scholarly journals Mechanism of Drug Resistance in Enterococci and Therapeutic Options - A Review

2021 ◽  
Vol 12 (1) ◽  
pp. 102-106
Author(s):  
Reena Rajan
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Agents ◽  
Therapeutic Option ◽  
Resistance Mechanism ◽  
Therapeutic Options ◽  
Fluoroquinolone Resistance ◽  
Beta Lactam ◽  
Empirical Observation ◽  
Enterococcal Infection ◽  
Acting Agent

Enterococci exhibit an array of ways for constitutional and extrinsic resistance to primary antimicrobial agents available for clinical use. Susceptibility of these agents to β lactams, aminoglycosides or glycopeptides antibiotics or low susceptibility to combination of these agents, monomicrobial or polymicrobial nature of the infection, the involvement of heart valves or other endovascular structures affects therapy of Enterococcal infection. Vancomycin-resistant phenotypes A and B are most prevalent among medically important Enterococci isolates. Due to poor uptake of aminoglycosides, moderate level inherent resistance was reported in Enterococci. Gentamicin and Streptomycin are among the aminoglycoside antibiotics recommended for synergistic combination therapy with a cell wall acting agent. Enterococci isolates display inherent resistance to beta-lactam antibiotics due to less affinity penicillin-binding proteins, class B. Resistance to macrolides, due to erm B genotype and efflux proteins are common in Enterococci. Fluoroquinolone resistance due to genetic changes in chromosomal resistance determining regions has been observed in Enterococci isolates. Despite studies on good invitro action of Daptomycin, Linezolid and Tigecycline on Enterococci, their use may be limited due to shortage of clinical data and emergence of drug resistance. Thus optimal therapeutic option for Multidrug-resistant Enterococci infection is based on empirical observation, higher doses and combination therapies. This article reviews the antimicrobial resistance mechanism in Enterococci and available therapeutic options. 

scholarly journals Clinical and drug resistance characteristics of Providencia stuartii infections in 76 patients

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096229
Author(s):  
Jiachang Liu ◽  
Ruikai Wang ◽  
Ming Fang
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Agents ◽  
Multiple Drug Resistance ◽  
Drug Susceptibility ◽  
Fourth Generation ◽  
Multiple Drug ◽  
Beta Lactam ◽  
Hospital Department ◽  
Extended Spectrum Beta Lactamase ◽  
Providencia Stuartii

Objectives To investigate the clinical and drug resistance characteristics of Providencia stuartii infections in the Huainan region of Anhui and provide a reference for the clinical selection of antimicrobial agents. Methods This single-center retrospective analysis included 76 patients with P. stuartii infection in Huainan during the period from October 2018 to March 2020. The hospital department in which the patients were treated and the drug susceptibility characteristics of the P. stuartii isolates were recorded. Results Among the 76 patients, the lung was the most common site of infection, and intensive care unit was the main hospital department. Extended spectrum beta-lactamase screening revealed expression by all 76 isolates of P. stuartii. Of the 76 isolates, 92.1% exhibited multiple drug resistance or extensive drug resistance. P. stuartii isolates were sensitive to cefepime and imipenem, but not to other beta-lactam antibiotics. Twenty isolates were resistant to all 21 types of antibiotics. Of the 20 patients infected with extensively drug-resistant isolates, nine (45%) died. Conclusions Drug resistance is increasing in P. stuartii. The antimicrobial agent imipenem may be effective for treatment of P. stuartii infections. Fluoroquinolones, aminoglycosides, and fourth-generation cephalosporins are suitable options for antibiotic therapy.

ACQUIRED DRUG RESISTANCE TO NRTI CLASS IN TREATMENT-EXPERIENCED HIV INFECTED PATIENTS FROM THE CONSTANTA COUNTY: THERAPEUTIC IMPLICATIONS

2017 ◽  
Vol 20 (3) ◽  
pp. 140-147
Author(s):  
Roxana-Carmen Cernat ◽  
◽  
Irina Magdalena Dumitru ◽  
D. Otelea ◽  
Sorin Rugina ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Option ◽  
Molecular Genetic ◽  
Therapeutic Options ◽  
Acquired Drug Resistance ◽  
Therapeutic Implications ◽  
Graphic Representations ◽  
Resistance Patterns ◽  
R Project ◽  
Version 2.0

