Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011-2017.

BACKGROUND: There is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The aim of this study was to evaluate the discontinuation of first ART before and after the availability of better tolerated and less complex regimens by comparing the frequency, reasons and associations with patient characteristics. METHODS: A total of 3019 ART-naive patients registered in the HIV-TR cohort who started ART between Jan 2011 and Feb 2017 were studied. Only the first modification within the first year of treatment for each patient was included in the analyses. Reasons were classified as listed in the coded form in the web-based database. Cumulative incidences were analysed using competing risk function and factors associated with discontinuation of the ART regimen were examined using Cox proportional hazards models and Fine-Gray competing risk regression models. RESULTS: The initial ART regimen was discontinued in 351 out of 3019 eligible patients (11.6%) within the first year. The main reason for discontinuation was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and provider preference (5.4%). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based (aHR = 4.4, [95% CI 3.0-6.4]; p < 0.0001) or protease inhibitor (PI)-based regimens (aHR = 4.3, [95% CI 3.1-6.0]; p < 0.0001) relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017) (aHR = 0.6, [95% CI 0.4-0.9]; p < 0.0001) was less likely to be discontinued. A lower rate of treatment discontinuation for intolerance/toxicity was observed with InSTI-based regimens (2.0%) than with NNRTI- (6.6%) and PI-based regimens (7.5%) (p < 0.001). The percentage of patients who achieved HIV RNA < 200 copies/mL within 12 months of ART initiation was 91% in the ART discontinued group vs. 94% in the continued group (p > 0.05). CONCLUSION: ART discontinuation due to intolerance/toxicity and virologic failure decreased over time. InSTI-based regimens were less likely to be discontinued than PI- and NNRTI-based ART.

International Nosocomial Infection Control Consortium (INICC) national report on device-associated infection rates in 19 cities of Turkey, data summary for 2003-2012.

BACKGROUND: Device-associated healthcare-acquired infections (DA-HAI) pose a threat to patient safety, particularly in the intensive care unit (ICU). We report the results of the International Infection Control Consortium (INICC) study conducted in Turkey from August 2003 through October 2012. METHODS: A DA-HAI surveillance study in 63 adult, paediatric ICUs and neonatal ICUs (NICUs) from 29 hospitals, in 19 cities using the methods and definitions of the U.S. NHSN and INICC methods. RESULTS: We collected prospective data from 94,498 ICU patients for 647,316 bed days. Pooled DA-HAI rates for adult and paediatric ICUs were 11.1 central line-associated bloodstream infections (CLABSIs) per 1000 central line (CL)-days, 21.4 ventilator-associated pneumonias (VAPs) per 1000 mechanical ventilator (MV)-days and 7.5 catheter-associated urinary tract infections (CAUTIs) per 1000 urinary catheter-days. Pooled DA-HAI rates for NICUs were 30 CLABSIs per 1000 CL-days, and 15.8 VAPs per 1000 MV-days. Extra length of stay (LOS) in adult and paediatric ICUs was 19.4 for CLABSI, 8.7 for VAP and 10.1 for CAUTI. Extra LOS in NICUs was 13.1 for patients with CLABSI and 16.2 for patients with VAP. Extra crude mortality was 12% for CLABSI, 19.4% for VAP and 10.5% for CAUTI in ICUs, and 15.4% for CLABSI and 10.5% for VAP in NICUs. Pooled device use (DU) ratios for adult and paediatric ICUs were 0.54 for MV, 0.65 for CL and 0.88 for UC, and 0.12 for MV, and 0.09 for CL in NICUs. The CLABSI rate was 8.5 per 1,000 CL days in the Medical Surgical ICUs included in this study, which is higher than the INICC report rate of 4.9, and more than eight times higher than the NHSN rate of 0.9. Similarly, the VAP and CAUTI rates were higher compared with U.S. NHSN (22.3 vs. 1.1 for VAP; 7.9 vs. 1.2 for CAUTI) and with the INICC report (22.3 vs. 16.5 in VAP; 7.9 vs. 5.3 in CAUTI). CONCLUSIONS: DA-HAI rates and DU ratios in our ICUs were higher than those reported in the INICC global report and in the US NHSN report.

