Overview of polymyxin resistance in Enterobacteriaceae

Silva, Késia Esther da; Rossato, Luana; Leite, Andressa Ferraz; Simionatto, Simone

doi:10.1590/0037-8682-0349-2021

Cited by 11 publications

(11 citation statements)

References 46 publications

(61 reference statements)

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“…Studies have suggested that alterations in mgrB and pmrAB may be responsible for polymyxin resistance in Gram-negative pathogens [ 13 , 29 , 30 , 31 ]. The inactivation of mgrB , which encodes a negative feedback regulator of the PhoQ-PhoP signaling system, was recently demonstrated to be a common mutational mechanism responsible for acquired polymyxin resistance among the clinical isolates of K. pneumoniae , Enterobacter spp., and E. coli [ 14 , 15 , 21 , 32 , 33 , 34 , 35 ]. Mutations in mgrB may be the main determinant for colistin resistance in K. aerogenes [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

Genetic Diversity of Virulent Polymyxin-Resistant Klebsiella aerogenes Isolated from Intensive Care Units

et al. 2022

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This study evaluated the scope and genetic basis of polymyxin-resistant Klebsiella aerogenes in Brazil. Eight polymyxin-resistant and carbapenemase-producing K. aerogenes strains were isolated from patients admitted to the ICU of a tertiary hospital. Bacterial species were identified by automated systems and antimicrobial susceptibility profile was confirmed using broth microdilution. The strains displayed a multidrug resistant profile and were subjected to whole-genome sequencing. Bioinformatic analysis revealed a variety of antimicrobial resistance genes, including the blaKPC-2. No plasmid-mediated colistin resistance gene was identified. Nonetheless, nonsynonymous mutations in mgrB, pmrA, pmrB, and eptA were detected, justifying the colistin resistance phenotype. Virulence genes encoding yersiniabactin, colibactin, and aerobactin were also found, associated with ICEKp4 and ICEKp10, and might be related to the high mortality observed among the patients. In fact, this is the first time ICEKp is identified in K. aerogenes in Brazil. Phylogenetic analysis grouped the strains into two clonal groups, belonging to ST93 and ST16. In summary, the co-existence of antimicrobial resistance and virulence factors is deeply worrying, as it could lead to the emergence of untreatable invasive infections. All these factors reinforce the need for surveillance programs to monitor the evolution and dissemination of multidrug resistant and virulent strains among critically ill patients.

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Section: Resultsmentioning

confidence: 99%

Genetic Diversity of Virulent Polymyxin-Resistant Klebsiella aerogenes Isolated from Intensive Care Units

et al. 2022

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“…2), whereas the global average remained at 10%. 40 A previous study has put the rate of Pol R among clinical Enterobacteriaceae isolates in India at 13.8%. 41 The present study revealed that GNB resistant to polymyxins is spread all over India, and States like Tamil Nadu, Uttar Pradesh, and Odisha have a higher prevalence of Pol R strains than the national average (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…2), whereas the global average remained at 10%. 40 A previous study has put the rate of Pol R among clinical Enterobacteriaceae isolates in India at 13.8%. 41…”

Section: Discussionmentioning

confidence: 99%

Prevalence of polymyxin resistant bacterial strains in India: a systematic review and meta-analysis

Dwibedy,

Padhy,

Panda

et al. 2023

Preprint

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IntroductionPolymyxins, the cationic lipopeptide antibiotics, are considered to be the last line of therapeutics against the multi-drug resistant (MDR) pathogenic Gram-negative bacteria. Unfortunately, the rising cases of polymyxin-resistant strains from across the globe have adversely impacted the available treatment options. While the molecular mechanisms responsible for developing polymyxin resistance (PolR) are understood to a great extent, the prevalence of PolRstrains in India is not investigated systematically.MethodFor this study, a systematic search for relevant articles was performed in the relevant databases for the period January 2015 to August 2023. A meta-analysis was performed using the comprehensive meta-analysis software (V.3) to determine the overall prevalence of PolRbacterial strains in India. Publication biases were assessed using funnel plots and Egger’s regression analysis.ResultConsidering a total of 79 studies selected based on the relevant inclusion and exclusion criteria, the present meta-analysis found the rate of PolRbacteria in India to be at 12.7%, which is higher than the global average. Among the Indian States, Tamil Nadu topped with the highest prevalence of PolRat 23%. Investigating the contribution of the mobile colistin resistance (mcr) genes, it was observed that among the PolRstrains, 8.6 % weremcrpositive.ConclusionThemcr-positive strains reported from India could be an underestimation of the actual numbers due to the non-inclusion ofmcrscreening in many previous studies. Our study provides insight into the state of the PolRsituation in India, which may be useful to develop a monitoring strategy to contain the spread of such strains and preserve the potency of the polymyxins.

