeruginosa (36%) were found among selected strains. Carbapenemase production was found in 385 isolates (77%). The main mechanism determining carbapenem resistance in P. aeruginosa was the production of blaVIM (100%). A. baumanii strains harbored OXA-23 (55%) and OXA-40 (45%) carbapenemases. The major determinant of carbapenem resistance in K. pneumoniae isolates was OXA-48 carbapenemase, detected in 63% strains, 13% of the strains possessed blaNDM-group, 16% isolates had a combination of blaNDM-group and blaOXA-48-like. Carbapenemase of KPC-group was found in 8% K. pneumoniae strains. OXA-48 carbapenemase prevailed (95%) among S. marcescens strains. Most of E. coli isolates harbored metallo-beta-lactamase NDM (89%). Other members of Enterobacterales most often had OXA-48 carbapenemase (57%), 39% of the isolates carried blaNDM-group. In one strain, a combination of blaNDM-group and blaOXA-48-like was discovered. RT-PCR is a fast and reliable method for the detection of acquired carbapenemases and can be recommended for routine use in bacteriological laboratories.
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Schimmenti, A., E. Brunetti, E. Seminari, B. Mariani, P. Cambieri, and P. Orsolini. "Prosthetic Joint Infection from Carbapenemase-Resistant Klebsiella pneumoniae Successfully Treated with Ceftazidime-Avibactam." Case Reports in Infectious Diseases 2018 (August 14, 2018): 1–5. http://dx.doi.org/10.1155/2018/1854805.
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Antimicrobial resistance in Gram-negative bacteria, particularly Enterobacteriaceae, has become a leading cause of morbidity and mortality and a serious public health concern. Gram-negative bacteria carrying extended-spectrum beta-lactamase (ESBL) enzymes now represent a significant proportion of all bacteria isolated from different countries worldwide. Furthermore, the increasing number of isolates carrying carbapenemases in recent years includes multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacteria. Here, we describe what, to our knowledge, is the first case of a patient with a prosthetic joint infection from carbapenemase-resistant Klebsiella pneumoniae (CRKP) successfully treated with ceftazidime-avibactam in Italy.
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Elrahem, Amira Abd, Noha El-Mashad, Mohammed Elshaer, et al. "Carbapenem Resistance in Gram-Negative Bacteria: A Hospital-Based Study in Egypt." Medicina 59, no. 2 (2023): 285. http://dx.doi.org/10.3390/medicina59020285.
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Background and Objectives: The global spread of carbapenem resistance and the resulting increase in mortality forced the World Health Organization (WHO) to claim carbapenem-resistant enterobacteriaceae (CRE) as global priority pathogens. Our study aimed to determine the prevalence of carbapenemase-encoding genes and major plasmid incompatibility groups among Gram-negative hospital-based isolates in Egypt. Material and Methods: This cross-sectional study was carried out at Mansoura University Hospitals over 12 months, from January to December 2019. All the isolates were tested for carbapenem resistance. The selected isolates were screened by conventional polymerase chain reaction (PCR) for the presence of carbapenemase genes, namely blaKPC, blaIMP, blaVIM, and blaNDM-1. PCR-based plasmid replicon typing was performed using the commercial PBRT kit. Results: Out of 150 isolates, only 30 (20.0%) demonstrated carbapenem resistance. Klebsiella pneumoniae was the most resistant of all isolated bacteria, and blaNDM was the predominant carbapenemases gene, while the most prevalent plasmid replicons were the F replicon combination (FIA, FIB, and FII) and A/C. Plasmids were detected only in Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Pseudomonas aeruginosa. Remarkably, we found a statistically significant association between carbapenemase genes and plasmid replicons, including blaNDM, IncA/C, and IncX. Conclusions: Our study demonstrated an alarming rise of plasmid-mediated carbapenem-resistant bacteria in our locality. The coexistence of resistance genes and plasmids highlights the importance of a targeted antibiotic surveillance program and the development of alternative therapeutic options at the local and international levels. Based on our results, we suggest a large-scale study with more Enterobacteriaceae isolates, testing other carbapenemase-encoding genes, and comparing the replicon typing method with other plasmid detection methods. We also recommend a national action plan to control the irrational use of antibiotics in Egypt.
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Z, Sahile. "The Epidemiology and Molecular Aspect of Carbapenemase Producing Enterobactericiae (CPE). A Review." Journal of Infectious Diseases & Travel Medicine 6, no. 1 (2022): 1–7. http://dx.doi.org/10.23880/jidtm-16000161.
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Carbapenems are the last line of defense against Gram-negative and Gram-positive bacteria that cause serious infections. Although they are resistant to most B-lactamases, the presence of carbapenem hydrolyzing enzymes known as carbapenemase has put their use as a last-resort antibiotic in jeopardy. These enzymes are produced most frequently by Enterobacteriaceae. True carbapenemase in Ambler molecular classes A, B, and D are frequently expressed by genes found in mobile genetic elements such plasmids, integrons, and transposons, which frequently contain many resistance determinants, further limiting treatment options. The worldwide development of carbapenem-resistant Gram-negative bacteria has resulted in a large number of nosocomial and community-acquired illnesses, which has become a major public health issue. In vitro evidence of the advantages of combination schemes against polymyxins is still available while polymyxins are still available.
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Irfan, Mohammad, Alhomidi Almotiri та Zeyad Abdullah AlZeyadi. "Antimicrobial Resistance and β-Lactamase Production in Clinically Significant Gram-Negative Bacteria Isolated from Hospital and Municipal Wastewater". Antibiotics 12, № 4 (2023): 653. http://dx.doi.org/10.3390/antibiotics12040653.
