Molecular Characterization of Tigecycline Non-Susceptibility among Extensively Drug-Resistant Acinetobacter baumannii Isolates of Clinical Origin

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Mehri Haeili ◽  
Ali Abdollahi ◽  
Amin Ahmadi ◽  
Amin Khoshbayan
Keyword(s):  
Acinetobacter Baumannii ◽  
Molecular Mechanisms ◽  
Efflux Pump ◽  
Genetic Alterations ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Transcriptional Level ◽  
Drug Resistant ◽  
Disk Diffusion Method ◽  
Extensively Drug Resistant

<b><i>Introduction:</i></b> Tigecycline (TGC) is one of the last-resort therapeutic agents for treating infections caused by extensively drug resistant <i>Acinetobacter baumannii</i> isolates. Although resistance to TGC is not common, non-susceptible <i>A. baumannii</i> (NSAB) isolates have been described. In the current study, we aimed to assess the molecular mechanisms mediating TGC non-susceptibility in 5 clinical isolates of <i>A. baumannii</i> with reduced susceptibility to TGC. <b><i>Methods:</i></b> Susceptibility of isolates to TGC as well as various classes of antibiotics was evaluated by broth dilution and disk diffusion methods, respectively. The presence of <i>tetX</i> and <i>tetX1</i> genes was investigated by PCR. The nucleotide sequences of <i>adeR</i> and <i>adeS</i> genes were assessed by PCR amplicon sequencing. To evaluate the association between reduced susceptibility to TGC and upregulation of AdeABC efflux pump, transcriptional level of <i>adeB</i> gene was quantified by RT-qPCR analysis. <b><i>Results:</i></b> All 5 TGC-NSAB isolates had a TGC MIC of ≥4 mg/L and were resistant to all antimicrobials tested by disk diffusion method except for minocycline and doxycycline for which a susceptibility rate of 40% and 20% was observed, respectively. The <i>tetX/X1</i> genes were not detected in any isolates. All TGC non-susceptible isolates harbored genetic alterations in the <i>adeRS</i> operon, including AdeS G186V, N268H, and D60N and AdeR A136V and V120I substitutions among, which G186V and D60N were predicted by PROVEAN tool analysis as inactivating alterations. Reduced TGC susceptibility was associated with upregulation of AdeABC efflux pump in all TGC non-susceptible isolates. <b><i>Conclusion:</i></b> It can be concluded from our results that reduced susceptibility to TGC in the studied isolates was mainly mediated by genetic alterations in the AdeRS system, which resulted in overexpression of AdeABC efflux pump. Emergence of TGC non-susceptibility among isolates that had not been previously exposed to TGC is an issue of great concern.

scholarly journals Antimicrobial Resistance Pattern of Extensively Drug Resistant Carbapenemase Producing Enterobacteriaceae

2019 ◽  
Vol 13 (2) ◽  
pp. 7-10
Author(s):  
Fatima Afroz ◽  
Shaheda Anwar ◽  
Mashrura Quraishi ◽  
GM Mohiuddin ◽  
SM Ali Ahmed ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Resistance Pattern ◽  
Drug Resistant ◽  
Disk Diffusion Method ◽  
Cross Sectional ◽  
Extensively Drug Resistant ◽  
Broth Microdilution Method

