Healthcare-associated Crimean-Congo haemorrhagic fever in Turkey, 2002-2014: a multicentre retrospective cross-sectional study.

Healthcare-related transmission of Crimean-Congo haemorrhagic fever (CCHF) is a well-recognized hazard. We report a multicentre retrospective cross-sectional study undertaken in Turkey in 2014 in nine hospitals, regional reference centres for CCHF, covering the years 2002 to 2014 inclusive. Data were systematically extracted from charts of all personnel with a reported health care injury/accident related to CCHF. Blood samples were tested for CCHF IgM/IgG by enzyme-linked immunosorbent assay and/or viral nucleic acid detection by PCR after the injury. Fifty-one healthcare-related exposures were identified. Twenty-five (49%) of 51 resulted in laboratory-confirmed infection, with a 16% (4/25) overall mortality. The main route of exposure was needlestick injury in 32/51 (62.7%). A potential benefit of post-exposure prophylaxis with ribavirin was identified.

Differences in the availability of diagnostics and treatment modalities for chronic hepatitis B across Europe.

The prevalence and management of chronic hepatitis B virus (HBV) infection differ among European countries. The availability and reimbursement of diagnostics and drugs may also vary, determining distinct treatment outcomes. Herein, we analyse differences in medical facilities for the care of patients with chronic HBV infection across Europe. A survey was sent to the members of the ESCMID Study Group for Viral Hepatitis, all of whom are experts in chronic HBV infection management. The comprehensive survey asked questions regarding hepatitis B surface antigen (HBsAg) prevalence, the availability of diagnostics and drugs marketed, and distinct clinical practice behaviours in the management of chronic HBV infection. World Bank data were used to assess the economic status of the countries. With 16 expert physicians responding (69%), the HBsAg prevalence rates were <1% in France, Hungary, Italy, The Netherlands, Portugal, Spain, and the UK, intermediate (1-5%) in Turkey, Romania, and Serbia, and high (>5%) in Albania and Iran. Regarding the availability and reimbursement of HBV diagnostics (HBV DNA and liver stiffness measurement), HBV drugs (interferon, lamivudine, tenofovir, and entecavir), HBV prophylaxis, and duration of HBeAg-positive and HBeAg-negative HBV infection, the majority of high-income and middle-income countries had no restrictions; Albania, Iran and Serbia had several restrictions in diagnostics and HBV drugs. The countries in the high-income group were also the ones with no restrictions in medical facilities, whereas the upper-middle-income countries had some restrictions. The prevalence of chronic HBV infection is much higher in southern and eastern than in western European countries. Despite the availability of European guidelines, policies for diagnostics and treatment vary significantly across European countries.

Current knowledge and future perspectives on acute hepatitis C infection.

Acute hepatitis C virus (HCV) infections are frequently seen worldwide in certain risk groups, with an annual incidence rate varying between 0.08% and 66%. Although this incidence is substantial, a delayed diagnosis during chronic infection is most often made in the absence of clinical symptoms in the acute phase of the infection. Currently used methods to diagnose acute HCV infection are IgG antibody seroconversion and repeated HCV RNA measurements, although no definitive diagnostic test is currently available. Progress in the field of adaptive and innate immune responses has aided both advances in the field of HCV vaccine development and a more basic understanding of viral persistence. The rapid changes in the treatment of chronic HCV infection will affect therapeutic regimens for acute HCV infection in the coming years, leading to shorter treatment courses and pegylated interferon-free modalities. This review gives an overview of the current knowledge and uncertainties, together with some future perspectives on acute hepatitis C epidemiology, virology, immunology, and treatment.

Predictors associated with treatment initiation and switch in a real-world chronic hepatitis B population from five European countries.

In Europe, healthcare systems differ between countries and different factors may influence Chronic hepatitis B (CHB) treatment choices in different counties. This analysis from a prospective, longitudinal, non-interventional study in five EU countries aimed to explore determinants associated with treatment initiation or switch in patients with CHB. A total of 1267 adult patients with compensated CHB in Germany, France, Poland, Romania and Turkey were prospectively followed for up to 2 years (March 2008-December 2010). Determinants of treatment initiation or switch were analysed using multivariate Cox proportional hazards regression. Median time since CHB diagnosis was 2.6 (0-37.7) years. Among 646 treatment-naïve patients, the probability of treatment initiation during follow-up was higher: in Germany (P = 0.0006), Poland (P < 0.0001) and Romania (P = 0.0004) compared with Turkey; in patients with alanine transaminase (ALT) 1-2 × upper limit of normal (ULN) (P = 0.0580) or >2 × ULN (P = 0.0523) compared with ALT ≤ 1 × ULN; and in patients with hepatitis B virus (HBV) DNA ≥ 2000 IU/mL (P < 0.0001) compared with HBV DNA <2000 IU/mL or undetectable. Among 567 treated patients, 87 switched treatment during follow-up. The probability of treatment switch was higher: in France (P = 0.0029), Germany (P = 0.0078) and Poland (P = 0.0329) compared with Turkey; and in patients with HBV DNA <2000 (P < 0.0001) or ≥ 2000 IU/mL (P < 0.0001), compared with undetectable. Viral load and ALT level were identified as the major drivers of treatment initiation. HBV DNA level was also a significant determinant of treatment switch. Results were statistically different across EU countries.

