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To the Editor—We read the paper of Mehmood et al1 with great interest. Their letter was based on a newspaper report of novel coronavirus (COVID-19) and Crimean–Congo hemorrhagic fever (CCHF) coinfection, and its scientific basis is questionable. 34462024

Background Increasing number of patients with COVID-19-associated mucormycosis have been reported, especially from India recently. We have described a patient with COVID-19-associated mucormycosis and, searched and analyzed current medical literature to delineate the characteristics of COVID-19-associated mucormycosis. Method We reported a patient developed mucormycosis during post-COVID period. We searched literature to describe the incidence, clinical features, and outcomes of COVID-19-associated mucormycosis. Demographic features, risk factors, clinical features, diagnostic methods, treatment and outcome were analyzed. Results We describe a 54-year-old male, hospitalized due to severe COVID-19 pneumonia. He was given long-term, high doses of systemic steroids. He developed maxillo-fascial mucormycosis and died of sepsis. Our literature search found 30 publications describing 100 patients including present case report. The majority (n = 68) were reported from India. 76% were male. The most commonly seen risk factors were corticosteroid use (90.5%), diabetes (79%), and hypertension (34%). Also, excessive use of broad-spectrum antibiotics were noted in cases. Most frequent involvements were rhino-orbital (50%), followed by rhino-sinusal (17%), and rhino-orbito-cerebral (15%). Death was reported as 33 out of 99 patients (33,3%). Conclusions Steroid use, diabetes, environmental conditions, excessive use of antibiotics, and hypoxia are main risk factors. Despite medical and surgical treatment, mortality rate is high. A multidisciplinary approach is essential to improve the conditions facilitating the emergence of COVID-19-associated mucormycosis.

Celikbilek, Mehmet/0000-0001-8890-3885; /0000-0002-0636-4214 WOS: 000402467500012 PubMed: 28373116 Nephrotoxicity has been associated with nucleos(t)ide analogues other than telbivudine (LdT). This study investigated the potential effects of LdT and lamivudine (LAM) on renal function in an experimental rat model of gentamicin-induced acute nephrotoxicity. A total of 28 healthy Wistar albino rats were randomly divided into four experimental groups: negative control; positive control (PC); LdT; and LAM. Nephrotoxicity was induced by gentamicin in the LdT, LAM and PC groups. LdT and LAM were administered to two groups for 6 weeks starting on the ninth day. Blood samples were collected weekly and cystatin C levels were measured by ELISA. Animals were sacrificed on the 50th day and the kidneys were removed for histological examination. Serum cystatin C levels differed significantly between the LdT and LAM groups (P < 0.007) and between the LdT and PC groups (P < 0.001). Renal function was significantly improved in the LdT group at the start of antiviral treatment on Day 8 and at the end of treatment on Day 50 (P = 0.001 and 0.007). Glomerular injury, acute tubular necrosis and total injury score were significantly reduced in the LdT group relative to the PC and LAM groups upon histopathological examination. LdT was associated with significant improvements in renal function as measured by biochemical and histopathological methods. The acute kidney injury model data should be supported by clinical studies to suggest that LdT treatment may have advantages for patients with underlying chronic kidney disease receiving chronic hepatitis B treatment. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. Bozok University Scientific Research Project UnitsBozok University [2014TF-A126] This research was supported by the Bozok University Scientific Research Project Units [Project No. 2014TF-A126].

