Publications by authors named "Bilgül Mete"

61 Publications

Clinical and microbiological characteristics of Aeromonas bacteremia in Turkey.

Acta Microbiol Immunol Hung 2021 Jun 16. Epub 2021 Jun 16.

5Department of Infectious Disease, Medical School of Cerrahpasa, Istanbul University, İstanbul, Turkey.

We investigated the cases with Aeromonas bacteremia in terms of clinical and microbiological characteristics, underlying disease and mortality rates. Patients with positive blood cultures were included in this research. Aeromonas bacteremia was diagnosed as at least one positive blood culture for Aeromonas species. The bacteremia was defined as community origin if the onset was in the community or within 72 hours of hospital admission. The others were considered as nosocomial. All bacteria were defined as Aeromonas with conventional method. Species identification was verified by VITEK system. Antibiotic susceptibility tests were analyzed with the disc diffusion, E-test method or VITEK system. Thirty-three patients were diagnosed with bacteremia due to Aeromonas spp. Hematologic and solid tumors were the leading underlying conditions, followed by cirrhosis. Two patients (6%) had community-acquired infections. Aeromonas hydrophila was the most common isolated bacterium. The crude mortality rate was 36%. 12 patients died and 6 deaths and 4 deaths were detected in patients with bacteremia caused by A. hydrophila and Aeromonas sobria respectively. All strains were resistant to ampicillin and more than 90% of the strains were susceptible to trimethoprim-sulfamethoxazole, fluoroquinolone, third generation cephalosporins, and carbapenems. Aeromonas sp. is not a frequent cause of bacteremia however, it may lead to high mortality rates, especially in the immunocompromised hosts and patients with liver cirrhosis. Nosocomial Aeromonas bacteremia is not uncommon in these populations. Broad-spectrum cephalosporins, piperacillin-tazobactam, fluoroquinolones, and carbapenems remain as effective antimicrobial agents for therapy of Aeromonas bacteremia.
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http://dx.doi.org/10.1556/030.2021.01449DOI Listing
June 2021

Tocilizumab in COVID-19: The Cerrahpaşa-PREDICT score.

J Infect Chemother 2021 May 12. Epub 2021 May 12.

Department of Infectious Diseases and Clinical Microbiology, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey.

Background: Cytokine release syndrome (CRS), characterized by overproduction of proinflammatory cytokines in the course of severe coronavirus disease 2019 (COVID-19), has been suggested as the major cause of mortality. Tocilizumab, a recombinant humanized monoclonal antibody against human IL-6 receptor, poses a therapeutic option for the treatment of CRS leading to severe acute respiratory syndrome in coronavirus-2 (SARS-CoV-2) infection.

Methods: We performed a single-center retrospective study to reveal the outcome of COVID-19 patients on tocilizumab and proposed "the Cerrahpaşa-PREDICT score", a new clinical scoring system using clinical and laboratory parameters that would help predicting the 28-day mortality of COVID-19 patients receiving tocilizumab.

Results: Eighty-seven patients (median age: 59 years) were included of whom 75.8% were male. Tocilizumab use significantly improved clinical and laboratory parameters. The 28-day mortality rate on tocilizumab was 16.1%. The Cerrahpaşa-PREDICT score, consisting of platelet counts, procalcitonin, D-dimer levels, SOR and the time from symptom onset to tocilizumab administration had a positive predictive value of 94.5% and negative predictive value of 92.9% for anticipating 28-day mortality.

Conclusions: Severe COVID-19 should closely be monitored for the signs of hyperinflammation. We showed that administration of tocilizumab early in the course of the disease (prior to ICU admission) resulted in a favorable outcome. Close monitoring usually aids identifying patients who would benefit from tocilizumab. In this regard, the Cerrahpaşa-PREDICT score might serve as a practical tool for estimating the 28-day mortality in COVID-19 patients who received tocilizumab and would facilitate timely recognition of fatal cases to be evaluated for other therapeutic options.
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http://dx.doi.org/10.1016/j.jiac.2021.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114762PMC
May 2021

Colistin resistance increases 28-day mortality in bloodstream infections due to carbapenem-resistant Klebsiella pneumoniae.

Eur J Clin Microbiol Infect Dis 2021 May 8. Epub 2021 May 8.

Istanbul Universitesi-Cerrahpasa, Cerrahpasa Faculty of Medicine, Cerrahpasa Tip Fakultesi, İstanbul, Turkey.

Mortality due to K. pneumoniae bacteremia is on rise, particularly in regions with high rates of carbapenem and colistin resistance. We aimed to define risk factors for colistin resistance and its impact on mortality. Patients diagnosed with "carbapenem-resistant K. pneumoniae (CRKp)" bacteremia between 2014 and 2018 were divided into two groups as "colistin susceptible (ColS)" and "colistin resistant (ColR)" based on broth microdilution method. Retrospective case-control study was conducted to compare characteristics and outcomes. Multiple logistic regression model was used to define independent risk factors for acquired colistin resistance and Cox proportional hazard model for 28-day mortality. A total of 82 patients (39 ColS and 43 ColR) were included. Mean age was 61.5 years, and 50 (61%) were male. Colistin resistance was significantly increased with duration of hospital stay (p = 0.007) and prior colistin use (p = 0.007). Overall, the 28-day mortality rate was 66%. Age (p = 0.014) and colistin resistance significantly increased 28-day (p = 0.009) mortality. Microbiological response to treatment within 7 days favors survival. PFGE analysis revealed an outbreak with K. pneumoniae ST78 and ST45 clones. Patients treated with combined antimicrobials had significantly lower 28-day mortality (p = 0.045) in comparison to monotherapy. However, types of combinations did not show significant superiority on each other. Colistin resistance increases 28-day mortality in CRKp bacteremia. Although combined regimens are more effective than monotherapy, existing antibacterial combinations have no apparent superiority to each other. New treatment options are pivotal.
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http://dx.doi.org/10.1007/s10096-020-04124-yDOI Listing
May 2021

The role of quantitative HBsAg in patients with HBV DNA between 2000-20,000 IU/ml.

