Tıp Fakültesi / Faculty of Medicine

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    The Turkish Clinical Microbiology and Infectious Diseases Society (KLIMIK) Evidence-Based Guideline for the Diagnosis and Treatment of Brucellosis, 2023
    (2023) Simsek-Yavuz, Serap; Ozger, Selcuk; Benli, Aysun; Ates, Can; Aydin, Mehtap; Aygun, Gokhan; Azap, Alpay; Azap, Ozlem; Basaran, Seniha; Demirturk, Nese; Ergonul, Onder; Kocagul-Celikbas, Aysel; Kuscu, Ferit; Saricaoglu, Elif Mukime; Sayin-Kutlu, Selda; Turker, Nesrin; Turkoglu-Yilmaz, Emine
    Although brucellosis is very common in the world and Turkiye, there are no evidence-based guidelines to guide the diagnosis and treatment of the disease. This guide has been prepared by the Turkish Society of Clinical Microbiology and Infectious Diseases to provide evidence-based recommendations to physicians from different specialties interested in the diagnosis and treatment of brucellosis. The recommendations of the Clinical Practice Guide Development Guide of the Infectious Diseases Society of America (IDSA) were taken as the basis for preparing this guide. The guideline preparation group determined 20 questions considered to be important in the diagnosis and treatment of brucellosis, and the publications that could answer these questions prepared in PICO (Population/Patient [P], Intervention [I], Comparison [C], Outcome [O]) format, were searched in ULAKBIM Tr Dizin, PubMed, Cochrane databases without date restrictions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group method was used to rank the evidence and determine the strength of the recommendations for each PICO question and for each individual outcome. Meta-analyses of comparative clinical studies were performed to answer the PICO questions. Individual participant data (IPD) meta-analyses with data obtained from case reports and case series were conducted in the absence of comparative clinical studies. It is planned to update the recommendations at regular intervals in line with the results of new studies.
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    European Society of Clinical Microbiology and Infectious Diseases Guidelines for Coronavirus Disease 2019: An Update on Treatment of Patients with Mild/Moderate Disease
    (2022) Bartoletti, Michele; Azap, Ozlem; Barac, Aleksandra; Bussini, Linda; Ergonul, Onder; Krause, Robert; Martin-Quiros, Alejandro; Pano-Pardo, Jose Ramon; Power, Nicholas; Sibani, Marcella; Szabo, Balint Gergely; Tsiodras, Sotirios; Zollner-Schwetz, Ines; Rodriguez-Bano, Jesus; 36028088
    Scope: Despite the large availability of vaccines, coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2, continues to be a major threat for health-care providers and fragile people. A number of options are now available for outpatients with mild-to-moderate COVID-19 at the risk of disease progression for the prevention of deaths or hospitalization. Methods: A European Society of Clinical Microbiology and Infectious Diseases COVID-19 guidelines task force was established by the European Society of Clinical Microbiology and Infectious Diseases Executive Committee. A small group was established, half appointed by the chair and the remaining selected based on an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the population, intervention, comparison, outcome format was developed at the beginning of the process. For each population, intervention, comparison, outcome, two panel members performed a literature search, with a third panelist involved in case of inconsistent results. Voting was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Recommendations: In this update, we focus on anti-viral agents, monoclonal antibodies (mAbs) and other treatment options proposed for patients with mild or moderate COVID-19 who are at the risk of hospitalization or death. Although the use of anti-virals is recommended, especially nirmatrelvir/ritonavir and remdesivir or, alternatively, molnupirarvir, the administration of mAbs against the spike protein strictly depends on circulating variants or the ability to test timely for variants and sub-variants. At the time of writing (AprileJune 2022), the only active mAb was tixagevimab/cilgavimab given the predominance of the Omicron BA.2, BA.3, BA.4 and BA.5 sub-lineages in Europe. However, considering that the epidemiological scenario is extremely dynamic, constant monitoring of variants of concern is mandatory. Michele Bartoletti, Clin Microbiol Infect 2022;28:1578