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Hospital and municipal wastewater contribute to the spread of antibiotic-resistant bacteria and genes in the environment. This study aimed to examine the antibiotic resistance and β-lactamase production in clinically significant Gram-negative bacteria isolated from hospital and municipal wastewater. The susceptibility of bacteria to antibiotics was tested using the disk diffusion method, and the presence of extended-spectrum β-lactamases (ESBL) and carbapenemases was determined using an enzyme inhibitor and standard multiplex PCR. Analysis of antimicrobial resistance of total bacterial strains (n = 23) revealed that most of them were resistant to cefotaxime (69.56%), imipenem (43.47%), meropenem (47.82%) and amoxicillin-clavulanate (43.47%), gentamicin (39.13%), cefepime and ciprofloxacin (34.78%), trimethoprim-sulfamethoxazole (30.43%). A total of 8 of 11 phenotypically confirmed isolates were found to have ESBL genes. The blaTEM gene was present in 2 of the isolates, while the blaSHV gene was found in 2 of the isolates. Furthermore, the blaCTX-M gene was found in 3 of the isolates. In one isolate, both the blaTEM and blaSHV genes were identified. Furthermore, of the 9 isolates that have been phenotypically confirmed to have carbapenemase, 3 were confirmed by PCR. Specifically, 2 isolates have the blaOXA-48 type gene and 1 have the blaNDM-1 gene. In conclusion, our investigation shows that there is a significant rate of bacteria that produce ESBL and carbapenemase, which can promote the spread of bacterial resistance. Identifying ESBL and carbapenemase production genes in wastewater samples and their resistance patterns can provide valuable data and guide the development of pathogen management strategies that could potentially help reduce the occurrence of multidrug resistance.
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Miguela-Villoldo, Pedro, Marta Hernández, Miguel Á. Moreno, et al. "Carbapenemase-Producing Elizabethkingia Meningoseptica from Healthy Pigs Associated with Colistin Use in Spain." Antibiotics 8, no. 3 (2019): 146. http://dx.doi.org/10.3390/antibiotics8030146.
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Carbapenems are considered last-resort antimicrobials, especially for treating infections involving multidrug-resistant Gram-negative bacteria. In recent years, extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Gram-negative bacteria have become widespread in hospitals, community settings, and the environment, reducing the range of effective therapeutic alternatives. The use of colistin to treat infection caused by these multi-drug bacteria may favour the selection and persistence of carbapenem-resistant bacteria. In this study, it is described, for the first time to our knowledge, a carbapenemase-producing isolate of Elizabethkingia meningoseptica from healthy pigs in Spain. The isolate we report was recovered during a study to detect colistin-resistant bacteria from faecal samples of healthy food-production animals using a chromogenic selective medium. Unexpectedly, we found an isolate of Elizabethkingia meningoseptica with high Minimum Inhibitory Concentration (MIC) values for several antibiotics tested. Molecular analysis did not show any mcr family genes related with colistin resistance, but two carbapenemase genes, blaB-12_1 and blaGOB-17_1, were detected. This finding in healthy animals could suggest that colistin may favour the selection and persistence of carbapenem-resistant bacteria.
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Akhtar, Sharmin, Md Ehsanul Haque, Abul Kalam, Shamima Akther, and Sultana Ruma Alam. "Detection of Carbapenemase Producing Uropathogens in a Tertiary Care Hospital, Chattogram." IAHS Medical Journal 6, no. 1 (2024): 10–14. http://dx.doi.org/10.3329/iahsmj.v6i1.75528.
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Background: Antimicrobial Resistance (AMR) posses a complex threat to global health security and universal health coverage. Gram negative bacteria have developed the broadest spectrum of resistance due to multiple structural adaptions and antibiotic degradation enzymes including Extended Spectrum Beta Lactamase, AmpC Cephalosporinase and Carbapenemase. Carbapenemases are beta-lactamases with versatile hydrolytic capacities. They have the ability to hydrolyze penicillins, cephalosporins, monobactam, and carbapenems. The classical phenotypic method cannot provide an efficient means of diagnosis of the carbapenemase producer. Multiplex PCR also helps in simultaneous detection of various genes, reducing materials, manpower and helps in determining epidemiology related to these genes and infection subsidence. This study was designed to determine the presence of carbapenemase producers among the carbapenem resistant uropathogens and to compare the phenotypic method with genotypic method along with the antimicrobial resistance patterns. Materials and methods: This cross-sectional study was carried out in the Department of Microbiology Chittagong Medical College, Chattogram for quantitative culture, mCIM test, and multiplex PCR for carbapenemase producers. A total 68 Gram negative uropathogens were isolated and identified by conventional methods. Antibiotic susceptibility test was performed by disk-diffusion technique. Carbapenemase producers were detected phenotypically by modified carbapenem inactivation method among the meropenem resistant isolates. Gene encoding bla NDM and coexistence of bla NDM +bal OXA-48 were identified by multiplex PCR. Results: Twenty (29.41%) meropenem resistant strains were detected among 68 Gram-negative uropathogens. The most common isolates were Escherichia coli and Pseudomonas spp. Among 20 meropenem resistant strains, 19(95%) carbapenemase producers were detected by multiplex PCR, 17(85%) by modified carbapenem inactivation method. The most prevalent gene was blaNDM (94.73%). More than one carbapenemase gene was present in one (5.6%) isolate. Overall, carbapenemase encoding genes were detected in 11.11% of the studied Gram negative uropathogenes. All of the carbapenemase producing organisms were 100% resistant to Ampicillin, Cefuroxime, Ceftriaxone, Ceftazidime, Aztreonam, 94.73% to both Cotrimoxazole and Nitrofurantoin, 68.42% to PipercillinTazobactam and 63.15%, to Amikacin. Conclusion: The study shows that rapid dissemination of blaNDM in Bangladesh demands the effective measures along with antibiotics policies in hospitals which combat the spread of this strains. IAHS Medical Journal Vol 6(1), June 2023; 10-14
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Bithika, Ray, Singhal Parul, and Agarwal Ritu. "Emerging Trends in Extended Spectrum Beta-lactamase and Carbapenemase Producers Among Gram-Negative Bacteria in the Intensive Care Unit." International Journal of Pharmaceutical and Clinical Research 15, no. 10 (2023): 817–24. https://doi.org/10.5281/zenodo.11267109.
