scholarly journals Role of efflux pump inhibitor in decreasing antibiotic cross-resistance of Pseudomonas aeruginosa in a burn hospital in Iran

2016 ◽  
Vol 10 (06) ◽  
pp. 600-604 ◽  
Author(s):  
Mahshid Talebi-Taher ◽  
َAli Majidpour ◽  
Abbas Gholami ◽  
Samira Rasouli-Kouhi ◽  
Maryam Adabi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Cross Resistance ◽  
Beta Lactams ◽  
Efflux Pump Inhibitor ◽  
Efflux Pump Inhibitors

Introduction: Multidrug resistance in Pseudomonas aeruginosa may be due to efflux pump overexpression. This study phenotypically examined the role of efflux pump inhibitors in decreasing antibiotic cross-resistance between beta-lactams, fluoroquinolones, and aminoglycosides in P. aeruginosa isolates from burn patients in Iran. Methodology: A total of 91 phenotypically and genotypically confirmed P. aeruginosa samples were studied. Multidrug cross-resistance was determined using the disk diffusion method and minimum inhibitory concentration (MIC) test. The contribution of efflux pumps was determined by investigating MIC reduction assay to markers of beta-lactams, fluoroquinolones, and aminoglycosides in the absence and presence of an efflux pump inhibitor. All the isolates were also tested by polymerase chain reaction for the presence of mexA, mexC, and mexE efflux genes. Results: Of the isolates, 81 (89%) and 83 (91.2%) were multidrug resistant according to the disk diffusion and MIC method, respectively. Cross-resistance was observed in 67 (73.6%) and 68 (74.7%) of isolates according to the disk diffusion and MIC method, respectively. In the presence of the efflux pump inhibitor, twofold or higher MIC reduction to imipenem, cefepime, ciprofloxacin, and gentamicin was observed in 59, 65, 55, and 60 isolates, respectively. Except for two isolates that were negative for mexC, all isolates were positive for mexA, mexC, and mexE genes simultaneously. Conclusion: Efflux pumps could cause different levels of resistance based on their expression in clinical isolates. Early detection of different efflux pumps in P. aeruginosa could allow the use of other antibiotics and efflux pump inhibitors in combination with antibiotic therapy.

Determination of imipenem efflux-mediated resistance in Acinetobacter spp., using an efflux pump inhibitor

2019 ◽  
Author(s):  
Ghazale Amiri ◽  
Maryam Abbasi Shaye ◽  
Masoumeh Bahreini ◽  
Asghar Mafinezhad ◽  
Kiarash Ghazvini ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Efflux Pumps ◽  
Diffusion Method ◽  
Efflux Pump Inhibitor ◽  
Acinetobacter Species ◽  
Fold Reduction ◽  
Carbonyl Cyanide ◽  
Acinetobacter Spp

Background and Objectives: In recent years, reports of Acinetobacter strains resistant to all known antibiotics have caused a great concern in medical communities. Overexpression of efflux pumps is one of the major causes of resistance in bacteria. The aim of this study was to investigate the role of efflux pumps in conferring resistance to imipenem in clinically important Acinetobacter spp; Acinetobacter baumannii and Acinetobacter lwoffii. Materials and Methods: A total number of 46 clinical Acinetobacter isolates, including 33 A. baumannii and 13 A. lwoffii isolates, previously collected from Shahid Kamyab and Ghaem hospitals of Mashhad, Iran were used in this study. Imipenem susceptibility testing was carried out by the disc diffusion method. Imipenem minimum inhibitory concentration (MIC) for resistant Acinetobacter isolates were determined both in the presence and absence of the efflux pumps inhibitor, carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Results: Resistance to imipenem was observed in 38 isolates including 30 A. baumannii and 8 A. lwoffii isolates. Experiments in the presence of CCCP showed a 2 to 16384 fold reduction in imipenem MICs in 14 A. baumannii and 2 A. lwoffii isolates. Conclusion: The results obtained showed high levels of resistance to imipenem and contribution of efflux pumps in conferring resistance in both Acinetobacter species in this study. Moreover, imipenem efflux mediated resistance highlights the importance of this mechanism not only in A. baumannii but also in non-baumannii Acinetobacter Spp. which have been neglected in antibiotic resistance studies.