[A case of Crimean-Congo hemorrhagic fever with long incubation period in Kocaeli, Turkey]. / Kocaeli'de Uzun Inkübasyon Süreli Sporadik Kirim-Kongo Kanamali Atesi Olgusu.

Crimean-Congo hemorrhagic fever (CCHF) is a viral hemorrhagic disease with high mortality rate. CCHF is endemic in Central Anatolia and East and Central Black Sea parts of Turkey, however sporadic cases have been detected in the other regions. The incubation period of the disease is between 1-3 days (maximum 12 days). In this report, a very rare CCHF case with a long incubation period of 30 days, was reported. A 40-year-old female patient living in a village of Kocaeli, Turkey was admitted to a health center in June 2010 with the complaints of headache, myalgia, nausea, vomiting, fatigue and fever. Since laboratory results revealed severe thrombocytopenia (18.300/mm3), the patient was referred to the university hospital in Kocaeli. It was learned from her history that she had been working in the garden and removed a tick from the skin of gluteal area a month ago without seeking any medical help. Physical examination of the patient revealed that her general condition was well, oriented and cooperative, body temperature was 36.6°C, pulse 82/minute, trombocyte count 69.400/mm3 and liver enzymes were elevated (ALT: 194 U/L, AST: 499 U/L, GGT: 384 U/L, LDH: 1290 U/L). Petecchial lesions were seen on hard palate and extremities and a hyperemic lesion was detected at the gluteal area where the tick had attached. In-house real-time polymerase chain reaction test for CCHF, performed at Refik Saydam National Public Health Agency, Virology Reference and Research Laboratory, revealed positive result. This case was presented to withdraw attention to a long incubation period CCHF and also of its epidemiological importance since it was the first case in Kocaeli province, Turkey.

[Early detection of methicillin resistance by real-time PCR in staphylococci isolated from blood cultures]. / Kan Kültürlerinde Üreyen Stafilokoklarda Metisilin Direncinin Gerçek Zamanli PCR ile Erken Tanisi

Bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) has a significant morbidity and mortality. The aim of this study was to evaluate the efficiency of real-time polymerase chain reaction (Rt-PCR) targeting nuc and mec genes in the culture extracts of blood culture systems for the early diagnosis of MRSA. A total of 48 samples that gave positive growth signal in BACTEC 9000 MB (BD, USA) and stained as gram-positive cocci, were included in the study. The samples were collected between 2009 and 2010. VITEC 2 (bioMerieux, France) system was used for the identification and antibiotic susceptibility testing of the isolates. According to the culture results, 15 of the isolates were methicillin-resistant coagulase-negative staphylococci (MRCNS), four were MRSA, 14 were methicillin-susceptible coagulase- negative staphylococci (MSCNS) and 15 were methicillin-susceptible S.aureus (MSSA). However, Rt-PCR yielded 17 MRCNS, eight MRSA, 10 MSCNS and 13 MSSA results. Our findings indicated lack of concordance between blood culture and PCR technique. When the blood culture results were accepted as the gold standard for the determination of methicillin resistance, sensitivity, specificity, positive and negative predictive values of Rt-PCR were found as 73%, 62%, 56% and 78%, respectively. In conclusion, in contrast to the expectations, Rt-PCR was not considered as an appropriate method for the detection of MRSA in routine diagnosis.

[Comparison of broth microdilution and E-test methods for the antifungal susceptibility testing of Candida spp. strains isolated from blood cultures]. / Kan kültürlerinden izole edilen Candida spp. suslarinin antifungal ilaçlara karsi duyarliliklarinin belirlenmesinde buyyon mikrodilüsyon ile E-test yöntemlerinin karsilastirilmasi.