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<strong>Background: </strong>The increasing prevalence of multidrug-resistant (MDR) bacteria in intensive care units (ICUs) poses a significant threat to patient clinical outcomes. Understanding the epidemiology and resistance patterns of these bacteria is crucial for effective infection control and treatment strategies. Studies from various regions have reported varying rates of MDR bacterial infections in ICUs, necessitating ongoing surveillance and tailored interventions to combat this growing public health concern. This study aimed to contribute valuable insights into the prevalence, distribution, and antibiotic resistance profiles of MDR bacteria in a specific ICU setting, helping guide evidence-based clinical practices. <strong>Methods: </strong>This cross-sectional study was conducted in a tertiary care ICU over two years, we collected data on demographics, comorbidities, prior antibiotic use, and infection sources. Blood cultures were processed, and antimicrobial susceptibility testing was performed. ESBL and carbapenemase production were assessed. Descriptive statistics characterized infection rates, bacterial species distribution, and resistance patterns. <strong>Results: </strong>The study included 323 patients in the intensive care unit. Gram-negative bacteria, particularly Klebsiella pneumoniae (20.8%) and Escherichia coli (26.3%), were the most prevalent pathogens. High levels of resistance were observed in commonly used antibiotics, with ceftriaxone and ceftazidime showing resistance rates of 45.5% and 44.9%, respectively. Extended-spectrum beta-lactamase (ESBL) production was detected in 29.3% of isolates. Carbapenemase production was identified in 16.4% of isolates. Clinical outcomes indicated longer ICU stays and higher mortality rates among patients with ESBL and carbapenemase-producing infections. <strong>Conclusion: </strong>In this study, we found a concerning prevalence of multidrug-resistant Gram-negative bacteria, including ESBL and carbapenemase producers. High rates of resistance to commonly prescribed antibiotics emphasize the need for antimicrobial stewardship.
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Haji, Sayran Hamad, Safaa Toma Hanna Aka, and Fattma A. Ali. "Prevalence and characterisation of carbapenemase encoding genes in multidrug-resistant Gram-negative bacilli." PLOS ONE 16, no. 11 (2021): e0259005. http://dx.doi.org/10.1371/journal.pone.0259005.
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Background Emerging worldwide in the past decade, there has been a significant increase in multidrug-resistant bacteria from serious nosocomial infections, especially carbapenemase-producing Gram-negative bacilli that have emerged worldwide. The objective of this study is to investigate carbapenem resistance in Gram-negative bacilli bacteria using phenotypic detection, antimicrobial resistance profiles and genotypic characterisation methods. Methods 200 Gram-negative bacilli isolates were collected from different clinical specimens. All clinical samples were exposed to isolation and identification of significant pathogens applying bacteriological examination and an automated Vitek-2 system. The isolates were subjected to susceptibility tests by the Vitek-2 automated system and those isolates that were resistant to beta-lactam drugs, including carbapenems, third-generation cephalosporines or cefoxitin, were selected for phenotyping using Carba plus disc system assay for detection of carbapenemase-producing isolates. These isolates were further confirmed by molecular detection. PCR was used for the detection carbapenem-resistant genes (OXA-48, IMP, NDM, VIM, and KPC). Results 110 (55%) of 200 Gram-negative bacilli were identified as beta-lactam-resistant isolates. The frequency of carbapenem-resistant isolates was calculated to be 30.9% (n = 34/110). A collection totalling 65/110 (59%) isolates were identified as carbapenemase producers by phenotypic method. Moreover, among the 65 carbapenemase-producing Gram-negative isolates with a positive phenotype-based result, 30 (46%), 20 (30%) and 18 (27%) isolates were positive for OXA-48, KPC and MBL enzymes, respectively, as well as the production of 27% of AmpC with porin loss. Tigecycline was the most effective antibiotic that affected 70% of MDR isolates, but high rates of resistance were detected to other tested antimicrobials. Of interest, a high incidence of MDR, XDR and PDR profiles were observed among all carbapenemase-producing isolates. 36% (24/65) of the tested isolates were MDR to 3 to 5 antimicrobial classes. 29% (17/65) of the recovered isolates were XDR to 6 to 7 antimicrobial classes. Alarmingly, 24% (16/65) of isolates displayed PDR to all the tested 8 antimicrobial classes. Genotype assay, including 53 phenotypically confirmed carbapenemase-producing isolates of Gram-negative bacilli, found 51(96%) isolates were harbouring one or more genes. The most common carbapenemase gene was bla NDM 83% (44/53) followed by bla OXA-48 75% (40/53), bla VIM 49% (26/53) and bla IMP 43% (23/53), while the gene bla KPC was least frequent 7% (4/53). 92% (46/51) of isolates were involved in the production of more than one carbapenemase gene. Conclusion This study demonstrated the emergence of carbapenemase-producing Gram-negative pathogens implicated in healthcare-related infections. Accurate identification of carbapenem-resistant bacterial pathogens is essential for patient treatment, as well as the development of appropriate contamination control measures to limit the rapid spread of pathogens. Tigecycline exhibited potent antimicrobial activity against MDR, XDR and PDR-producing strains that establish a threatening alert which indicates the complex therapy of infections caused by these pathogens.
