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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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    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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    Investigation of Streptococcus agalactiae Colonisation in pregnant women using culture and a novel qPCR Kit
    (Elsevier Science Inc, 2026) Mazlumoglu, Bilge; Genc, Leyla; Ince, Sule Ule Birol; Pelit, Suleyman; Tanriverdi, Elif Seren; Aktas, Elif
    Background: Maternal colonisation with Streptococcus agalactiae (GBS) is the most important risk factor for earlyonset sepsis in newborns. We aimed to determine the rate of GBS colonisation in pregnant women evaluate the concordance between culture and a novel commercial polymerase chain reaction (PCR) test for screening. We also aimed to investigate the presence of the hypervirulent ST-17 clone and the potential risk factors that may affect colonisation. Material and Methods: A total of 365 rectovaginal samples from pregnant women >= 36 weeks were investigated. Lim Broth was used for culture. PCR was done by the Bio-Speedy GBS (Group B Streptococcus) qPCR kit. The presence of the hypervirulent ST-17 clone was evaluated by PCR. Potential risk factors were evaluated via a survey. Results: GBS was detected in 12.3 % (95 % CI: 9.3-16.1) of pregnant women by culture, in 15.3 % (95 % CI: 11.9-19.5) by direct qPCR and in 19.5 % (95 % CI: 15.6-23.9) by enrichment qPCR. Cohen's Kappa analysis revealed an 'almost perfect' level of agreement between culture and direct qPCR (kappa = 0.85; 95 % CI: 0.74-0.97). Discordant results were observed in 13 cases (12 qPCR positive / culture negative, and one qPCR-negative / culture-positive). All isolates were susceptible to penicillin, while resistance to erythromycin and clindamycin were 37.8 % (95 % CI 25.1-52.4) and 33.3 % (95 % CI 21.4-47.9), respectively. ST-17 clone constituted 7 % (95 % CI:1.9-17.0) of the positive samples. GBS colonisation showed an association with sexual activity that approached the statistical significance threshold, and a significant association with education level. Conclusion: Using a novel PCR test, almost perfect agreement was found between qPCR and culture, while the detection of colonisation was higher by qPCR. This study highlights the diagnostic contribution of molecular methods in GBS screening, even providing results after the onset of labor. The high prevalence of GBS, along with the circulation of hypervirulent clones underscores the critical importance of routine screening in pregnant women.