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The development of antibiotic resistance is increasing worldwide. Third-generation cephalosporins-resistant Enterobacterales (ESBL-E) and carbapenems-resistant Enterobacterales (CRE) have been placed in the critical category by the World Health Organization on its list of global priority pathogens. ESBL-E is a group of Enterobacterales bacteria that exhibit resistance to beta-lactams, broad-spectrum beta-lactams, and third-generation cephalosporins. The CTX-M-15 enzyme, responsible for resistance, is the most identified identified in the ESBL-E group bacteria. In parallel with the increase in infectious diseases caused by the ESBL-E group bacteria, the use of carbapenems increased, resulting in an increase in carbapenem resistance. Carbapenemases are classified into three groups: A, B, and D. OXA (Oxacillin-hydrolyzing carbapenemase) enzymes that form Class D carbapenemases are endemic in Türkiye. The first CRE strain was detected in the 1980s and soon spread worldwide. Carbapenemase groups A, B, and D are observed in various countries and are even considered endemic in some, such as Türkiye. At EUCAST (European Committee on Antimicrobial Susceptibility Testing) and CLSI (Clinical and Laboratory Standards Institute) guidelines, the carbapenem group of antibiotics are suggested as preferred agents for the treatment of ESBL-producing Enterobacterales serious infections. There are three approaches for treating infections caused by carbapenem-resistant Enterobacterales: 1) re-evaluation of treatment options with existing antibiotics (fosfomycin, colistin, tigecycline, such as the use of older antibiotics), 2) treatment with two carbapenems (combination of two different carbapenems), 3) treatment with new β-lactam and beta-lactamase inhibitor combinations or with new antibiotics (Ceftazidime/avibactam, Meropenem/vaborbactam, Plazomicin, Eravacyclin; the use of new antibiotics). An increase in the prevalence of multidrug-resistant bacterial infections such as CRE and ESBL-E is causing antibiotic resistance to pose a global threat today. An international, multidisciplinary approach is needed to combat this global threat. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii is recognized as a major threat that causes healthcare-associated infections and causes a huge challenge to the health system worldwide. This research study was designed to detect the types and profiles of antibiotics tested against A. baumannii clinical strains in Turkey to evaluate their effectiveness and reevaluate their usage. The study depended on data search strategy using the online electronic database. We carried out a detailed analysis to all original research articles from 2011 to 2022 all conducted in Turkey. The study involved 91 articles and revealed about 40 antibiotics tested from 2006 to 2021 against A. baumannii with a different frequency. The more frequency antibiotics tested by health institutions in Turkey during this period included 15 antibiotics which are (Amikacin, Gentamicin, Imipenem, Meropenem, Cefoperazone–sulbactam, Ceftazidime, Cefepime, Ampicillin/sulbactam, Piperacillin, Piperacillin/tazobactam, Ciprofloxacin, Levofloxacin, Trimethoprim–Sulfamethoxazole, Colistin and Tigecycline). The frequency of resistance rate with percentage of (80–100%) shown by A. baumannii against these antibiotics was as follows (40.96%, 50.64%, 77.77%, 78.31%, 46.15%, 94.11%, 88.23%, 80.85%, 95.46%, 91.93%, 93.42%, 82.85%, 53.57%, 2.66%, 3.70%), respectively. From 2016 to 2021, an increase in resistance rates by A. baumannii against Colistin and Tigecycline was indicated noticeably. The 0% resistance rates during this period against Colistin were reported in a percentage of 16.6%, while the appearance of highly noticeable resistance (from 80 to 100 = 3.70%) against Tigecycline and the continuous elevation of resistance rates against this drug was worrisome. Short conclusion: Stability in high resistance rates against some antibiotics for the last 10 years and the increase in resistance rates against effective antibiotics by A. baumannii should undergo for more studies and re-evaluation. [ABSTRACT FROM AUTHOR]