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Popov, D. A., N. A. Zubareva, and A. A. Parshakov. "Aztreonam: clinical and pharmacological characteristics at the present stage." Clinical Microbiology and Antimicrobial Chemotherapy 25, no. 1 (2023): 19–25. http://dx.doi.org/10.36488/cmac.2023.1.19-25.
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One of the urgent problems of modern health care is the growing resistance of microorganisms to antibiotics, including carbapenems, which until recently were considered as the drugs of choice in the treatment of life-threatening infections. Enzymatic inactivation of antibiotics, including through the production of carbapenemase, is the main mechanism of resistance in Gram-negative bacteria. The treatment of these infections presents significant difficulties due to the extremely limited arsenal of effective drugs. Aztreonam is currently the first and only monocyclic beta-lactam antibiotic, monobactam, which is used in clinical practice for the treatment of infections caused by gram-negative bacteria. The data obtained in vitro and clinical observations are presented. These results justify the use of the drug in infections caused by a number of «problem» Gram-negative pathogens, including those resistant to carbapenems. Aztreonam has a high potential and should be used to treat patients with nosocomial infections – the focus of its use is Gram-negative bacteria-producers of metallo-beta-lactamases.
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Chelaru, Edgar-Costin, Mădălina-Maria Muntean та Andrei-Alexandru Muntean. "β-LACTAMASE PRODUCING GRAM NEGATIVE BACTERIA: MAIN ISSUES, DIAGNOSTIC METHODS AND MEANS OF REDUCING THEIR BURDEN IN ROMANIA". Romanian Archives of Microbiology and Immunology 81, № 2 (2022): 107–13. http://dx.doi.org/10.54044/rami.2022.02.05.
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Bacterial resistance to antibiotics is a globally recognized healthcare problem. Β-lactam resistance în Gram negative bacteria, mediated through mecanisms like ESBLs (extended spectrum beta-lactamases), cephalosporinases and carbapenemases, is one of the most important. This study aims to identify the most important tests which can be applied in the laboratory in order to correctly identify Gram-negative bacteria (Enterobacterales, Pseudomonas spp., Acidentobacter spp.) which are resistant to this class of antibiotics and their resistance mechanisms, apply them on the microorganisms isolated in a clinical hospital from Bucharest, Romania, describe and report the findings, followed by the proposal of measures that can reduce the burden of these bacteria and their resistance mechanisms. In order to support the national effort in the fight against the antimicrobial resistance phenomenon, a new phenotipic laboratory identification test is proposed, using resources available in Romania. Keywords: antimicrobial resistance, β-lactamase, carbapenemase
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Vintilă, Camelia, Răzvan Lucian Coșeriu, Anca Delia Mare, et al. "Biofilm Formation and Antibiotic Resistance Profiles in Carbapenemase-Producing Gram-Negative Rods—A Comparative Analysis between Screening and Pathological Isolates." Antibiotics 13, no. 8 (2024): 687. http://dx.doi.org/10.3390/antibiotics13080687.
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(1) Background: Carbapenem-resistant (CR) bacteria pose a significant global public health challenge due to their ability to evade treatment with beta-lactam antibiotics, including carbapenems. This study investigates the biofilm-forming capabilities of CR clinical bacterial isolates and examines the impact of serum on biofilm formation. Additionally, the study evaluates the resistance profiles and genetic markers for carbapenemase production. (2) Methods: Bacterial isolates were collected from the microbiology laboratory of Mures County Clinical Hospital between October 2022 and September 2023. Pharyngeal and rectal swabs were screened for carbapenem-resistant bacteria using selective media. Lower respiratory tract samples were also analyzed for CR Gram-negative bacteria. The isolates were tested for their ability to form biofilms in the presence and absence of fetal bovine serum at 24 and 48 h. Carbapenemase production was detected phenotypically and confirmed via PCR for relevant genes. (3) Results: Out of 846 screened samples, 4.25% from pharyngeal swabs and 6.38% from rectal swabs tested positive for CR bacteria. Acinetobacter baumannii and Klebsiella pneumoniae were the most common species isolated. Biofilm formation varied significantly between clinical isolates and standard strains, with clinical isolates generally showing higher biofilm production. The presence of serum had no significant effect on biofilm formation in Klebsiella spp., but stimulated biofilm formation for Acinetobacter spp. Carbapenemase genes blaKPC, blaOXA-48-like, and blaNDM were detected in various isolates, predominantly in Klebsiella spp., but were not the main determinants of carbapenem resistance, at least in screening isolates. (4) Conclusions: This study highlights the variability in biofilm formation among CR clinical isolates and underscores the differences between the bacteria found as carriage versus infection. Both bacterial species and environmental factors variably influence biofilm formation. These insights are crucial for the development of effective treatment and infection control strategies in clinical settings.
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Nordmann, Patrice, and Laurent Poirel. "Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria." Clinical Infectious Diseases 69, Supplement_7 (2019): S521—S528. http://dx.doi.org/10.1093/cid/ciz824.
