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

  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.

2016 ◽  
Vol 10 (06) ◽  
pp. 600-604 ◽  
Author(s):  
Mahshid Talebi-Taher ◽  
َAli Majidpour ◽  
Abbas Gholami ◽  
Samira Rasouli-Kouhi ◽  
Maryam Adabi

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.


2020 ◽  
Vol EJMM29 (4) ◽  
pp. 17-25
Author(s):  
Asmaa M. Elbrolosy ◽  
Amira H. Elkhayat ◽  
Dina M. Hassan ◽  
Eman H. Salem

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.


2016 ◽  
Vol 53 ◽  
pp. 57-64
Author(s):  
Radia Mahboub ◽  
Faiza Memmou

We have studied the antimicrobial properties of 6-bromoeugenol and eugenol by three strains:Pseudomonas aeruginosa(S1),Escherichia coli(S2) andStaphylococcus aureus(S3). We have determined the minimum inhibitory concentration (MIC) for a range of concentrations using the disc diffusion method. We note that all samples present an antimicrobial activity toward the tested bacterial strains at different concentrations (1, 0.5 and 0.25 mg/ml). The 6-bromoeugenol gives modest activity with (S1) and (S3). Eugenol reacts positively with thePseudomonas aeruginosa(S1) at all concentrations and with theEscherichiacoli(S2) at 0.5 mg/ml. We remark that thePseudomonas aeruginosa(S1) is the more sensitive strain thanEscherichiacoli(S2) andStaphylococcus aureus(S3). We have estimated the activity coefficient which has confirmed the antimicrobial activity of the different samples. So, 6-bromoeugenol has shown his efficiency as antimicrobial agent.


2020 ◽  
Vol 10 (02) ◽  
pp. 195-199
Author(s):  
Abdalkader Saeed Latif ◽  
Majida G. Magtooph ◽  
Alia Essam Mahmood Alubadi

Molecular docking performed to evaluate the effect of five quinoline derivatives on the MexB protein of Pseudomonas aeruginosa as a potential inhibitor by utilizing the 3D structure of each quinoline compounds (C1, C2, C3, C4, and C5), and the crystal structure of the protein, C4 showed the greatest potential with -31.4 kcal/mol binding energy, and the lowest potential was for C1 with (-18.5 kcal/mol) compared with ciprofloxacin. Fifty samples were collected from different sites from patients who are attending to the medical city of Baghdad and private Dhelal Beirut Center, Baghdad, 36 of the samples were diagnosed as P. aeruginosa by routine culture test and confirmed by VITEK2, and those isolates were subjected to the susceptibility test against carbapenems, carbenicillin, levofloxacin, and erythromycin by disc diffusion method. The isolates that showed resistance to all of four antibiotics were based to evaluate the activity of quinoline derivatives by using the agar well diffusion method, where compounds C4 and C5 showed the highest line of activity as the minimum inhibitory concentration (MIC) was 256 μg/mL, meanwhile, C1 showed the lowest activity with MIC of 1,024 μg/mL.


2020 ◽  
Author(s):  
Javad rasouli ◽  
Behnam hashemi ◽  
Hamed Afkhami ◽  
Mansoor Khaledi ◽  
Reza valadan ◽  
...  

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.


2020 ◽  
Vol 21 (10) ◽  
pp. 997-1004
Author(s):  
Leila Azimi ◽  
Sahel V. Tahbaz ◽  
Reza Alaghehbandan ◽  
Farank Alinejad ◽  
Abdolaziz R. Lari

Background: Burn is still an important global public health challenge. Wound colonization of antibiotic resistant bacteria such as Acinetobacter baumannii can lead to high morbidity and mortality in burn patients. The aim of this study was to evaluate the inhibitory effect of tazobactam on efflux pump, which can cause aminoglycoside resistant in A. baumannii isolated from burn patients. Methods: In this study, 47 aminoglycoside resistant A. baumannii spp. were obtained from burn patients, admitted to the Shahid Motahari Burns Hospital in Tehran, Iran, during June-August 2018. The inhibitory effect of tazobactam against adeB such as efflux pump was evaluated by Minimum Inhibitory Concentration (MIC) determination of amikacin alone and in combination with tazobactam. Fractional Inhibitory Concentration index (FIC) was used to determine the efficacy of tazobactam/ amikacin combination. Further, semi-quantitative Real- Time PCR was performed to quantify the expression rates of the adeB gene before and after addition of tazobactam/amikacin. Results: The MIC values were significantly reduced when a combined amikacin and tazobactam was utilized. The most common interaction observed was synergistic (78.2%), followed by additive effects (21.8%), as per FIC results. The adeB mRNA expression levels were found to be downregulated in 60.7% of isolates treated with tazobactam. Conclusions: Tazobactam can have impact on resistance to aminoglycoside by inhibiting efflux pump. Thus, the combination of tazobactam with amikacin can be used as an alternative treatment approach in multidrug resistant A. baumannii infections.