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    Epidemiology, Species Distribution, Clinical Characteristics and Mortality of Candidaemia in A Tertiary Care University Hospital in Turkey, 2007-2014
    (2017) Yesilkaya, Aysegul; Azap, Ozlem; Aydin, Mehtap; Ok, Mehtap Akcil; https://orcid.org/0000-0003-0225-6416; https://orcid.org/0000-0002-3171-8926; https://orcid.org/0000-0003-4044-9366; 28338249; A-8902-2013; AAK-4089-2021; HLX-0937-2023; AAZ-8170-2020
    Candidaemia still continues to be a serious medical concern and the epidemiology of candidaemia varies according to geographical areas. We aim to determine the incidence, local epidemiology, Candida species distribution and crude mortality rates of candidaemia. We retrospectively evaluated candidaemia episodes in between January 2007 and August 2014. We compared demographic, clinical, microbiological findings and mortality rates of episodes caused by Candida albicans and non-albicans Candida species. Overall the candidaemia incidences were 1.23 episodes/1000 admissions. A significant negative slope among candidaemia episodes and years was determined. Overall C. albicans (54.6%) was the most common species followed by Candida glabrata, Candida tropicalis and Candida parapsilosis respectively. Preinfection hospital stay and length of hospital stay were statistically longer in patients with non-albicans Candida candidaemia than in patients with C.albicans candidaemia. The source of candidaemia was unknown in 52.5% of all episodes. Central venous catheters among non-albicans Candida candidaemia episodes and urinary system among C.albicans candidaemia episodes were common source of candidaemia compared to each other. Previous antifungal therapy preceding candidaemia and concomitant bacteraemia were significantly associated with non-albicans Candida candidaemia. Continuous local surveillance will preserve its pivotal importance in formulating empirical antifungal therapy and improving management of candidaemia.
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    Inappropriate use of ivermectin during the COVID-19 pandemic: primum non nocere!
    (2022) Barac, Aleksandra; Bartoletti, Michele; Azap, Ozlem; Bussini, Linda; Ergonul, Onder; Krause, Robert; Ramon Pano-Pardo, Jose; Power, Nicholas R.; Rodriguez-Bano, Jesus; Sibani, Marcella; Szabo, Balint Gergely; Tsiodras, Sotirios; Verweij, Paul E.; Martin Quiros, Alejandro; Zollner-Schwetz, Ines; 35337977
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    Comparison Of Ceftazidime-Avibactam Susceptibility Testing Methods Against OXA-48-Like Carrying Klebsiella Blood Stream Isolates
    (2022) Isler, Burcu; Vatansever, Cansel; Ozer, Berna; Cinar, Gule; Aslan, Abdullah Tarik; Stewart, Adam; Simos, Peter; Falconer, Caitlin; Bauer, Michelle J.; Forde, Brian; Harris, Patrick; Simsek, Funda; Tulek, Necla; Demirkaya, Hamiyet; Menekse, Sirin; Akalinj, Halis; Balkan, Ilker Inanc; Aydin, Mehtap; Tigen, Elif Tukenmez; Demir, Safiye Koculu; Kapmaz, Mahir; Keske, Siran; Dogan, Ozlem; Arabaci, Cigdem; Yagci, Serap; Hazirolan, Gulsen; Bakir, Veli Oguzalp; Gonen, Mehmet; Saltoglu, Nese; Azap, Alpay; Azap, Ozlem; Akova, Murat; Ergonul, Onder; Paterson, David L.; Can, Fusun; 35843111
    Ceftazidime-avibactam exhibits good in vitro activity against carbapenem resistant Klebsiella carrying OXA-48-like enzymes. We tested two hundred unique carbapenem resistant Klebsiella blood stream isolates (71% with single OXA-48-like carbapenemases, including OXA-48, n = 62; OXA-232, n = 57; OXA-244, n = 17; OXA-181, n = 5) that were collected as part of a multicentre study against ceftazidime-avibactam using Etest (bioMerieux, Marcyl'Etoile, France), 10/4 mg disc (Thermo Fisher) and Sensititre Gram Negative EURGNCOL Plates (Lyophilized panels, Sensititre, Thermo Fisher) with the aim of comparing the performances of the Etest and disc to that of Sensititre. Ceftazidime-avibactam MIC50/90 was 2/> 16 mg/L for the entire collection and was 2/4 mg/L for single OXA-48-like producers. Categorical and essential agreements between the Etest and Sensititre were 100% and 97%, respectively. Categorical agreement between the disc and Sensititre was 100%. Etest and 10/4 mg discs are suitable alternatives to Sensititre for ceftazidime-avibactam sensitivity testing for OXA-48-like producers. (C) 2022 Elsevier Inc. All rights reserved.