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Abstract Carbapenem resistance in gram-negative bacteria has caused a global epidemic that continues to grow. Although carbapenemase-producing Enterobacteriaceae have received the most attention because resistance was first reported in these pathogens in the early 1990s, there is increased awareness of the impact of carbapenem-resistant nonfermenting gram-negative bacteria, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Moreover, evaluating the problem of carbapenem resistance requires the consideration of both carbapenemase-producing bacteria as well as bacteria with other carbapenem resistance mechanisms. Advances in rapid diagnostic tests to improve the detection of carbapenem resistance and the use of large, population-based datasets to capture a greater proportion of carbapenem-resistant organisms can help us gain a better understanding of this urgent threat and enable physicians to select the most appropriate antibiotics.
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Garg, Atul, Jaya Garg, G. C. Upadhyay, Anurag Agarwal, and Amitabha Bhattacharjee. "Evaluation of the Rapidec Carba NP Test Kit for Detection of Carbapenemase-Producing Gram-Negative Bacteria." Antimicrobial Agents and Chemotherapy 59, no. 12 (2015): 7870–72. http://dx.doi.org/10.1128/aac.01783-15.
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ABSTRACTRecently, bioMérieux, France, introduced the Rapidec Carba NP test kit for rapid detection of carbapenemase-producing Gram-negative bacteria. This kit was evaluated in this study, and we report sensitivity, specificity, and positive and negative predictive values of 92.6%, 96.2%, 95.83%, and 92.6%, respectively. The test was easy to perform and interpret and relatively inexpensive ($5/Rs 300 per test) and provides a practical solution for early detection of carbapenemase-producing, multidrug-resistant Gram-negative bacteria.
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Raveendran, Sreejith, Deepashree Rajshekar, Sujatha S R, and Krishna Karthik M V S. "Evaluation of phenotypic carbapenem inactivation methods among carbapenem resistant gram-negative bacteria isolated from blood culture specimens and their synergy testing." Indian Journal of Microbiology Research 11, no. 3 (2024): 175–79. http://dx.doi.org/10.18231/j.ijmr.2024.032.
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: Carbapenem-resistant Enterobacterales (CRE) are a significant public health threat due to their resistance to antibiotics, leading to serious infections, increased healthcare expenses, and higher mortality rates. Accurate identification of CRE is essential for effective treatment and infection control. Phenotypic methods like the modified Carbapenemase Inactivation Method (mCIM) and the EDTA-Carbapenem Inactivation Method (eCIM) are practical approaches for identifying production carbapenemase. As a result, the current study aims to analyse the efficacy of phenotypic carbapenem inactivation approaches in detecting carbapenem-resistant Gram-negative bacteria isolated from blood culture specimens, as well as the synergy of ceftazidime-avibactam and aztreonam in treating such infections. This laboratory based prospective study was adopted to evaluate the efficacy of phenotypic carbapenem inactivation methods in detecting carbapenem-resistant Gram-negative bacteria isolated from blood culture specimens and assess the synergy of ceftazidime-avibactam and aztreonam in treating these infections.: Gram-negative bacteria isolated from positive blood cultures were evaluated for carbapenemase activity using mCIM and eCIM, respectively. Synergy testing was conducted using ceftazidime-avibactam and aztreonam to evaluate potential therapeutic benefits. Among 383 blood cultures, 153 (39.94%) were MDROs, predominantly (57.5%). Of these, 123 (81%) were carbapenem-resistant. The mCIM and eCIM tests identified 67 (54%) serine carbapenemase and 54 (45.5%) metallo beta-lactamases. Synergy testing with ceftazidime-avibactam and aztreonam showed positive results in 43 (68.25%) of the 63 CZA-resistant isolates.: The study confirms that mCIM and eCIM tests effectively detect carbapenemase production in blood culture isolates, identifying 54% serine carbapenemases and 45.5% metallo beta-lactamases. Additionally, synergy testing with ceftazidime-avibactam and aztreonam demonstrated a 68.25% success rate in CZA-resistant isolates, indicating a promising treatment option for these resistant infections.
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Debabza, Manel, Raoudha Dziri, Abdelbasset Mechai, Amel Bouguessa, Naouel Klibi, and Hadda Imene Ouzari. "Characterization of carbapenemase-producing Gram-negative bacilli: first report of blaNDM-1 in Enterobacter cloacae." Journal of Infection in Developing Countries 17, no. 09 (2023): 1300–1309. http://dx.doi.org/10.3855/jidc.18031.
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Introduction: The spread of multidrug-resistant bacteria, particularly carbapenem-resistant Gram-negative bacilli (CR-GNB), has become a serious challenge for clinicians due to limited therapeutic options. The aim of the study was to investigate the prevalence of carbapenemase production among clinical isolates recovered from 352 samples collected in Tebessa hospital, Algeria. Methodology: Bacterial isolates were identified by 16S RNA gene sequencing and susceptibility to antibiotics was determined by disk diffusion method. Carbapenem-resistant isolates were screened for carbapenemase production using modified carba Nordmann-Poirel test, modified Hodge test and imipenem-EDTA combined disc test. Extended-spectrum β-lactamases (ESBL) were detected using double-disk synergy test. Molecular characterization of carbapenemases and ESBL genes was performed by polymerase chain reaction (PCR) and sequencing. Results: A total of 85 Gram-negative bacilli isolates were recovered mainly from urine samples and were identified as: Klebsiella pneumoniae (17.65%), Serratia odorifera (15.29%), Escherichia coli (12.94%), Raoultella ornithinolytica, Enterobacter cloacae (11.76%), Serratia marcescens (10.59%), Morganella morganii (7.06%), Proteus mirabilis (5.88%), Acinetobacter baumannii (4.70%) and Pseudomonas aeruginosa (2.35%). All strains were resistant or intermediate to imipenem and/or ertapenem. ESBL, carbapenemase and metallo-beta-lactamases (MBL) phenotypes were detected in 19 (22.35%), 9 (10.59%) and 2 (2.35%) GNB isolates, respectively. PCR results in nine carbapenemase-producing GNB strains chosen showed the presence of one to four carbapenemase genes (blaGES, blaSME, blaNDM-1, blaVIM, blaGIM, blaSPM, blaOXA-48) in four strains; however, seven strains had at least one ESBL gene (blaTEM-1, blaCTXM-15, blaSHV). Conclusions: In this study, we report the first incidence of blaNDM-1 gene in Enterobacter cloacae isolated from urine sample in Algeria.