The incidence of serious fungal infections, particularly invasive Candida infections exhibit an increasing trend in the last decades since the number of patients receiving immunosuppressive treatment is increasing. This situation eventually results in an increment in resistance to antifungal agents. The aim of this study was to compare the standard broth microdilution (BMD) and E-test methods for antifungal susceptibility testing of Candida species isolated from blood cultures in our hospital, against fluconazole, voriconazole, caspofungin and amphotericin B. A total of 46 Candida strains isolated from the blood cultures by BACTEC 9000 (Becton Dickinson, USA) and identified by conventional techniques and API 20C AUX (BioMerieux, France) during January 2006-December 2007, were included into this study. The identification results of the isolates were as follows: C. albicans (23), C. parapsilosis (10), C. tropicalis (5), C. krusei (3), C. famata (2), C. glabrata (1), C. guilliermondii (1), C. kefyr (1). The antifungal susceptibilities were determined by BMD method described in Clinical and Laboratory Standards Institute M27-A3 document and E-test. Only two isolates (C. albicans and C. globrata) were found to be resistant to fluconazole with E-test but susceptible with BMD. The minimal inhibitory concentration (MIC) values of caspofungin were higher (MIC = 1-2 microg/ml) in C. parapsilosis compared to other Candida species using E-test. Only one C. albicans was resistant to voriconazole by E-test (MIC = 4 microg/ml), but it was susceptible by BMD (MIC = 0.08 microg/ml). Since definite resistance breakpoints do not yet exist for amphotericin B, MIC values were considered for amphotericin B and it was found that all strains had identical low MIC values (< 0.002-0.5). When E-test results were compared with the standard BMD results, MIC values were in agreement 80.4% for fluconazole, 84.7% for amphotericin B, 95.6% for voriconazole and 93.4% for caspofungin. These results indicated that the most frequently isolated Candida species among blood cultures was C. albicans, followed by C. parapsilosis and these isolates had low antifungal resistance rates. When voriconazol and caspofungin susceptibilities were considered, both E-test and BMD susceptibility results were in good aggreement in comparison to fluconazol and amphotericin B. E-test can be considered as a compatible method for the antifungal susceptibility testing of Candida species compared to standard broth microdilution method.

Genotyping of Brucella melitensis by rpoB gene analysis and re-evaluation of conventional serotyping method.

In Turkey, where brucellosis is endemic, a comparison of conventional and molecular genotyping methods has not been published to date. In this study, we investigated the efficacy of single nucleotide polymorphism (SNP) analysis of rpoB gene in the genotyping of Brucella melitensis strains by sequencing. In light of the molecular genotyping method available now in Turkey, the adequacy of serological typing alone should be re-evaluated as a tool for epidemiologic studies of B. melitensis.

Pseudo-outbreak of Serratia marcescens in a tertiary care hospital.

The aim of this study was to describe a pseudo-outbreak due to Serratia marcescens associated with laboratory contamination, and also the epidemiologic and laboratory methods used to determine the source of contamination. An apparent increase in positive culture results for Serratia marcescens was observed in the Clinical Microbiology Laboratory of Kocaeli University Hospital between September and November 2007. An outbreak investigation including retrospective and prospective studies using chart review, environmental sampling and random arbitrary polymorphic DNA-polymerase chain reaction (RAPD-PCR) of randomly selected isolates were performed by the Infection Control Committee. Nine out of 67 strains belonged to a real infection. S. marcescens was also isolated from saline solution in the specimen processing area of the laboratory. It was recognized that the technician has been using the same stock saline solution for processing specimens without changing the injector. RAPD patterns of the clinical isolates were identical to the pattern of saline strain. The contaminated saline solution was discarded, the technician was trained and no additional cases of suspected contamination have been observed. This pseudo-outbreak emphasize the importance of the observation of specimen processing procedures and the training of laboratory workers.

[Analysis of the results of NEQAS international external quality assessment programme for hepatitis B and C virus nucleic acid tests]. / Hepatit B ve C virus nükleik asit testlerinde NEQAS uluslararasi dis kalite kontrol degerlendirme programi sonuçlarinin analizi.

