Mechanisms of antimicrobial resistance in Gram-negative bacilli

Abstract

The burden of multidrug resistance in Gram-negative bacilli (GNB) now represents a daily issue for the management of antimicrobial therapy in intensive care unit (ICU) patients. In Enterobacteriaceae, the dramatic increase in the rates of resistance to third-generation cephalosporins mainly results from the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL), especially those belonging to the CTX-M family. The efficacy of beta-lactam/beta-lactamase inhibitor associations for severe infections due to ESBL-producing Enterobacteriaceae has not been adequately evaluated in critically ill patients, and carbapenems still stands as the first-line choice in this situation. However, carbapenemase-producing strains have emerged worldwide over the past decade. VIM- and NDM-type metallo-beta-lactamases, OXA-48 and KPC appear as the most successful enzymes and may threaten the efficacy of carbapenems in the near future. ESBL- and carbapenemase-encoding plasmids frequently bear resistance determinants for other antimicrobial classes, including aminoglycosides (aminoglycoside-modifying enzymes or 16S rRNA methylases) and fluoroquinolones (Qnr, AAC(6′)-Ib-cr or efflux pumps), a key feature that fosters the spread of multidrug resistance in Enterobacteriaceae. In non-fermenting GNB such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, multidrug resistance may emerge following the sole occurrence of sequential chromosomal mutations, which may lead to the overproduction of intrinsic beta-lactamases, hyper-expression of efflux pumps, target modifications and permeability alterations. P. aeruginosa and A. baumannii also have the ability to acquire mobile genetic elements encoding resistance determinants, including carbapenemases. Available options for the treatment of ICU-acquired infections due to carbapenem-resistant GNB are currently scarce, and recent reports emphasizing the spread of colistin resistance in environments with high volume of polymyxins use elicit major concern.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-015-0061-0) contains supplementary material, which is available to authorized users.

Hospital Acquired Infection: Bacteriological Profile of Species from Environmental Surfaces of Cotonou 5 Hospital in South Benin (West Africa)

“…Based on the analysis results, enterobacteria were predominant (62.16%) in Gram-negative bacilli, followed by 33.33% non-fermenting Gram-negative bacilli (NFGNB). Gramnegative bacilli (GNB) acquire genes that code for antibiotic resistance mechanisms and thus exacerbate the resulting infections (Ruppé et al, 2015). The rate of enterobacteria isolated in our study is higher than the 10.70% isolated by Jalalpoor (2011) and is lower than 74.51% reported by Debabza (2015).…”

Phenotypic Detection and Antimicrobial susceptibility Profile of ESBL, AmpC and Carbapenemase producing Gram-negative isolates from Outpatient clinic specimens

“…A result which is in agreement with other study in Sothern Saudi Arabia which showeda percentage of77%, 16% and 7% for the isolated organisms in outpatient UTI ( El-Kersh et al, 2015). Previous studies (Gupta et al, 2011;AlJiffri et al, 2011;Pondei et al, 2012;Ahmad, 2012) (Ruppe et al, 2015). The existing data showed a wide variation in the prevalence of ESBL, AmpC and Carbapenemase from region to region or even from hospital to hospital in the same region ( Babypadmini and Appalaraju, 2004 Kumar et al, 2014 documented that antimicrobial sensitivity pattern of ESBL-producing E. coli showed that it was 100% susceptible to Imipenem however their results were not in agreement with our results in that the susceptibility to ESBL inhibitor combination drugs was almost the same as compared to non-ESBL producing E. coli.…”

Bacterial sepsis

“…If ESBL producers are to be expected, carbapenems should generally be preferred, even though several clinically relevant ESBL variants (temoneira β-lactamase, TEM; sulfhydryl variable type β-lactamase, SHV; cefotaxime-Munich β-lactamase, CTX-M) may retain susceptibility to piperacillin/tazobactam [154]. If the antibiogram reveals an ESBL pathogen to be susceptible to piperacillin/tazobactam, treatment of urinary tract infections is usually unproblematic; however, for bacteremia, no consensus has been reached regarding the adequacy of therapy due to the inoculum effect [155] and the serious implications of altered β-lactam pharmacokinetics in sepsis patients [156,157]. Whether antibiogram-directed treatment against ESBL-synthesizing pathogens should be conducted with piperacillin/tazobactam thus remains a decisionthatmustbe made on the basis of an individual risk-benefit assessment.…”