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    Antimicrobial susceptibility profile of ceftolozane/tazobactam, ceftazidime/avibactam and cefiderocol against carbapenem-resistant Pseudomonas aeruginosa clinical isolates from Türkiye
    (Springer, 2024) Buyukyanbolu, Ecem; Genc, Leyla; Cyr, Elizabeth A.; Karakus, Mehmet; Comert, Fusun; Otlu, Baris; Aktas, Elif
    Purpose Carbapenem resistant Pseudomonas aeruginosa (CR-PA) is escalating worldwide and leaves clinicians few therapeutic options in recent years, beta-lactam/beta-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of P. aeruginosa infection and have shown potent activity against isolates defined as carbapenem resistant. The aim of this study was to determine the phenotypic profile of these agents against CR-PA in the emerging setting of carbapenemases. Methods CR-PA clinical isolates were collected from three teaching hospitals in different geographical regions between January 2017-December 2021. All isolates were subjected to phenotypic carbapenemase testing using modified carbapenem inactivation method. MICs were determined by reference broth microdilution and evaluated according to EUCAST standards, while genotypic profiling was determined using PCR methods. Results 244 CR-PA sourced most frequently from the respiratory tract (32.2%), blood (20.4%) and urine (17.5%) were evaluated. Of all isolates, 32 (13.1%) were phenotypically and 38 (15.6%) were genotypically defined as carbapenemase-positive. The most common carbapenemase was GES (63.1%), followed by VIM (15.8%). The MIC50/90(S%) of ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol in all CR-PA isolates were 4 and 32 (80%), 1 and > 64 (69%) and 0.25 and 1 mg/L (96%), respectively. Cefiderocol was also the most active agent in carbapenemase-positive isolates (90%). Conslusion While ceftolozane/tazobactam and ceftazidime/avibactam remained highly active against CR-PA devoid of carbapenemases, cefiderocol provided potent in vitro activity irrespective of carbapenemase production. When considering the potential clinical utility of newer agents against CR-PA, regional variations in carbapenemase prevalence must be considered.
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    Determination of the presence of carbapenemase enzymes in carbapenem-resistant Pseudomonas aeruginosa isolates by susceptibility test based algorithm
    (Elsevier Science Inc, 2024) Ocal, Murat; Buyukyanbolu, Ecem; Karakus, Mehmet; Koca, Oznur; Tanriverdi, Seren; Erdogan, Fatma; Comert, Fusun
    Purpose: Phenotypic methods have been proposed for the detection of carbapenemase production. These tests can have slower turnaround times. With the sensitivity-based algorithm described by Gill et al. will be possible to detect the carbapenemase. Methods: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates from three hospitals between January 2017 and December 2021 were included. The modified carbapenemase-inactivation-method(mCIM) and two algorithms were used, defined as primary algorithm, i.e. ceftazidime and cefepime non-susceptible in addition to imipenem or meropenem resistance and secondary algorithm, i.e. ceftolozane/tazobactam non-susceptible in addition to imipenem or meropenem resistance. PCR testing was performed on all isolates. Results: 256 CRPA isolates were included in the study. When the primary or secondary algorithm criteria were applied, there were 173 isolates that met one or both of them. Of these, 29 were CIM-positive isolates. Conclusion: In our study, the use of the algorithm reduced the need for CIM testing by 32 %.
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    Dose optimization of piperacillin/tazobactam, cefepime, and ceftazidime for carbapenem-resistant Pseudomonas aeruginosa isolates in Turkiye
    (Springer, 2025) Buyukyanbolu, Ecem; Gill, Christian M.; Genc, Leyla; Karakus, Mehmet; Comert, Fusun; Otlu, Baris; Aktas, Elif
    Introduction Although CRPA may test susceptible to other beta-lactams such as ceftazidime (CAZ), cefepime (FEP), and piperacillin/tazobactam (TZP), reduced potency has been observed. We assessed the adequacy of EUCAST Susceptible (S) or Susceptible Increased Exposure (SIE)/(I) doses for CAZ, FEP, and TZP against CRPA clinical isolates. Methods CRPA isolates were collected from patients at three Turkish hospitals. CAZ, FEP, and TZP MICs were determined using broth microdilution. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for a free time above the MIC (fT > MIC) targets for various doses of each agent against isolates defined as susceptible. fT > MIC targets were 70% for CAZ or FEP and 50% for TZP. Cumulative fraction of response (CFR) was calculated. Optimal PTA and CFR was 90% target achievement. Results The percentages of isolates SIE/I to CAZ, FEP, and TZP were 49,8%, 47%, and 31,8% respectively. Reduced potency was noted with 54,1% of CAZ-S isolates having MICs of 4 or 8 mg/L. Of the FEP and TZP-S isolates, MICs at the breakpoint (8 and 16 mg/L, respectively) were the mode with 45,2 and 53,9% of isolates for each, respectively. At an MIC of 8 mg/L for CAZ, the EUCAST standard dose was insufficient (CFR of 85%). 3 h infusions of EUCAST SIE doses were required for 90% PTA at MIC of 8 mg/L and an optimized CFR of 100%. For FEP, the SIE dose of 2 g q8h 0.5 h infusion of was effective (CFR 96%), utilization of an extended 3 h infusion further optimized the PTA at 8 mg/L (CFR 99%). For TZP, the standard dose of 4.5 q6h administered as a 0.5 h infusion was inadequate (CFR 86%). A standard TZP dose with an extended infusion (4.5 g q8h over 4 h) and the SIE dose 4.5 g q6h 3 h infusion resulted in CFRs > 95%. Conclusion These data support the EUCAST SIE breakpoints for FEP and TZP. To optimize PTA at the SIE breakpoint for CAZ, prolonged infusion is required.