External quality assessment (EQA) has been playing an increasingly important role in the implementation of nucleic acid amplification techniques (PCR) for clinical diagnosis. In this study, the results of HBV-DNA quantification and HCV-RNA detection tests evaluated by United Kingdom National External Quality Assessment Scheme for Microbiology (NEQAS) were analysed and the performance of our laboratory was evaluated. Between April 2006-January 2008, in four different distribution panels including 16 freeze-dried serum and six plasma specimens for HBV-DNA and HCV-RNA testing, respectively, were received. Viral nucleic acids were extracted by magnetic particle technology (NucliSENS-easyMAG, bioMérieux, Boxtel, Holland). HBV-DNA and HCV-RNA tests were performed by Fluorion HBV quantitative v2.0 and Fluorion HCV quantitative v2.1 (lontek AS, Istanbul, Turkey) kits in real-time PCR (iCycler IQ v3.0a - BioRad Laboratories, Hercules, CA, USA) platform. The performance scores of all the quantification tests of HBV-DNA were 2 (completely correct result) and a strong correlation (r= 0.987) between the quantitative HBV data and the target values was found by linear regression analysis. The NEQAS scores of HCV-RNA testing, except for a false negative result (since the viral load in this specimen was very low--79 IU/ml--it was not scored by NEQAS), were 2 in all specimens. The evaluation of the data revealed 100% detection in HBV-DNA and 83.3% detection in HCV-RNA. In conclusion, the results of this study showed high accuracy of HBV quantification in the samples of HBV infected patients under antiviral therapy. However, the analytical sensitivity of HCV-RNA quantitative kit should be improved for the purpose of reliable HCV-RNA results. External quality control panels are important tools for monitoring the quality of diagnostic laboratory tests. Therefore, PCR laboratories should always have EQA in routine procedures.

[Elimination of PCR inhibitors in routine diagnostic real-time PCR assay and results of internal amplification control]. / Rutin gerçek zamanli PCR tani testlerinde PCR inhibitörlerinin eliminasyonu ve internal amplifikasyon kontrol sonuçlari.

Polymerase chain reaction (PCR) inhibitors which can be found in the clinical specimens lead to increased cost of these tests and also cause delay in the results particularly in the routine laboratories. Lysis/dilution methods are effective on the removal of PCR inhibitors and the performance of internal amplification control (IAC). This study was aimed to evaluate the effects of some methods, such as lysis (freezing and thawing) and dilution (1/10) of serum samples, used for the removal of PCR inhibitors, on IAC results. This evaluation was done by investigating the results of 1440 HCV-RNA and 2754 HBV-DNA (Fluorion HCV QNP and HBV QNP; Iontek, Turkey) tests that were performed in our laboratory during January 2005-October 2006 period. The nucleic acid isolation was done by "spin colon" (Qiagen, QIAamp DNA Mini Kit, Germany) and "magnetic particle" (Qiagen, BioRobot EZ1, Germany) technologies and PCR was performed by real-time PCR (iCycler IQ - BioRad Lab., USA). False negative IAC was detected in 211 samples during HCV-RNA tests and correct results were obtained in 66.4% of these when inhibitors were removed by lysis in 121 and by serum dilution in 19 of the samples. For HBV-DNA tests false negative IAC was detected in 15 samples and application of lysis method yielded correct results in 73.3% (11/15) of these. By the application of inhibitor removal methods the rate of false negative IAC decreased from 14.6% to 4.9% (71/1440) in HCV PCR and from 0.5% to 0.1% (4/2754) in HBV PCR. These data indicated that lysis/dilution methods were simple, economical and effective methods that could be used in routine PCR laboratories for the removal of PCR inhibitors and to achieve effective IAC.

Evaluation of clinical, laboratory, and therapeutic features of 145 tularemia cases: the role of quinolones in oropharyngeal tularemia.

Tularemia outbreaks have occurred in various regions of Turkey in recent years. In this study, clinical (145 patients) and laboratory (97 patients) features of patients with oropharyngeal tularemia were evaluated during the tularemia outbreak in the district of Gölcük in Kocaeli, Turkey. We analyzed the risk factors for therapeutic failure and prolonged recovery time, and compared the efficacy of three antibiotic groups, namely aminoglycoside, tetracycline and quinolone. The most common physical sign and laboratory findings in patients were lymphadenopathy (LAP) and increased erythrocyte sedimentation rate, respectively. Treatment failure was observed in 55 of the 145 (38%) patients during one-year follow-up and the most successful results were obtained in the quinolone group. It was determined that antimicrobial therapy initiated 14 days after onset of symptoms was a statistically significiant risk factor, reducing the success rate (p=0.0001, OR=13.10, 95% CI=5.69-30.15) and prolonging the recovery period (p=0.001, OR=3.23, 95% CI=1.63-6.40) in oropharyngeal tularemia cases. These results suggest that antimicrobial treatment should be started early, and quinolones such as moxifloxacin and ciprofloxacin seem to be new alternatives in the treatment of oropharyngeal tularemia.