MexAB-OprM and MexXY-OprM efflux pumps overexpression; additional mechanism for carbapenems resistance among nosocomial Pseudomonas aeruginosa isolates

2020 ◽  
Vol EJMM29 (4) ◽  
pp. 17-25
Author(s):  
Asmaa M. Elbrolosy ◽  
Amira H. Elkhayat ◽  
Dina M. Hassan ◽  
Eman H. Salem
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Target Genes ◽  
Efflux Pump ◽  
Early Recognition ◽  
Efflux Pumps ◽  
Diffusion Method ◽  
University Hospitals ◽  
Pcr Assay ◽  
Efflux Pump Inhibitor ◽  
Disk Diffusion Method

Background: Multidrug-resistant pathogens have been on the rise during the last few years. Pseudomonas aeruginosa is commonly encountered in nosocomial infections with remarkable ability to develop antimicrobial resistance of which carbapenems are of great concern. Objectives: To explore the role of MexAB-OprM and MexXY-OprM efflux pumps overexpression as carbapenems resistance mechanisms among nosocomial P. aeruginosa isolates at both Menoufia and Kasr Al Ainy University Hospitals by phenotypic and molecular characterization methods. Methodology: A total of 120 P. aeruginosa isolates were collected from patients with hospital-acquired infections and subjected to antibiotic susceptibility testing by the Kirby-Bauer disk diffusion method. Carbapenems-resistant isolates were selected and investigated phenotypically for the contribution of MexAB-OprM and MexXY-OprM efflux pumps by both disk synergy and MIC reduction assays with cyanide-m-chlorophenyl hydrazone (CCCP) as an efflux pump inhibitor. Real time PCR assay verified the existence of mexA and mexX genes as regulators of MexAB-OprM and MexXY-OprM overexpression. Laboratory results were correlated with data regarding patients' clinical findings as well as risk factors. Results: Out of 120 P. aeruginosa isolates, 88 (73.3%) isolates were carbapenems-resistant of which 100% were MDR isolates. The highest resistance rate was for piperacillin and piperacillin/tazobactam (100% for each) and the lowest rate was seen against colistin (7.5%).The RT-PCR assay revealed that, 54/88 (61.3%) P. aeruginosa isolates harbored the target genes: 21 isolates (38.9%) were positive for mexA alone, 12 isolates (22.2%) were positive for mexX alone and 21 isolates (38.9%) showed co-existence of the two genes. In relation to PCR results, the sensitivity, specificity and accuracy of CCCP disk synergy test respectively were 46%, 94% and 64.8% while, those for MIC method were 88.9%, 55.9% and 76.1% respectively. Conclusion: Carbapenems resistance mediated by the overexpression of efflux pumps has also now emerged. Early recognition of this resistance mechanism to allow the use of alternative b-lactams is imperative.

scholarly journals Antibiotic resistance patterns of efflux pumps MexAB-Opr M in pathogenic Pseudomonas aeruginosa isolates

2020 ◽  
Author(s):  
Javad rasouli ◽  
Behnam hashemi ◽  
Hamed Afkhami ◽  
Mansoor Khaledi ◽  
Reza valadan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Drug Susceptibility ◽  
Diffusion Method ◽  
Efflux Pump Inhibitor ◽  
Disk Diffusion Method ◽  
Burn Victims ◽  
Resistance Patterns