Background: Carbapenemase production is an issue of significant clinical and public health concern, because of the shortage of effective antimicrobial agents available for treatment. Here, we present antimicrobial susceptibility data of ceftazidime-avibactam, cefiderocol, and other clinically relevant antibiotics for carbapenemase-producing Enterobacterales bloodstream isolates, in accordance with European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Methods: A total of 133 carbapenemase producing Enterobacterales bloodstream isolates from May 2010 to September 2018 were included in the study. Species were identified using matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (Bruker Daltonics, Germany). The presence of the blaKPC, blaNDM, blaOXA-48, blaVIM, and blaIMP carbapenemase genes were investigated by BD Max CRE assay (Becton Dickinson, USA) and in-house PCR. Antimicrobial susceptibility testing was performed by the BD Phoenix automated system (Becton Dickinson, USA), except cefiderocol and colistin. Cefiderocol and colistin susceptibility was determined by disk diffusion and broth microdilution method, respectively. Results: Except for cefiderocol and ceftazidime-avibactam, the percentage of susceptible isolates did not exceed 90% for any of the antibiotics tested. Although none of the isolates were resistant to cefiderocol, the ceftazidimeavibactam resistance rate was 9.8%. All of the ceftazidime-avibactam resistant strains were NDM (New Delhi metallo-beta-lactamases) producers. Among the other clinically relevant antibiotics tested, only amikacin, colistin, tigecycline, and fosfomycin susceptibility rates exceeded 50%. Of the 133 isolates 22.6% were resistant to colistin which is the preferred antibiotic with a second active agent for infections caused by metallo-beta-lactamase producing Enterobacterales in Turkey. Conclusions: In our study, resistance to ceftazidime-avibactam was detected only in metallo-beta-lactamase producing Enterobacterales isolates, while cefiderocol was found to be effective against all strains. It is important to monitor regional antimicrobial susceptibility data, as the emergence of antimicrobial resistant phenotypes is directly linked to the use of any given antimicrobial agent. [ABSTRACT FROM AUTHOR]

What is known and objective: The frequency of multidrug‐resistant bacterial infections is increasing worldwide. Tigecycline may be an important option for children with life‐threatening nosocomial infections due to multidrug‐resistant bacteria. However, there are few published data on the use of tigecycline in paediatric patients. By examining the results of tigecycline use in children, we aimed to draw attention to the fact that tigecycline may be an alternative in the treatment of resistant infections in children. Methods: Paediatric patients treated with tigecycline from 1 January 2010 to 31 October 2018 at Eskişehir Osmangazi University Medical Faculty, which is a tertiary hospital, were analysed retrospectively to assess the efficacy and safety of tigecycline treatment in children. Patients using tigecycline were identified using the pharmacy database. Clinical and laboratory data were obtained from the files. Results and discussion: This study included 91 children aged 7 months to 17.5 years; 52 were female (57.1%). At least one predisposing factor was present in 98.9% of the patients. Fifty‐one bacteria were isolated from 44 patients. The tigecycline resistance rate was 3.9%. Only 2 of 91 patients experienced one or more side effects of tigecycline. Tigecycline can be used as salvage therapy in resistant infections where options are limited, although definitive conclusions about the efficacy and safety of tigecycline in children cannot be reached. What is new and conclusion: Tigecycline may be a safe and important option in paediatric nosocomial infections due to resistant bacteria. Resistant bacterial infections have become more common in recent years, its treatment becomes a difficult problem. Tigecycline has a broad‐spectrum antibacterial activity including resistant pathogens. [ABSTRACT FROM AUTHOR]