Leblebicioglu, Hakan/0000-0002-6033-8543; Beeching, Nicholas/0000-0002-7019-8791; Fletcher, Tom/0000-0002-3712-415X WOS: 000476864600046 PubMed: 31262565 Background Data describing the coagulopathy of Crimean-Congo haemorrhagic fever are scarce. We did rotational thromboelastometry (ROTEM) and conventional coagulation testing in patients with Crimean-Congo haemorrhagic fever to increase our understanding of the coagulopathy of this infectious disease. Methods We did a prospective observational cohort study of adults aged 18 years and older and admitted to hospitals with PCR-confirmed Crimean-Congo haemorrhagic fever in Samsun and Tokat, Turkey. Demographic, clinical, and laboratory data were collected and blood samples for ROTEM analysis and coagulation testing were drawn at admission and during hospital admission and convalescence (up to 30 days after onset of illness). For the ROTEM analysis we recorded the following extrinsically activated ROTEM (EXTEM S) variables, with normal ranges indicated: clotting time (38-79 s), clot formation time (34-159 s), amplitude at 10 min after clotting time (43-65 mm), maximum clot firmness (50-72 mm), and maximum lysis (> 15% at 1 h). The following fibrin-specific ROTEM (FIBTEM S) variables were also recorded: amplitude at 10 min after clotting time (normal range 7-23 mm) and maximum clot firmness (9-25 mm). Disease severity was assessed by Swanepoel criteria, severity grading score (SGS), and the severity scoring index (SSI), with mild disease defined as meeting no Swanepoel criteria, graded mild by SSI, and graded low risk by SGS. Findings Between May 27, 2015, and Aug 2, 2015, 65 patients with confirmed Crimean-Congo haemorrhagic fever were recruited and had blood taken at 110 time points. Most were male (40 [62%] of 65) with mild disease (49 [75%] of 65). Haemorrhage occurred in 13 (20%; 95% CI 11.1-31.8) of 65 patients and 23 (35%) of 65 received blood products (15 received fresh frozen plasma and eight received red blood cell concentrates), and 21 patients received platelet transfusions. At admission, the following EXTEM S variables differed significantly between mild cases and moderate to severe cases: median clotting time 56 s (range 42-81; IQR 48-64) versus 69 s (range 48-164; IQR 54-75; p=0.01); mean amplitude at 10 min after clotting time 45.1 mm (SD 7.0) versus 33.9 mm (SD 8.6; p 15%). Interpretation Coagulopathy of Crimean-Congo haemorrhagic fever is related to defects in clot development and stabilisation that are more marked in severe disease than in mild disease. The combination of normal and slightly deranged coagulation screens and FIBTEM results with the absence of hyperfibrinolysis suggests that the coagulopathy of Crimean-Congo haemorrhagic fever relates to platelet dysfunction. Copyright (C) 2019. The Author(s). Published by Elsevier Ltd. Wellcome TrustWellcome Trust [104480/Z/14/Z]; UK Ministry of Defence TF is funded by the Wellcome Trust (104480/Z/14/Z) and the UK Ministry of Defence. RH and NJB are affiliated with the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England, in collaboration with the Liverpool School of Tropical Medicine. RH is based at Public Health England Porton and NJB is based at the Liverpool School of Tropical Medicine. The views expressed are those of the authors and not necessarily those of their respective institutions, the UK National Health Service (NHS), the National Institute for Health Research Health, the UK Department of Health, Public Health England, or the Ministry of Health, Turkey.

The conflict in Syria is a big humanitarian emergency. More than 200,000 Syrians have been killed, with more than half of the population either having been displaced or having immigrated. Healthcare has been interrupted due to the destruction of facilities, a lack of medical staff, and a critical shortage of life-saving medications. It produced suitable conditions leading to the re-emergence of tuberculosis, cutaneous leishmaniasis, polio, and measles. Lebanon and Jordan reported increased rates of tuberculosis among Syrian refugees. Cutaneous leishmaniasis outbreaks were noted not only in Syria but also in Turkey, Jordan, and Lebanon. After a polio-free 15 years, Syria reported a polio outbreak. Ongoing measles outbreaks in the region was accelerated by the conflict. Iraq declared a cholera outbreak among the Syrian refugees. The healthcare facilities of the countries hosting immigrants, mainly Turkey, Lebanon, Jordan, Iraq, and Egypt, are overburdened. The majority of the immigrants live in crowded and unsanitary conditions. Infectious diseases are big challenges for Syria and for the countries hosting immigrants. More structured support from international organizations is needed for the prevention, control, diagnosis, and treatment of infectious diseases.

Leblebicioglu, Hakan/0000-0002-6033-8543; cerik, idris bugra/0000-0003-1419-3950 WOS: 000452543100008 PubMed: 28590307 …

Crimean-Congo hemorrhagic fever (CCHF) is endemic in Eurasian countries such as, Turkey, Pakistan, Afghanistan and Iran. CCHF virus is spread by the Hyalomma tick, which is found mainly on cattle and sheep. Muslim countries, in which these animals are sacrificed during Eid-Al-Adha, are among the countries where CCHF is endemic, and it has been observed that CCHF is associated with practices surrounding the Eid-ad-Adha festival. The dates for Eid-Al-Adha drift 10 days earlier in each year according to Georgian calendar. In previous years Eid-al-Adha occurred in autumn-winter months however in the next 10-15 years it will be take place in the summer months when CCHF is more prevalent. This may lead to a rise in the number of cases due to increased dissemination of CCHF virus with uncontrolled animal movements in and between countries. This consensus report focuses on the variable practices regarding animal handling in different regions and possible preventative measures to reduce the incidence of CCHF. Environmental hygiene and personal protection are essential parts of prevention. There is a need for international collaborative preparedness and response plans for prevention and management of CCHF during Eid-Al-Adha in countries where the disease is prevalent.