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Aliyu, Shamsudin. "Controlling the spread of carbapenemase-producing Gram-negative bacteria." Annals of Nigerian Medicine 7, no. 2 (2013): 45. http://dx.doi.org/10.4103/0331-3131.133094.
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Aliyu, Shamsudin. "Treating infections caused by carbapenemase producing Gram-negative bacteria." Annals of Nigerian Medicine 8, no. 1 (2014): 1. http://dx.doi.org/10.4103/0331-3131.141020.
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Pasteran, Fernando, Lisandro J. Gonzalez, Ezequiel Albornoz, Guillermo Bahr, Alejandro J. Vila, and Alejandra Corso. "Triton Hodge Test: Improved Protocol for Modified Hodge Test for Enhanced Detection of NDM and Other Carbapenemase Producers." Journal of Clinical Microbiology 54, no. 3 (2015): 640–49. http://dx.doi.org/10.1128/jcm.01298-15.
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Accurate detection of carbapenemase-producing Gram-negative bacilli is of utmost importance for the control of nosocomial spread and the initiation of appropriate antimicrobial therapy. The modified Hodge test (MHT), a carbapenem inactivation assay, has shown poor sensitivity in detecting the worldwide spread of New Delhi metallo-β-lactamase (NDM). Recent studies demonstrated that NDM is a lipoprotein anchored to the outer membrane in Gram-negative bacteria, unlike all other known carbapenemases. Here we report that membrane anchoring of β-lactamases precludes detection of carbapenemase activity by the MHT. We also show that this limitation can be overcome by the addition of Triton X-100 during the test, which allows detection of NDM. We propose an improved version of the assay, called the Triton Hodge test (THT), which allows detection of membrane-bound carbapenemases with the addition of this nonionic surfactant. This test was challenged with a panel of 185 clinical isolates (145 carrying known carbapenemase-encoding genes and 40 carbapenemase nonproducers). The THT displayed test sensitivity of >90% against NDM-producing clinical isolates, while improving performance against other carbapenemases. Ertapenem provided the highest sensitivity (97 to 100%, depending on the type of carbapenemase), followed by meropenem (92.5 to 100%). Test specificity was not affected by the addition of Triton (87.5% and 92.5% with ertapenem and meropenem, respectively). This simple inexpensive test confers a large improvement to the sensitivity of the MHT for the detection of NDM and other carbapenemases.
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Elshamy, Ann A., Sarra E. Saleh, Mohammad Y. Alshahrani, Khaled M. Aboshanab, Mohammad M. Aboulwafa, and Nadia A. Hassouna. "OXA-48 Carbapenemase-Encoding Transferable Plasmids of Klebsiella pneumoniae Recovered from Egyptian Patients Suffering from Complicated Urinary Tract Infections." Biology 10, no. 9 (2021): 889. http://dx.doi.org/10.3390/biology10090889.
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Gram-negative bacteria are common causes of urinary tract infections (UTIs). Such pathogens can acquire genes encoding multiple mechanisms of antimicrobial resistance, including carbapenem resistance. The aim of this study was to detect the carbapenemase-producing ability of some Gram-negative bacterial isolates from urine specimens of patients suffering from complicated UTIs at two vital tertiary care hospitals in Cairo, Egypt; to determine the prevalence of carbapenemase genes among plasmid-bearing isolates; and explore the possibility of horizontal gene transfer to other bacterial species. The collected isolates were subjected to antimicrobial susceptibility testing, phenotypic analysis of carbapenemase production, and molecular detection of plasmid-borne carbapenemase genes, then the extracted plasmids were transformed into competent E. coli DH5α. A total of 256 Gram-negative bacterial clinical isolates were collected, 65 (25.4%) isolates showed carbapenem resistance of which 36 (55.4%) were carbapenemase-producers, and of these 31 (47.7%) harbored plasmids. The extracted plasmids were used as templates for PCR amplification of blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP carbapenemase genes. The blaOXA-48 gene was detected in 24 (77.4%) of the tested isolates while blaVIM gene was detected in 8 (25.8%), both blaKPC and blaNDM genes were co-present in 1 (3.2%) isolate. Plasmids carrying the blaOXA-48 gene from 4 K. pneumoniae clinical isolates were successfully transformed into competent E. coli DH5α. The transformants were carbapenemase-producers and acquired resistance to some of the tested antimicrobial agents as compared to untransformed E. coli DH5α. The study concluded that the rate of carbapenem resistance among Gram-negative bacterial uropathogens in Cairo, Egypt is relatively high and can be transferred horizontally to other bacterial host(s).
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Haque, Md Ahsanul, Md Shah Alam, Farjana Kabir, Rozina Aktar Zahan, Md Mottalib Hossain Khan, and MM Washee Parvez. "Phenotypic Detection of Carbapenemase-producing WHO-declared Deadliest Drug-resistant Bacteria in the Rajshahi Region." TAJ: Journal of Teachers Association 35, no. 1 (2022): 91–98. http://dx.doi.org/10.3329/taj.v35i1.61161.