[A small water-borne tularemia outbreak]. / Su kaynakli küçük bir tularemi salgini.

The aim of this study was to investigate a small tularemia outbreak in a village of Karamürsel county of Kocaeli province (located in North-west part of Turkey), between 22 January - 8 March 2005 and to present the anti-epidemic measures implemented. Following diagnosis of oropharyngeal tularemia in two patients living in the same village, a field investigation was performed at this region. All patients have undergone physical examination. Blood samples and if possible throat swabs and lymph node aspirates were taken from the patients and water samples from the natural spring water suspected to be the source of the infection, were also taken. Cultures were performed from the clinical samples and filtrated water samples. Francisella tularensis antibodies were screened by microagglutination (MA) test in the serum samples of the patients. F. tularensis DNA was investigated in the filtrated water samples by real-time PCR assay. A total of 17 patients were diagnosed as tularemia with their clinical features and MA test results (> or = 1/80). All the patients had oropharyngeal tularemia except one who had ulceroglandular form. The age range of the patients was 27-80 years (mean age: 48 +/- 17 years), and 10 (59%) were female. Weakness (100%), swelling on the neck (94%) and sore throat (88%) were the most common symptoms, whereas cervical lymphadenopathy (94%) was the most frequently seen clinical finding. F. tularensis could not be grown in the cultures, however F. tularensis DNA was detected in the samples of the natural spring water by real time PCR. The patients were treated with streptomycin, ciprofloxacin, or doxycycline, and all the patients have recovered. The outbreak was taken under control after cleaning the spring water tank and chlorination of the water.

[Is serologic screening necessary in the donor bloods for cytomegalovirus seronegative blood transfusion to risky patients?]. / Riskli gruplara sitomegalovirus seronegatif kan transfüzyonu için bagisçi kanlarinda tarama gerekli mi?

Cytomegalovirus (CMV) infections are commonly seen in humans and are usually mild or asymptomatic. However, these infections have significant medical risks in pregnant women, newborns and immunocompromised patients. Seronegative subjects and infants acquire CMV through infected blood products or direct contact with infected people. The use of seronegative blood products for selected patients, as in newborns and/or immunosuppressed patients has vital importance in medical management. Providing seronegative blood in countries where the prevalence of CMV is high (>90%), is difficult since this requires screening of a great number of blood donations. The aim of this study was to detect the CMV seroprevalence among voluntary blood donors in Kocaeli (located at northwestern region of Turkey) and to determine whether the screening procedure was cost-effective. CMV-IgG was investigated by a commercial ELISA method (AXSYM, Abbott, USA) in 1264 blood donors who were voluntarily admitted to donate blood for newborns between January to December 2006. In 1229 (97.2%) of these donors CMV-IgG was found positive while it was negative in 35 (2.8%). It was estimated that CMV-IgG screening was not cost-effective to provide seronegative blood donations because of the high rate of seropositivity in Kocaeli as well as other regions of Turkey, so it would be more favorable to apply alternative methods such as leukocyte reduction.

[Pulmonary nocardiosis with a large solitary cavitary nodule caused by Nocardia cyriacigeorgica in a patient receiving corticosteroid therapy]. / Kortikosteroid tedavisi alan hastada Nocardia cyriacigeorgica'nin neden oldugu soliter kaviter nodül yapan pulmoner nokardiyoz.

Nocardiosis is a rare disease generally caused by members of Nocardia asteroides complex, particularly in immunosupressed patients. Nocardia cyriacigeorgica is a newly described member of this complex. In this article, a case of pulmonary nocardiosis with a large solitary cavitary nodule caused by N. cyriacigeorgica, in a patient receiving corticosteroid therapy was presented. A 29 years old male patient receiving prednisolone for 5 months was admitted to our hospital with fever, cough, right thoracic pain and night sweats. Computed tomography scan of chest demonstrated a large solitary cavitary nodule in the right lower lobe. Gram stained smear of the sputum revealed gram-positive, beaded, branched filamentous bacilli. On the third day of his admission, a catalase positive, oxidase negative and immotile bacilli, compatible with Nocardia spp., were isolated from the sputum sample taken at the day of admission. The isolated bacterium was identified as N. cyriacigeorgica by reference laboratory (Lyon, France). Oral trimethoprim (320 mg/day) and sulfamethoxazole (1600 mg/day) therapy given for three months, resulted in complete cure of the lesion without any sequela. This was the fourth case of pulmonary nocardiosis caused by N. cyriacigeorgica reported from Turkey. Microbiological examination of sputum is the most important tool for the diagnosis. Treatment with appropriate antibiotics may achieve complete cure even in large cavitary lesions. In conclusion, pulmonary nocardiosis should be considered in differential diagnosis of solitary cavitary nodules, especially in immunocompromised patients.