Leblebicioglu, Hakan/0000-0002-6033-8543; yanik yalcin, tugba/0000-0001-5996-8639; atilla, aynur/0000-0001-8027-1991; Beeching, Nicholas/0000-0002-7019-8791; Fletcher, Tom/0000-0002-3712-415X; Kilic, Suleyman sirri/0000-0003-1255-9939 WOS: 000410001100007 PubMed: 28886039 Background Crimean Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection that presents significant risk of nosocomial transmission to healthcare workers. Aim Evaluation of CCHF infection prevention and control (IP&C) practices in healthcare facilities that routinely manage CCHF cases in Eurasia. Methods A cross-sectional CCHF IP&C survey was designed and distributed to CCHF centers in 10 endemic Eurasian countries in 2016. Results Twenty-three responses were received from centers in Turkey, Pakistan, Russia, Georgia, Kosovo, Bulgaria, Oman, Iran, India and Kazakhstan. All units had dedicated isolation rooms for CCHF, with cohorting of confirmed cases in 15/23 centers and cohorting of suspect and confirmed cases in 9/23 centers. There was adequate personal protective equipment (PPE) in 22/23 facilities, with 21/23 facilities reporting routine use of PPE for CCHF patients. Adequate staffing levels to provide care reported in 14/23 locations. All centers reported having a high risk CCHFV nosocomial exposure in last five years, with 5 centers reporting more than 5 exposures. Education was provided annually in most centers (13/23), with additional training requested in PPE use (11/23), PPE donning/doffing (12/23), environmental disinfection (12/23) and waste management (14/23). Conclusions Staff and patient safety must be improved and healthcare associated CCHF exposure and transmission eliminated. Improvements are recommended in isolation capacity in healthcare facilities, use of PPE and maintenance of adequate staffing levels. We recommend further audit of IP& C practice at individual units in endemic areas, as part of national quality assurance programs. Wellcome TrustWellcome Trust [104480/Z/14/Z]; UK Ministry of Defence; National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections; University of Liverpool, Liverpool School of Tropical Medicine and Public Health England (PHE) There was no specific funding for this study. TF is funded by Wellcome Trust (104480/Z/14/Z) and the UK Ministry of Defence. NJB is partially supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections, a partnership between the University of Liverpool, Liverpool School of Tropical Medicine and Public Health England (PHE). The views expressed are those of the author(s) and not necessarily those of their respective institutions or Ministries of Health.; There was no specific funding for this study. TF is funded by Wellcome Trust (104480/Z/14/Z) and the UK Ministry of Defence. NJB is partially supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections, a partnership between the University of Liverpool, Liverpool School of Tropical Medicine and Public Health England (PHE). The views expressed are those of the author(s) and not necessarily those of their respective institutions or Ministries of Health.

WOS: 000363949900018 PubMed: 26232090 Babesiosis is a zoonotic disease that may be asymptomatic or result in severe clinical conditions, with severe hemolysis, hepatic, and renal failure, in humans. Clinical symptoms depend on the species and immune status of the host. The disease is especially severe in those of advanced age, those with an immune deficiency, and the splenectomized. A severe case of babesiosis that developed in a splenectomy patient is presented here; the patient was admitted from a rural region with severe anemia and a deterioration in her general condition, with an initial diagnosis of malaria. In such situations, an exchange transfusion (ET), in addition to antimicrobial treatment, could be lifesaving. (C) 2015 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Hakyemez, Ismail Necati/0000-0001-6133-9604; Mert, Ali/0000-0001-8945-2385; YILMAZ, Mesut/0000-0001-8022-7325 WOS: 000394632300009 PubMed: 28013184 Aim: To examine the variables associated with mortality in patients with Acinetobacter baumannii-related central nervous system infections treated with intrathecal colistin. Materials and methods: This multi-centre retrospective case control study included patients from 11 centres in Turkey, as well as cases found during a literature review. Only patients with CNS infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii treated with intrathecal colistin were included in this study. The variables associated with mortality were determined by dividing the patients into groups who died or survived during hospitalisation, and who died or survived from Acinetobacter meningitis. Results: Among the 77 cases enrolled in the study, 35 were found through a literature review and 42 were cases from our centres. Forty-four cases (57.1%) were male and the median age was 48 years (range: 20-78 years). Thirty-seven patients (48%) died during hospitalisation. The variables associated with increased all-cause mortality during hospitalisation included old age (odds ratio, 1.035; 95% confidence interval (Cl), 1.004-1.067; p = 0.026) and failure to provide cerebrospinal fluid sterilisation (odds ratio, 0.264; 95% confidence interval, 0.097-0.724; p = 0.01). There is a trend (P=0.062) towards higher mortality with using of meropenem during meningitis treatment. Fifteen cases (19%) died from meningitis. There were no significant predictors of meningitis-related mortality. Conclusions: The mortality rate for central nervous system infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii is high. Old age and failure to provide CSF sterilisation are associated with increased mortality during hospitalisation. (C) 2016 Published by Elsevier B.V.

Crimean–Congo hemorrhagic fever (CCHF) is a potentially fatal tick-borne viral infection that is widely distributed worldwide. The diagnosis is frequently missed due to the non-specific initial symptoms and the differential diagnosis included many infectious and non-infectious causes. This retrospective study describes the clinical features and final diagnoses of 116 suspect CCHF cases that were admitted to a tertiary CCHF center in Turkey, and were CCHF IgM and PCR negative.