Wien Klin Wochenschr 2021 Jul 29;133(13-14):647-653. Epub 2021 Apr 29.

Department of Infectious Disease, Medical School of Cerrahpasa, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Aims: We aimed to determine the contribution of quantitative HBsAg in differentiating chronic infections from chronic hepatitis in HBeAg negative patients with HBV DNA 2000-20,000 IU/ml.

Material And Methods: A total of 79 untreated HBeAg negative patients were included. Patients were divided into 3 groups based on HBV DNA levels: group 1 (HBV DNA ≤ 2000 IU/ml), group 2 (HBV DNA: 2000-20,000 IU/ml) and group 3 (HBV DNA > 20,000 IU/ml). We collected serum from all patients for quantitative HBsAg analysis. We compared serum quantitative HBsAg levels with biochemical parameters, HBV DNA and liver biopsy results.

Results: In this study 46 patients were female and the mean age was 42 years. Serum quantitative HBsAg levels were found to be significantly lower in chronic infections compared with chronic hepatitis. There was a positive correlation between quantitative HBsAg and HBV DNA, ALT (alanine aminotransferase), HAI score (histological activity index), fibrosis score and disease stage. The cut-off level of quantitative HBsAg was determined as 4425 IU/ml to differentiate chronic infection from chronic hepatitis. With the test specificity of 95%, we found quantitative HBsAg cut-off values 1026 IU/ml and 20,346 IU/ml for the diagnosis of chronic infection and chronic hepatitis, respectively.

Conclusion: Our study suggests that the quantitative HBsAg ≤ 1000 IU/ml limit value might be used for the diagnosis of chronic infection not only in HBV DNA ≤ 2000 IU/ml but also in patients with HBV DNA between 2000-20,000 IU/ml. In addition, antiviral treatment could be considered in patients with quantitative HBsAg > 20,000 IU/ml and HBV DNA > 2000 IU/ml without further examinations such as liver biopsy.
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http://dx.doi.org/10.1007/s00508-021-01854-7DOI Listing
July 2021

The effect of methotrexate monotherapy on treatment-resistant idiopathic granulomatous mastitis patients.

Surgeon 2021 Apr 6. Epub 2021 Apr 6.

Istanbul University-Cerrahpasa, Cerrahpaşa Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Turkey. Electronic address:

Background: Idiopathic granulomatous mastitis (IGM) is a disease of unknown etiology, involving a chronic inflammatory process, characterized by noncaseating granuloma formation. IGM can mimic a tumor clinically and radiologically. Since we are a tertiary referral center, most of our patients (n = 56, 87.5%) are secondary admissions who have previously had antibiotics and steroid treatments; therefore, we accept these patients as resistant cases. Here, we aim to present our single-center series of 64 patients with resistant IGM who underwent methotrexate monotherapy. To the best of our knowledge, our study includes the highest number of patients described in the literature with IGM who have undergone this treatment.

Methods: This study included 64 patients, 56 of which were resistant cases, diagnosed with IGM between January 2013 and January 2020 at Istanbul University Cerrahpasa, Cerrahpasa Medical Faculty, General Surgery Breast Outpatient Clinic that were followed-up at least once. These patients were administered oral methotrexate monotherapy 15 mg/week for 24 weeks, and in relapsed cases, the treatment was up to 20 mg/week for 1 year. Folic acid 10 mg/week was given as a supplement to all patients.

Results: Complete recovery was observed in 52 (81.25%) of the 64 patients. Follow-up was discontinued by 4 patients. The dose was increased and the duration of treatment was extended up to 1 year when relapse was observed in 8 patients and complete response was then obtained in these cases. Only 3 patients (4.69%) experienced side effects and were switched to subcutaneous treatment due to nausea.

Conclusion: Considering the high patient compliance, low recurrence, minimal side effects, and overall success of the treatment, we believe that methotrexate monotherapy may be used in treatment-resistant IGM patients and may also be the first choice for first-line treatment in the future.
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http://dx.doi.org/10.1016/j.surge.2021.03.001DOI Listing
April 2021

Candida auris Fungemia and a local spread taken under control with infection control measures: First report from Turkey.

Indian J Med Microbiol 2021 Apr 27;39(2):228-230. Epub 2021 Mar 27.

Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey. Electronic address:

Candidaauris, draws attention as a new emerging antifungal resistant pathogen, leading to healthcare-associated infections and outbreaks. This is the first report of C. auris fungemia in a 81-year-old patient, confirmed by sequential analysis, from Turkey. Although the source of the isolate could not be identified, its spread in the hospital has been taken under control by effective infection control measures.
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http://dx.doi.org/10.1016/j.ijmmb.2021.03.007DOI Listing
April 2021

Efficacy and safety of co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-positive patients: real-world data.

Int J STD AIDS 2021 May 18;32(6):562-569. Epub 2021 Feb 18.