Virulence genes fliC, toxA and phzS are common among Pseudomonas aeruginosa isolates from diabetic foot infections.

BACKGROUND: Outcomes of antibiotic treatment of diabetic foot infections (DFIs) may depend not only on the antimicrobial susceptibility of the aetiologic agents, but also their ability to produce virulence factors. This study aimed to use polymerase chain reaction (PCR) with specific primers to investigate the presence of virulence genes among isolates of Pseudomonas aeruginosa isolates cultured from specimens from diabetic foot and other infections. METHODS: We examined 63 P. aeruginosa isolates from inpatients at two University Hospitals for the presence of 23 known bacterial virulence genes, including lasI, lasR, lasA, lasB, rhll, rhlR, rhlAB, aprA, fliC, toxA, plcH, plcN, ExoS, ExoT, ExoU, ExoY, phzI, phzII, phzM, phzS, pvdA, pilA and pilB. RESULTS: Seven virulence genes (lasl, lasR, lasB, rhll, rhlR, rhlABand Exo T) were present in each isolate. No isolate expressed or presented aprA gene. We found that fliC (p = .01), toxA (p = .041) and phzS (p < .001) were statistically and significantly more common in diabetic foot isolates, while plcH (p < .001) was significantly more common in other infections. CONCLUSIONS: Among clinical isolates of P. aeruginosa from patients with DFIs, three virulence genes that can play important roles in tissue penetration (fliC), tissue damage and survival under anaerobic condition (phzS) and cell death (toxA) were significantly more common than isolates from other infections. The Multilocus sequence typing (MLST) analysis of diabetic foot isolates failed to point/indicate the existence of a specific clone or was not able to characterize/identify a specific clone/clonal complex group. Development of new agents to inhibit the synthesis of these genes may improve outcomes in DFIs treatment.

[Can HBsAg levels guide to differentiate inactive HBsAg carriers from HBeAg negative chronic B hepatitis?]. / Inaktif HBsAg tasiyiciligi ile HBeAg negatif kronik B hepatiti ayiriminda HBsAg düzeyleri yol gösterici olabilir mi?

It is valuable to differentiate the inactive HBsAg carrier state from HBeAg negative chronic B hepatitis (CBH) which develops due to precore or core promoter region mutations in hepatitis B virus (HBV). The aim of this study was to investigate the role of HBsAg S/N (sample rate/index calibrator mean rate) levels in the differentiation of inactive HBsAg carriers from HBeAg negative CBH cases. A total of 134 HBsAg positive patients followed-up in Kocaeli University Medical Faculty hospital between June 2004-September 2005, were included to the study. The patients were classified into four groups according to their serological patterns (Group 1: HBeAg and HBV-DNA negative 34 cases with normal ALT levels; Group 2: HBeAg negative, anti-HBe positive, HBV-DNA >10(5) copies/ml, 36 cases with increased ALT levels; Group 3: HBeAg negative, anti-HBe positive, HBV-DNA 102-10(5) copies/ml, 32 cases with normal ALT levels; Group 4: HBeAg positive, HBV-DNA >10(5) copies/ml, 32 cases with increased ALT levels). The age and gender distributions of the groups were similar. HBV markers have been detected by microparticle enzyme immunoassay (AxSYM System, v3.0, Abbott Laboratories, USA), and viral load were investigated by real-time polymerase chain reaction (iCycler IQ, v3.0a, Bio Rad Laboratories, USA). As a result, the mean HBsAg S/N level in group 2 who were HBeAg negative with a viral load of >10(5) copies/ml, was found significantly higher than group 1 who were inactive HBsAg carriers (285.9+/-78.8 and 214.4+/-108.6, respectively; p<0.05). In contrast there was no statistically significant difference between group 1 (HBV-DNA negative) and group 3 (HBV-DNA <10(5) copies/mL) by means of mean HBsAg S/N levels (214.4+/-108.6 and 216.3+/-57.2, respectively; p>0.05). Although HBsAg levels seem to guide the differentiation of inactive HBsAg carriers from HBeAg negative CBH cases with high viral loads (>10(5) copies/ml), advanced studies are needed to clarify this relationship with the use of quantitative HBsAg measurements (IU/ml) in large patient groups and by performing mutation analysis.