Leblebicioglu, Hakan/0000-0002-6033-8543; Fletcher, Tom/0000-0002-3712-415X WOS: 000390557700023 PubMed: 27486029 Infective endocarditis (IE) is life-threatening condition with a highly variable clinical presentation. We report a case of acute IE with delayed diagnosis which resulted due to an initial misdiagnosis of Crimean Congo Hemorrhagic Fever (CCHF) in an endemic area. A case was due to Staphylococcus aureus and requiring valve replacement. They serve to emphasize the importance of careful history taking, physical examination and a broad range of different diagnostic techniques in the context of suspected viral hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a geographically widespread tick-borne zoonosis. The clinical spectrum of the illness varies from mild infection to severe disease and death. In severe cases, hemorrhagic manifestations develop, with fatality rates of 4-20%, depending on the geographic region and quality of the health care. Although vast majority of the CCHF cases were reported from Turkey, mortality rate is lower than the other regions, which is 5% on average. Prediction of the clinical course of the disease enables appropriate management planning by the physician and prompt transportation, if needed, of the patient to a tertiary care hospital for an intensive therapy. Thus, predicting the outcome of the disease may avert potential mortality. There are numerous studies investigating the prognostic factors of CCHF in the literature. Majority of them were reported from Turkey and included investigations on clinical and biochemical parameters, severity scoring systems and some novel biomarkers. Somnolence, bleeding, thrombocytopenia, elevated liver enzymes and prolonged bleeding times are the most frequently reported prognostic factors to predict the clinical course of the disease earlier. High viral load seems to be the strongest predictor to make a clinical decision about the patient outcome. The severity scoring systems based on clinically important mortality-related parameters are especially useful for clinicians working in the field to predict the course of the disease and to decide which patient should be referred to a tertiary care hospital for intensive care. In the light of the pathophysiological characteristics of CCHF, some new biomarkers of prognosis including cytokines, soluble adhesion molecules, genetic polymorphisms and coagulopathy parameters were also investigated. However most of these tests are not available to clinicians and they were obtained mostly for research purposes. In spite of the various studies about prognostic factors, they have several inherent limitations, including large variability in the results and confusing data that are not useful for clinicians in routine practice. In this paper, the results of diverse studies of the prediction of the prognosis in CCHF based on epidemiological, clinical and laboratory findings of the disease were summarized and suggestions for future studies are provided.

Leblebicioglu, Hakan/0000-0002-6033-8543; Beeching, Nicholas/0000-0002-7019-8791 WOS: 000374007100002 PubMed: 27077310 Crimean-Congo hemorrhagic fever (CCHF) is endemic in Turkey, with peak incidence of hospital admissions in the summer months. The aim of this pilot study was to evaluate the role of the severity grading score (SGS) in predicting length of hospital stay, laboratory usage, need for blood products, and hence total costs of patients. Thirty-five patients admitted to one specialist center in Turkey in 2013 and 2014 with PCR-proven CCHF. The mean (SD) age was 55 (+/- 14) and 63% of the patients were male, with 8 (22.9%) mortality. Patients were classified by SGS into three groups with mortality as follows: low risk (0/19); intermediate (6/14); and high (2/2). The direct hospital cost of these admissions was at least $41 740 with median (range) of $1210 ($97-$13 054) per patient. There was a significant difference between low-risk and combined (intermediate-high) risk groups as 635 (97-1500) and 2264.5 (154-13 054), respectively (p = 0.012). In conclusion, a clinical grading score can be used to predict illness severity and to predict associated health care costs. National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections; University of Liverpool, Liverpool School of Tropical Medicine; Public Health England (PHE) The authors declared that there are no conflicts of interest. NJB is partially funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections, a partnership between the University of Liverpool, Liverpool School of Tropical Medicine and Public Health England (PHE). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, or PHE.

yapar, derya/0000-0003-3566-9751; Leblebicioglu, Hakan/0000-0002-6033-8543 WOS: 000371935300009 PubMed: 26828701 …

WOS: 000379252100027, PubMed ID: 27085724, There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Department of Infectious Diseases and Clinical Microbiology, Ondokuz Mayis University Medical School, Samsun, Turkey Liverpool School of Tropical Medicine, Liverpool, United Kingdom, Department of Intensive Care, Ondokuz Mayis University Medical School, Samsun, Turkey Department of Haematology, Ondokuz Mayis University Medical School, Samsun, Turkey NIHR Helalth Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool L69 7BE, United Kingdom

WOS: 000384527500014, PubMed ID: 27625226, Aims: There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. Materials and Methods: This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. Results: In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27u86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for 9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68u19.57]). According to linear regression analysis, fever was significantly persisting (7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. Conclusions: In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.