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    Characteristics And Outcomes Of Carbapenemase Harbouring Carbapenem-Resistant Klebsiella Spp. Bloodstream Infections: A Multicentre Prospective Cohort Study In An OXA-48 Endemic Setting
    (2022) Isler, Burcu; Ozer, Berna; Cinar, Gule; Aslan, Abdullah Tarik; Vatansever, Cansel; Falconer, Caitlin; Dolapci, Istar; Simsek, Funda; Tulek, Necla; Demirkaya, Hamiyet; Menekse, Sirin; Akalin, Halis; Balkan, Ilker Inanc; Aydin, Mehtap; Tigen, Elif Tukenmez; Demir, Safiye Koculu; Kapmaz, Mahir; Keske, Siran; Dogan, Ozlem; Arabaci, Cigdem; Yagci, Serap; Hazirolan, Gulsen; Bakir, Veli Oguzalp; Gonen, Mehmet; Chatfield, Mark D.; Forde, Brian; Saltoglu, Nese; Azap, Alpay; Azap, Ozlem; Akova, Murat; Paterson, David L.; Can, Fusun; Ergonul, Onder; 35301623
    A prospective, multicentre observational cohort study of carbapenem-resistant Klebsiella spp. (CRK) bloodstream infections was conducted in Turkey from June 2018 to June 2019. One hundred eighty-seven patients were recruited. Single OXA-48-like carbapenemases predominated (75%), followed by OXA-48-like/NDM coproducers (16%). OXA-232 constituted 31% of all OXA-48-like carbapenemases and was mainly carried on ST2096. Thirty-day mortality was 44% overall and 51% for ST2096. In the multivariate cox regression analysis, SOFA score and immunosuppression were significant predictors of 30-day mortality and ST2096 had a non-significant effect. All OXA-48-like producers remained susceptible to ceftazidime-avibactam.
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    ESCMID COVID-19 Living Guidelines: Drug Treatment And Clinical Management
    (2022) Bartoletti, Michele; Azap, Ozlem; Barac, Aleksandra; Bussini, Linda; Ergonul, Onder; Krause, Robert; Ramon Pano-Pardo, Jose; Power, Nicholas R.; Sibani, Marcella; Szabo, Balint Gergely; Tsiodras, Sotirios; Verweij, Paul E.; Zollner-Schwetz, Ines; Rodriguez-Bano, Jesus; https://orcid.org/0000-0002-3171-8926; 34823008; AAK-4089-2021
    Scope: In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19. Methods: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach. Questions addressed by the guideline and recommendations: A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon beta-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon beta-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19. Scope: The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised. (C) 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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    Evaluation of extensively drug-resistant gram-negative bacteremia among solid-organ transplant recipients: a multicenter study
    (2021) Yanik Yalcin, Tugba; Azap, Ozlem; Kose, Adam; Bayindir, Yasar; Saricaoglu, Elif Mukime; Cinar, Gule; Uygun Kizmaz, Yesim; Kursun, Ebru; Aliskan, Hikmet Eda; Tezer Tekce, Yasemin; Eren Kutsoylu, Oya Ozlem; Egeli, Tufan; Ari, Alpay; Albayrak, Yurdagul; Cabadak, Hatice; Deniz, Secil; Demir Onder, Kubra; Kizilates, Filiz; Ozger, Selcuk; Guzel Tunccan, Ozlem; Haberal, Mehmet; 0000-0001-9060-3195; 0000-0002-3462-7632; 33865241; AAE-2282-2021; AAJ-8097-2021
    Background/aim: The aim of this study is to evaluate the distribution, sources, clinical features, and mortality rates of bacteremia due to evaluation of extensively drug-resistant (XDR) gram negative among solid-organ transplant (SOT) recipients. Materials and methods: A retrospective study of SOT recipients with bacteremia due to XDR gram-negative pathogens in 11 centers between 2016 and 2018 was conducted. Patients' records were evaluated. Results: Of 171 bacteremia that occurred in 164 SOT recipients, 93 (56.7%) were liver, 46 (28%) kidney, 14 (8.5%) heart, and 11 (6.7%) lung recipients. Bacteremia episodes were recorded in the first year in 63.7% of the patients (n = 109), early-onset bacteremia was recorded in 45% (n = 77) of the episodes. In multivariate analysis, catheter-associated bacteremia was an independent risk factor for 7-day mortality (p = 0.037), and early-onset bacteremia was found as an independent risk factor for 30-day mortality (p = 0.017). Conclusion: Difficult-to-treat infections due to XDR bacteria in SOT recipients shadow the success of transplantation. Central venous catheters seem to be the main risk factor. Judicious use of medical devices is of pivotal importance.