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“…Polymyxins exert their antibacterial effect by increasing the permeability of the bacterial outer membrane through interaction with lipopolysaccharides in the outer membrane of gram-negative bacteria. 26 As a novel β-lactam/β-lactamase inhibitor combination, CAZ-AVI exhibits activity against various clinically important β-lactam-resistant bacteria producing class A and K. pneumoniae carbapenemases and class C and certain class D enzymes, but not against the metallo-β-lactamases (MBL) of class B enzymes. 27 Consequently, the distinct action mechanisms of the two drugs contribute different clinical effectiveness.…”

Section: Discussionmentioning

confidence: 99%

“…However, given the availability of such drugs, CAZ-AVI and polymyxins-containing regimens have been highly recommended as the frontline agents in the treatment of multidrug-resistant gram-negative bacterial infections in China. Polymyxins exert their antibacterial effect by increasing the permeability of the bacterial outer membrane through interaction with lipopolysaccharides in the outer membrane of gram-negative bacteria 26. As a novel β-lactam/β-lactamase inhibitor combination, CAZ-AVI exhibits activity against various clinically important β-lactam-resistant bacteria producing class A and K. pneumoniae carbapenemases and class C and certain class D enzymes, but not against the metallo-β-lactamases (MBL) of class B enzymes 27.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of ceftazidime–avibactam versus polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infection: a systematic review and meta-analysis

Yang

Wang

et al. 2023

BMJ Open

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ObjectivesCarbapenem-resistant Enterobacteriaceae is increasingly recognised as a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) and polymyxins are considered as the last therapeutic options worldwide. This is the first meta-analysis of recently published data to compare the clinical efficacy and safety of CAZ-AVI with polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase and the Cochrane Library were systematically searched, for publications in any language, from database inception to February 2023.Eligibility criteria for selecting studiesStudies comparing the clinical efficacy and safety of CAZ-AVI with polymyxins were included. Mortality, clinical success, microbiological eradication and nephrotoxicity were assessed as the main outcomes.Data extraction and synthesisLiterature screening, data extraction and the quality evaluation of studies were conducted by two researchers independently, with disagreements resolved by another researcher. The Newcastle–Ottawa Scale was used to assess the bias risk for the included studies. Review Manager V.5.3 was employed for the meta-analysis.ResultsThe meta-analysis included seven retrospective and four prospective cohort studies with 1111 patients enrolled. The CAZ-AVI groups demonstrated a lower 30-day mortality (risk ratio (RR)=0.48, 95% CI of 0.37 to 0.63, I2=10%, p<0.0001) in nine studies with 766 patients; higher clinical success (RR=1.71, 95% CI 1.33 to 2.20, I2=35%, p<0.0001) in four studies with 463 patients; and lower nephrotoxicity in seven studies with 696 patients (RR=0.42, 95% CI 0.23 to 0.77, I2=35%, p<0.05). However, no significant difference in microbiological eradication rates was observed in 249 patients from two studies (RR=1.16, 95% CI 0.97 to 1.39, I2=0, p>0.05).ConclusionAvailable evidence suggested that CAZ-AVI treatment held a dominant position with respect to efficacy and safety compared with polymyxins in carbapenem-resistant Enterobacteriaceae infections. However, the analysis included only observational studies, and high-quality, large-scale, multicentre, double-blind randomised controlled trials are needed to confirm the advantage of CAZ-AVI.

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Overview of polymyxin resistance in Enterobacteriaceae

Cited by 11 publications

References 46 publications

Genetic Diversity of Virulent Polymyxin-Resistant Klebsiella aerogenes Isolated from Intensive Care Units

Genetic Diversity of Virulent Polymyxin-Resistant Klebsiella aerogenes Isolated from Intensive Care Units

Prevalence of polymyxin resistant bacterial strains in India: a systematic review and meta-analysis

Efficacy and safety of ceftazidime–avibactam versus polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infection: a systematic review and meta-analysis

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