Prevalence, susceptibility profile and proteinase production of yeasts causing vulvovaginitis in Turkish women.

In this study the prevalence of vulvovaginal candidiasis (VVC), antifungal susceptibility and proteinase production of isolated Candida species were investigated. Vaginal swabs were collected from symptomatic women with vulvovaginitis attending the Obstetrics and Gynecology Clinic of Kocaeli University, Turkey. The relation between risk factors, such as pregnancy, diabetes mellitus, antibiotic and corticosteroid use, history of sexually transmitted diseases and contraceptive methods, was recorded. Candida spp. were identified by conventional methods, then evaluated for proteinase secretion in a medium containing casein. Antifungal susceptibility was determined according to the NCCLS microdilution method. The prevalence of women with vulvovaginitis was 35.7% (170/6080) and 16% (28/170) of them were diagnosed as VVC. Candida albicans was the dominant species: 21 (75%), followed by 4 C. glabrata (14%), 2 C. tropicalis (7%), and one C. krusei (3.5%). All isolates were susceptible to fluconazole, itraconazole and amphotericin B, except one C. krusei, one C. glabrata and one C. albicans that were resistant to fluconazole. Proteinase production was determined in 19 (90.5%) C. albicans and in all C. tropicalis isolates. Proteinase activity was not associated with antifungal resistance. No association was found between risk factors and VVC.

Efficacies of caspofungin and a combination of caspofungin and meropenem in the treatment of murine disseminated candidiasis.

Disseminated candidiasis is relatively common in immunocompromised patients. The treatment protocol of these patients usually includes broad-spectrum antibiotics and also emprical antifungals initiated due to unresponsiveness to antibiotics. In this study the efficacies of caspofungin and meropenem - separately and together - in mice with disseminated candidiasis were studied. Immunocompetent mice were infected intravenously with 2x10(6) CFU of Candida albicans. At 24 h postinfection, intraperitoneal therapy was initiated and was continued for 7 days. Therapy groups included those given caspofungin (0.5, 1.25, 5 mg/kg/day), meropenem (20 mg/kg/day), and a combination of the two drugs. The outcome of therapy was evaluated by kidney tissue burden studies and histologic examination. In vitro, drug susceptibilities were tested by checkerboard analysis. Kidney CFU counts showed that mice that had received both drugs had lower residual burdens. Caspofungin was effective at doses of 0.5, 1.25, 5 mg/kg compared to infected untreated controls. In vitro, MICs of caspofungin and meropenem were <0.075 micro g/ml and >64 micro g/ml, respectively. Synergism was observed with the combination. Histopathology showed that the degree of inflammation was 25% less and tubular necrosis was more restricted in combined therapy than monotherapy. The results indicate that concurrent caspofungin and meropenem therapy may be beneficial.

[Low positive anti-HCV microparticle enzyme immunoassay results: do they predict hepatitis C virus infection?]. / Mikropartikül enzim immunoassay ile düsük titrede saptanan anti-HCV pozitifligi hepatit C virus enfeksiyonunun tanisinda kullanilabilir mi?

