Molecular epidemiology &amp; therapeutic options of carbapenem-resistant Gram-negative bacteria

Garg, Atul; Garg, Jaya; Kumar, Sanjay; Bhattacharya, Amitabh; Agarwal, Saurabh; Upadhyay, G. C.

doi:10.4103/ijmr.ijmr_36_18

Cited by 39 publications

(26 citation statements)

References 15 publications

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“…Previous studies found the efflux pump by the molecular technique such as PCR and observed that AcrAB efflux pump and mdtK efflux pump existed in CRE isolates. 23,41 In the current study, carbapenemase enzymes were detected by Carba NP test and MHT in 98% and 95%, respectively, which was in line with another study carried by Elawady et al 44 and Garg et al 45 who reported good sensitivity and specificity of Carba NP test.…”

Section: Discussionsupporting

confidence: 92%

Evaluation of Resistance Mechanisms in Carbapenem-Resistant Enterobacteriaceae

Alizadeh¹,

Rezaee²,

Kafil³

et al. 2020

IDR

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Background: Carbapenem-resistant Enterobacteriaceae (CRE) is a major concern leading to morbidity and mortality in the world. CRE often is becoming a cause of therapeutic failure in both hospital and community-acquired infections. Aim: This study aimed to investigate the resistance mechanisms of CRE by phenotypic and molecular methods. Materials and Methods: Sixty CRE (50 Klebsiella pneumoniae, 6 Escherichia coli, and 4 Enterobacter spp.) were isolated from October 2018 to June 2019. Antimicrobial susceptibility testing was carried out using phenotypic methods. The carbapenem resistance mechanisms including efflux pump hyperexpression, AmpC overproduction, carbapenemase genes, and deficiency in OmpK35 and OmpK36 were determined by phenotypic and molecular methods, respectively. Results: Sixty CRE (50 Klebsiella pneumoniae, 6 Escherichia coli, and 4 Enterobacter spp.) were isolated from October 2018 to June 2019. Amikacin was found to be the most effective drug against CRE isolates. All isolates were resistant to imipenem and meropenem by the micro-broth dilution. AmpC overproduction was observed in all Enterobacter spp. and three K. pneumoniae isolates. No efflux pump activity was found. Carba NP test and Modified Hodge Test could find carbapenemase in 59 (98%) isolates and 57 (95%) isolates, respectively. The most common carbapenemase gene was bla OXA-48-like (72.8%) followed by bla NDM (50.8%), bla IMP (18.6%), bla VIM (11.8%), and bla KPC (6.7%). The ompK35 and ompK36 genes were not detected in 10 and 7 K. pneumoniae isolates, respectively. Conclusion: The amikacin is considered as a very efficient antibiotic for the treatment of CRE isolates in our region. Carbapenemase production and overproduction of AmpC are the main carbapenem resistance mechanisms in CRE isolates. Finally, Carba NP test is a rapid and reliable test for early detection of carbapenemase-producing isolates.

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Section: Discussionsupporting

confidence: 92%

Evaluation of Resistance Mechanisms in Carbapenem-Resistant Enterobacteriaceae

Alizadeh¹,

Rezaee²,

Kafil³

et al. 2020

IDR

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“…The unusually high prevalence of bla VIM (50% of bla NDM positive isolates) was also reported previously from our centre (Rahman et al, 2018). Another study from North India reported bla VIM in 18.4% (52/ 282) of carbapenem resistant isolates (Garg et al, 2019). Aminoglycosides in combination with other antibiotics such as tigecycline are often used for treating infections caused by carbapenem and colistin resistant K. pneumoniae (Petrosillo et al, 2019).…”

Section: Discussionsupporting

confidence: 81%

Genetic Characterisation of Colistin Resistant Klebsiella pneumoniae Clinical Isolates From North India

Singh

Pathak

Rahman

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundIncreasing use of colistin has led to the world-wide emergence of mobile colistin resistant gene (mcr). The present study aimed to identify and characterise mcr and other drug-resistant genes in colistin resistant Klebsiella pneumoniae clinical isolates.MethodsTwenty-two colistin resistant K. pneumoniae were analysed for mcr and other drug-resistant genes, efflux pumps, and virulence genes, and for their biofilm forming ability. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed for all mcr-1 positive isolates. S1-PFGE and Southern hybridisation were performed for localisation of mcr-1 and blaNDM.ResultsNineteen colistin resistant K. pneumoniae harboured mcr-1 and 3 had mgrB disruption. All isolates harboured blaOXA-48-type and ESBL genes; eight strains (five with mcr-1 and three with mgrB disruption) co-harboured blaNDM. Efflux pumps genes AcrAB and mdtK were detected in all 22 and tol-C in 21 isolates. Virulence-related genes entB and irp-1 were detected in all 22, mrkD in 20, and fimH-1 in 18 isolates; 11 isolates were strong biofilm producers. PFGE clustered mcr-1 positive isolates into eight groups based on ≥90% similarity; MLST revealed diverse sequence types, predominant being ST-15 (n = 4) and ST-16 (n = 4). Both mcr-1 and blaNDM were localised on plasmid and chromosome; mcr-1 was present on IncFII type and blaNDM on IncFIB and IncA/C type plasmids.ConclusionsColistin resistance in K. pneumoniae was predominantly mediated by mcr-1. Co-existence of colistin, carbapenem, and other drug-resistant genes along with efflux pumps indicates towards enormous genomic plasticity in K. pneumoniae with ability to emerge as super-spreader of drug-resistance.

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“…In a cross-sectional, multicenter survey from Dubai, all the studied P. aeruginosa isolates were colistin sensitive [ 194 ]. On the other hand, the rate of resistance was 22% in a report from India [ 195 ], and 15% in a nationwide Italian survey [ 196 ]. Ongoing surveillance is needed on a global scale, to observe and mitigate the spread of polymyxin resistance in this hostile pathogen.…”

Section: Special Features and Spread Of Polymyxin Resistance Amongmentioning

confidence: 99%

Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance

2020

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Following their initial discovery in the 1940s, polymyxin antibiotics fell into disfavor due to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the rising global prevalence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria have both rejuvenated clinical interest in these polypeptide antibiotics. Parallel to the revival of their use, investigations into the mechanisms of action and resistance to polymyxins have intensified. With an initial known effect on biological membranes, research has uncovered the detailed molecular and chemical interactions that polymyxins have with Gram-negative outer membranes and lipopolysaccharide structure. In addition, genetic and epidemiological studies have revealed the basis of resistance to these agents. Nowadays, resistance to polymyxins in MDR Gram-negative pathogens is well elucidated, with chromosomal as well as plasmid-encoded, transferrable pathways. The aims of the current review are to highlight the important chemical, microbiological, and pharmacological properties of polymyxins, to discuss their mechanistic effects on bacterial membranes, and to revise the current knowledge about Gram-negative acquired resistance to these agents. Finally, recent research, directed towards new perspectives for improving these old agents utilized in the 21st century, to combat drug-resistant pathogens, is summarized.

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Molecular epidemiology & therapeutic options of carbapenem-resistant Gram-negative bacteria

Cited by 39 publications

References 15 publications

<p>Evaluation of Resistance Mechanisms in Carbapenem-Resistant <em>Enterobacteriaceae</em></p>

<p>Evaluation of Resistance Mechanisms in Carbapenem-Resistant <em>Enterobacteriaceae</em></p>

Genetic Characterisation of Colistin Resistant Klebsiella pneumoniae Clinical Isolates From North India

Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance

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