Effectiveness of a multidimensional approach for prevention of ventilator-associated pneumonia in 11 adult intensive care units from 10 cities of Turkey: findings of the International Nosocomial Infection Control Consortium (INICC).

PURPOSE: To evaluate the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional approach on the reduction of ventilator-associated pneumonia (VAP) in adult patients hospitalized in 11 intensive care units (ICUs), from 10 hospitals, members of the INICC, in 10 cities of Turkey. METHODS: A prospective active before-after surveillance study was conducted to determine the effect of the INICC multidimensional approach in the VAP rate. The study was divided into two phases. In phase 1, active prospective surveillance of VAP was conducted using the definitions of the Centers for Disease Control and Prevention National Health Safety Network, and the INICC methods. In phase 2, we implemented the multidimensional approach for VAP. The INICC multidimensional approach included the following measures: (1) bundle of infection control interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback of VAP rates, and (6) performance feedback of infection control practices. We compared the rates of VAP obtained in each phase. A time series analysis was performed to assess the impact of our approach. RESULTS: In phase 1, we recorded 2,376 mechanical ventilator (MV)-days, and in phase 2, after implementing the multidimensional approach, we recorded 28,181 MV-days. The rate of VAP was 31.14 per 1,000 MV-days during phase 1, and 16.82 per 1,000 MV-days during phase 2, amounting to a 46 % VAP rate reduction (RR, 0.54; 95 % CI, 0.42-0.7; P value, 0.0001.) CONCLUSIONS: The INICC multidimensional approach was associated with a significant reduction in the VAP rate in these adult ICUs of Turkey.

Device-associated hospital-acquired infection rates in Turkish intensive care units. Findings of the International Nosocomial Infection Control Consortium (INICC).

We conducted a prospective study of targeted surveillance of healthcare-associated infections (HAIs) in 13 intensive care units (ICUs) from 12 Turkish hospitals, all members of the International Nosocomial Infection Control Consortium (INICC). The definitions of the US Centers for Disease Control and Prevention National Nosocomial Infections Surveillance System (NNISS) were applied. During the three-year study, 3288 patients for accumulated duration of 37 631 days acquired 1277 device-associated infections (DAI), an overall rate of 38.3% or 33.9 DAIs per 1000 ICU-days. Ventilator-associated pneumonia (VAP) (47.4% of all DAI, 26.5 cases per 1000 ventilator-days) gave the highest risk, followed by central venous catheter (CVC)-related bloodstream infections (30.4% of all DAI, 17.6 cases per 1000 catheter-days) and catheter-associated urinary tract infections (22.1% of all DAI, 8.3 cases per 1000 catheter-days). Overall 89.2% of all Staphylococcus aureus infections were caused by methicillin-resistant strains, 48.2% of the Enterobacteriaceae isolates were resistant to ceftriaxone, 52.0% to ceftazidime, and 33.2% to piperacilin-tazobactam; 51.1% of Pseudomonas aeruginosa isolates were resistant to fluoroquinolones, 50.7% to ceftazidime, 38.7% to imipenem, and 30.0% to piperacilin-tazobactam; 1.9% of Enterococcus sp. isolates were resistant to vancomycin. This is the first multi-centre study showing DAI in Turkish ICUs. DAI rates in the ICUs of Turkey are higher than reports from industrialized countries.

In vitro bacterial adherence to teicoplanin and calcium sulfate-soaked bone cement.

