scholarly journals PHENOTYPIC DETECTION OF EFFLUX MECHANISM IN AMIKACIN-RESISTANT ACINETOBACTER ISOLATES FROM TWO DIFFERENT STATES IN SOUTH INDIA

2021 ◽  
Vol 10 (4) ◽  
pp. 3346-3352
Author(s):  
Fathimunnisa Koka

Acinetobacter has already gained resistance to the majority of antibiotics available. Aminoglycosides are commonly used to treat invasive infections. Aminoglycoside resistance is associated with decreased drug absorption, aminoglycoside modification, and aminoglycoside efflux. The aim of this study was to detect the presence of an efflux mechanism in amikacin-resistant Acinetobacter isolated from hospital wards using Carbonyl Cyanide 3- Chlorophenylhydrazone (CCCP). One hundred isolates of Acinetobacter were isolated from tertiary care hospitals in two distinct South Indian states. Antibacterial susceptibility patterns were discovered between 2017 and 2019. Amikacin minimum inhibitory concentration (MIC) for resistant Acinetobacter isolates was determined using Clinical and Laboratory Standards Institute (CLSI) standards. The efflux system activity was determined using CCCP. Among 100 Acinetobacter baumannii isolates, 49 isolates with amikacin resistance were found. The MIC’s of Acinetobacter ranged between 2 – 1024 μg/mL for the amikacin studied. After treatment with the efflux pump inhibitor, 38.77% of isolates became less resistant to amikacin, as determined by phenotypic detection of efflux pumps, showing a decrease in antibiotic MICs of at least four fold. The data demonstrated the importance of efflux pump activity conferring amikacin resistance on Acinetobacter clinical isolates.

2011 ◽  
Vol 55 (5) ◽  
pp. 2256-2264 ◽  
Author(s):  
Agatha N. Jassem ◽  
James E. A. Zlosnik ◽  
Deborah A. Henry ◽  
Robert E. W. Hancock ◽  
Robert K. Ernst ◽  
...  

ABSTRACTBurkholderia cepaciacomplex (BCC) bacteria are opportunistic pathogens that can cause severe disease in cystic fibrosis (CF) patients and other immunocompromised individuals and are typically multidrug resistant. Here we observed that unlike other BCC species, most environmental and clinicalBurkholderia vietnamiensisisolates were intrinsically susceptible to aminoglycosides but not to cationic antimicrobial peptides or polymyxin B. Furthermore, strains acquired aminoglycoside resistance during chronic CF infection, a phenomenon that could be induced under tobramycin or azithromycin pressurein vitro. In comparing susceptible and resistantB. vietnamiensisisolates, no gross differences in lipopolysaccharide structure were observed, all had lipid A-associated 4-amino-4-deoxy-l-arabinose residues, and all were resistant to the permeabilizing effects of aminoglycosides, a measure of drug entry via self-promoted uptake. However, susceptible isolates accumulated 5 to 6 times more gentamicin than a resistant isolate, and aminoglycoside susceptibility increased in the presence of an efflux pump inhibitor.B. vietnamiensisis therefore unusual among BCC bacteria in its susceptibility to aminoglycosides and capacity to acquire resistance. Aminoglycoside resistance appears to be due to decreased cellular accumulation as a result of active efflux.


2020 ◽  
Author(s):  
Stefany Plasencia-Rebata ◽  
Saul Levy-Blitchtein ◽  
Isaac Peña-Tuesta ◽  
Miguel Angel Aguilar-Luis ◽  
William Vicente Taboada ◽  
...  

Abstract Objetive: To analyze the contribution of the active efflux system to quinolones and aminoglycosides resistance in selected outbreak A. baumannii clinical isolates using the efflux pump inhibitor PAβN.Results: A total of nineteen Acinetobacter baumannii strains were included in the study. All were positive for the blaOXA-51 gene by PCR and had clinical information associated. The samples were non-duplicate and collected from different sources. Non-susceptibility rates were as following: tobramycin 31.6% (6), ciprofloxacin 31.6% (6), levofloxacin 21.1% (4), nalidixic acid 26.3% (5) and amikacin 15.8% (3). A total of eight strains (42,1%) demonstrated an increase in the susceptibility rates and sixteen (84,2%) expressed efflux pumps.


2021 ◽  
Vol 12 ◽  
pp. 215013272110002
Author(s):  
Gayathri Thiruvengadam ◽  
Marappa Lakshmi ◽  
Ravanan Ramanujam

Background: The objective of the study was to identify the factors that alter the length of hospital stay of COVID-19 patients so we have an estimate of the duration of hospitalization of patients. To achieve this, we used a time to event analysis to arrive at factors that could alter the length of hospital stay, aiding in planning additional beds for any future rise in cases. Methods: Information about COVID-19 patients was collected between June and August 2020. The response variable was the time from admission to discharge of patients. Cox proportional hazard model was used to identify the factors that were associated with the length of hospital stay. Results: A total of 730 COVID-19 patients were included, of which 675 (92.5%) recovered and 55 (7.5%) were considered to be right-censored, that is, the patient died or was discharged against medical advice. The median length of hospital stay of COVID-19 patients who were hospitalized was found to be 7 days by the Kaplan Meier curve. The covariates that prolonged the length of hospital stay were found to be abnormalities in oxygen saturation (HR = 0.446, P < .001), neutrophil-lymphocyte ratio (HR = 0.742, P = .003), levels of D-dimer (HR = 0.60, P = .002), lactate dehydrogenase (HR = 0.717, P = .002), and ferritin (HR = 0.763, P = .037). Also, patients who had more than 2 chronic diseases had a significantly longer length of stay (HR = 0.586, P = .008) compared to those with no comorbidities. Conclusion: Factors that are associated with prolonged length of hospital stay of patients need to be considered in planning bed strength on a contingency basis.