Carbapenems, often agents of last resort for multidrug resistant bacterial infections are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Production of carbapenemases remain the most clinically important mechanism of carbapenem resistance in Enterobacteriaceae. The objective of this study was to determine the antibiogram pattern of carbapenemase producing Enterobacteriaceae. A cross sectional study was conducted at department of Microbiology and Immunology, BSMMU from September 2018 to August 2019. A total of 145 CRE isolates from different clinical samples were studied.Antimicrobial susceptibility was examinedby disk diffusion method and MIC of colistin by broth microdilution method. Resistant carbapenemase genes NDM and OXA-48 were identified by polymerase chain reaction. Out of 145 CRE isolates, 104 were NDM, 73 were OXA-48and 34 isolates were both NDM and OXA-48 co-producers. All the NDM and OXA-48 carbapenemase producing isolates were 100% resistant to meropenem, imipenem, ertapenem, ceftriaxone, ceftazidime, cefotaxime, cefuroxime, amoxicillin + clavulanic acid and piperacillin + tazobactam. Resistance rates of reserved antimicrobials to treat CRE isolates were also alarming. Thirty seven percent, 9.6% and 5.5 % of OXA-48 carbapenemase producers and 26.0%, 10.6% and 2.9% of NDM carbapenemase producers were resistant to colistin, polymyxin B and tigecycline respectively.Among the carbapenemase producing isolates, 16.6% (24) were multidrug resistant (MDR), 82.1% (119) were extensively drug resistant (XDR) and 1.3% (2) isolates were pan drug resistantwhich highlights the emerging therapeutic challenge for these superbugs. Bangladesh J Med Microbiol 2019; 13 (2): 7-10

scholarly journals The Dissemination of Multidrug Resistance (MDR) and Extensively Drug Resistant (XDR) among Uropathogenic E. coli (UPEC) Isolates from Urinary Tract Infection Patients in Babylon Province, Iraq

2019 ◽  
Vol 16 (4(Suppl.)) ◽  
pp. 0986
Author(s):  
Al-Hasnawy Et al.
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Drug Resistant ◽  
Disk Diffusion Method ◽  
E Coli ◽  
Extensively Drug Resistant

Antibiotic resistance is a problem of deep scientific concern both in hospital and community settings. Rapid detection in clinical laboratories is essential for the judicious recognition of antimicrobial resistant organisms. So, the growth of Uropathgenic Escherichia coli (UPEC) isolates with Multidrug-resistant (MDR) and Extensively Drug-resistant (XDR) profiles that thwart therapy for (UTIs) has been detected and has straight squeezed costs and extended hospital stays. This study aims to detect MDR- and XDR-UPEC isolates. Out of 42 UPEC clinical isolates were composed from UTI patients. The bacterial strains were recognized by standard laboratory protocols. Susceptibility to antibiotic was measured by the standard disk diffusion method Out of 42 Uropathogenic E. coli, 37 (88.09%) were found to be MDR while 5 isolates (11.90%) were XDR. The present study concluded high prevalence of uropathogenic Escherichia coli (UPEC) with Multidrug-resistant (MDR) isolated from urinary tract infection in Babylon province – Iraq.

Whole genome analysis of extensively drug-resistant Acinetobacter bau-mannii clinical isolates in Thailand

2020 ◽  
Vol 20 ◽  
Author(s):  
Peechanika Chopjitt ◽  
Anusak Kerdsin ◽  
Dan Takeuchi ◽  
Rujirat Hatrongjit ◽  
Parichart Boueroy ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Acinetobacter Baumannii ◽  
Genome Sequencing ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistant Genes ◽  
Extensively Drug Resistant ◽  
Antibiotic Efflux

