Effect of an efflux pump inhibitor on the MIC of nalidixic acid for Acinetobacter baumannii and Stenotrophomonas maltophilia clinical isolates

Ribera, Anna; Ruiz, Joaquı́m; Anta, M Teresa Jiminez de; Vila, Jordi

doi:10.1093/jac/49.4.697

Cited by 81 publications

(50 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At a lower concentration of 25 g/ml, their effect on reversing resistance is quite limited, while at a higher concentration of 100 g/ml, NMP has a stronger effect on restoring drug susceptibility than that of PA␤N (550); this difference is likely to be due to the poor permeation across the OM by NMP, in contrast to PA␤N, which permeates this membrane by perturbing its structure (see Efflux Pump Inhibitors, below). In other studies, PA␤N at 10 g/ml decreased the MIC values of chloramphenicol, clindamycin, and trimethoprim against clinical isolates regardless of the adeFGH expression status mostly 2-to 4-fold (552), while PA␤N at 20 g/ml reduced the nalidixic acid MIC up to 16-fold but displayed little effect on ciprofloxacin susceptibility (553). PA␤N and NMP, each at 100 g/ ml, restored susceptibility to fluoroquinolone (2-to 16-fold reduction of MICs) and tigecycline (mostly by a 2-fold MIC decrease) (554).…”

Section: Acinetobacter Sppmentioning

confidence: 74%

“…PA␤N and NMP, each at 100 g/ ml, restored susceptibility to fluoroquinolone (2-to 16-fold reduction of MICs) and tigecycline (mostly by a 2-fold MIC decrease) (554). Apparently, these EPIs have a stronger effect on resistance reversal with agents that have relatively high MIC values, such as chloramphenicol, clarithromycin, clindamycin, linezolid, rifampin, and trimethoprim (552,553,555), agents whose OM penetration is likely to be slow. Intriguingly, one study revealed that NMP at 64 g/ml increased the tigecycline MIC 2-fold, although no effect on susceptibility to doxycycline, minocycline, and tetracycline was observed (551).…”

Section: Acinetobacter Sppmentioning

confidence: 99%

See 1 more Smart Citation

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

View full text Add to dashboard Cite

SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

show abstract

Section: Acinetobacter Sppmentioning

confidence: 74%

Section: Acinetobacter Sppmentioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

View full text Add to dashboard Cite

show abstract

Section: Efflux Pump Inhibitorsmentioning

confidence: 99%

“…It has also been tested in Acinetobacter baumannii clinical isolates [89,92,107]. Reduction in the MIC of nalidixic acid after PAβN addition was observed, though there was no effect in the case of ciprofloxacin [107]. Recently study, demonstrated decrease of tigecycline MIC and other antimicrobials, including gentamicin, tobramycin, chloramphenicol, and several β-lactams after exposure to PAβN [92].…”

Section: Efflux Pump Inhibitorsmentioning

confidence: 99%

Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

Wieczorek

Sacha²,

Hauschild³

et al. 2008

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Abstract:Acinetobacter baumannii is an opportunistic pathogen which play the more and more greater role in the pathogenicity of the human. It is often attached with the hospital environment, in which is able easily to survive for many days even in adverse conditions. Acinetobacter baumannii is the species responsible for a serious nosocomial infections, especially in the intensive care units. Option of surviving in natural niches, and in the hospital environment could also be associated with the efflux pump mechanisms. Mechanisms of efflux universally appear in all cells (eukaryotic and prokaryotic) and play the physiological important role. In prokaryote, the main functions are evasion of such naturally produced molecules, removal of metabolic products and toxins. These pumps could also be involved in an early stage of infection, such as adhesion to host cells and the colonization. Importantly, they remove commonly used antibiotics from the cell in therapy of infections caused by these bacteria. Efflux pumps exemplify a unique phenomenon in drug resistance: a single mechanism causing resistance against several different classes of antibiotics. In Acinetobacter baumannii, the AdeABC efflux pump, a member of the resistance-nodulation-cell division family (RND), has been well characterized. Aminoglicosides, tetracyclines, erythromycin, chloramphenicol, trimethoprim, fluoroquinolones, some β-lactams, and also recently tigecycline, were found to be substrates for this pump. Drugs, as substrates for the AdeABC pump, can increase the expression of the AdeABC genes, leading to multidrug resistance (MDR). From this reason, treatment failure and death caused by Acinetobacter baumannii infections or underlying diseases are common. Because the AdeABC pump is widespread in Acinetobacter baumannii, similarly to other pumps in Gram-negative and Gram-positive bacteria, exists a need of searching a new therapeutic solutions. Specific efflux inhibitors of pumps (EPIs), including AdeABC inhibitors, could be suppress the activity of pumps and restore the sensitivity of such important bacteria as Acinetobacter baumannii to commonly used antibiotic.

show abstract

“…After adding L-PAβN, the MIC of the strains resistant to imipenem or meropenem decreased by more than 4-fold. This suggested that the efflux pump plays an important role in the mechanism of drug resistance in these strains (Ribera et al, 2002). …”

Section: Efflux Pump Phenotypic Screening Testmentioning

confidence: 99%

LC-MS/MS: a rapid and simple new method for the determination of carbapenem β-lactamases

Shen¹,

Xu²,

She³

2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. We investigated the application of liquid chromatographytandem mass spectrometry (LC-MS/MS) for pan-drug-resistant Acinetobacter baumannii (PDR-AB) with carbapenem resistance. Eight strains were randomly selected from 84 clinical isolates of PDR-AB strains obtained by the Kirby-Bauer and agar dilution methods. An efflux pump inhibition test was used to screen for the efflux pump phenotype. An ethylenediaminetetraacetic acid (EDTA) synergy test was used to screen for the β-lactamase phenotype, and a three-dimensional test was used to detect extended spectrum β-lactamase (ESBL) and ampicillin C, KPC, and carbapenemase. ESBL genes were amplified by polymerase chain reaction and sequenced. Outer membrane proteins were extracted from a sensitive strain and the PDR-AB strains by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and subjected to LC-MS/ MS. Peptide mass fingerprinting data were retrieved, and proteins with differential expression were identified. Results of the efflux pump inhibition tests showed that the minimum inhibitory concentrations for meropenem were decreased in 4 of the 8 strains by at least 25% of the original value. The results of the EDTA synergy test were negative, and the modified Hodge's tests were positive for all strains. PCR and sequencing confirmed that seven, five, and all eight of the PDR-AB strains contained blaOXA-23, blaTEM-1, and KPC-2, respectively. OXA-23 and CsuC proteins were differentially expressed between the drug-resistant and -sensitive strains. Production of blaOXA-23 enzyme and pilus molecular chaperone to guide synthesis of CsuC protein may be involved in the resistance of A. baumannii to carbapenems. LC-MS/ MS provides a quick and easy method for carbapenemase detection.

show abstract

Effect of an efflux pump inhibitor on the MIC of nalidixic acid for Acinetobacter baumannii and Stenotrophomonas maltophilia clinical isolates

Cited by 81 publications

References 2 publications

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

LC-MS/MS: a rapid and simple new method for the determination of carbapenem β-lactamases

Contact Info

Product

Resources

About