WOS: 000384856200002, PubMed ID: 27424492, Introduction: The information of discharge criteria in patients with Crimean-Congo Hemorrhagic Fever (CCHF) is limited. In this study, we aimed to determine the clinical and laboratory parameters used in discharging the patients by the experienced centers. Materials and methods: The study was done in 9 reference centers of CCHF from May 1, 2015 to December 1, 2015 and included laboratory-confirmed patients with CCHF. The study was prospective, observational and non-interventional. Results: The study included 260 patients. Mean age was 51.3 +/- 16.3 years; 158 (60.8%) were male. Mean hospital stay was 7 +/- 2.6 days. The decision of discharging was taken considering clinical and laboratory findings. On discharge, no patients had fever or hemorrhage. The patients were followed-up clinically and a repeat CCHF PCR was not studied. All centers considered the following criteria for discharge: no fever and hemorrhage, improvement in clinical findings and laboratory studies. For all patients except one, platelet count was >50,000/mm(3) and had a tendency to increase. Prothrombin time and international normalized ratio (INR) were normal in 258 (99.6%) and 254 (98.1%) patients respectively. Alanine aminotransferase (ALT) was either normal or not higher than 10-fold and had a tendency to decrease in 259 (99.6%) patients. ALT and aspartate aminotransferase (AST) levels were not taken as discharge criteria with priority. During 30 days following the discharge, complication, relapse, or secondary transmission were not reported. Conclusions: The discharging practice of the centers based on clinical and laboratory parameters seems safe considering no complications, relapses, or secondary infection thereafter. Current discharge practice of the centers composed of no fever and hemorrhage, improvement in clinical findings, platelet count of either >100,000/mm(3) or >50,000/mm(3) with a tendency to increase, and normal bleeding tests can be used as the criteria of discharge. (C) 2016 Elsevier B.V. All rights reserved.

Leblebicioglu, Hakan/0000-0002-6033-8543 WOS: 000392324300011 PubMed: 27903130 Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been known as a nosocomial pathogen, both for the last 10 years in Turkey and for 20 years worldwide. Due to limited treatment options and high mortality rates, despite improvements in the field of medicine at the present time, CRKP is still a big threat for public health. This study was carried out between the dates of January 2010 and September 2014. Patients >= 18 who were hospitalized for at least 72 h and who also had CRKP growth were included in the study as a case group. In the same period patients, who were hospitalized in the same ward and did not have CRKP growth were selected as the control group. It was determined that no glycopeptides and steroids use nor tracheostomy as protective factors would be employed in terms of non-development of CRKP. Mechanical ventilation, tracheostomy, urinary catheter presence, central venous catheterization, nasogastric tube placement, advanced age, acute renal insufficiency, total parenteral nutrition, carbapenem, glycopeptide, and piperacillin tazobactam were all detected as risk factors in terms of CRKP infection development. As a result, rational usage of antibiotics for preventing infections developing with CRKP should be targeted.

WOS: 000386954300001, PubMed: 27809934, Background: The aim of this study was to assess health-related quality of life (HRQOL) among chronic hepatitis B (CHB) patients in Turkey and to study related factors. Methods: This multicenter study was carried out between January 01 and April 15, 2015 in Turkey in 57 centers. Adults were enrolled and studied in three groups. Group 1: Inactive HBsAg carriers, Group 2: CHB patients receiving antiviral therapy, Group 3: CHB patients who were neither receiving antiviral therapy nor were inactive HBsAg carriers. Study data was collected by face-to-face interviews using a standardized questionnaire, Short Form-36 (SF-36) and Hepatitis B Quality of Life (HBQOL). Values equivalent to p < 0.05 in analyses were accepted as statistically significant. Results: Four thousand two hundred fifty-seven patients with CHB were included in the study. Two thousand five hundred fifty-nine (60.1 %) of the patients were males. Groups 1, 2 and 3, consisted of 1529 (35.9 %), 1721 (40.4 %) and 1007 (23.7 %) patients, respectively. The highest value of HRQOL was found in inactive HBsAg carriers. We found that total HBQOL score increased when antiviral treatment was used. However, HRQOL of CHB patients varied according to their socio-demographic properties. Regarding total HBQOL score, a higher significant level of HRQOL was determined in inactive HBV patients when matched controls with the associated factors were provided. Conclusions: The HRQOL score of CHB patients was higher than expected and it can be worsen when the disease becomes active. Use of an antiviral therapy can contribute to increasing HRQOL of patients.