Department of Infectious Diseases and Clinical Microbiology, Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.

Objectives: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a recommended and widely used regimen for HIV infection. In this study, we aimed to determine the efficacy and safety of E/C/F/TAF in people living with HIV (PLWH), who are either treatment-naïve or switched from any tenofovir disoproxil fumarate-containing regimen. For switched patients, we aimed to determine the impact of switching from tenofovir disoproxil fumarate (TDF) to TAF on lipid profile and kidney functions.

Methods: ACTHIV-IST Study Group produced a database, and five dedicated HIV centres in Istanbul entered data of PLWH who switched from any TDF-containing regimen to E/C/F/TAF and treatment-naïve patients who were initiated with the E/C/F/TAF regimen between January 2017 and December 2019. Clinical findings, viral parameters, lipid studies, renal function tests, adverse events and adherence to the treatment were recorded in this prospective observational study.

Results: The study included a total of 614 switched and treatment-naïve patients. Of 430 treatment-experienced patients, 89% (382) were men, and the mean age was 42 ± 12 years. Among them, 47% (181/382) self-identified as men who have sex with men (MSM). The median duration of HIV diagnosis was 54 ± 29 months. The median duration of E/C/F/TAF use was 20 ± 36 months and that of previous treatment was 23 ± 18 months. HIV-RNA was undetectable at baseline and month 12 in 84.1% (360/428) and 86.1% (328/381) of patients, respectively ( > 0.05). Mean CD4 counts were 708 ± 287 cells/µL and 802 ± 305 cells/µL at baseline and month 12, respectively ( < 0.001). Serum creatinine levels remained stable during the treatment period. Mean total cholesterol levels at baseline and month 12 were 172 and 211 mg/dL ( < 0.01), LDL-cholesterol 104 and 138 mg/dL ( < 0.01), HDL-cholesterol 39 and 49 mg/dL ( < 0.01) and triglycerides 134 and 174 mg/dL ( < 0.01), respectively. The treatment was generally well tolerated. Eight patients discontinued the therapy (drug interaction: 3; lost to follow-up: 1; pregnancy: 1; pulmonary tuberculosis: 1; side effect: 1; patient's decision: 1). Of 184 treatment-naïve patients, 88% (162) were men, and the mean age was 36.5± 12 years. Among them, 50% (81/162) self-identified as MSM. The mean duration of HIV infection was 21.6 ± 17.1 months. The mean duration of E/C/F/TAF use was 16 ± 4 months. HIV-RNA was undetectable at baseline and month 12 in 1% and 89.1% of patients, respectively. Mean CD4 counts at baseline and month 12 were 469 ± 223 cells/µL and 740 ± 298 cells/µL, respectively. During the treatment period, creatinine levels remained stable. Total cholesterol, LDL-cholesterol, triglyceride and also HDL-cholesterol levels increased. Mean total cholesterol levels at baseline and month 12 were 167 and 211 mg/dL ( < 0.01), LDL-cholesterol 108 and 143 mg/dL ( < 0.01), HDL-cholesterol 41 and 47 mg/dL ( < 0.01) and triglycerides 136 and 172 mg/dL, respectively ( < 0.01). The treatment was generally well tolerated. Three patients discontinued the therapy (drug interaction: 1; non-responder: 1; patient's decision: 1).

Conclusion: Starting with or switching to E/C/F/TAF in PLWH effectively suppresses HIV infection, is associated with an increase in CD4 cell count and is well tolerated in a real-life setting. Renal functions remained stable during the treatment. E/C/F/TAF use was associated with an increase in LDL-cholesterol and triglyceride levels along with an increase in HDL-cholesterol levels.
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http://dx.doi.org/10.1177/0956462420983692DOI Listing
May 2021

Change in species distribution and antifungal susceptibility of candidemias in an intensive care unit of a university hospital (10-year experience).

Eur J Clin Microbiol Infect Dis 2021 Feb 15;40(2):325-333. Epub 2020 Sep 15.

Department of Infectious Diseases and Clinical Microbiology, Medical Faculty, Istanbul Medipol University, Istanbul, Turkey.

Candidemia is a nosocomial infection mostly found in critically ill patients. Our objectives were to evaluate the change in distribution and resistance profile of Candida spp. isolated from candidemic patients in our intensive care unit over two 5-year periods spanning 15 years and to evaluate the risk factors. Records from the microbiology laboratory were obtained, from January 2004 to December 2008 and from January 2013 to December 2017, retrospectively. Antifungal susceptibility was performed by E-test and evaluated according to EUCAST breakpoints. A total of 210 candidemia cases occurred; 238 Candida spp. were isolated in 197 patients (58.8% male; mean age, 59.2 ± 19.6 years). The most predominant risk factor was central venous catheter use. Species distribution rates were 32%, 28%, 17%, and 11% for C. albicans (n = 76), C. parapsilosis (n = 67), C. glabrata (n = 40), and C. tropicalis (n = 27), respectively. Resistance rate to anidulafungin was high in C. parapsilosis over both periods and increased to 73% in the second period. Fluconazole showed a remarkable decrease for susceptibility in C. parapsilosis (94 to 49%). The prevalence of MDR C. parapsilosis (6%/33%) and C. glabrata (0%/44%) increased in the second period. We observed a predominance of non-albicans Candida spp., with C. parapsilosis being the most frequent and C. glabrata infections presenting with the highest mortality. High level of echinocandin resistance in C. parapsilosis and increasing prevalences of MDR C. parapsilosis and C. glabrata seem emerging challenges in our institution.
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http://dx.doi.org/10.1007/s10096-020-03994-6DOI Listing
February 2021

Risk factors for development of vancomycin-resistant enterococcal bacteremia among VRE colonizers : A retrospective case control study.