Abstract Objectives Pseudomonas aeruginosa is one of the most important causes of Hospital infection especially in burn victims. The current study aimed to determine antibiotic resistance of the efflux Pumps MexAB-Opr M. In the present study, 115 samples of urine, blood, sputum, and ICU were collected from the reconstructive section of the patients. The drug susceptibility patterns were determined by disk diffusion method. Phenotypic activity of the efflux pump from the E-test was evaluated, in the presence and without the presence of efflux pump inhibitor. The MexAB gene was analyzed by PCR reaction. Results The resistant isolated was shown to be Ciprofloxacin 33.91%, Nurfloxacin 38.26%, Gentamicin 71.7%, Nalidixic acid 95.95%, Ceftazidim 38.46%, Emipenem 24.34%, Meropenem 26.36%, and Cefotaxim 40.86%. The highest and lowest resistance rates were Co-trimoxazole and Piperacilin, respectively. The findings of PCR reaction among 115 P. aeruginosa isolates indicated that 62.62% was MexAB gene. The results of MIC with E-test revealed that the role of efflux pumps in antibiotic resistance was 19 isolated. Due to the importance of antibiotic resistance to investigate other efflux pumps, comparison of efflux pump involvement in antibiotic resistance, and relationship between efflux pumps MexAB-Opr M are highly required and suggested.

scholarly journals Curcumin as Efflux Pump Inhibitor Agent for Enhancement Treatment Against Multidrug Resistant Pseudomonas aeruginosa Isolates

2020 ◽  
pp. 59-67
Author(s):  
Sulaiman D. Sulaiman ◽  
Ghusoon A. Abdulhasan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Inhibitory Concentration ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Disc Diffusion Method ◽  
Efflux Pump Inhibitor ◽  
Before And After ◽  
Chromogenic Agar ◽  
Susceptibility Patterns

  Pseudomonas aeruginosa is considered as a developing opportunistic nosocomial pathogen and is well-known for its multidrug resistance that can be efficiently treated by a combination of antibiotics andefflux pump inhibitors (EPI). Therefore, the purpose of this study was to investigate the effect of curcumin as an EPI for the enhancement of the effectiveness of antibiotics against multidrug resistant (MDR) isolates ofP. aeruginosa. Susceptibility patterns of suspected bacteria was determined using the disc diffusion method andresistant bacteria were identified using chromogenic agar and 16S rDNA. The effectsof curcuminon the enhancement of antibiotics’s activity was evaluated usingthe broth microdilution method.The susceptibility patterns for 50 (67.6%) suspectedP. aeruginosaisolates showed that 36 (72%) of these isolateswere resistant to one of the used antibiotics,whereasonly 21 (42%) were MDR. The highest percentage of resistance was observedtoceftazidime (66%) followed by ciprofloxacin and levofloxacin (40%). Only 35 isolates were specified by chromogenic agar and 16S rDNAas P. aeruginosa.The minimal inhibitory concentration (MIC) of 35 isolates for ciprofloxacin resistant was between 4 and128 µg/ml while for ceftazidime was between 64and 512 µg/ml. After the addition of 50 μg/ml curcumin with ciprofloxacin, there wasa significant increase in the sensitivity (p≤ 0.01) of 13 MDR P.aeroginosa isolates whereas no differences in the sensitivity to ceftazidime were recorded before and after addition ofcurcumin. In conclusion, the results of this study show that curcumin can decrease the MIC value of ciprofloxacin in MDR isolates of P. aeruginosaand can be used as a native compound to enhance the treatment of resistant isolates with ciprofloxacin.

QSAR Studies on Bacterial Efflux Pump Inhibitors

2015 ◽  
pp. 238-268 ◽  
Author(s):  
Khac-Minh Thai ◽  
Trong-Nhat Do ◽  
Thuy-Viet-Phuong Nguyen ◽  
Duc-Khanh-Tho. Nguyen ◽  
Thanh-Dao Tran
Keyword(s):  
Bacterial Resistance ◽  
Efflux Pump ◽  
Current Knowledge ◽  
Efflux Pumps ◽  
Quantitative Structure Activity Relationship ◽  
Antimicrobial Drug Resistance ◽  
Qsar Studies ◽  
Hospital Stays ◽  
Efflux Pump Inhibitors

