Antimicrobial Drug Efflux Pumps in Enterobacter and Klebsiella

Davin-Régli, Anne; Masi, Muriel; Bialek, Suzanne; Nicolas–Chanoine, Marie–Hélène; Pagès, Jean‐Marie

doi:10.1007/978-3-319-39658-3_11

Cited by 11 publications

(11 citation statements)

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“…Efflux also affects biocidal agents comprising disinfectants, antiseptics, and preservatives that are commonly practiced in medicine [11,12]. Moreover, it is also involved in bacterial colonization and virulence [10,[13][14][15][16] and contributes to the acquisition of additional mechanisms of resistance that includes the mutation in antibiotic targets (e.g. mutation in gyrase/topoisomerase for quinolone) or the production of enzymes that degrade antibiotics (e.g.…”

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confidence: 99%

Multidrug efflux pumps and their role in antibiotic and antiseptic resistance: a pharmacodynamic perspective

Alibert

Diarra

Hernandez

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Worrying levels of bacterial resistance have been reported worldwide involving the failure of many available antibiotic treatments. Multidrug resistance (MDR) in Gram-negative bacteria is often ascribed to the presence of multiple and different resistance mechanisms in the same strain. RND efflux pumps play a major role and are an attractive target to discover new antibacterial drugs. Areas covered: This review discusses the prevalence of efflux pumps, their overexpression in clinical scenarios, their polyselectivity, their effect on the intracellular concentrations of various antibiotics associated with the alteration of the membrane permeability and their involvement in pathogenicity are discussed. Expert opinion: Efflux pumps are new targets for the development of adjuvant in antibiotic treatments by of efflux pump inhibition. They may allow us to rejuvenate old antibiotics acting on their concen-tration inside the bacteria and thus potentiating their activity while blocking the release of virulence factors. It is a pharmacodynamic challenge to finalize new combined therapy. KEYWORDSEfflux pump; Gram-negative bacteria; antibiotic; multidrug resistance; inhibitor Article highlights• Efflux pumps play a major role in multidrug resistance in Gram-negative bacteria • The pharmacodynamic role of RND efflux pumps in antibiotic resis-tance opens up new perspectives to alternative therapeutics • Targeting efflux pumps consists in solving the problems of polyse-lectivity, drug accumulation, membrane permeability and pathogeni-city related to bacterial resistance mechanisms • How to validate efflux pumps as target for new combined therapy?• Efflux pump inhibitor could be used as adjuvant in antibiotic treatments

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confidence: 99%

Multidrug efflux pumps and their role in antibiotic and antiseptic resistance: a pharmacodynamic perspective

Alibert

Diarra

Hernandez

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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“…Also, resistance to third-generation cephalosporin in Enterobacteriaceae is always associated with ESBL, whereas resistance to carbapenems can be caused by production of an ESBL or plasmid mediated coded AmpC cephalosporinase combined with an efflux pump system or a decrease in outer membrane permeability [ 35 – 37 ]. It is reported that the mutation rate of the membrane permeability of Enterobacteriaceae is relatively high [ 38 , 39 ], so when dealing with meningitis caused by EPE, even if it is treated with carbapenem antibiotics, good clinical outcomes may not be obtained. All of the 220 cases of Enterobacteriaceae in this study were sensitive to polymyxin B, which maybe the last line of defence against EPE or Carbapenem-resistant Enterobacteriaceae (CRE).…”

Section: Discussionmentioning

confidence: 99%

Phenotype, molecular characterisation and risk factors for postoperative meningitis caused by ESBL-producing-Enterobacteriaceae: a six years multi-Centre comparative cohort study

et al. 2021

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Background To determine the phenotype, molecular characterisation and risk factors of postoperative meningitis induced by Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (EPE) in China. Methods We performed a multi-centre comparative cohort study of postoperative meningitis patients infected with Enterobacteriaceae in 4 neurosurgical centres in China from January 2014 to December 2019. Phenotype and molecular characteristics of the isolates were reviewed and tested, and independent risk factors of the EPE meningitis were evaluated by binary logistic regression. Results In total, 220 Enterobacteriaceae include 78 EPE were available in this study. 85.6% (67/78) ESBL-related genes were tested, and blaSHV (14.9%) and blaSHV + blaTEM + blaCTX-M-9 (20.9%) were found to be the most frequent mono and combined ESBL-related genes harboured by Enterobacteriaceae. On binary logistic analysis, craniotomy (OR. 2.583, 95% C.I. 1.274–5.235, P = 0.008) and malignancy (OR. 2.406, 95% C.I. 1.299–4.456, P = 0.005) were the associated independent risk factors to meningitis induced by EPE. Conclusions To the best of our knowledge, this is the largest series focusing on risk factors of EPE meningitis which has been conducted in China. Craniotomy and malignancy were independent risk factors for EPE meningitis. The risk factors identified may be further utilized in clinical practice and research to avoid and reduce the mortality in future.

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“…K. pneumoniae K. pneumoniae comes after E. coli, the main enterobacterial species involved in nosocomial infections, with the highest proportion of isolates producing plasmid-mediated extended-spectrum β-lactamases and carbapenemases [40][41][42][43]. Two major RND pumps and their regulatory elements are characterized in K. pneumoniae, AcrAB and OqxAB [40,44]. The oqxAB operon was originally described on plasmid carried by an E. coli strain conferring resistance to chloramphenicol and quinolones [44].…”

Section: Enterobacteriaceaementioning

confidence: 99%

Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria

2021

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Antibiotic efflux is a mechanism that is well-documented in the phenotype of multidrug resistance in bacteria. Efflux is considered as an early facilitating mechanism in the bacterial adaptation face to the concentration of antibiotics at the infectious site, which is involved in the acquirement of complementary efficient mechanisms, such as enzymatic resistance or target mutation. Various efflux pumps have been described in the Gram-negative bacteria most often encountered in infectious diseases and, in healthcare-associated infections. Some are more often involved than others and expel virtually all families of antibiotics and antibacterials. Numerous studies report the contribution of these pumps in resistant strains previously identified from their phenotypes. The authors characterize the pumps involved, the facilitating antibiotics and those mainly concerned by the efflux. However, today no study describes a process for the real-time quantification of efflux in resistant clinical strains. It is currently necessary to have at hospital level a reliable and easy method to quantify the efflux in routine and contribute to a rational choice of antibiotics. This review provides a recent overview of the prevalence of the main efflux pumps observed in clinical practice and provides an idea of the prevalence of this mechanism in the multidrug resistant Gram-negative bacteria. The development of a routine diagnostic tool is now an emergency need for the proper application of current recommendations regarding a rational use of antibiotics.

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Antimicrobial Drug Efflux Pumps in Enterobacter and Klebsiella

Abstract: International audienc

Cited by 11 publications

References 149 publications

Multidrug efflux pumps and their role in antibiotic and antiseptic resistance: a pharmacodynamic perspective

Multidrug efflux pumps and their role in antibiotic and antiseptic resistance: a pharmacodynamic perspective

Phenotype, molecular characterisation and risk factors for postoperative meningitis caused by ESBL-producing-Enterobacteriaceae: a six years multi-Centre comparative cohort study

Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria

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