Wien Klin Wochenschr 2021 May 10;133(9-10):478-483. Epub 2020 Sep 10.

Department of Infectious Disease, Medical School of Cerrahpasa, Istanbul University, Istanbul, Turkey.

Aims: We aimed to determine the proportion of vancomycin-resistant enterococci (VRE) colonized patients among all inpatients who later developed VRE bacteremia during hospital stay and to identify the risk factors for VRE bacteremia at a tertiary hospital.

Material And Methods: Patients with positive rectal screening or any clinically significant positive culture results for VRE were included in 1‑year follow-up. Colonization with VRE was defined as a positive culture (rectal, stool, urinary) for VRE without infection and VRE bacteremia was defined as positive blood culture if the signs and symptoms were compatible with infection. To determine the risk factors for VRE bacteremia among VRE colonized patients, a retrospective case control study was performed. The two groups were compared in terms of variables previously defined as risk factors in the literature.

Results: Of 947 positive samples, 17 VRE bacteremia were included in the analysis. Cephalosporin use for more than 3 days within 3 months was a significant risk factor for bacteremia (p = 0.008). Prior use of carbapenems was found to be statistically significant for bacteremia (p = 0.007). In multivariate analyses the use of carbapenems and cephalosporins was an independent risk factor for developing bacteremia among VRE colonizers (odds ratio, OR, 6.67; 95% confidence interval, CI, 1.30-34; p = 0.022 and OR 4.32, 95% CI 1.23-15; p = 0.022, respectively).

Conclusion: A VRE colonization in patients receiving broad-spectrum beta-lactam antibiotics including carbapenems and cephalosporins may result in bacteremia. It is possible to keep mortality at very low levels in VRE bacteremia with effective infection control measures, rapid infectious diseases consultation and rational antimicrobial treatment based on current epidemiological data.
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http://dx.doi.org/10.1007/s00508-020-01733-7DOI Listing
May 2021

Kidney function on admission predicts in-hospital mortality in COVID-19.

PLoS One 2020 3;15(9):e0238680. Epub 2020 Sep 3.

Department of Nephrology, Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, Istanbul, Turkey.

Background: Recent data have suggested the presence of a reciprocal relationship between COVID-19 and kidney function. To date, most studies have focused on the effect of COVID-19 on kidney function, whereas data regarding kidney function on the COVID-19 prognosis is scarce. Therefore, in this study, we aimed to investigate the association between eGFR on admission and the mortality rate of COVID-19.

Methods: We recruited 336 adult consecutive patients (male: 57.1%, mean age: 55.0±16.0 years) that were hospitalized with the diagnosis of COVID-19 in a tertiary care university hospital. Data were collected from the electronic health records of the hospital. On admission, eGFR was calculated using the CKD-EPI formula. Acute kidney injury was defined according to the KDIGO criteria. Binary logistic regression and Cox regression analyses were used to assess the relationship between eGFR on admission and in-hospital mortality of COVID-19.

Results: Baseline eGFR was under 60 mL/min/1.73m2 in 61 patients (18.2%). Acute kidney injury occurred in 29.2% of the patients. In-hospital mortality rate was calculated as 12.8%. Age-adjusted and multivariate logistic regression analysis (p: 0.005, odds ratio: 0.974, CI: 0.956-0.992) showed that baseline eGFR was independently associated with mortality. Additionally, age-adjusted Cox regression analysis revealed a higher mortality rate in patients with an eGFR under 60 mL/min/1.73m2.

Conclusions: On admission eGFR seems to be a prognostic marker for mortality in patients with COVID-19. We recommend that eGFR be measured in all patients on admission and used as an additional tool for risk stratification. Close follow-up should be warranted in patients with a reduced eGFR.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238680PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470363PMC
September 2020

An eleven-year cohort of bloodstream infections in 552 febrile neutropenic patients: resistance profiles of Gram-negative bacteria as a predictor of mortality.

Ann Hematol 2020 Aug 20;99(8):1925-1932. Epub 2020 Jun 20.

Department of Infectious Diseases and Clinical Microbiology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, 34098, Istanbul, Turkey.

Antimicrobial stewardship is of major importance in patients with febrile neutropenia (FN). In this study, we aimed to investigate the trends in resistance and the relationship with mortality rates in patients with FN. The single-center surveillance data of inpatients with FN and diagnosed as microbiologically confirmed bloodstream infections (BSIs) between 2006 and 2016 were reviewed retrospectively. A total of 950 episodes in 552 patients with BSIs were analyzed. Of whom, 55.9% were male, the median age was 43 years, and 35.6% had acute myeloid leukemia. In total, 1016 microorganisms were isolated from blood cultures. Gram-negatives accounted for 42.4% (n = 403) of the episodes. Among Gram-negatives, Enterobacteriaceae accounted for 346 (86%) (E. coli, n = 197; 34% extended-spectrum β-lactamases (ESBL) producers, and Klebsiella spp., n = 120; 48.3% ESBL producers). Also, 24 (20.0%) of Klebsiella spp. had carbapenemase activity. There were 6 (5.0%) colistin-resistant Klebsiella spp. Thirteen (26.5%) of Pseudomonas spp. and 17 (60.7%) of Acinetobacter spp. had carbapenemase activity. There were 2 (5.6%) colistin-resistant Acinetobacter spp. The 30-day mortality rates were 12.0%, 21.5%, 34.6%, and 29.0% in BSIs due to Gram-positive, Gram-negative bacterial, fungal, and polymicrobial etiology respectively (p = 0.001). BSIs with ESBL-producing (p = 0.001) isolates, carbapenem (p < 0.001), and colistin-resistant isolates (p < 0.001) were associated with increased mortality risk. The tremendous rise in resistance rates among Gram-negatives is dreadfully related to increasing mortality and leads to sharp shifts toward extreme restrictions of unnecessary antibiotic uses. Antimicrobial stewardship in patients with FN requires vigilance and tailoring of treatment upon local surveillance data.
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http://dx.doi.org/10.1007/s00277-020-04144-wDOI Listing
August 2020