Leblebicioglu, Hakan/0000-0002-6033-8543 WOS: 000374876700577 …

The conflict in Syria is a big humanitarian emergency. More than 200,000 Syrians have been killed, with more than half of the population either having been displaced or having immigrated. Healthcare has been interrupted due to the destruction of facilities, a lack of medical staff, and a critical shortage of life-saving medications. It produced suitable conditions leading to the re-emergence of tuberculosis, cutaneous leishmaniasis, polio, and measles. Lebanon and Jordan reported increased rates of tuberculosis among Syrian refugees. Cutaneous leishmaniasis outbreaks were noted not only in Syria but also in Turkey, Jordan, and Lebanon. After a polio-free 15 years, Syria reported a polio outbreak. Ongoing measles outbreaks in the region was accelerated by the conflict. Iraq declared a cholera outbreak among the Syrian refugees. The healthcare facilities of the countries hosting immigrants, mainly Turkey, Lebanon, Jordan, Iraq, and Egypt, are overburdened. The majority of the immigrants live in crowded and unsanitary conditions. Infectious diseases are big challenges for Syria and for the countries hosting immigrants. More structured support from international organizations is needed for the prevention, control, diagnosis, and treatment of infectious diseases.

EASL International Liver Congress -- APR 13-17, 2016 -- -- Barcelona, SPAIN, WOS: 000398711700582, …, EASL

Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility.

Leblebicioglu, Hakan/0000-0002-6033-8543; Husa, Petr/0000-0002-9190-2610; Ruta, Simona/0000-0002-2492-6073; Pineda, Juan A./0000-0002-3751-0296; Santos, Lurdes/0000-0002-0622-6823; Lazarevic, Ivana/0000-0001-6795-1378; Puca, Edmond/0000-0002-0621-4865; Abuova, Gulzhan/0000-0002-1210-2018; Koulentaki, Mairi/0000-0002-5665-6741; Vince, Adriana/0000-0003-2355-6573 WOS: 000425078700002 PubMed: 29217468 Background. Treatment with direct acting antiviral agents (DAAs) has provided sustained virological response rates in > 95% of patients with chronic hepatitis C virus (HCV) infection. However treatment is costly and market access, reimbursement and governmental restrictions differ among countries. We aimed to analyze these differences among European and Eurasian countries. Methods: A survey including 20-item questionnaire was sent to experts in viral hepatitis. Countries were evaluated according to their income categories by the World Bank stratification. Results: Experts from 26 countries responded to the survey. As of May 2016, HCV prevalence was reported as low (

WOS: 000364000400001, PubMed ID: 26538030, Background: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem. This study aimed to evaluate drug resistance profiles of TBM isolates in adult patients in nine European countries involving 32 centers to provide insight into the empiric treatment of TBM. Methods: Mycobacterium tuberculosis was cultured from the cerebrospinal fluid (CSF) of 142 patients and was tested for susceptibility to first-line antituberculosis drugs, streptomycin (SM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB). Results: Twenty of 142 isolates (14.1 %) were resistant to at least one antituberculosis drug, and five (3.5 %) were resistant to at least INH and RIF, [multidrug resistant (MDR)]. The resistance rate was 12, 4.9, 4.2 and 3.5 % for INH, SM, EMB and RIF, respectively. The monoresistance rate was 6.3, 1.4 and 0.7 % for INH, SM and EMB respectively. There was no monoresistance to RIF. The mortality rate was 23.8 % in fully susceptible cases while it was 33.3 % for those exhibiting monoresistance to INH, and 40 % in cases with MDR-TBM. In compared to patients without resistance to any firstline drug, the relative risk of death for INH-monoresistance and MDR-TBM was 1.60 (95 % CI, 0.38-6.82) and 2.14 (95 % CI, 0: 34-13: 42), respectively. Conclusion: INH-resistance and MDR rates seemed not to be worrisome in our study. However, considering their adverse effects on treatment, rapid detection of resistance to at least INH and RIF would be most beneficial for designing anti-TB therapy. Still, empiric TBM treatment should be started immediately without waiting the drug susceptibility testing.

Background/aim: This study aimed to evaluate the superiority of procalcitonin (PCT), C-reactive protein (CRP) levels, white blood cell (WBC) counts, and erythrocyte sedimentation rate (ESR) in discriminating among infection, systemic inflammatory response syndrome (SIRS), and sepsis, and their differences according to age groups. Materials and methods: The patients were divided into an adult group and a geriatric group (over 65 years) and classified according to the presence of infection, SIRS, and sepsis. The patients' laboratory values (PCT, CRP, WBC, ESR), demographic characteristics, and vital signs were taken into consideration. Results: When the laboratory parameters were evaluated, there were no significant differences in the PCT, WBC, and ESR values between the age groups (P > 0.05). CRP was significantly higher in the adult patient group compared to the geriatric group (P < 0.001). When the two groups were compared in terms of infection, there were no significant differences in the PCT levels and the WBC count (P > 0.05) in SIRS and sepsis. In addition, the CRP levels and the ESR were significantly higher in the adult sepsis patients when compared with the geriatric patients (P < 0.001). Conclusion: PCT levels do not distinguish among infection, SIRS, and sepsis in adult and geriatric age groups.