Objective. To determine the prevalence of acquired drug resistance (ADR) and of resistance patterns in treatment-experienced HIV infected patients from Constanta in order to establish the best therapeutic options in NRTI class. Material and methods. A retrospective study which included 144 treatment-experienced HIV patients with confirmed viral failure. The strains isolated from these patients were analysed in the Molecular Genetic Laboratory of „Matei Bals“ National Institute of Infectious Diseases, Bucharest and the resulting sequences were saved in FASTA format. The HIV-1 subtyping was based on „REGA HIV01&2 Automated subtyping tool version 2.0“ algorithm. „Stanford HIVdb Program version 8.4“ was used in order to determine the therapeutic options. For statistical calculations, the R-Project software was used. Graphic representations were performed using GNUPLOT program. Results. The prevalence of the acquired drug resistance was 92.36%. The most frequent mutation occurred at the level of the codon 184. The TAM-2 path was more frequently selected compared to TAM-1. Association between TAM1 and TAM 2 were also found, mutation K65R being rarely met. Conclusions. The prevalence of the acquired drug resistance in our study was high, The most valuable therapeutic option in the INRT class remains tenofovir, due to the mutational profile, which was selected on account of the extensive use of thymidine analogues.

scholarly journals Antimicrobial resistance in non-typhi Salmonella enterica isolated from humans and poultry in Palestine

2011 ◽  
Vol 6 (02) ◽  
pp. 132-136 ◽  
Author(s):  
Rula AL-Dawodi ◽  
Mohammad A Farraj ◽  
Tamer Essawi
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Resistance ◽  
Nalidixic Acid ◽  
Gene Mutation ◽  
Direct Sequencing ◽  
Resistance Mechanism ◽  
Fluoroquinolone Resistance ◽  
Mutation Pattern ◽  
Resistance Rates ◽  
Prevalent Mutation

Introduction: The efficacy of chemotherapy can be compromised by drug resistance.  This study was undertaken to describe the resistance profiles and fluoroquinolone resistance mechanism of non-typhoidal Salmonella (NTS) isolated from humans and poultry in West Bank, Palestine. Methodology: One hundred and fifty-one isolates of NTS, obtained from humans (71) and poultry (80), collected between September 2005 and January 2007, were tested for susceptibility to ampicillin, gentamicin, tetracycline ceftriaxone, nalidixic acid and ciprofloxacin. Mutation patterns within gyrA were determined by direct sequencing or by digestion of PCR-amplified DNA fragments with the restriction enzyme HinfI. Results: Resistance rates among human and poultry isolates were respectively 59% and 51% for ampicillin, 31% and 10% for gentamicin, 59% and 80% for tetracycline, 59% and 45% for nalidixic acid, and 30% and 15% for ciprofloxacin. All the isolates were susceptible to ceftriaxone. Mutations at positions 83 and/or 87 were detected in gyrA of isolates with resistance to nalidixic acid. Isolates which were resistant to nalidixic acid but susceptible to ciprofloxacin had a single gyr A gene mutation at point 87.  This gene mutation was sufficient to induce a new phenotype (6 isolates) with decreased susceptibility to ciprofloxacin. Conclusion: Mutations in gyrA at positions 83 or 87 were the most prevalent mutation pattern of fluoroquinolone resistant NTS isolates but other unknown mechanisms are also present. Continued surveillance of antimicrobial resistance among NTS isolates is needed to mitigate the increasing prevalence of quinolone resistance.

scholarly journals PSI-25 development of local Kansas E. coli UTI antibiograms to improve antimicrobial stewardship in companion animal medicine

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 241-241
Author(s):  
Brianna Salgado ◽  
Katherine KuKanich ◽  
Brian Lubbers
Keyword(s):  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Fluoroquinolone Resistance ◽  
Beta Lactam ◽  
E Coli ◽  
Animal Medicine ◽  
Amoxicillin Clavulanate ◽  
The One ◽  
Tract Infections

Abstract Urinary tract infections are common in dogs, but rare in cats. Antimicrobial susceptibility testing of urine isolates is required to determine optimal antimicrobial therapy, but empirical antimicrobial guidelines are needed while culture is pending or if testing is declined. Antibiograms are summaries of local susceptibility trends that assist clinicians in selecting empirical antimicrobial therapy. Antibiograms were developed from E. coli feline (N = 138) and canine (N = 640) urinary isolates submitted by the KSU Veterinary Health Center and private veterinary practices from 2013–2017. Results showed a high prevalence of resistance among feline isolates to amoxicillin-clavulanate (99.3%, S ≤ 0.25) and ampicillin (99.3%, S ≤ 0.25), but lower prevalence among canine isolates (amoxicillin/clavulanate 7.7% S ≤ 8), ampicillin 46.7%, S ≤ 8). Resistance to other antimicrobials was uncommon, with no antimicrobial agents demonstrating resistance above 6% in feline isolates, or above 14% in canine isolates. Canine isolates from private veterinary practices had increased resistance as compared with KSU isolates to orbifloxacin (9.5% vs 0.1%) and pradofloxaxin (9.4% vs 0.1%). Application of different breakpoints and differences in antibiotic exposures may explain the disparity of Beta-Lactam resistance between cats and dogs. Different use patterns between hospitals may explain the disparity between fluoroquinolone resistance. These findings emphasize the need for definitive urine culture and susceptibility testing in pets with UTIs, so that appropriate and effective antimicrobial therapy can be prescribed. Veterinary clinicians in Kansas can use these antibiogram results in addition to following stewardship guidelines to maximize successful UTI therapy for veterinary patients and minimize development of antimicrobial resistance for the One Health community.

scholarly journals Mechanisms of Resistance to Quinolones and Epidemiological Significance of Salmonella spp.