Prevalence and mortality of cancer among people living with HIV and AIDS patients: a large cohort study in Turkey.

East Mediterr Health J 2020 Mar 24;26(3):276-282. Epub 2020 Mar 24.

Istanbul University, Cerrahpasa Medical School, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey.

Background: Cancer is responsible for elevated human immunodeficiency virus (HIV)-related mortality but there are insufficient data about cancer in HIV-positive patients in Turkey.

Aims: We aimed to investigate the prevalence and mortality of cancer among people living with HIVand AIDS patients in Istanbul, Turkey.

Methods: Between January 1998 and December 2016, people living with HIVand AIDS patients were enrolled in this study by the ACTHIV-IST Study Group, which consists of 5 centres to follow-up HIV-positive patients in Istanbul. The cancer diagnoses included AIDS-defining cancers (ADCs) and non AIDS-defining cancers (NADCs).

Results: Among 1872 patients, 37 (1.9%) were diagnosed with concurrent cancer. Eleven patients were diagnosed during follow-up; the prevalence of cancer among people living with HIVand AIDS patients was 2.6%. Among 48 cancer patients, 35 patients had ADCs, and 32 of them were diagnosed at their first hospital admission. There were 1007 late presenters and 39 of them had cancer (29 were ADCs). The most prevalent NADCs were gastrointestinal, genitourinary, and pulmonary cancers. NADCs were mostly diagnosed during follow-up of patients. The mortality of this group was significantly higher than that of patients with ADCs (53.9% vs 22.9%).

Conclusions: These results indicate the importance of cancer screening at diagnosis and during follow-up of HIV infection. A detailed physical examination contributes to diagnosis of the most prevalent ADCs (Kaposi's sarcoma and non-Hodgkin's lymphoma), especially in late presenters. For NADCs, individual risk factors should be considered.
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http://dx.doi.org/10.26719/emhj.19.030DOI Listing
March 2020

A prospective pharmacovigilance study in the infectious diseases unit of a tertiary care hospital.

J Infect Dev Ctries 2019 07 31;13(7):649-655. Epub 2019 Jul 31.

Infectious Diseases and Clinical Microbiology Department, Istanbul Medipol University Medical Faculty, Istanbul, Turkey.

Introduction: The frequency, causality, severity, preventability and risk factors of ADRs (adverse drug reactions) in infectious disease units are not well defined in the literature. Thus, the aim of this study was to determine the characteristics of the ADRs encountered in an infectious disease unit of a tertiary teaching hospital.

Methodology: The patients who were admitted to the infectious disease unit of a tertiary teaching hospital longer than 24 hours between January and December of 2016 were followed prospectively. Patients were observed and questioned for any sign of ADRs. The proportion of ADRs and patient characteristics were investigated. Causality was evaluated by the Naranjo algorithm, severity was determined using the Hartwig classification, and preventability was assessed using the Schumock and Thornton scale.

Results: 210 patients were admitted to the unit during the study period, of whom 44 patients (20.9%) experienced 51 ADRs. 5.9% of ADRs were found to be serious according to the Hartwig severity classification. In addition, 88.1% of ADRs were not preventable. The most frequently detected ADR was skin and subcutaneous tissue reactions (33.3%), and systemic antimicrobials were the most common type of drugs that caused an ADR. Prolonged hospitalization (p < 0.001) and usage of an increased number of drugs (p < 0.001) were found to be significant risk factors for ADR development.

Conclusions: Prolonged hospital stay and polypharmacy are significant risk factors that increase the incidence of ADRs in infectious disease units. The likelihood of unavoidable ADRs should arouse the attention of clinicians when prescribing antimicrobials.
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http://dx.doi.org/10.3855/jidc.11503DOI Listing
July 2019

HIV care in Istanbul, Turkey: How far is it from the UNAIDS 90-90-90 targets?

Int J STD AIDS 2019 11 15;30(13):1298-1303. Epub 2019 Nov 15.

Department of Infectious Diseases and Clinical Microbiology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey.

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http://dx.doi.org/10.1177/0956462419866342DOI Listing
November 2019

Late presentation among patients with human immunodeficiency virus infection in Turkey.

Cent Eur J Public Health 2019 Sep;27(3):229-234

Department of Infectious Diseases and Clinical Microbiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.

Objective: Late presentation of the patients with human immunodeficiency virus (HIV) infection is associated with less favourable treatment responses, more accelerated clinical progression, and a higher mortality risk. Although HIV prevalence is low in Turkey, it is steadily increasing and the information about late presentation among HIV-positives is limited. We aimed to analyze the status of late presentation among HIV-positive patients in Turkey.