Medicina ◽  
2008 ◽  
Vol 45 (1) ◽  
pp. 1
Author(s):  
Asta Dambrauskienė ◽  
Dalia Adukauskienė ◽  
Jolanta Jeroch ◽  
Astra Vitkauskienė

Aim of the study. To determine the associations between the source of infection and antibiotic resistance in patients with Pseudomonas aeruginosa bacteremia. Material and methods. A retrospective analysis of 50 patients with Pseudomonas aeruginosa bacteremia was carried out. If sepsis was suspected, blood culture was incubated in an automatic system BACTEC 9240. Then bacteria were identified, and their antibiotic resistance was estimated by disc diffusion method. If Pseudomonas aeruginosa strains were resistant to three or more antibiotics, they were considered as multidrug-resistant.Results. The origin of bacteremia was confirmed in 33 (66%) patients. Lower respiratory tract was the predominant source of Pseudomonas aeruginosa bacteremia (81.8%, n=27) as compared with infection of wound (39.4%, n=13), urinary tract (15.2%, n=5), and drain or cerebrospinal fluid (9.1%, n=3) (P<0.05). Eighteen percent (n=9) of strains, which caused bacteremia, were resistant to ceftazidime; 38% (n=19), to piperacillin; 22% (n=11), to imipenem; 26% (n=13), to meropenem; 24% (n=12), to ciprofloxacin; 40% (n=20), to gentamicin; and only 8% (n=4), to amikacin. Multidrug-resistant Pseudomonas aeruginosa strains were more frequently isolated if a source of infection was wound comparing to a source of other localization (61.5%, n=8 and 20.0%, n=4, respectively; P<0.05). Resistance of Pseudomonas aeruginosa strains to imipenem was associated with resistance to ciprofloxacin (13.2%, n=5 and 50.0%, n=6, retrospectively; P<0.05), but resistance to meropenem – both to ciprofloxacin and amikacin. Conclusions. The predominant source of Pseudomonas aeruginosa bacteremia was lower respiratory tract, and multidrug-resistant strains caused bacteremia more frequently if a source infection was wound. Pseudomonas aeruginosa resistance to carbapenems was associated with resistance to ciprofloxacin and resistance to meropenem – also to amikacin. Resistance of strains to ceftazidime and piperacillin was associated with resistance to gentamicin.


Author(s):  
Florence Chijindu Ugwuanyi ◽  
Abraham Ajayi ◽  
David Ajiboye Ojo ◽  
Adeyemi Isaac Adeleye ◽  
Stella Ifeanyi Smith

Abstract Background Pseudomonas aeruginosa an opportunistic pathogen, is widely associated with nosocomial infections and exhibits resistance to multiple classes of antibiotics. The aim of this study was to determine the antibiotic resistance profile, biofilm formation and efflux pump activity of Pseudomonas strains isolated from clinical samples in Abeokuta Ogun state Nigeria. Methods Fifty suspected Pseudomonas isolates were characterized by standard biochemical tests and PCR using Pseudomonas species -specific primers. Antibiotic susceptibility testing was done by the disc diffusion method. Efflux pump activity screening was done by the ethidium bromide method and biofilm formation assay by the tissue plate method. Genes encoding biofilm formation (pslA & plsD) and efflux pump activity (mexA, mexB and oprM) were assayed by PCR. Results Thirty-nine Pseudomonas spp. were identified of which 35 were Pseudomonas aeruginosa and 4 Pseudomonas spp. All 39 (100%) Pseudomonas isolates were resistant to ceftazidime, cefuroxime and amoxicillin-clavulanate. Thirty-six (92%), 10(25.6%), 20 (51.2%), 11(28%) and 9(23%) of the isolates were resistant to nitrofurantoin, imipenem, gentamicin, cefepime and aztreonam respectively. All the isolates had the ability to form biofilm and 11 (28%) of them were strong biofilm formers. They all (100%) harboured the pslA and pslD biofilm encoding genes. Varied relationships between biofilm formation and resistance to ciprofloxacin, ofloxacin, cefixime, gentamicin, imipenem, and aztreonam were observed. Only 23(59%) of the Pseudomonas isolates phenotypically exhibited efflux pump activity but mexA gene was detected in all 39 (100%) isolates while mexB and oprM genes were detected in 91%, 92%, and 88% of strong, moderate and weak biofilm formers respectively. Conclusion Multidrug resistance, biofilm and efflux pump capabilities in Pseudomonas aeruginosa have serious public health implications in the management of infections caused by this organism.


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