Background:: Acinetobacter baumannii is recognized as a majority opportunistic nosocomial pathogen and caus-ing hospital-acquired infection worldwide. The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a rising concern in healthcare facilities and has impeded public health due to limitation of therapeutic options and are associated with high morbidity and mortality as well as longer hospitalization. Whole-genome sequencing of highly multidrug resistant A. baumannii will increase understanding of resistant mechanisms, the emergence of novel re-sistance, genetic relationships among the isolates, source tracking, and treatment decisions in selected patients. Objective:: This study revealed the genomic analysis to explore blaOXA-23 harboring XDRAB isolates in Thailand. Methods:: Whole-genome sequencing of the two XDRAB isolates was carried out on a HiSeq2000 Illumina platform and susceptibility on antimicrobials was conducted. Results:: Both isolates revealed sequence types of international, clone II-carrying, multiple antimicrobial-resistant genes—ST195 and ST451. They were resistant to antimicrobial agents in all drug classes tested for Acinetobacter spp. They carried 18 antimicrobial-resistant genes comprising of 4 -lactamase genes (blaOXA-23, blaOXA-66, blaTEM-1D, blaADC-25), 4 aminogly-coside-resistant genes (armA, aph(3')-Ia, aph(3'')-Ib, aph(6)-Id), 3 macrolide-resistant genes (amvA, mphE, msrE), 1 sulfon-amide-resistant gene (sul-2), 2 tetracycline-resistant genes (tetB, tetR), 1 resistant-nodulation-cell division (RND) antibiotic efflux pump gene cluster, 2 major facilitator superfamily (MFS) antibiotic efflux pump genes (abaF, abaQ), and 1 small multidrug-resistant (SMR) antibiotic efflux pump gene (abeS). Mutation of gyrA (S81L) occurred in both isolates. Conclusions:: Whole-genome sequencing revealed both blaOXA-23 harboring XDRAB isolates were clustered under interna-tional clone II with difference STs and carrying multiple antimicrobial-resistant genes conferred their resistance to antimi-crobial agents. Inactivation of antimicrobials and target modification by enzymes, and pumping antibiotics by efflux pump are mainly resistance mechanism of the XDRAB in this study.

Ceftazidime – Avibactam susceptibility among carbapenem-resistant Enterobacterales in a pilot study in Turkey

2021 ◽  
Author(s):  
Hasan Selcuk Ozger ◽  
Ebru Evren ◽  
Serap Suzuk Yildiz ◽  
Cigdem Erol ◽  
Fatma Bayrakdar ◽  
...  
Keyword(s):  
Practical Method ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Drug Resistant ◽  
Chain Reaction ◽  
Disk Diffusion Method ◽  
Carbapenem Resistant ◽  
Therapeutic Choice ◽  
Polymerase Chain

AbstractThis study aimed to detect carbapenemase genes and to determine the in vitro susceptibility of Ceftazidime-Avibactam (CZA) in Enterobacterales isolates. Carbapenemase genes were detected by polymerase chain reaction. CZA sensitivity of isolates was evaluated with broth microdilution (BMD) and disk diffusion methods. A total of 318 carbapenem-resistant Enterobacterales isolates were included. Most of the isolates (n = 290, 91.2%) were identified as Klebsiella pneumoniae. The most common carbapenemase type was OXA-48 (n = 82, 27.6%). CZA susceptibility was evaluated in 84 isolates with OXA-48 and KPC carbapenemase activity. Both BMD and disk diffusion methods revealed that 95.2% of the isolates were sensitive to CZA; whereas, 4 (4.76%) isolates were resistant to CZA. Among colistin resistant isolates, 96.5% (n = 80) of them were susceptible to CZA. Our study demonstrated high in vitro efficacy of CZA in Enterobacterales isolates producing OXA-48 carbapenemase. High susceptibility rates against colistin resistant isolates which generally are also pan drug resistant, makes CZA a promising therapeutic choice for difficult-to-treat infections. Due to its high correlation with the BMD, disk diffusion method is a suitable and more practical method in detecting CZA in vitro activity.

scholarly journals Extensively Drug-Resistant Salmonella typhi XDR Infection at Rawalpindi Medical University and Allied Hospitals

2020 ◽  
Vol 24 (4) ◽  
pp. 406-411
Author(s):  
Kausar Izhar ◽  
Kiran Ahmed ◽  
Maryyam Rehan ◽  
Muhammad Umar ◽  
Nadeem Ikram ◽  
...  
Keyword(s):  
Blood Culture ◽  
Simple Random Sampling ◽  
Salmonella Typhi ◽  
Cross Sectional Study ◽  
Diffusion Method ◽  
Drug Resistant ◽  
Disk Diffusion Method ◽  
Cross Sectional ◽  
Extensively Drug Resistant ◽  
Antibiotics Susceptibility