WOS: 000358623200015, PubMed ID: 25779579, Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

Kurtaran, Behice/0000-0002-2081-4664; balkan, ilker inanc/0000-0002-8977-5931; Mert, Ali/0000-0001-8945-2385 WOS: 000354195100020 PubMed: 25698311 The aim of this study was to determine the independent risk factors, morbidity, and mortality of central nervous system (CNS) infections caused by Listeria monocytogenes. We retrospectively evaluated 100 episodes of neuroinvasive listeriosis in a multinational study in 21 tertiary care hospitals of Turkey, France, and Italy from 1990 to 2014. The mean age of the patients was 57 years (range, 19-92 years), and 64% were males. The all-cause immunosuppression rate was 54 % (54/100). Forty-nine (49 %) patients were referred to a hospital because of the classical triad of symptoms (fever, nuchal rigidity, and altered level of consciousness). Rhombencephalitis was detected radiologically in 9 (9 %) cases. Twenty-seven (64 %) of the patients who had cranial magnetic resonance imaging (MRI) performed had findings of meningeal and parenchymal involvement. The mean delay in the initiation of specific treatment was 6.8 +/- 7 days. Empiric treatment was appropriate in 52 (52 %) patients. The mortality rate was 25 %, while neurologic sequelae occurred in 13 % of the patients. In the multivariate analysis, delay in treatment [odds ratio (OR), 1.07 [95 % confidence interval (CI), 1.01-1.16]] and seizures (OR, 3.41 [95 % CI, 1.05-11.09]) were significantly associated with mortality. Independent risk factors for neurologic sequelae were delay in treatment (OR, 1.07 [95 % CI, 1.006-1.367]) and presence of bacteremia (OR, 45.2 [95 % CI, 2.73-748.1]). Delay in the initiation of treatment of neuroinvasive listeriosis was a poor risk factor for unfavorable outcomes. Bacteremia was one of the independent risk factors for morbidity, while the presence of seizures predicted worse prognosis. Moreover, the addition of aminoglycosides to ampicillin monotherapy did not improve patients' prognosis.

Ebola virus disease (EVD) is a potentially fatal haemorrhagic disease of humans. The last and most serious outbreak of Ebola virus (EBOV) started in December 2013 in West Africa and also affected other continents. Animals such as fruit bats and non-human primates are potential sources of EBOV. This review highlights the clinical features of EVD in humans and animals and addresses the public health implications of EVD outbreaks from the veterinary perspective.

Leblebicioglu, Hakan/0000-0002-6033-8543; WOS: 000387464200059 PubMed: 27043022 …

Yalcin, Ata Nevzat/0000-0002-7243-7354; dursun, oguz/0000-0001-5482-3780; Oncul, Oral/0000-0002-1681-1866; Leblebicioglu, Hakan/0000-0002-6033-8543; demirdal, tuna/0000-0002-9046-5666; Ciftci, Ergin/0000-0002-4955-160X; Erben, Nurettin/0000-0003-0373-0132; Kendirli, Tanil/0000-0001-9458-2803; Acar, Ali/0000-0003-2008-5112; Geyik, Mehmet Faruk/0000-0002-0906-0902; Dursun, Oguz/0000-0001-5482-3780; KAYA, ZEYNEP/0000-0002-8468-2103; KARABAY, OGUZ/0000-0003-1514-1685; Karabay, Oguz/0000-0003-0502-432X; Kaya, Sehnaz/0000-0003-0002-1517 WOS: 000347654600011 PubMed: 25564124 Background: Surgical site infections (SSIs) are a threat to patient safety; however, there were no available data on SSI rates stratified by surgical procedure (SP) in Turkey. Methods: Between January 2005 and December 2011, a cohort prospective surveillance study on SSIs was conducted by the International Nosocomial Infection Control Consortium (INICC) in 20 hospitals in 16 Turkish cities. Data from hospitalized patients were registered using the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) methods and definitions for SSIs. Surgical procedures (SPs) were classified into 22 types according to International Classification of Diseases, Ninth Revision criteria. Results: We recorded 1879 SSIs, associated with 41,563 SPs (4.3%; 95% confidence interval, 4.3-4.7). Among the results, the SSI rate per type of SP compared with rates reported by the INICC and CDC NHSN were 11.9% for ventricular shunt (vs 12.9% vs 5.6%); 5.3% for craniotomy (vs 4.4% vs 2.6%); 4.9% for coronary bypass with chest and donor incision (vs 4.5 vs 2.9); 3.5% for hip prosthesis (vs 2.6% vs 1.3%), and 3.0% for cesarean section (vs 0.7% vs 1.8%). Conclusions: In most of the 22 types of SP analyzed, our SSI rates were higher than the CDC NHSN rates and similar to the INICC rates. This study advances the knowledge of SSI epidemiology in Turkey, allowing the implementation of targeted interventions. Copyright (C) 2015 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

