Faruk Karakecili

In vitro Activity of Colistin in Combination with Tigecycline against Carbapenem-Resistant Acinetobacter baumannii Strains Isolated from Patients with Ventilator-Associated Pneumonia.

Objective: This study investigated the minimum inhibitory concentration (MIC) values and in vitro activity of colistin in combination with tigecycline against carbapenem-resistant Acinetobacter baumannii strains isolated from patients with ventilator-associated pneumonia (VAP) using the E-test method. Methods: A total of 40 A. baumannii strains, identified using the Phoenix Automated Microbiology System (Becton, Dickinson and Co., Franklin Lakes, NJ, USA) by conventional methods, were included in this study. Pulsed-field gel electrophoresis was performed to examine the clonal relationships between isolates. The carbapenem resistance of the strains to colistin and tigecycline was assessed using the E-test method (Liofilchem, Roseto Degli Abruzzi, Italy). The in vitro activity of colistin in combination with tigecycline was evaluated using the fractional inhibitor concentration (FIC) index. Results: While only 1 of 40 A. baumannii strains was determined to be colistin resistant, 6 were tigecycline resistant. The MIC50, MIC90, and MIC intervals of the A. baumannii strains were 0.19, 1.5, and 0.064‒4 μg/ml for colistin and 1, 8, and 0.094‒256 μg/ml for tigecycline, respectively. No synergistic effect was observed using the FIC index; 8 strains exhibited an indifferent effect and 32 exhibited an antagonist effect. Three of the six strains that were resistant to tigecycline were indifferent; the remaining three were antagonistic. The colistin-resistant strain also exhibited an antagonist effect. Conclusion: In contrast to their synergistic effect against carbapenem-resistant A. baumannii isolates, colistin and tigecycline were highly antagonistic to carbapenem-resistant A. baumannii strains isolated from patients with VAP when the drugs were administered together. Therefore, alternative treatment options should be used during the treatment of VAP attributed to A. baumannii.

Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C

BACKGROUND Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. MATERIALS AND METHODS 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. RESULTS In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. CONCLUSION We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment.

Asymmetrical Dimethylarginine Levels in Hepatitis B Virus-Positive Patients

Background High asymmetrical dimethylarginine (ADMA) levels have been associated with endothelial dysfunction and contribute to the development of several diseases. However, data on the relationship between hepatitis B virus (HBV) and ADMA are limited. The aim of our study was to explore the relationship between ADMA and HBV by comparing the ADMA levels in patients with chronic active hepatitis B (CHB), inactive HBV carriers (carriers), and healthy volunteers (controls). Methods The participants were divided into three groups: 90 patients with CHB, 90 HBV carriers, and 90 controls. Serum ADMA levels were quantified using an ELISA kit (Cusabio, Wuhan, China). The data were analyzed using an ANOVA or the Kruskal-Wallis test as appropriate, with P<0.05 considered significant. Results Serum ADMA levels were significantly higher in patients with CHB (228.35±91.10 ng/mL) than in HBV carriers (207.80±75.80 ng/mL) and controls (207.61±89.10 ng/mL) (P=0.049). The clinical scores of the patients were positively correlated with ADMA levels. Conclusions The elevated serum ADMA levels in patients with CHB confirm that HBV plays a role in vasculitis. Further investigation of the mechanisms contributing to the high levels of ADMA in CHB may contribute toward development of new treatment modalities.