Antimicrobial drug resistance occurs when bacteria undergo certain modifications to eliminate the effectiveness of drugs, chemicals, or other agents designed to cure infections. To date, the burden of resistance has remained one of the major clinical concerns as it renders prolonged and complicated treatments, thereby increasing the medical costs with lengthier hospital stays. Of complex causes for bacterial resistance, there has been increasing evidence that proved the significant role of efflux pumps in antibiotic resistance. Coadministration of Efflux Pump Inhibitors (EPIs) with antibiotics has been considered one of the promising ways not only to improve the efficacy but also to extend the clinical utility of existing antibiotics. This chapter begins with outlining current knowledge about bacterial efflux pumps and drug designs applied in identification of their modulating compounds. Following, the chapter addresses and provides a discussion on Quantitative Structure-Activity Relationship (QSAR) analyses in search of novel and potent efflux pump inhibitors.

scholarly journals Efflux Pump-Driven Antibiotic and Biocide Cross-Resistance in Pseudomonas aeruginosa Isolated from Different Ecological Niches: A Case Study in the Development of Multidrug Resistance in Environmental Hotspots

2020 ◽  
Vol 8 (11) ◽  
pp. 1647 ◽  
Author(s):  
Anteneh Amsalu ◽  
Sylvia A. Sapula ◽  
Miguel De Barros Lopes ◽  
Bradley J. Hart ◽  
Anh H. Nguyen ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Antimicrobial Resistance ◽  
Molecular Mechanisms ◽  
Efflux Pump ◽  
Principal Component ◽  
Cross Resistance ◽  
Clinical Samples ◽  
Ecological Niches ◽  
Efflux Pump Inhibitor

Pseudomonas aeruginosa is an opportunistic pathogen displaying high intrinsic antimicrobial resistance and the ability to thrive in different ecological environments. In this study, the ability of P. aeruginosa to develop simultaneous resistance to multiple antibiotics and disinfectants in different natural niches were investigated using strains collected from clinical samples, veterinary samples, and wastewater. The correlation between biocide and antimicrobial resistance was determined by employing principal component analysis. Molecular mechanisms linking biocide and antimicrobial resistance were interrogated by determining gene expression using RT-qPCR and identifying a potential genetic determinant for co- and cross-resistance using whole-genome sequencing. A subpopulation of P. aeruginosa isolates belonging to three sequence types was resistant against the common preservative benzalkonium chloride and showed cross-resistance to fluoroquinolones, cephalosporins, aminoglycosides, and multidrug resistance. Of these, the epidemiological high-risk ST235 clone was the most abundant. The overexpression of the MexAB-OprM drug efflux pump resulting from amino acid mutations in regulators MexR, NalC, or NalD was the major contributing factor for cross-resistance that could be reversed by an efflux pump inhibitor. This is the first comparison of antibiotic-biocide cross-resistance in samples isolated from different ecological niches and serves as a confirmation of laboratory-based studies on biocide adapted isolates. The isolates from wastewater had a higher incidence of multidrug resistance and biocide-antibiotic cross-resistance than those from clinical and veterinary settings.

scholarly journals Use of an Efflux Pump Inhibitor To Determine the Prevalence of Efflux Pump-Mediated Fluoroquinolone Resistance and Multidrug Resistance in Pseudomonas aeruginosa

2005 ◽  
Vol 49 (2) ◽  
pp. 565-570 ◽  
Author(s):  
Jane Kriengkauykiat ◽  
Edith Porter ◽  
Olga Lomovskaya ◽  
Annie Wong-Beringer
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Substrate Specificity ◽  
Efflux Pump ◽  
Fluoroquinolone Resistance ◽  
Cross Resistance ◽  
Broth Microdilution ◽  
Efflux Pump Inhibitor ◽  
Broad Substrate Specificity ◽  
Resistant Strains