The most common gram-negative pathogens in urinary tract infections are Escherichia coli and Klebsiella pneumoniae. Therapy that is often empirical relies on local antibiotic resistance data, hence monitorization of antimicrobial resistance periodically in each hospital is a requirement. In this study, antibiotic susceptibility profiles of consecutive urinary isolates (E. coli [n = 235] and K. pneumoniae [n = 56]) of adult patients collected between February 2018 and February 2019 from inpatients in Hacettepe University Hospital were assessed. Isolates resistant to fosfomycin (minimum inhibitory concentration >32 mg/L) were further investigated for the presence of fosA, fosA3, and fosC2. Fosfomycin susceptibility was determined by agar dilution method. Broth microdilution method was performed for amikacin, gentamicin, ceftazidime, ceftriaxone, meropenem, ciprofloxacin, tigecycline, trimethoprim/sulfamethoxazole (TMP/SMX), colistin, and piperacillin/tazobactam (PIP/TAZ). PCR method was employed to investigate fosA, fosA3, fosC2, and blaCTX-M. Existence of fosA3 gene was confirmed by sequencing. Resistance rates to amikacin, gentamicin, ceftazidime, ceftriaxone, meropenem, ciprofloxacin, tigecycline, TMP/SMX, colistin, and PIP/TAZ were 2.7%, 18.5%, 25.4%, 33.0%, 3.4%, 45.4%, 2.4%, 43.6%, 6.2%, and 23.7%, respectively. Sixteen isolates (5.5%) were resistant to fosfomycin. Resistance was most frequently observed in K. pneumoniae (n = 9). fosA3 gene was detected in one fosfomycin-resistant K. pneumoniae isolate. This isolate also carried blaCTX-M.fosC2 and fosA genes could not be detected in any of the isolates. In this study, we report for the first time the existence of fosA3 in Turkey and its association with the blaCTX-M gene. As a result of increasing blaCTX-M producing Enterobacterales isolates globally, increase in fosfomycin resistance may be expected in near future. [ABSTRACT FROM AUTHOR]

Objective: In this study, it was aimed to investigate the change of antibiotic susceptibility of Acinetobacter baumannii strains over the years and to help develop antibiotic use policy by determining the multiple antibiotic resistance rate. Methods: Acinetobacter species isolated from various clinical samples sent to Necip FazılCity Hospital Microbiology Laboratory between January 2013 and December 2018 were included. Vitek 2 Compact (bioMérieux-SE, France) automated systems were used for the identification and antibiotic susceptibility of the isolates. Results: Acinetobacter isolates were isolated at the most from tracheal aspirate samples (n=73; 35%) and samples sent from Anesthesia and Reanimation intensive care unit(n=160; 68%). The distribution of antibiotic sensitivity percentages (%) was given as yearly, three-year averages for 2013-2015, 2016-2018, and the total average for 2013-2018. In the study period, the highest sensitivity was determined to colistin at 97% and the lowest to ceftriaxone at 5%. When the antibiotic sensitivity rates of A. baumannii are evaluated roughly; In the period of 2016-2018, compared to 2013-2015, there was a decrease in sensitivity to amikacin, ampicillin-sulbactam, cefepime, ceftriaxone, colistin and tigecycline, while sensitivity to other antibiotics was observed. Multiple antibiotic resistance was examined in a total of 237 A. baumannii isolated. Multidrug resistant (MDR) resistance was 92%, Extensively Drug Resistant (XDR) resistance was 84% and Pan Drug Resistant(PDR) resistance was 3%. Conclusion: It is observed that resistance against some antibiotics has increased in A. baumannii over the years, and resistance to some antibiotics has decreased. It seems that our XDR resistance rate is very high. Our PDR resistance rate is higher than that of America, but lower than many European countries. In the other hand our result is lower than the average of Turkey. [ABSTRACT FROM AUTHOR]

Introduction: Carbapenem-Resistant Klebsiella pneumoniae (CRKP) is difficult to treat due to resistance to conventional antibiotics. A difficultto-treat critically ill septic patient with a ventriculoperitoneal shunt (VPS) infection associated with CRKP is presented. Case: A 19-year-old male with a history of decompression surgery and VPS due to spontaneus subarachnoid hemorrhage was admitted to ICU with unconsciousness, seizure and fever. His APACHE II score was 17, SOFA score 6, and GCS 4 at ICU admission. He was intubated and meropenemvancomycin combination therapy was initiated for preliminary diagnosis of sepsis due to VPS-related ventriculitis. Surveillance cultures indicated CRKP. On 5th day of ICU admission, ventriculer drainage tube (VDT) was placed after hydrosephalus was detected in the cranial computed tomography. On 10th day Polymixin E was added to antibiotherapy due to the development of CRKP bacteremia and ventilator-associated pneumonia. Septic shock developed again after cessation of antibiotherapy. Ceftazidime-avibactam treatment was started for CRKP detected in CSF cultures as well as blood and endotracheal aspirate. Meropenem and polymyxin E were restarted due to ceftazidime-avibactam resistance and intraventricular (ivt) polymyxin E was added. VPS was removed because of multiple septic shock attacks and continued CRKP growth in CSF and blood cultures. As a salvage treatment, meropenem, tigecycline (iv and ivt) polymyxin B was administered. After 14 days of no growth in control cultures and clinical response, VDT was removed and a new VPS was inserted. He was discharged to home from the hospital on the 185th day of ICU admission. Discussion: The blood-brain and blood-CSF barriers make it difficult for many anti-infective drugs to reach effective concentrations in the CNS after systemic administration. Treatment options for sepsis due to CNS infections with CRKP are quite limited. This is the first successful treatment of a VPS related septic shock patient with ivt tigecycline from Turkey. [ABSTRACT FROM AUTHOR]