The aim of this study was to assess in vitro the improvement in release kinetics for teicoplanin and the inhibition of bacterial adhesion on calcium sulfate-soaked PMMA discs. Calcium sulfate has been used in vivo and shown to be biocompatible, and prevention of bacterial adhesion may be expected with calcium sulfate-soaked polymethylmethacrylate (PMMA). Discs were made by adding teicoplanin and calcium sulfate in powder form to PMMA powder. The antibiotic concentration eluted from PMMA discs was assayed by agar diffusion assay. Nonadherent bacteria were removed by washing and adherent bacteria were detached by sonication. The suspension including nonadherent bacteria was seeded on sheep blood agar plate and incubated for 24 h at 37 degrees C for the growth of microorganisms. The teicoplanin released from discs containing calcium sulfate was higher than that released from discs which had not been soaked with calcium sulfate. The count of bacteria adhering to the calcium sulfate-soaked discs was lower than that from the discs without calcium sulfate. In conclusion, the addition of calcium sulfate to teicoplanin-loaded PMMA bone cement may provide local antibiotic concentrations higher than MIC values due to increased antibiotic release. Furthermore, calcium sulfate was found to be effective in reducing bacterial adherence to treated discs.

Acute hepatitis B virus infection in Turkey: epidemiology and genotype distribution.

The aim of this study was to investigate the prevalence of hepatitis B virus (HBV) genotypes in Turkey. Epidemiological and clinical data for 158 patients with acute HBV infection from 22 medical centres in the period February 2001 to February 2002 were collected prospectively. HBV genotyping was based on analysis of restriction fragment length polymorphisms and nested PCR. There were 59 female and 99 male patients, with a mean age of 34.2 +/- 15.6 years. The most common probable transmission route was blood contact in 63 (41.1%) cases, but was unknown in 78 (49.4%) cases. The mean alanine aminotransferase level was 1718 +/- 1089 IU/L. Four of the 158 patients (2.5%) died because of fulminant hepatitis. One year after discharge, 11 (10.6%) of 103 cases were positive for hepatitis B surface antigen (HBsAg) and 80 (77.7%) were positive for anti-HBsAg. Genotype determination was unsuccessful in 11 cases because of a negative PCR; genotype D was found in the remaining 147 cases. The results suggested that acute HBV infection constitutes a significant health problem in Turkey and that genotype D is predominant.

Distinguishing hepatitis B virus (HBV) genotype D from non-D by a simple PCR.

Different HBV genotypes have characteristic geographical distribution, which is important epidemiologically. HBV strains have been classified into eight different genotypes (A-H) on the basis of >8% differences in the entire genomic sequence. Genotypes A and D are predominant in Europe, Africa, and the USA, genotypes B and C are restricted to East Asia, genotype E is found in Africa, and genotype F is found in indigenous populations in Central and South America. Genotype D is prevalent in the Turkish population. HBV genotype D shows a 33-bp deletion in the pre-S1 region that accounts for their smaller genomic size (3182 bp). This deletion can be used to facilitate the identification of genotype D. A primer in the pre-S1 region was designed to discriminate genotype D from non-D by PCR. Sixty genotype D (40 acute and 20 chronic) and 4 genotype A sera identified by restriction fragment length polymorphism (RFLP) were included in the study. Using this simple PCR method, all genotype D sera were identified correctly and the test was able to detect HBV DNA at 1000 genomes per ml. An advantage of this method is that it can differentiate in a mixture of genotypes (genotype D from non-D) provided that one isn't present below 1 x 10(4) copies/ml. In conclusion this method is rapid (approximately 5h) and it will contribute to the epidemiological study of HBV in high prevalence areas of genotype D. It can also differentiate between genotype D from non-D in cases of co-infection.

Resistance emergence among P. aenrginosa in a rat thigh-abscess model. Comparison of imipenem and meropenem treatment.

Resistance emergence to carbapenem antibiotics was studied in a rat-thigh abscess model. Abscesses were developed in three groups with a total of 15 P. aeruginosa strains (three rats per strain). Groups were assigned to imipenem or meropenem treatment while one was left antibiotic-free. Test strains were fully susceptible to these antibiotics and the "Mutant Preventing Concentrations" of imipenem and meropenem over these strains were comparable. Antibiotic serum levels, assessed by serum bioassay test, were similar among therats. After four days, rats (n=45) were sacrificed and carbapenem resistant mutants were selected on imipenem (4 mg/L) and meropenem (4 mg/L) supplemented agar plates. Resistant variants of three strains, from four abscesses, were detected; one in the meropenem group, two in the imipenem and one in the untreated group. The MICs of imipenem and meropenem for the mutants were increased fourfold times or even higher of their counterparts. Resistance emergence under antibiotic pressure in P. aeruginosa has been shown in various conditions. To our knowledge, however, resistance emergence in abscess and also the comparison of imipenem and meropenem in this regard has not been studied before.

Informal consultations in infectious diseases and clinical microbiology practice.