Methods: All newly diagnosed HIV/AIDS patients from 2003 to 2016 were enrolled in this study by five dedicated centres in Istanbul, Turkey. Demographic data, CD4+ counts, and HIV RNA were collected from medical records and were transferred to a HIV database system. Late pre- sentation was defined as presentation for care with a CD4 count < 350 cells/mm or presentation with an AIDS-defining event, regardless of the CD4 cell count. A medical literature search was done for the analysis of late presentation in Turkey.

Results: The cohort included 1,673 patients (1,440 males, median age 35 years). Among them, 847 (50.6%) had an early diagnosis, with a CD count of more than 350 cells/mm. The remaining 826 were late presenters. Among late presenters, 427 (25.5% of all, 51.7% of late presenters) presented with advanced HIV disease. Late presenters were more elderly and less educated. The gender seemed comparable between groups. Late presentation was more likely among married patients. Early presenters were more likely among homosexuals, those diagnosed in screening studies, and in lower HIV-RNA viral load category. There has been a decreasing trend among late presenters in 2011-2016 when compared to 2003-2011 period.

Conclusion: Current data suggest that half of HIV-infected patients present late in Turkey. In our cohort, those presented late were more elderly, less educated, married and had heterosexual intercourse. On admission, late presenters had more HIV-related diseases and were more likely in higher HIV-RNA category. In the cohort, men having sex with men were less likely late presenters. Efforts to reduce the proportion of late presentation are essential for almost every country. The countries should identify the risk factors of late presentation and should improve early diagnosis and presentation for HIV care.
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http://dx.doi.org/10.21101/cejph.a5416DOI Listing
September 2019

Assessment of the 24th Week Success of Anti-Retroviral Therapy in the Action against HIV in Istanbul Database: Results from a Region with Increasing Incidence.

Jpn J Infect Dis 2019 May 31;72(3):173-178. Epub 2019 Jan 31.

Department of Infectious Diseases and Clinical Microbiology, Istanbul University, Cerrahpasa Medical School.

We aimed to assess the 24-week virological and immunological success of the treatment of treatment-naive and treatment-experienced patients included in the Action against HIV in Istanbul (ACTHIV-IST) database. The ACTHIV-IST database was screened retrospectively from January 2012 to January 2014. The data for these patients such as age, sex, treatment-naive or treatment-experienced status, date of diagnosis, date of commencing antiretroviral therapy, antiretroviral therapy regimen, CD4+ cell count, and viral load before and after therapy were analyzed. In the 24th week of antiretroviral therapy, there were 40 (17.9%) and 29 (14.1%) virological and immunological failures, respectively. Virological failure (VF) was associated with a baseline viral load > 100,000 copies (p = 0.004). A CD4+ cell count lower than 200 cells/μl was not found to be associated with VF (p = 0.843). Immunological failure was substantially rare in patients with a baseline CD4+ cell count > 200 cells/μl (p = 0.005). Although an HIV-RNA ≤ 100,000 copies/ml was protective against VF in the 24th week, in individuals with an HIV-RNA > 100,000 copies/ml, VF was 3.2 times more likely to occur. Baseline VF was the most predictive parameter to estimate 24th week virological success and VF. VF is an important prognostic parameter resulting in CD4+ cell depletion, AIDS-related events, and increased mortality.
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http://dx.doi.org/10.7883/yoken.JJID.2018.105DOI Listing
May 2019

Resolved hepatitis B virus infection: an unresolved issue of terminology.

Eur J Gastroenterol Hepatol 2018 11;30(11):1389

Infection Department, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.

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http://dx.doi.org/10.1097/MEG.0000000000001209DOI Listing
November 2018

On hepatitis B virus and vasculitis.

Rheumatol Int 2018 08 13;38(8):1585-1586. Epub 2018 Jun 13.

Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s00296-018-4079-0DOI Listing
August 2018

Does resolved HBV or anti-HBc-only carry the same risk of HBV reactivation?

J Oncol Pharm Pract 2018 09 20;24(6):477-479. Epub 2018 Jun 20.

4 Infection Dept. Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.

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http://dx.doi.org/10.1177/1078155218782593DOI Listing
September 2018

Human immunodeficiency virus and tuberculosis coinfection: clinical features and predictors of mortality

Turk J Med Sci 2018 Jun 14;48(3):503-508. Epub 2018 Jun 14.

Background/aim: This study was undertaken to identify subjects with human immunodeficiency virus and tuberculosis (HIV/TB) coinfection in a group of HIV-positive patients followed at five different healthcare centers, and to determine the demographic and clinical characteristics of these subjects as well as the predictors of mortality. Materials and methods: A database search for subjects with TB coinfection was performed among 1475 HIV-positive adult patients and a total of 66 individuals were identified with HIV/TB coinfection. Results: There were 66 patients (4.5%) with TB coinfection. Twenty-one percent (n = 14) of the patients with TB coinfection died during the study period and these patients had significantly lower baseline CD4 counts at the time of TB diagnosis (P = 0.005). None of the patients with CD4 count of ≥200 cells/mm3 died during follow-up and a low CD4 count at the time of TB diagnosis (<200 cells/ mm3) was associated with poor survival (P = 0.012). However, none of the parameters emerged as significant independent predictors of survival in multivariate analysis. Conclusion: Coexistence of TB and HIV infection is associated with many clinical challenges and a better understanding of patient characteristics as well as the parameters impacting the outcome will improve the quality of care provided for this group of patients.
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http://dx.doi.org/10.3906/sag-1706-76DOI Listing
June 2018

Adherence to Antiretroviral Therapy in Turkey: Results from the ACTHIV-IST Study Group.