Purpose: Acinetobacter baumannii is a non-fermenting aerobic gram-negative bacteria and one of the important nosocomial pathogens, especially in intensive care units (ICUs). In recent years, multidrug-resistant (MDR) isolates have been an emerging problem, with limited therapeutic options. Tigecycline is a novel antimicrobial, with its in vitro activity against most gram-positive and gram-negative pathogens. Methods: This is a retrospective study that was conducted in a tertiary care hospital with 550 beds in Ankara, Turkey, from January 2009 to July 2010. Thirty-three patients who had carbapenem-resistant Acinetobacter spp. infections and received tigecycline alone or in combination with other antibiotics for at least 3 days were included. Results: The median age of the patients was 62 (18-87) years. All of the patients were diagnosed and treated in the ICU. Clinical responses were observed in 23 patients (69.7%). Ten patients (30%) had clinical failure. There was no significant difference between ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) in terms of clinical or microbiological outcome ( p > 0.05). The microbiological response rate was 50%. Superinfection was detected in 13 patients (43.3%) and Pseudomonas aeruginosa was the most frequently isolated pathogen. The 30-day overall mortality rate and attributable mortality rates were 57.6 and 24.2%, respectively. The attributable mortality rate was higher in the group in which microbiological eradication was not provided. Conclusions: Although it is approved by the Food and Drug Administration (FDA) for the treatment of complicated intra-abdominal infections, complicated skin and soft tissue infections, and community-acquired bacterial pneumonia, emerged resistance of Acinetobacter spp. and limited therapeutic options left physicians no choice but to use tigecycline for off-label indications. [ABSTRACT FROM AUTHOR]

