Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item In Vitro Efficacy of Ceftazidime-avibactam Against blaOXA-48-producing Klebsiella pneumoniae Isolates(2023) Cag, Yasemin; Kocoglu, Mucahide Esra; Caskurlu, Hulya; Haciseyitoglu, Demet; Mirza, Hasan Cenk; Guclu, Aylin Uskudar; Cetinkaya, Riza Aytac; Vahaboglu, Haluk; 0000-0002-8853-3893; F-1232-2015Introduction: The healthcare burden of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) infections is growing. The newly developed beta-lactam/beta-lactamase inhibitor combination, ceftazidime-avibactam, shows promise in the treatment of such infections. We aimed to explore the in vitro efficacy of ceftazidime-avibactam against carbapenem-resistant K. pneumoniae isolates carrying the blaOXA-48 gene.Materials and Methods: The isolates were identified using MALDI-TOF MS (Brucker, USA). The isolates that were non-susceptible to imipenem, meropenem, or ertapenem by the disk diffusion method using the European Committee of Antimicrobial Susceptibility Testing (EUCAST) breakpoints were screenes. Minimum inhibitory concentration (MIC) values were determined via broth microdilution according to the EUCAST criteria. A time-kill study was performed according to Clinical and Laboratory Standards Institute guidelines. Beta-lactamase genes were screened for using polymerase chain reaction with previously published primers.Results: A total of 129 K. pneumoniae isolated between April 2011 and February 2021 were studied. Of these, 98, 23, and eight isolates carried the blaOXA-48, blaNDM, and blaOXA-48 with blaNDM genes, respectively. All isolates carrying the blaNDM gene were resistant to ceftazidime-avibactam. Approximately 79.6% of the blaOXA-48-positiveisolates were susceptible to ceftazidime-avibactam. The time-kill study for ceftazidime-avibactam was performed with one blaOXA-48-positive isolate (MIC, 4 mg/l). Ceftazidime-avibactam time-kill kinetics were evaluated in multiples of MIC. There was a decrease of >= 3-log10 in CFU/ml count at a concentration of 8, 16, and 32 MIC at 6 hours. The minimum bactericidal concentration was 8 mg/l.Conclusion: Ceftazidime-avibactam is an important treatment alternative alternative for blaOXA-48 positive carbapenem-resistant K. pneumoniae infections. The most rational approach to the treatment of carbapenem-resistant K. pneumoniae infections appears to be the initiatiion of targeted therapy according to culture antibiogram results or revision of the empirically initiated combination or monotherapy as early as possible according to culture antibiogram results.Item Comparative in Vitro Activities of Omadacycline, Eravacycline and Tigecycline Against Non-ESBL- Producing ESBL- Producing and Carbapenem- Resistant Isolates of K. Pneumoniae(2022) Mirza, Hasan Cenk; Guclu, Aylin Uskudar; Ceviz, Gizem Ince; Basustaoglu, Ahmet; 0000-0002-8853-3893; 0000-0002-1872-028X; 36301611; F-1232-2015; AAU-6196-2020Introduction. Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant Enterobacte-riaceae are characterized by the World Health Organization as pathogens for which new antibiotics are urgently needed. Oma-dacycline and eravacycline are two novel antibacterials within the tetracycline class.Gap Statement. There are limited data regarding the comparison of the activities of omadacycline, eravacycline and tigecycline against K. pneumoniae isolates with different antimicrobial susceptibility profiles.Aim. Our objective was to compare the in vitro activities of omadacycline, eravacycline and tigecycline against a collection of K. pneumoniae isolates, including non- ESBL-producing, ESBL-producing and carbapenem-resistant strains.Methodology. Ninety-four K. pneumoniae isolates, including 30 non- ESBL-producing, 30 ESBL-producing and 34 carbapenem-resistant (22 carrying blaOXA-48, 12 carrying blaNDM) strains were included in the study. ESBL and carbapenemase genes were detected by conventional PCR. Omadacycline, eravacycline and tigecycline MICs were determined by the gradient diffusion method and interpreted using US Food and Drug Administration (FDA)-defined breakpoints.Results. Overall, the percentage of tigecycline-susceptible strains (97.9 %) was higher than the percentage of omadacyline-susceptible (75.5 %) and eravacycline-susceptible (72.3 %) strains. The omadacycline and eravacycline susceptibility rates were 83.3 % among non- ESBL-producing isolates and 66.7 % among ESBL-producing isolates. The most common ESBL gene detected was blaCTX-M (90 %), followed by blaTEM (50 %) and blaSHV (50 %). The omadacycline and eravacycline susceptibility rate among isolates carrying blaTEM was 33.3 %, whereas it was 100 % among isolates that do not carry blaTEM. The omadacycline and eravacycline susceptibility rates among carbapenem-resistant isolates were 76.5 and 67.6 %, respectively. The omadacycline susceptibility rates among blaOXA-48-positive and blaNDM-positive isolates were 77.3 and 75.0 %, respectively. The eravacycline susceptibility