AIDS Res Hum Retroviruses 2017 12 11;33(12):1192-1198. Epub 2017 Oct 11.

3 Department of Infectious Diseases and Clinical Microbiology, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey .

Maintaining optimal adherence to antiretroviral therapy (ART) is essential for optimizing the management of HIV infection. The aim of this study is to explore ART adherence rates in Turkey. Included in this study were a total of 263 HIV-infected patients followed up by the ACTHIV-IST (ACTion against HIV in Istanbul) Study Group affiliated with four tertiary hospitals. The study population included patients 18 years of age or older who were on ART for over 12 months. Adherence was assessed by the medication possession ratio (MPR) calculated for each patient using data (a list of all drugs dispensed within the previous year for that patient) obtained from pharmacy medication records. In addition, patients completed a self-report questionnaire addressing missed doses and the AIDS Clinical Trials Group (ACTG) adherence questionnaire. The study was reviewed and approved by the Ethics Committee of Cerrahpasa Medical Faculty. Patient ages ranged from 19 to 71 years. Two hundred and thirty-one patients were male (88%). Two hundred and twenty-four patients (85%) had optimal adherence (MPR ≥95%). During the course of ART, 236 patients (90%) reported no missed doses in the past 4 days of their treatment, whereas 206 patients (78%) reported no missed doses in the past month. Simply forgetting was the most common reason for nonadherence. MPR was associated with virologic rebound. Major factors affecting adherence were being female, taking antituberculosis drugs, having an opportunistic infection, being able to take all or most of the medication as directed, and being aware of the need to take medication exactly as instructed to prevent the development of drug resistance. Adherence to ART measured by MPR and self-report surveys is relatively high in Turkey when compared with other countries, which probably led to high ART success rates.
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http://dx.doi.org/10.1089/AID.2016.0266DOI Listing
December 2017

Reactivation of Hepatitis B Virus Following Treatment of Hepatitis C Virus Infection in Coinfected Patients.

Clin Infect Dis 2017 05;64(10):1461-1462

Infectious Diseases Department, Cerrahpasa Medical School, Istanbul University, Turkey.

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http://dx.doi.org/10.1093/cid/cix211DOI Listing
May 2017

Occult Hepatitis B and Risk of Reactivation After Hepatitis C Treatment With Direct-Acting Antivirals.

Clin Gastroenterol Hepatol 2017 04 3;15(4):605. Epub 2016 Dec 3.

Infectious Diseases Department, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.

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http://dx.doi.org/10.1016/j.cgh.2016.11.030DOI Listing
April 2017

Investigation of carbapenem resistance and the first identification of Klebsiella pneumoniae carbapenemase (KPC) enzyme among Escherichia coli isolates in Turkey: A prospective study.

Travel Med Infect Dis 2016 Nov - Dec;14(6):572-576. Epub 2016 Nov 23.

Cerrahpasa Medical School of Istanbul University, Department of Medical Microbiology, Istanbul, Turkey. Electronic address:

Background: The aim of this study was to determine the presence of carbapenem resistance and carbapenemase production in Escherichia coli isolates from clinical samples in Turkey.

Methods: The prospective study included a total of 4.052 Escherichia coli isolates collected from patients admitted to a hospital from March 2011 to May 2012. We used ertapenem disc for screening carbapenemase production, and the confirmation was performed by using Etest. The resistance mechanisms and genetic relatedness of the carbapenem resistant strains were investigated by using PCR (polymerase chain reaction) and pulsed-field gel electrophoresis (PFGE), respectively.

Results: Among the 4.052 E. coli isolates, 24 (0.59%) were found to be carbapenem resistant. Of these, only 5 isolates were positive for OXA-48 and 2 isolates were positive for Klebsiella pneumoniae carbapenemase (KPC)-2. The KPC-2 producing E. coli strains (n = 2) were both isolated from the same patient. The bla genes were confirmed using DNA sequence analysis. The genetic relationship between the 24 E. coli strains studied by PFGE revealed that the strains were genetically unrelated.

Conclusions: This article confirms, to our knowledge for the first time, the detection of KPC-2-producing E. coli in Turkey, with OXA-48 being the most frequent carbapenemase in the study.
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http://dx.doi.org/10.1016/j.tmaid.2016.11.006DOI Listing
May 2017

Changes in HIV demographic patterns in a low prevalence population: no evidence of a shift towards men who have sex with men.

Int J Infect Dis 2016 Jul 9;48:52-6. Epub 2016 May 9.

Department of Infectious Diseases and Clinical Microbiology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.

Objectives: This study aimed to examine the changes in HIV demographics over time in an exceptionally low prevalence population, with particular emphasis on men who have sex with men (MSM).

Methods: A total of 1292 newly diagnosed HIV-positive patients registered in the ACTHIV-IST Study Group database between 2000 and 2014 were included. The changes occurring over time in the characteristics of patients at the time of initial admission were examined retrospectively.

Results: A gradual increase in the total number of newly diagnosed patients was evident during the study period; however, it was not possible to show an increase in the proportion of MSM within the study population (p=0.63). There was a male predominance throughout the study (85% vs. 15%), with further increases in the proportion of males in recent years. The mean age was lower at the end of the study (p<0.05) and there was an increase in the number of unmarried patients (p<0.05).