Introduction: The widespread use of tigecycline raises the question of increasing infection rates of Pseudomonas aeruginosa (PA) in ICUs which are not affected by this antibiotic., Objective: The aim of this study was to determine if treatment with tigecycline is a risk factor for PA infection in ICU patients., Methodology: A retrospective and observational study was conducted at Erciyes University Hospital, Turkey, between 2008 and 2010. The Erciyes University Hospital is a 1300-bed tertiary care facility. The patients included in this study were hospitalized in four adult ICUs. Patients with PA infections (case group) were compared with patients with nosocomial infection other than PA (control group)., Results: A total of 1,167 patients with any nosocomial infections were included in the study. Two hundred and seventy eight (23.8%) of the patients had PA infection during their ICU stay. Fifty nine patients (21.2%) in the case group received tigecycline before developing PA infections, which were found to be significantly more frequent than in the controls (p < 0.01). Multivariate analysis showed that risk factors for PA infection were previous tigecycline use (4 times), external ventricular shunt (4.2 times), thoracic drainage catheter (2.5 times) and tracheostomy (1.6 times)., Conclusion: Our results contribute to the need for new studies to determine the safety of tigecycline use, especially for the treatment of critically ill patients. Since tigecycline seems to be an alternative for the treatment of multidrug resistant (MDR) microorganisms, rational use of this antibiotic in ICU patients is essential.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as one of the most troublesome pathogens in healthcare settings worldwide. The present study was conducted to analyze the genes encoding resistance to carbapenems and to determine in vitro activity of colistin and tigecycline against CRAB isolates from blood culture of hospitalized patients at Istanbul University Cerrahpasa Medical School hospital., Methods: Between January 2012 and June 2014, a total of 72 CRAB isolates were isolated by conventional methods from blood cultures of patients with bacteremia who were hospitalized in intensive care units and in various departments of the hospital. The isolates were confirmed using a Phoenix automated system. Antibiotic susceptibilities were determined by disk diffusion method and Etest. Molecular detection of resistance genes were screened by multiplex real time polymerase chain reaction (qPCR) and PCR parameters., Results: CRAB isolates were highly resistant to tetracycline (86.1%), trimethoprim/sulfamethoxazole (84.7%), ceftazidime (83.3%), cefepime (81.9%), ciprofloxacin (81.9%), amikacin (75.0%), piperacillin/tazobactam (75.0%), cefotaxime (72.2%), and gentamicin (69.4%). Tigecycline and colistin resistance were not detected. MIC50 and MIC90 of tigecycline (MIC ranges 0.016-1 µg/mL) and colistin (MIC ranges 0.125-1.5 µg/mL) were found to be 0.5 µg/mL and 1 µg/mL, respectively. All isolates were positive for OXA-51 that shows molecular identification of A. baumannii. Fifty-one (70.8%) and 2 (2.8%) of these isolates were positive for OXA-23 and OXA-58 genes, re- spectively., Conclusions: This study indicated the most of the CRAB isolates in our hospital carry the OXA-23 gene. Colistin and tigecycline resistance were not detected. However, significant effort must be done to prevent the spread of OXA-23-producing CRAB-isolates and continuous monitoring of drug resistance is necessary in clinical settings.

Background: We compared the in vitro activities of tigecycline with those of other agents against 97 Streptococcus pneumoniae, 140 Haemophilus influenzae and 54 Moraxella catarrhalis strains isolated in two large university hospitals in Istanbul., Methods: For analysis, the agar dilution method was used., Results: For S. pneumoniae isolates, 32% were not susceptible to penicillin (28.9% intermediate and 3.1% resistant). Cefotaxime, telithromycin, moxifloxacin and linezolid were fully active. Tigecycline had a 90% minimum inhibitory concentration (MIC(90)) of 0.12 microg/ml. For H. influenzae, 8.57% were not susceptible to ampicillin, among which 8 possessed beta-lactamase (5.7%). Four (2.87%) H. influenzae isolates with beta-lactamase-negative and ampicillin-resistant phenotype were found. All isolates were susceptible to ceftriaxone, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin. MIC(90) for tigecycline was 0.5 microg/ml. Of 54 M. catarrhalis isolates, 88.9% possessed beta-lactamase. Tigecycline and fluoroquinolones were highly active (MIC(90) < or =0.12 microg/ml)., Conclusions: Linezolid, telithromycin, newer fluoroquinolones and tigecycline all have excellent in vitro activities against the 3 respiratory pathogens., (Copyright 2009 S. Karger AG, Basel.)

Multidrug-resistant (MDR) Acinetobacter baumannii is one of the most important pathogens in intensive care units related to morbidity and mortality, especially in ventilator-associated pneumonia (VAP). In this study, 80.5% of isolates were MDR. The antimicrobial susceptibilities for 12 different antibiotics of MDR A. baumannii isolated from VAP were tested. Among the MDR A. baumannii isolates, resistance rates were found to be 95.5%, 72.7%, 80.3%, 71.2% and 68.2% for ciprofloxacin, cefepime, imipenem, meropenem and cefoperazone/sulbactam, respectively. Netilmicin resistance was detected in 30.3% of the isolates. Resistance rates for colistin and tigecycline were 0% and 25.8%, respectively. It is obvious that new alternative drugs are needed for the treatment of MDR A. baumannii-related VAP owing to high resistance to carbapenems, quinolones, aminoglycosides and cefoperazone/sulbactam. Although colistin appears to be a good choice, adverse reactions and unavailability of colistin limit its wide usage in Turkey. Tigecycline, which will shortly be introduced commercially in Turkey, is very effective against MDR A. baumannii isolates and shows promising results to solve the problem, however resistance rates should be monitored closely.