Antibody screening tests for hepatitis C virus (anti-HCV) can yield false positive results among populations such as Turkey, with a low prevalence of HCV infection. This may lead to the unnecessary use of expensive tests like HCV RNA for confirmation. However, HCV RNA is not always positive in samples with low S/Co (signal to cutoff) ratios. This retrospective study was conducted to determine the frequency of HCV RNA positivity in the samples with low anti-HCV levels. A total of 655 patients who were positive for anti-HCV by microparticle enzyme immunoassay (MEIA; v 3.0, AxSYM System, Abbott Laboratories, USA) and positive for HCV RNA by real-time polymerase chain reaction (PCR; iCycler IQ, v 3.0a, Bio Rad Laboratory, USA) between June, 2002 and November, 2005 were evaluated. Anti-HCV positivity was found in 368 (56%) patients and HCV RNA was not detected in samples with S/Co ratios lower than 3.8. As a result, for the confirmation of the samples yielding low and/or indeterminate grey zone anti-HCV levels, immunoblot methods, retesting of the same sample with another enzyme immunassay or testing of a new sample, would be appropriate and economical prior to use of HCV RNA tests.

Epidemiological and molecular characteristics of meticillin-resistant Staphylococcus aureus in Turkey: A multicentre study.

The aim of this study was to investigate the epidemiological and molecular features of clinical meticillin-resistant Staphylococcus aureus (MRSA) isolates in Turkey. MRSA isolates were collected from six regions of Turkey. The mecA and nuc genes were detected by PCR. Antimicrobial susceptibilities were determined by the disk diffusion method. Staphylococcal cassette chromosome mec (SCCmec) and staphylococcal protein A (spa) typing were performed by the sequencing method for 270 randomly selected MRSA isolates. The US Centers for Disease Control and Prevention (CDC) definition was used for epidemiological diagnosis of community-associated MRSA (CA-MRSA). Resistance rates of MRSA to ciprofloxacin, gentamicin, clindamycin, erythromycin, rifampicin, trimethoprim/sulfamethoxazole and tetracycline were 93.4%, 81.2%, 38.5%, 57.8%, 93.9%, 1.1% and 93.1%, respectively. The most frequent SCCmec type was SCCmec III (91.1%). SCCmec type IV was found in 5.2% of the isolates. The most frequent spa type was t030 (81.1%). Five isolates were CA-MRSA if only the epidemiological definition was used (5/725; 0.7%). Two isolates were defined as CA-MRSA both by epidemiological features and SCCmec typing (2/270; 0.7%). Of 14 SCCmec type IV isolates, 12 were not defined as CA-MRSA by epidemiological features. In conclusion, this is the most comprehensive multicentre study in Turkey investigating MRSA using both epidemiological and genotypic features. The CA-MRSA rate is low in Turkey. Combined use of epidemiological and genotypic methods is the most accurate approach for the diagnosis of CA-MRSA.

HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey.

HIV-1 replication is rapid and highly error-prone. Transmission of a drug-resistant HIV-1 strain is possible and occurs within the HIV-1-infected population. In this study, we aimed to determine the prevalence of transmitted drug resistance mutations (TDRMs) in 1,306 newly diagnosed untreated HIV-1-infected patients from 21 cities across six regions of Turkey between 2010 and 2015. TDRMs were identified according to the criteria provided by the World Health Organization's 2009 list of surveillance drug resistance mutations. The HIV-1 TDRM prevalence was 10.1% (133/1,306) in Turkey. Primary drug resistance mutations (K65R, M184V) and thymidine analogue-associated mutations (TAMs) were evaluated together as nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations. NRTI TDRMs were found in 8.1% (107/1,306) of patients. However, TAMs were divided into three categories and M41L, L210W, and T215Y mutations were found for TAM1 in 97 (7.4%) patients, D67N, K70R, K219E/Q/N/R, T215F, and T215C/D/S mutations were detected for TAM2 in 52 (3.9%) patients, and M41L + K219N and M41L + T215C/D/S mutations were detected for the TAM1 + TAM2 profile in 22 (1.7%) patients, respectively. Nonnucleoside reverse transcriptase inhibitor-associated TDRMs were detected in 3.3% (44/1,306) of patients (L100I, K101E/P, K103N/S, V179F, Y188H/L/M, Y181I/C, and G190A/E/S) and TDRMs to protease inhibitors were detected in 2.3% (30/1,306) of patients (M46L, I50V, I54V, Q58E, L76V, V82A/C/L/T, N83D, I84V, and L90M). In conclusion, long-term and large-scale monitoring of regional levels of HIV-1 TDRMs informs treatment guidelines and provides feedback on the success of HIV-1 prevention and treatment efforts.