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 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 Delafloxacin against Methicillin-Resistant Staphylococcus aureus Isolated from Various Clinical Specimens(2021) Mirza, Hasan Cenk; Basustaoglu, Ahmet; Yanik Yalcin, Tugba; 0000-0002-8853-3893; F-1232-2015Introduction: Delafloxacin is a novel fluoroquinolone which has anionic and weak acid character at neutral pH. Activity of delafloxacin is reported to be increased in acidic environments. Many infections are characterized by acidic pH. Staphylococcus aureus is a microorganism which can survive and multiply in mildly acidic environments. The aim of this study was to compare the activity of delafloxacin and other fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) against MRSA isolates at neutral (7.4) and acidic (5.5) pH. Materials and Methods: A total of 51 MRSA isolated from various clinical specimens were included in the study. Disk diffusion method was used for antimicrobial susceptibility testing. The pH of Mueller Hinton Agar was adjusted to 7.4 or 5.5, and used as the medium for antimicrobial susceptibility testing. EUCAST breakpoints were used for ciprofloxacin, levofloxacin and moxifloxacin. FDA breakpoints were used for delafloxacin. Results: The most active fluoroquinolones against MRSA isolates at neutral pH were delafloxacin and moxifloxacin. Delafloxacin and moxifloxacin susceptibility rates of isolates were same (82.4%) at neutral pH. Of the isolates, 9.8% and 17.6% were resistant to delafloxacin and moxifloxacin, respectively. Four moxifloxacin-resistant isolates were categorized as intermediate to delafloxacin. Of the isolates, 76.5% and 78.4% were 'I - susceptible, increased exposure' to ciprofloxacin and levofloxacin, respectively. Of the isolates, 23.5% and 21.6% were resistant to ciprofloxacin and levofloxacin, respectively. At acidic pH; ciprofloxacin, levofloxacin and moxifloxacin susceptibility rates of isolates were not changed. However, all delafloxacin resistant/intermediate isolates at neutral pH became susceptible to delafloxacin at acidic pH. Conclusion: Delafloxacin was the most active fluoroquinolone against MRSA isolates at acidic pH. Based on our findings, delafloxacin may represent a treatment option for MRSA infections characterized by low pH.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 Comparison of Antimicrobial Susceptibilities of Escherichia coli Isolated From Urinary Cultures of Different Patient Groups: A University Hospital Experience(2020) Mirza, Hasan Cenk; Sancak, Banu; F-1232-2015Objective: Our objective was to investigate the antimicrobial susceptibilities of Escherichia coli isolated from urinary cultures in Central Laboratory of Hacettepe University Faculty of Medicine Hospital and to examine the differences between antimicrobial susceptibilities of E. coli isolated from different patient groups. Methods: E. coli isolated from urinary cultures between January 1, 2017 and April 30, 2018 were included in our study. Automated systems, i.e. VITEK (R) 2 Compact (bioMerieux, Marcy l'Etoile, France) and BD Phoenix (Becton Dickinson, Sparks, MD, USA) and disk diffusion test were used for the determination of antimicrobial susceptibilities. The patients from whom the bacteria were isolated were divided into groups according to age (<18 years, 18-64 years, and >64 years), gender and patient care (outpatients/inpatients). Results: The highest susceptibility rates were observed for carbapenems (>99%), fosfomycin (98.5%), nitrofurantoin (98.3%) and amikacin (94.2%), whereas the highest resistance rates were observed for ampicillin (61.3%) and amoxicillin-clavulanate (37.5-45.7%). Antimicrobial resistance rates of isolates from patients aged 65 years and over were higher than those of patients in other age groups, with the exception of piperacillintazobactam, amikacin and ertapenem. The resistance rates of isolates belonging to male patients were higher than those belonging to female patients for all antimicrobials. Also, the resistance rates of isolates belonging to inpatients were higher than those belonging to outpatients for all antimicrobials. When the rates of extended-spectrum beta-lactamase (ESBL)-producing E. coli from different age groups were compared, the highest rate (34.2%) was observed among the isolates from patients aged 65 years and over. The rates of ESBL-producing E. coli from males (33.9%) and inpatients (36.3%) were higher than those from females (23.8%) and outpatients (23.3%), respectively. Conclusions: Antimicrobial susceptibilities of E. coli isolates may vary among different patient groups. Demographic features of patients may guide for selecting the antimicrobials for empiric treatment of urinary tract infections.