Objective: To evaluate the prevalence of extensively drug-resistant Salmonella typhi (XDR) in RMU Allied Hospitals. Study Design: A descriptive cross-sectional study. Material and Methods: It is a cross-sectional, prospective study conducted at RMU Allied Hospitals from January 2019–December 2019. Blood culture samples were received in the pathology lab, they were collected by simple random sampling and processed by conventional incubation. Antibiotic susceptibility of the isolates was done on Muller Hinton agar using modified Kirby Bauer disk diffusion method and antibiotic zone diameters were measured according to CLSI guidelines. Results: Out of the total 8045 cultures, 911 (11%) showed growth, among which 179 (20%) were Salmonella typhi and 135 (15%) XDR Salmonella. Meropenem revealed the highest sensitivity, Chloramphenicol, and Augmentin revealed the highest resistance. Conclusion: Blood culture results revealed Salmonella typhi 20% with a significant number of XDR Salmonella 15%. Antibiotics susceptibility pattern exhibits Meropenem and Azithromycin as the only antibiotics for XDR Salmonella. Salmonella typhi infection has a significantly high prevalence among children as compared to adults. (p=0.0017) Injudicious use of antibiotics is one of the important aspects of the occurrence of antibiotic-resistant Salmonella.

scholarly journals Effect of antibiotic combinations by break-point checkerboard plate and disk diffusion method against drug-resistant Pseudomonas aeruginosa

2014 ◽  
Vol 63 (1) ◽  
pp. 18-23
Author(s):  
Hiromi MORISHIGE ◽  
Yoshihito OTSUKA ◽  
Akihiro TOGUCHI ◽  
Masako HIRATA ◽  
Kohei HASHIMOTO ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Break Point ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Drug Resistant ◽  
Disk Diffusion Method

scholarly journals Phenotypic screening of metallo--lactamase in multi-drug-resistant Pseudomonas aeruginosa using a combined disk diffusion method

2013 ◽  
Vol 7 (45) ◽  
pp. 5195-5199 ◽  
Author(s):  
Erfani Yousef ◽  
Fallah Fatemeh ◽  
Sadat Sajadi Nia Raheleh ◽  
Rasti Arezoo ◽  
Heydarian Moghadam Mohammad
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Phenotypic Screening ◽  
Drug Resistant ◽  
Disk Diffusion Method

scholarly journals Fluoroquinolone resistance conferred by gyrA, parC mutations, and AbaQ efflux pump among Acinetobacter baumannii clinical isolates causing ventilator-associated pneumonia

2019 ◽  
pp. 1-5 ◽  
Author(s):  
Nancy M. Attia ◽  
Amira ElBaradei
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Ventilator Associated Pneumonia ◽  
Drug Resistant ◽  
The Novel ◽  
New Mutation ◽  
Extensively Drug Resistant ◽  
High Level

Acinetobacter baumannii has emerged as an important nosocomial pathogen due to its ability to survive in hospital settings and its antimicrobial resistance. It is one of the key pathogens in ventilator-associated pneumonia (VAP). The aim of this study was to characterize the mechanisms of quinolone resistance among A. baumannii isolates causing VAP and to investigate the presence of the novel abaQ gene among them. Quinolone-resistant A. baumannii isolates causing VAP were collected over a period of 4 months. Mutations within gyrA and parC were analyzed and the presence of qnrA, qnrB, qnrS, and abaQ was investigated genotypically. Twenty-one A. baumannii isolates were collected, most of them (76.2%) were extensively drug-resistant (XDR) and only one isolate (4.8%) was pandrug-resistant (PDR). All isolates showed high level of resistance to ciprofloxacin, while qnrA, qnrB and qnrS were absent among our isolates. This is the first report of A. baumannii isolates co-harboring Ser81Leu in gyrA and Ser84Leu in parC together with the novel abaQ gene. Interestingly, a new mutation in gyrA quinolone resistance-determining region Arg89Cys was detected among two of our isolates. The emergence of XDR and PDR isolates among A. baumannii causing VAP is an alarming threat.

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