Author(s):  
Paramanandham Krishnamoorthy ◽  
Subramanium Sudhagar ◽  
Akshata Lokanath Goudar ◽  
Siju Susan Jacob ◽  
Kuralayanapalya Puttahonappa Suresh

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 577
Author(s):  
Douweh Leyla Gbian ◽  
Abdelwahab Omri

The eradication of Pseudomonas aeruginosa in cystic fibrosis patients has become continuously difficult due to its increased resistance to treatments. This study assessed the efficacy of free and liposomal gentamicin and erythromycin, combined with Phenylalanine arginine beta-naphthylamide (PABN), a broad-spectrum efflux pump inhibitor, against P. aeruginosa isolates. Liposomes were prepared and characterized for their sizes and encapsulation efficiencies. The antimicrobial activities of formulations were determined by the microbroth dilution method. Their activity on P. aeruginosa biofilms was assessed, and the effect of sub-inhibitory concentrations on bacterial virulence factors, quorum sensing (QS) signals and bacterial motility was also evaluated. The average diameters of liposomes were 562.67 ± 33.74 nm for gentamicin and 3086.35 ± 553.95 nm for erythromycin, with encapsulation efficiencies of 13.89 ± 1.54% and 51.58 ± 2.84%, respectively. Liposomes and PABN combinations potentiated antibiotics by reducing minimum inhibitory and bactericidal concentrations by 4–32 fold overall. The formulations significantly inhibited biofilm formation and differentially attenuated virulence factor production as well as motility. Unexpectedly, QS signal production was not affected by treatments. Taken together, the results indicate that PABN shows potential as an adjuvant of liposomal macrolides and aminoglycosides in the management of lung infections in cystic fibrosis patients.


Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 470
Author(s):  
Dipu T. Sathyapalan ◽  
Jini James ◽  
Sangita Sudhir ◽  
Vrinda Nampoothiri ◽  
Praveena N. Bhaskaran ◽  
...  

Polymyxins being last resort drugs to treat infections triggered by multidrug-resistant pathogens necessitates the implementation of antimicrobial stewardship program (ASP) initiatives to support its rational prescription across healthcare settings. Our study aims to describe the change in the epidemiology of polymyxins and patient outcomes following the implementation of ASP at our institution. The antimicrobial stewardship program initiated in February 2016 at our 1300 bed tertiary care center involved post-prescriptive audits tracking polymyxin consumption and evaluating prescription appropriateness in terms of the right indication, right frequency, right drug, right duration of therapy and administration of the right loading dose (LD) and maintenance dose (MD). Among the 2442 polymyxin prescriptions tracked over the entire study period ranging from February 2016 to January 2020, the number of prescriptions dropped from 772 prescriptions in the pre-implementation period to an average of 417 per year during the post-implementation period, recording a 45% reduction. The quarterly patient survival rates had a significant positive correlation with the quarterly prescription appropriateness rates (r = 0.4774, p = 0.02), right loading dose (r = 0.5228, p = 0.015) and right duration (r = 0.4361, p = 0.04). Our study on the epidemiology of polymyxin use demonstrated favorable effects on the appropriateness of prescriptions and mortality benefits after successful implementation of antimicrobial stewardship in a real-world setting.


2001 ◽  
Vol 45 (12) ◽  
pp. 3422-3426 ◽  
Author(s):  
Siddhartha Roychoudhury ◽  
Tracy L. Twinem ◽  
Kelly M. Makin ◽  
Mark A. Nienaber ◽  
Chuiying Li ◽  
...  

ABSTRACT The in vitro development of resistance to the new nonfluorinated quinolones (NFQs; PGE 9262932, PGE 4175997, and PGE 9509924) was investigated in Staphylococcus aureus. At concentrations two times the MIC, step 1 mutants were isolated more frequently with ciprofloxacin and trovafloxacin (9.1 × 10−8 and 5.7 × 10−9, respectively) than with the NFQs, gatifloxacin, or clinafloxacin (<5.7 × 10−10). Step 2 and step 3 mutants were selected via exposure of a step 1 mutant (selected with trovafloxacin) to four times the MICs of trovafloxacin and PGE 9262932. The step 1 mutant contained the known Ser80-Phe mutation in GrlA, and the step 2 and step 3 mutants contained the known Ser80-Phe and Ser84-Leu mutations in GrlA and GyrA, respectively. Compared to ciprofloxacin, the NFQs were 8-fold more potent against the parent and 16- to 128-fold more potent against the step 3 mutants. Mutants with high-level NFQ resistance (MIC, 32 μg/ml) were isolated by the spiral plater-based serial passage technique. DNA sequence analysis of three such mutants revealed the following mutations: (i) Ser84-Leu in GyrA and Glu84-Lys and His103-Tyr in GrlA; (ii) Ser-84Leu in GyrA, Ser52-Arg in GrlA, and Glu472-Val in GrlB; and (iii) Ser84-Leu in GyrA, Glu477-Val in GyrB, and Glu84-Lys and His103-Tyr in GrlA. Addition of the efflux pump inhibitor reserpine (10 μg/ml) resulted in 4- to 16-fold increases in the potencies of the NFQs against these mutants, whereas it resulted in 2-fold increases in the potencies of the NFQs against the parent.


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