2016 ◽  
Vol 66 (2) ◽  
pp. 147-159 ◽  
Author(s):  
Maja Velhner
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Quinolone Resistance ◽  
Beta Lactam ◽  
Foodborne Illnesses ◽  
Salmonella Spp ◽  
Over Expression ◽  
Beta Lactam Antibiotics ◽  
Chromosomal Mutations

Abstract Bacteria develop resistance to antimicrobial agents by a number of different mechanisms. The resistance to (fluoro)quinolones in Salmonella is of particular importance especially if therapy in humans is required. For decades there has been a significant interest in studying the biology of Salmonella because these bacteria are among the leading causes of foodborne illnesses around the globe. To this date, two main mechanisms of quinolone resistance have been established: alteration in the targets for quinolones, decreased accumulation inside bacteria due to impermeability of the membrane and/or an over expression of the efflux pump systems. Both of these mechanisms are chromosomally mediated. Furthermore, mobile elements have been described carrying the qnr gene which confers resistance to quinolones. The plasmid encoded QNR proteins belong to the pentapeptide repeat family of proteins. The plasmid mediated quinolone resistance (PMQR) is often associated with the resistance to beta lactam antibiotics. It was noticed that PMQR is backing up chromosomal mutations for quinolone resistance, hence becoming an important resistance mechanism worldwide. Even with our knowledge expanding over the years, it is not possible to predict how bacteria will respond in the future, if they are exposed to new external challenges. The possibility that they will find a way to survive by introducing new mutations or by exchanging mobile genetic elements and subsequently developing resistance to survive in the environment should not be underestimated.

scholarly journals Need for Annual Surveillance of Antimicrobial Resistance in Streptococcus pneumoniae in the United States: 2-Year Longitudinal Analysis

2001 ◽  
Vol 45 (4) ◽  
pp. 1037-1042 ◽  
Author(s):  
Daniel F. Sahm ◽  
James A. Karlowsky ◽  
Laurie J. Kelly ◽  
Ian A. Critchley ◽  
Mark E. Jones ◽  
...  
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
The United States ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Resistance Patterns ◽  
Changing Patterns ◽  
Resistance To Penicillin

ABSTRACT Although changing patterns in antimicrobial resistance inStreptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniaeantimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997–1998 and 1998–1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997–1998 were encountered in 1998–1999. This longitudinal surveillance study of resistance inS. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

scholarly journals Molecular modeling study on the drug resistance mechanism of NS5B polymerase to TMC647055

2016 ◽  
Vol 94 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Huiqun Wang ◽  
Wei Cui ◽  
Chenchen Guo ◽  
Bo-Zhen Chen ◽  
Mingjuan Ji
Keyword(s):  
Drug Resistance ◽  
Free Energy ◽  
Rational Design ◽  
Binding Free Energy ◽  
Resistance Mechanism ◽  
Free Energy Calculations ◽  
Side Chain ◽  
Free Energy Decomposition ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

NS5B polymerase plays an important role in viral replication machinery. TMC647055 (TMC) is a novel and potent non-nucleoside inhibitor of the HCV NS5B polymerase. However, mutations that result in drug resistance to TMC have been reported. In this study, we used molecular dynamics (MD) simulations, binding free energy calculations, and free energy decomposition to investigate the drug resistance mechanism of HCV to TMC resulting from L392I, P495T, P495S, and P495L mutations in NS5B polymerase. From the calculated results we determined that the decrease in the binding affinity between TMC and NS5BL392I polymerase is mainly caused by the extra methyl group at the CB atom of Ile. The polarity of the side-chain of residue 495 has no distinct influence on residue 495 binding with TMC, whereas the smaller size of the side-chain of residue 495 causes a substantial decrease in the van der Walls interaction between TMC and residue 495. Moreover, the longer length of the side-chain of residue 495 has a significant effect on the electrostatic interaction between TMC and Arg-503. Finally, we performed the same calculations and detailed analysis on other 3 mutations (L392V, P495V, and P495I). The results further confirmed our conclusions. The computational results not only reveal the drug resistance mechanism between TMC647055 and NS5B polymerase, but also provide valuable information for the rational design of more potent non-nucleoside inhibitors targeting HCV NS5B polymerase.

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