WOS: 000353295400011, PubMed ID: 25634680, Predicting unfavorable outcome is of paramount importance in clinical decision making. Accordingly, we designed this multinational study, which provided the largest case series of tuberculous meningitis (TBM). 43 centers from 14 countries (Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria, Turkey) submitted data of microbiologically confirmed TBM patients hospitalized between 2000 and 2012. Unfavorable outcome was defined as survival with significant sequela or death. In developing our index, binary logistic regression models were constructed via 200 replicates of database by bootstrap resampling methodology. The final model was built according to the selection frequencies of variables. The severity scale included variables with arbitrary scores proportional to predictive powers of terms in the final model. The final model was internally validated by bootstrap resampling. A total of 507 patients' data were submitted among which 165 had unfavorable outcome. Eighty-six patients died while 119 had different neurological sequelae in 79 (16 %) patients. The full model included 13 variables. Age, nausea, vomiting, altered consciousness, hydrocephalus, vasculitis, immunosuppression, diabetes mellitus and neurological deficit remained in the final model. Scores 1-3 were assigned to the variables in the severity scale, which included scores of 1-6. The distribution of mortality for the scores 1-6 was 3.4, 8.2, 20.6, 31, 30 and 40.1 %, respectively. Altered consciousness, diabetes mellitus, immunosuppression, neurological deficits, hydrocephalus, and vasculitis predicted the unfavorable outcome in the scoring and the cumulative score provided a linear estimation of prognosis.

Leblebicioglu, Hakan/0000-0002-6033-8543 WOS: 000364616000059 PubMed: 26518971 …

Leblebicioglu, Hakan/0000-0002-6033-8543; Yasar, Kadriye Kart/0000-0003-2963-4894; hatipoglu, mustafa/0000-0001-9910-1650 WOS: 000367218200001 PubMed: 26690093 Background: Leptospirosis is a common zoonotic infection in the world. In patients with leptospirosis, in case of presence of Systemic Inflammatory Response Syndrome (SIRS), clinical and laboratory findings can be mistaken for sepsis due to other causes of infection. The purpose of this study is to assess the clinical and laboratory parameters of patients with leptospirosis in terms of the presence of SIRS and to examine the association of these with mortality. Methods: One hundred fifty-seven patients were included in the study. The patients were classified according to the presence or absence of SIRS and divided into SIRS (+) and SIRS (-). Patient files were retrospectively evaluated. Clinical features and laboratory data were compared, and risk factors associated with mortality were determined. Results: SIRS (+) was found in 70 % (n = 110) of patients who had signs on admission. Comparison of the clinical symptoms and findings of organ systems in the SIRS (+) and SIRS (-) showed that abdominal pain and vomiting were significantly more common in the SIRS (+) than in the SIRS (-) (p = 0.025 and p = 0.046, respectively). BUN and serum creatinine levels were significantly higher in the SIRS (+) than in the SIRS (-) (p = 0.002 and p < 0.001, respectively). In follow-up posterior-anterior chest radiography, pathological findings improved in 58.8 % (n = 40) of patients in the SIRS (+) and 27.3 % (n = 9) of patients in the SIRS (-) (p = 0.003). The mortality rate of the SIRS (+) and SIRS (-) was not significantly different (p = 0.868). Conclusion: In patients with positive SIRS findings, while examining the etiology of sepsis, leptospirosis should come to mind especially in endemic areas for differential diagnosis. Early initiation of antibiotic and supportive therapy can be lifesaving in these patients.

Leblebicioglu, Hakan/0000-0002-6033-8543 WOS: 000356622900019 PubMed: 26122444 …

WOS: 000368479700012, PubMed ID: 26196597, …, Wellcome Trust [100890, 104480/Z/14/Z]

Ecthyma gangrenosum is a rare skin infection caused by Pseudomonas aeruginosa. It is usually seen in immunocompromised and critically ill patients. We report one such case in a previously healthy 20-year old male. Ecthyma gangrenosum can occur in healthy patients without bacteremia.

Objective: The current study investigated the applicability of the VAP prevention bundle and its effect on rates of VAP. Methods: This study was performed in the intensive care units (ICU) of anesthesia (AICU) and the neurology (NICU) in the Medical Faculty of Ondokuz Mayis University from October 2011 to September 2012 (for one year). Mechanically ventilated patients in the ICU for 48 hours were included. The bundle components were patient’s head elevated to 30–45°, assessment of daily extubation status (weaning), peptic ulcer prophylaxis, deep vein thrombosis (DVT) prophylaxis, and oral care with chlorhexidine. The VAP rate and ventilator usage rates were calculated and compared in quarterly periods for one year. Results: In the study, 35 patients developed VAP. There was full compliance with the prevention bundle in 30.5% of cases. No VAP developed in 51 patients whose compliance with the prevention bundle was 100%. In patients (n=35) whose compliance with prevention bundle was more than 50%, VAP (n=6) developed in 19% of the patients. But, in patients (n=35) whose compliance with prevention bundle was less than 50%, VAP (n=29) developed in 82.8% of the patients. There was a significant relationship between compliance with the prevention bundle and development of VAP (P