Conclusions: Sexual preference patterns of HIV patients in extremely low prevalence populations may be different, possibly due to an early phase of the epidemic. Nevertheless, MSM still represent a target subgroup for interventions, since they account for a substantial proportion of cases and a resurgent epidemic may be expected among this group in later phases of the epidemic.
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http://dx.doi.org/10.1016/j.ijid.2016.05.006DOI Listing
July 2016

Diagnostic value of F-18 FDG PET/CT in patients with spondylodiscitis: Is dual time point imaging time worthy?

Diagn Microbiol Infect Dis 2016 Jul 31;85(3):381-385. Epub 2016 Mar 31.

Istanbul University, Cerrahpasa Medical Faculty, Department of Nuclear Medicine, Istanbul, Turkey.

Purpose: In this retrospective study, we aimed to investigate the value of FDG-PET/CT in the diagnosis of spondylodiscitis (SD), the significance of dual time point imaging (DTPI) for SD diagnosis and the worth of SUVmax data for distinguishing tuberculous vs. non-tuberculous SD.

Materials And Methods: 32 patients with suspected SD were scanned with FDG-PET/CT. For quantitative analysis maximum standardized uptake value (SUVmax) of the lesion area was measured. Nineteen patients had DTPI of FDG-PET/CT. The final diagnoses were achieved by histopathological, microbiological, and clinical results.

Results: Specific pathogens were isolated in 21 patients; other patients were accepted as nonspecific bacterial SD. In all patients, FDG-PET/CT results were compatible with SD diagnosis. The SUVmax data for tuberculous and non-tuberculous SD and DTPI results were statistically insignificant.

Conclusion: FDG-PET/CT is a successful modality for SD diagnosis; additionally, DTPI protocol for FDG-PET/CT in SD diagnosis and SUVmax data for differentiation between non-tbc SD and tbc SD are useless.
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http://dx.doi.org/10.1016/j.diagmicrobio.2016.03.021DOI Listing
July 2016

Elimination of mother-to-child transmission of hepatitis B.

Lancet Infect Dis 2016 Jan;16(1):20-21

Istanbul University, Cerrahpasa Medical School, Infectious Diseases Department, TR-34098 Istanbul, Turkey.

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http://dx.doi.org/10.1016/S1473-3099(15)00473-9DOI Listing
January 2016

Successful treatment of post-transplant hepatitis C virus cirrhosis with daclatasvir and asunaprevir.

J Gastrointestin Liver Dis 2015 Sep;24(3):393-4

Infectious Diseases Dept., Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.

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September 2015

Secondary Infections in Febrile Neutropenia in Hematological Malignancies: More Than Another Febrile Neutropenic Episode.

Turk J Haematol 2015 Sep;32(3):243-50

Introduction: Febrile neutropenic episodes (FNEs) are among major causes of mortality in patients with hematological malignancies. Secondary infections develop either during the empirical antibiotic therapy or one week after cessation of therapy for a FNE. The aim of the study was to investigate the risk factors associated with secondary infections in febrile neutropenic patients.

Methods: We retrospectively analyzed 750 FNEs in 473 patients between January 2000 and December 2006.

Results: Secondary infections were diagnosed in 152 (20%) of 750 FNEs. The median time to develop secondary infection was 10 days (range 2-34 days). The duration of neutropenia over 10 days significantly increased the risk of secondary infections (p<0.001). The proportion of patients with microbiologically documented infections was found to be higher in primary infections (271/750, 36%) compared to secondary infections (43/152, 28%) (p=0.038). Age, sex, underlying disease, antibacterial, antifungal or antiviral prophylaxis, blood transfusion or bone marrow transplantation, central venous catheter or severity of neutropenia did not differ significantly between primary and secondary infections (p>0.05) While fever of unknown origin (FUO) (p=0.005) and catheter-related bacteremia (p<0.001) were less frequently observed in secondary infections, the frequency of microbiologically (p=0.003) and clinically (p<0.001) documented infections, fungal pneumonias (p<0.001), infections related with gram positive bacteria (p=0.04) and fungi (p<0.001) and 30-day mortality rate (p<0.001) were significantly higher in secondary infections (p<0.001).

Discussion And Conclusion: Secondary infections should be regarded as life-threatening complications of febrile neutropenia. Secondary infections represent a more severe and mortal complication and cannot be regarded just as another febrile neutropenic episode.
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http://dx.doi.org/10.4274/tjh.2013.0422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563200PMC
September 2015

The Changing Epidemiology of Bloodstream Infections and Resistance in Hematopoietic Stem Cell Transplantation Recipients.

Turk J Haematol 2016 Sep 4;33(3):216-22. Epub 2015 May 4.

İstanbul University Cerrahpaşa Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, İstanbul, Turkey Phone : +90 212 414 30 95 E-mail:

Objective: Patients receiving hematopoietic stem cell transplantation (HSCT) are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs) are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively.

Materials And Methods: The epidemiological properties of 312 patients with HSCT were retrospectively evaluated.

Results: A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62%) and allogeneic (38%) HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28%) and Hodgkin lymphoma (21.5%). A total of 142 (45%) patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011), and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2%) and Acinetobacter baumannii (8.8%) were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively.

Conclusion: A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs.
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http://dx.doi.org/10.4274/tjh.2014.0378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111467PMC
September 2016
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