rates among blaOXA-48-positive and blaNDM- positive isolates were 68.2 and 66.7 %, respectively. One carbapenem-resistant isolate was intermediate and one ESBL-producing isolate was resistant to tigecycline.Conclusion. Overall, tigecycline was the most active tetracycline against isolates. Omadacycline and eravacycline showed excellent activity against ESBL-producing K. pneumoniae isolates that do not carry blaTEM. Omadacycline showed reasonable activity against carbapenem-resistant K. pneumoniae isolates carrying blaOXA-48 or blaNDM.Item Clinical Strains of Chryseobacterium and Elizabethkingia spp. Isolated from Pediatric Patients in a University Hospital: Performance of MALDI-TOF MS-Based Identification, Antimicrobial Susceptibilities, and Baseline Patient Characteristics(2017) Mirza, Hasan Cenk; Tuncer, Ozlem; Olmez, Serpil; Sener, Burcin; Tugcu, Gokcen Dilsa; Ozcelik, Ugur; Gursoy, Nafia Canan; Otlu, Baris; Buyukcam, Ayse; Kara, Ates; Sancak, Banu; https://orcid.org/0000-0002-8853-3893; 29227188; F-1232-2015Our objective was to evaluate the performance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification of the Chryseobacterium and Elizabethkingia spp. isolated from pediatric patients at Hacettepe University Hospital using 16S rRNA gene sequencing as the gold standard and to determine the antimicrobial susceptibility patterns of the isolates and baseline characteristics of patients. All stored Chryseobacterium and Elizabethkingia spp. isolated from various clinical specimens (sputum, blood, and urine) of pediatric patients at Hacettepe University Hospital between 2012 and 2016 were included in this study. Minimum inhibitory concentrations of 10 antimicrobial agents were determined by Etest for all isolates. To determine the baseline characteristics of patients, medical records of all patients were retrospectively reviewed. In total, 18 isolates of Chryseobacterium spp. (16 C. indologenes, 2 C. gleum) and 5 isolates of Elizabethkingia spp. (3 E. meningoseptica, 2 E. anophelis) were identified by 16S rRNA sequencing. MALDI-TOF MS correctly identified 19 (82.6%) isolates to the species level. The quinolones (ciprofloxacin and levofloxacin), trimethoprim/sulfamethoxazole and piperacillin/tazobactam showed the highest spectrum of activity against the overall collection of isolates. Cystic fibrosis (CF) was the underlying disease in 81.8% of patients. To our knowledge, this study includes the largest number of Chryseobacterium spp. isolated from clinical specimens of pediatric patients in Turkey. In this study, we also report the first clinical isolate of E. anophelis in Turkey. Since, the majority of strains were isolated from patients with CF; larger, prospective clinical studies are needed to establish whether chryseobacteria could be considered as an emerging opportunistic pathogen in patients with CF.Item Investigation of anti-cholinesterase and anti-amyloidogenic activities of beta-lactam antibiotics(2022) Ozer, Eda Ozturan; Mirza, Hasan Cenk; Tan, Oya Unsal; Turkoglu, Suna; 0000-0002-8853-3893; 0000-0003-4805-1918; F-1232-2015; AAJ-2243-2021Objectives: Neuroinflammation is an important factor in the pathogenesis of neurodegenerative disesases. The following study aimed to clarify the effects of beta-lactam antibiotics to the cholinergic system, on acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activities, considering the structural differences of antibiotics, to evaluate the underlying mechanism of effects provided by protein-antibiotic interactions, and to clarify possible effects of the antibiotics on the aggregation of A beta-peptides. Methods: The inhibition/activation mechanisms for each antibiotic were examined kinetically by Ellman method. Destabilization effects of them on amyloid peptide fibrillation were examined and protein-ligand interactions were evaluated with most potent antibiotics by molecular docking studies. Results: The most powerful inhibitions were detected by the inhibition studies of AChE with ceftazidime (CAZ) and BuChE with amoxicillin (AMX). CAZ was exhibited dose-related dual effect on AChE activity. CAZ was actually the dose-related modifier of AChE. At higher concentrations, CAZ was a nonessential activator of AChE. Molecular docking studies have been confirmed by kinetic studies. Interested beta-lactam antibiotics did not prevent fibrillation rate as rifampicin. Conclusion: Inhibition/activation behaviours of studied beta-lactam antibiotics on both cholinesterases may suggest that cholinergic transmission is one of the crucially important components of the beta-lactam antibiotics-induced central nervous system adverse reactions.Item Co-existence of Multiple Resistance Mechanisms in Clinical Isolates of Carbapenem-Resistant Pseudomonas Aeruginosa(2022) Uskudar-Guclu, Aylin; Mirza, Hasan Cenk; Unlu, Sezin; https://orcid.org/0000-0002-1872-028X; https://orcid.org/0000-0002-8853-3893; AAU-6196-2020; F-1232-2015Introduction: Multidrug resistance phenotype