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Background: Carbapenem resistance is a major and ongoing public health problem globally and locally. It occurs mainly among Gram-negative pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Most of the carbapenemase-producing bacteria are multidrug resistant, including 3rd generation of cephalosporin and carbapenems. It may be intrinsic or mediated by transferable carbapenemase-encoding genes. This type of resistance gene is already widespread in certain parts of the world, mainly Europe, Asia, and South America. Objective: To isolate and identify WHO-declared carbapenemase-producing deadliest drug resistance bacteria with their antibiogram in the Rajshahi region.
 Materials Method: Cross sectional descriptive study was done from July 2017 to June 2018. Wound swab was collected in different surgical and burn units of Rajshahi Medical College Hospital. The specimens were inoculated in blood agar, nutrient agar, and MacConkey's agar media and incubated aerobically at 370 C for 24 hours. Susceptibility tests of the bacterial isolates were done by using the modified Kirby Bauer disk diffusion method on Mueller Hinton agar media. Carbapenemase-producing bacteria were identified by using the modified Hodge test.
 Results: Out of the total 250 samples, culture yielded growth in 213(85.2%) cases, and 37(14.8%) yielded no increase. Females were predominant 146(58.4%) in comparison to males 104(41.6%), with a male-female ratio of 1: 1.4. A maximum of 47.2% of cases were between 19-30 years old. Among the culture-positive isolates, gram-negative organisms were higher (58.8%) than gram-positive (41.2%). S. aureus was the predominant organism 71(30.8%), followed by P. aeruginosa 47(20.3%), E.coli 43(18.7%), and Acinetobacter baumannii 07 (3%). Among seven isolated Acinetobacter baumannii, 47 isolated P. aeruginosa, and 82 isolated Enterobacteriaceae: 6(85.7%), 33(70.2%), and 53(64.6%) were MDR; and 4(57.1%), 12(25.5%) and 14(17%) were carbapenemase-producers respectively.
 Conclusion: Most of the isolated carbapenemase-producing bacteria are multidrug resistant, and they tend to cause complicated infections. In addition, the expression of specific virulent factors, difficulty in diagnosis, and the non-availability of newer generation antibiotics make them one of the deadliest bacteria.
 TAJ 2022; 35: No-1: 91-98
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Yadav, Santosh Kumar, Rajshree Bhujel, Shyam Kumar Mishra, Sangita Sharma, and Jeevan Bahadur Sherchand. "Carbapenem Resistance in Non-Fermentative Gram-Negative Bacilli Isolated from Intensive Care Unit Patients of a Referral Hospital." Journal of Nepal Health Research Council 19, no. 1 (2021): 55–61. http://dx.doi.org/10.33314/jnhrc.v19i1.3240.
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Background: Non-fermentative Gram-negative bacilli or non-fermenters are opportunistic pathogens associated with serious infections in intensive care unit patients. Although carbapenems were considered as a backbone of treatment for life-threatening infections, these bacteria are increasingly acquiring resistance to carbapenems. Carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are prioritized as critical pathogens by the World Health Organization. The objective of the study was to document the status of carbapenem-resistant and carbapenemase-producing non-fermenters isolated from intensive care unit patients.Methods: This study was conducted at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. The clinical specimens collected from intensive care unit patients were processed for isolation and identification of non-fermenters and antibiotic susceptibility profile of bacterial isolates was determined. The multidrug-resistant isolates were identified and carbapenemase enzyme was detected in the carbapenem-resistant isolates.Results: A total of 157 non-fermenters were isolated from 1063 samples which included Acinetobacter species (n=85), Pseudomonas aeruginosa (n=55), Burkholderia cepacia complex (n=15), and Stenotrophomonas maltophilia (n=2). Carbapenem resistance was reported in 85.9%, 72.7%, and 33.3% of Acinetobacter species, Pseudomonas aeruginosa, and Burkholderia cepacia complex, respectively. Among total non-fermenters, 91.1% isolates were multidrug-resistant and 60.8% carbapenem-resistant isolates were carbapenemase producers. The carbapenem-resistant isolates demonstrated an extremely high degree of resistance than carbapenem-susceptible isolates towards other antimicrobial classes.Conclusions: This study reported high rates of carbapenem-resistant, carbapenemase-producing, and multidrug-resistant non-fermenters isolates. Therefore, preventing the spread of these superbugs among the critically ill patients in intensive care units should be a major initiative in hospitals.Keywords: Carbapenem-resistant; carbapenemase; intensive care unit; non-fermentative Gram-negative bacilli
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Rangel, Rafaela Linhares Ponte, Izabelly Linhares Ponte Brito, Amanda Barbosa Linhares, et al. "Dissemination of Carbapenemases in Gram-negative Bacteria in Brazilian Hospitals: A Review." Archives of Current Research International 25, no. 1 (2025): 167–81. https://doi.org/10.9734/acri/2025/v25i11048.
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Antimicrobial resistance in bacteria with carbapenemase activity is a growing public health problem of global proportions. This integrative review synthesizes data from 26 scientific articles published between 2020 and 2024 to analyze the dissemination and genetic diversity of carbapenemases in Brazil. Data were retrieved from the National Library of Medicine (PubMed) and the regional portal of the Virtual Health Library (BVS). The review highlights significant regional variability in carbapenemase prevalence, with the blaKPC gene being the most frequently identified resistance mechanism across multiple Brazilian states. The identification of novel trends, including the simultaneous presence of blaNDM and blaKPC genes in isolates of Proteus mirabilis and Serratia marcescens, in addition to the observation of blaNDM in Klebsiella aerogenes, highlights the intricate nature of antimicrobial resistance patterns. The state of Pernambuco is notable for reporting the first identification of blaVIM-2 in Acinetobacter baumannii and the blaOXA-23-like and blaOXA-143 genes. These findings emphasize the widespread cohabitation of resistance genes, with mobile genetic elements facilitating intra- and interspecies transfer among Gram-negative bacilli. Understanding this genetic diversity is crucial for developing targeted public health interventions. The study underscores the urgent need for enhanced genomic surveillance, robust infection prevention measures, and strengthened antimicrobial stewardship programs to address the growing threat of multidrug-resistant organisms in Brazil and mitigate their impact on global health.