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    Ceftazidime - Avibactam susceptibility among carbapenem-resistant Enterobacterales in a pilot study in Turkey
    (2021) Erol, Cigdem; Azap, Ozlem; 0000-0002-2535-2534; 34324428; AAJ-1219-2021
    This study aimed to detect carbapenemase genes and to determine the in vitro susceptibility of Ceftazidime-Avibactam (CZA) in Enterobacterales isolates. Carbapenemase genes were detected by polymerase chain reaction. CZA sensitivity of isolates was evaluated with broth microdilution (BMD) and disk diffusion methods. A total of 318 carbapenem-resistant Enterobacterales isolates were included. Most of the isolates (n = 290, 91.2%) were identified as Klebsiella pneumoniae. The most common carbapenemase type was OXA-48 (n = 82, 27.6%). CZA susceptibility was evaluated in 84 isolates with OXA-48 and KPC carbapenemase activity. Both BMD and disk diffusion methods revealed that 95.2% of the isolates were sensitive to CZA; whereas, 4 (4.76%) isolates were resistant to CZA. Among colistin resistant isolates, 96.5% (n = 80) of them were susceptible to CZA. Our study demonstrated high in vitro efficacy of CZA in Enterobacterales isolates producing OXA-48 carbapenemase. High susceptibility rates against colistin resistant isolates which generally are also pan drug resistant, makes CZA a promising therapeutic choice for difficult-to-treat infections. Due to its high correlation with the BMD, disk diffusion method is a suitable and more practical method in detecting CZA in vitro activity.
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    Differences in Antibody Responses Between an Inactivated SARS-CoV-2 Vaccine and the BNT162b2 mRNA Vaccine in Solid-Organ Transplant Recipients
    (2021) Erol, Cigdem; Yalcin, Tugba Yanik; Sari, Nuran; Bayraktar, Nilufer; Soy, Ebru Ayvazoglu; Colak, Meric Yavuz; Azap, Ozlem; Arslan, Hande; Haberal, Mehmet; 0000-0002-3462-7632; 0000-0002-2535-2534; 0000-0002-0993-9917; 0000-0002-5708-7915; 0000-0001-5996-8639; 0000-0002-3165-4520; 34951350; AAJ-1219-2021; AAC-5566-2019; AAJ-8097-2021; ABG-7034-2021; AAA-4708-2022
    Objectives: Vaccination against SARS-CoV-2 may reduce COVID-19 mortality and complications in solidorgan transplant recipients, and we evaluated the associated antibody responses and adverse effects in this high-risk population. Materials and Methods: This prospective observational study (April-June 2021) included 10 liver and 38 kidney transplant recipients who received 2 vaccine doses (Sinovac, n = 31; or BioNTech, n = 17) and 56 healthy adults (Sinovac), all of whom provided 3 blood samples (prevaccination, 4 weeks after first dose, and 4-6 weeks after second dose) for quantitative tests (Abbott Quant assay for immunoglobulin G antibodies against SARS-CoV-2 spike protein). Type I error was alpha = .05 in all statistical analyses (SPSS, version 25). Results: We analyzed demographic data, antibody responses, and adverse events after 2 doses of SARS-CoV-2 vaccine, compared immune responses from solidorgan transplant recipients (median age, 36.5 years) versus healthy patients (median age, 37.5 years), and observed significantly higher seropositivity in healthy versus transplant patients after Sinovac vaccination (100% vs 67.5%; P = .001). However, we observed no significant seropositive differences for Sinovac versus BioNTech second doses in transplant recipients. Median SARS-CoV-2 immunoglobulin G level after second dose was significantly higher in BioNTech (1388.6 AU/mL) versus Sinovac patients (136.6 AU/mL) (P = .012). The seropositivity difference between the 2 vaccines was significant in participants 24 to 44 years old (P = .040). The rate of at least 1 side effect was 82.4% (n = 14) for BioNTech vaccine and 32.3% (n = 10) for Sinovac vaccine, and the difference was statistically significant. The most common side effect was arm pain (significantly higher in BioNTech group). Conclusions: Solid-organ transplant recipients demonstrated inadequate vaccine responses (higher risk of complications and mortality) versus healthy patients. Furthermore, immune responses may differ between vaccines. Therefore, additional vaccine doses and strict control measures remain crucial.