of Pseudomonas aeruginosa utilizes several resistant mechanisms to overcome the action of antibiotics. This phenotype is caused by several resistance mechanisms or a combination of thereof. This study aimed to evaluate various resistance mechanisms by phenotypic methods. Materials and Methods: Carbapenem-resistant P. aeruginosa were included in this study. Antimicrobial resistance mechanisms such as efflux pump activity, reduced outer membrane permeability (OMP), various beta-lactamase activities, and biofilm formation ability of clinical P aeruginosa isolates were determined by phenotypic methods. Results: Of the P aeruginosa isolates, 33.7% (n= 33/98) had a positive efflux pump activity. The co-existence of positive efflux pump activity and Metallo beta-lactamase (MBL) production was detected in 30.3% (10/33) of the isolates. In 34.7% of the clinical P. aeruginosa isolates, reduced OMP was detected and 70.6% of them were also biofilm producers. Totally 21.4% (21/98) of P aeruginosa isolates were evaluated as extended-spectrum beta-lactamase (ESBL) positive. AmpC beta-lactamase was detected in 15.3% (n= 15/98) of the clinical P. aeruginosa isolates. MBL activity was detected in 33.7% (n= 33/98) of the clinical P. aeruginosa isolates. Of the MBL-positive isolates, 69.7% were biofilm producers. The co-existence of MBL and reduced OMP was detected in 36.4% (n= 12/33). Conclusion: High resistance of P. aeruginosa was attributed to several resistance mechanisms or a combination of thereof. This infections caused by multidrug-resistant (MDR) P. aeruginosa are difficult to treat due to the co-existence of different resistance mechanisms.Item In vitro activity of ceftolozane-tazobactam and ceftazidime-avibactam against clinical isolates of meropenem-non-susceptible Pseudomonas aeruginosa: A two-centre study(2020) Mirza, Hasan Cenk; Hortac, Elvan; Kocak, Aylin Altay; Demirkaya, M. Hamiyet; Yayla, Buket; Guclu, Aylin Uskudar; Bustaoglu, Ahmet; 0000-0002-1872-028X; 0000-0002-8853-3893; 0000-0002-0451-0142; 0000-0002-4335-6897; 31568882; AAU-6196-2020; F-1232-2015; AAI-8012-2021Objectives: This study aimed to compare the activity of ceftazidime-avibactam (C/A), ceftolozane-tazobactam (C/T) and three anti-pseudomonal beta-lactams (piperacillin-tazobactam, ceftazidime and cefepime) against a collection of meropenem-non-susceptible Pseudomonas aeruginosa (P. aeruginosa) clinical isolates recovered from two centres in Turkey. Methods: A total of 102 unique patient isolates of meropenem-non-susceptible P. aeruginosa were included in the study. MICs of antimicrobials were determined by the gradient diffusion method. Results: Overall susceptibility rates for C/A and C/T were 83.3% and 82.4%, respectively. Both C/A and C/T had better activity than any one of the three anti-pseudomonal beta-lactams. According to the MIC50 values, C/T was the most potent agent against isolates. Although the susceptibility rates of isolates to C/T and C/A were similar, C/T (MIC50, 1 mg/mL) was four-fold more potent than C/A (MIC50, 4 mg/mL). The MIC50 values of C/A and C/T for the isolates that were non-susceptible to three beta-lactams were significantly higher than those for isolates that were non-susceptible to zero, one or two beta-lactams. Also, the C/A MIC50 value for the isolates that were non-susceptible to two beta-lactams was higher than that for isolates which were non-susceptible to one beta-lactam. Conclusions: C/A and C/T showed good activity against meropenem-non-susceptible P. aeruginosa isolates. However, resistance to these agents was not uncommon among these isolates. The overall beta-lactam susceptibility profile of isolates seems to have an effect on the probability of susceptibility to C/A and C/T. Antimicrobial susceptibility testing should be performed for C/A and C/T if these agents are considered for treatment of infections caused by meropenem-non-susceptible P. aeruginosa. (C) 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd.Item Prevention of Candida biofilm formation over polystyrene by plasma polymerization technique(2020) Kaleli-Can, Gizem; Hortac-Istar, Elvan; Ozguzar, Hatice Ferda; Mutlu, Mehmet; Mirza, Hasan Cenk; Basustaoglu, Ahmet; Gocmen, Julide Sedef; 0000-0002-8853-3893; 0000-0002-2571-0637; F-1232-2015; AAI-8926-2021This work investigates the antifungal effect of plasma polymer films produced by low-pressure RF-generated plasma system using acrylic acid, 2-hydroxyethyl methacrylate, and diethyl phosphite (DEP). Unmodified and plasma-modified polystyrene (PS) microplate wells were tested by 30 biofilm-positive Candida spp. isolated from blood samples and two control strains using a quantitative plaque assay method. Regardless of the precursors and plasma parameters, biofilm formation was inhibited for all plasma-modified microplate wells. The most significant anti-biofilm effect was observed on PS modified by DEP at 90 W plasma power with the inhibition of all Candida species' biofilm formation.