ABSTRACT Fluoroquinolone-resistance in Pseudomonas aeruginosa may be due to efflux pump overexpression (EPO) and/or target mutations. EPO can result in multidrug resistance (MDR) due to broad substrate specificity of the pumps. MC-04,124, an efflux pump inhibitor (EPI) shown to significantly potentiate activity of levofloxacin in P. aeruginosa, was used to examine the prevalence of EPO in clinical isolates. MICs were determined for ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin with or without EPI and for other antipseudomonal agents by using broth microdilution against P. aeruginosa isolates from adults (n = 119) and children (n = 24). The prevalence of the EPO phenotype (≥8-fold MIC decrease when tested with EPI) was compared among subgroups with different resistance profiles. The EPO phenotype was more prevalent among levofloxacin-resistant than levofloxacin-sensitive strains (61%, 48/79 versus 9%, 6/64). EPO was present in 60% of fluoroquinolone-resistant strains without cross-resistance, while it was present at variable frequencies among strains with cross-resistance to other agents: piperacillin-tazobactam (86%), ceftazidime (76%), cefepime (65%), imipenem (56%), gentamicin (55%), tobramycin (48%), and amikacin (27%). The magnitude of MIC decrease with an EPI paralleled the frequency of which the EPO phenotype was observed in different subgroups. EPI reduced the levofloxacin MIC by as much as 16-fold in eight strains for which MICs were 128 μg/ml. Efflux-mediated resistance appears to contribute significantly to fluoroquinolone resistance and MDR in P. aeruginosa. Our data support the fact that increased fluoroquinolone usage can negatively impact susceptibility of P. aeruginosa to multiple classes of antipseudomonal agents.

scholarly journals Antistaphylococcal and Antibiotic Resistance Modulatory Activities of Thirteen Cameroonian Edible Plants against Resistant Phenotypes

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Brice E. N. Wamba ◽  
Armelle T. Mbaveng ◽  
Paul Nayim ◽  
Joachim K. Dzotam ◽  
Ornella J. T. Ngalani ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Edible Plants ◽  
Bacterial Strains ◽  
Efflux Pump Inhibitor ◽  
Dacryodes Edulis

Background. In this study, 18 methanol extracts from Cameroonian edible plants were tested for their antibacterial activities against 26 strains ofS. aureus; the role of efflux pumps in the resistance of tested bacteria and the antibiotic resistance-modulating activities against selected multidrug-resistant (MDR) phenotypes were also investigated.Methods. Broth microdilution assay was used to evaluate the antibacterial activity, the role of efflux pumps, and the antibiotic resistance-modulating effects of plant extracts.Results. Extracts fromDacryodes edulisseeds (DES) andDacryodes edulisbark (DEB) were active against all 26 tested bacterial strains, within the minimal inhibitory concentration (MIC) range of 256–1024 µg/mL. MIC values varied from 64 to 1024 µg/mL against 96.2% of the 26 tested bacteria forPhaseolus vulgarisleaves (PVL), 92.3% forAzadirachta indicabark (AIB),Dacryodes edulisleaves (DEL), andRicinodendron heudelotiileaves (RHL). The lowest MIC value of 64 µg/mL was obtained with the extract fromCucurbita maximabeans (CMB) against MRSA4 strain and fromUapaca guineensisbark (UGB) against MRSA9 strain. Bacterial efflux pump inhibitor (EPI), carbonyl cyanidem-chlorophenyl hydrazone (CCCP), improved the activity of DES and UGB as well as that of extracts fromHibiscus esculentusleaves (HEL) andUapaca guineensisleaves (UGL) against resistantS. aureusstrains. Antibiotic-modulating effects against more than 70% of theS. aureusstrains tested were obtained when RHL (at MIC/2) was combined with CIP, ERY, and KAN (88.89%), CHL (88.89%), TET (77.78%), and STR (88.89%).Conclusion. The present study demonstrated that the 13 tested plants had antistaphylococcal effects and that DES, HEL, UGL, and UGB could be used in combination with EPI to combat resistance toStaphylococcus aureus. Also, it demonstrated that some studied extracts and mostly RHL could be used as antibiotic resistance modulators to fight against resistant strains ofS. aureus.

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