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Livermore, David M., David P. Nicolau, Katie L. Hopkins, and Danièle Meunier. "Carbapenem-Resistant Enterobacterales, Carbapenem Resistant Organisms, Carbapenemase-Producing Enterobacterales, and Carbapenemase-Producing Organisms: Terminology Past its “Sell-By Date” in an Era of New Antibiotics and Regional Carbapenemase Epidemiology." Clinical Infectious Diseases 71, no. 7 (2020): 1776–82. http://dx.doi.org/10.1093/cid/ciaa122.
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Abstract Carbapenem resistance in Gram-negative bacteria is a public health concern. Consequently, numerous government and agency reports discuss carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant organisms (CROs). Unfortunately, these terms are fuzzy. Do they include (1) Proteeae with inherent imipenem resistance; (2) porin-deficient Enterobacterales resistant to ertapenem but not other carbapenems; (3) Enterobacterales with OXA-48–like enzymes that remain “carbapenem susceptible” at breakpoint; and (4) Pseudomonas aeruginosa that merely lack porin OprD? Counting CPE or CPOs is better but still insufficient, because different carbapenemases have differing treatment implications, particularly for new β-lactam/β-lactamase inhibitor combinations. At the least, it is essential for authors, journals, and regulatory agencies to specify the carbapenemases meant. The future may demand even greater precision, for mutations can alter hydrolytic activity, and the ability to confer resistance, within carbapenemase families.
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Brauncajs, Małgorzata, Filip Bielec, Anna Macieja, and Dorota Pastuszak-Lewandoska. "Carbapenem-Resistant Gram-Negative Fermenting and Non-Fermenting Rods Isolated from Hospital Patients in Poland—What Are They Susceptible to?" Biomedicines 10, no. 12 (2022): 3049. http://dx.doi.org/10.3390/biomedicines10123049.
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Gram-negative fermenting and non-fermenting bacteria are important etiological factors of nosocomial and community infections, especially those that produce carbapenemases. Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the most frequently-detected carbapenemase-producing microorganisms. The predominant type of resistance is metallo-β-lactamase (MBL). These bacteria are predominantly isolated from bronchial alveolar lavage, urine, and blood. Carbapenemase-producing Enterobacterales (CPE) strains are always multi-drug-resistant. This significantly limits the treatment options for this type of infection, extends the time of patient hospitalization, and increases the risk of a more severe and complicated disease course. Preventing the transmission of these microorganisms should be a major public health initiative. New antibiotics and treatment regimens offer hope against these infections.
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Rana Essa muslem, Rana H Raheema, and Qasim Dawood Yasir. "Molecular detection of carbanemase in gram negative bacteria Isolated from intensive care unit patients Molecular detection of carbanemase in gram negative bacteria Isolated from intensive care unit patients in wasit province, Iraqin wasit province, Iraq." World Journal of Biology Pharmacy and Health Sciences 12, no. 2 (2022): 130–39. http://dx.doi.org/10.30574/wjbphs.2022.12.2.0177.
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ICUs are crucial medical facilities for treating life-threatening diseases, and bacterial contamination of ICU equipment and devices is a significant cause of nosocomial infections. In this study, a total of 100 clinical specimens (urine, sputum and pus) were collected from patients admitted in the ICU. Results showed eighty two were positive growth culture. 30(36.5%) were female and 52( 63.5%) were male patients admitted to the intensive care unit distributed 69 (84.1%) gram-negative bacteria .while gram positive 13(15.8%), as well as 20 pure isolates of some places, materials and equipment distributed 12 (75%) Gram negative bacteria .While 8 (25%) it is gram positive bacteria. Results of antibiotic susceptibility test only Trimethoprime was effective choice against Acinetobacter baumannii. Phenotypically survey of carbapenem klebsiella pneumoniae were 9(47%), pseudomonas aeruginosa was 7(35% of MBL and Carbapenemase and the result of MBL and Carbapenemase for E. Coli 7(43%) similar results (40%). Whereas, Genotypically the most prevalent gene in E.Coli 1 (10%), the result was for Burkholderia cepacia blaVIM 1(100%), its prevalence was 7 (53%) among bacteria Klebsiella pneumonia for NDM, the result of bacteria Pseudomonas aeruginosa for this gene was 4(33.3%) and Escherichia Coli was 1(10%), its prevalence was (100%) among klebsiella oxytoca for KPC.
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Bennett, Jason W., Monica L. Herrera, James S. Lewis, Brian W. Wickes, and James H. Jorgensen. "KPC-2-Producing Enterobacter cloacae and Pseudomonas putida Coinfection in a Liver Transplant Recipient." Antimicrobial Agents and Chemotherapy 53, no. 1 (2008): 292–94. http://dx.doi.org/10.1128/aac.00931-08.
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ABSTRACT Carbapenemases are among the newest resistance mechanisms to emerge in some gram-negative bacteria. We describe bacteremia in a critically ill liver transplant recipient infected with KPC-2-producing Enterobacter cloacae and Pseudomonas putida. Although this enzyme has been previously described in Enterobacter spp., this is the first report of KPC carbapenemase in P. putida.