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    Evaluation of emm gene types, toxin gene profiles and clonal relatedness of group A streptococci
    (Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, 2013) Mengeloglu, Firat Zafer; Aktas, Elif; Otlu, Baris; Comert, Fusun; Kulah, Canan; Tas, Ebru; Sumbuloglu, Vildan
    The aim of this study is to evaluate antibiotic susceptibilities, emm gene types, toxin gene profiles and clonal relatedness of group A streptococci (GAS) isolates obtained from patients and carriers. A total of 79 clinical isolates from patients and 60 isolates from carriers were included in the study. Emm typing, toxin gene detection for speA, speB, speC, speG and smeZ genes and pulsed-field gel electrophoresis (PFGE) was performed. Twenty-one distinct emm types were detected; the most common types were emm12, emm89, emm1, emm77, emm4 and emm3. The. detection rates of both emm types and the toxin genes didn't differ significantly between patients and carriers. The presence of speA and smeZ was significantly higher in emm1 and speG was significantly lower in emm4 when compared to the other emm types. The rate of clustering obtained with PFGE wasn't significantly different in patients and carriers. As a result, twelve of the 21 emm types detected in this study were covered by the 26-valent vaccine, constituting 77.7% of the emm typeable isolates; however the emm4 type which is one of the most common types in the present study is not among this coverage. (C) 2013 Association of Basic Medical Sciences of FB&H. All rights reserved
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    Evaluation of the Carbapenem Inactivation Method for Detection of Carbapenemase-Producing Gram-Negative Bacteria in Comparison with the RAPIDEC CARBA NP
    (Mary Ann Liebert, Inc, 2017) Aktas, Elif; Malkocoglu, Gulsah; Otlu, Baris; Cicek, Aysegul Copur; Kulah, Canan; Comert, Fusun; Sandalli, Cemal
    Timely detection of carbapenemases by both phenotypic and genotypic methods is essential for developing strategies to control the spread of infections by carbapenem-resistant isolates and related morbidity and mortality. The aim of this study was to compare the performance of a commercial kit, the RAPIDEC (R) CARBA NP, and an in-house technique, the carbapenem inactivation method (CIM), against a panel of 136 carbapenemase and noncarbapenemase-producing Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates. RAPIDEC CARBA NP displayed 99% sensitivity and 100% specificity, whereas the sensitivity and specificity were 78% and 100% for the CIM test, respectively. A slight modification of the CIM test, a prolonged incubation time of 4 hours instead of two, increased the sensitivity of the test to 90% by diminishing false negativity particularly for A. baumannii. In conclusion, both tests possess a high performance and are practical for the detection of carbapenemases. Although RAPIDEC CARBA NP is a more rapid and reliable method, the CIM test may represent a useful tool for microbiology laboratories due to its simplicity and availability at any laboratory with low cost.
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    Investigation of EDTA-CarbaNP-direct test for the detection of metallo-β-lactamases in Pseudomonas aeruginosa
    (Elsevier Science Inc, 2025) Tutan, Hanife; Mazlumoglu, Bilge; Cizmeci, Zeynep; Cekin, Zuhal Kalayci; Comert, Fusun; Tanriverdi, Elif Seren; Aktas, Elif
    Background: WHO has included carbapenem-resistant Pseudomonas aeruginosa (CR-Pa) in the high priority pathogens list. Ceftazidime-avibactam (CZA) is one of the limited treatment options in CR-Pa infections. Early detection of metallo-beta-lactamases (MBL) is important because CZA is not effective against MBL-producing isolates. Aim: To modify the CarbaNP-direct test (CNPdt) with EDTA and evaluate its use in MBL detection and prediction of CZA resistance CR-Pa isolates. Methods: 398 CR-Pa isolates from five centres in T & uuml;rkiye were included. Susceptibility tests were done using EUCAST criteria. The isolates were tested for blaVIM, blaIMP, blaNDM, blaOXA-48, blaKPC and blaGES genes using Biospeedy Carbapenem-Resistance qPCR kit and GES Antibiotic-Resistance kit (Bioeksen, T & uuml;rkiye). We modified CNPdt described by Pasteran et al. by adding a third tube with ethylenediaminetetraacetic acid (EDTA). The isolates with carbapenemase genes were subjected to CNPdt and EDTA-CNPdt. EDTA-CNPdt was considered positive if the tube without EDTA turned yellow while the tube with EDTA remained red and negative if both tubes turned yellow (Fig. 1). Results: Carbapenemase genes were detected in 55 (13.8 %) of the isolates. CNPdt was positive in 31 of the isolates. Of the 31 isolates, 23 were positive for EDTA-CNPdt. All of these 23 isolates were MBL producers and resistant to CZA. PCR, CNPdt, EDTA-CNPdt and CZA susceptibility test results are shown in Table 2. Conclusion: The positivity of CNPdt in CR-Pa is limited, but EDTA-CNPdt detected 100 % of MBL-producing isolates when CNPdt was positive. This test can be used for MBL detection and prediction of CZA resistance in CNPdt positive isolates.