Informed consultation between physicians is an important part of medical practice. The aim of the study was to evaluate the nature and frequency of such consultations in infectious diseases and clinical microbiology practice. This study was done in five university hospitals. Twenty-one infectious diseases and clinical microbiology specialists participated in informal ('curbside') consultations. In a written questionnaire, physicians were asked to report the number and nature of the informal consultations (ICs) they were asked to provide. A total three hundred and sixty-two such consultations were carried out during a three-month period. The ICs occurred most frequently in the hospital (82.3%). Most of the ICs from outside the hospital were by telephone. Most of the ICs (54.4%) were requested by fellows of specialists. 78.7% of the ICs were requested during working hours. 58.8% of consultations took less than 5 min, 18.8% took 6-10 min, 15.2% took 11-20 min, and 7.2% took over 20 min. The four most common reasons for obtaining ICs were to: help to select an appropriate treatment plan (41.4%), help to select an appropriate prophylaxis (19.3%), interpret laboratory data (10.2%), and provide information about antibiotics (10.2%). 30.1% of ICs resulted in subsequent formal consultation and only four patients (1.1%) were transferred to the consultants' clinics. Informal consultations are a frequent occurrence in the practice of infectious diseases and clinical microbiology (ID&CM). Physicians use this sort of consultation to select an appropriate treatment plan and obtain medical information. This study confirms the importance of the ID&CM specialists as a resource for medical personnel.

Hospital-acquired urinary tract infections in Turkey: a nationwide multicenter point prevalence study.

Hospital-acquired urinary tract infection (UTI) is the most common infection acquired in hospitals. The aim of the study was to determine the prevalence of UTIs in Turkey. A nationwide one day point-prevalence survey was conducted. Centers for Diseases Control and Prevention (CDC) standard definitions for nosocomial UTIs were used. Data were collected by detailed uniform questionnaires for each patient with UTI. A total of 13269 patients were investigated, the number of patients observed in each hospital varied from 21 to 1329 patients, an average of 458 patients per prevalence study per hospital. The overall prevalence of UTI was 1.7%. Fifty-eight (26.1%) of the patients had sepsis or septic shock. Twenty-five (11.3%) patients had culture-proven bloodstream infection. Over 60% (65.3%) of urinary tract infections were associated with urinary catheters. Overall, 78.4% of UTIs were culture-proven. Escherichia coli (32.4%) was the most common reported pathogen, followed by Klebsiella spp. (17.0%), Candida spp. (12.8%),Pseudomonas aeruginosa (11.7%) and enterococci 8.5%. The prevalence of ampicillin-resistant E. coli was 23.9% and accounted for 73.8% of all E. coli isolated from UTI 8.2%, and 24.6% of E. coli were resistant to quinolones and ceftriaxone, respectively. There were no resistance to carbapenems in E. coli but 6.25, 40.6, 59.4% of Klebsiella spp. were resistant to carbapenems, quinolones and ceftriaxone, respectively. The results of this first national point-prevalence study offers a reliable measure of the prevalence of nosocomial UTIs at hospitals in Turkey and provides a baseline for future studies which will enable the monitoring of trends over time.

Thrombocytopenia complicating the clinical course of leptospiral infection.

Leptospirosis can present with a wide clinical spectrum, and haematological manifestations are often apparent. We retrospectively analysed platelet counts in 49 patients with leptospirosis. Forty-three patients (87.8%) had thrombocytopenia. Mean baseline platelet counts rose from 69 x 10(9)/l to 151 x 10(9)/l following treatment. Haemorrhagic episodes were observed in 11 patients. Platelet nadir was 29 x 10(9)/l in the group experiencing bleeding and 64 x 10(9)/l in the remainder. Six patients died due to bleeding and one due to sepsis. Thirty-six patients (73.5%) had acute renal failure; their means platelet count was 46 x 10(9)/l. Liver enzyme levels were elevated in all patients. Thrombocyte count, liver enzyme levels and bilirubin levels were significantly correlated. Forty-three (87.8%) patients showed signs of sepsis; mean thrombocyte count was 46 x 10(9)/l in these patients, and 133 x 10(9)/l in those without sepsis. Multiple organ involvement and fulminant disease is usually associated with renal failure and/or thrombocytopenia in leptospirosis.

Surveillance of antimicrobial resistance in gram-negative isolates from intensive care units in Turkey: analysis of data from the last 5 years.

A multicenter antimicrobial surveillance program was established in Turkey in 1995 to monitor the predominant Gram-negative pathogens from intensive care units (ICUs) and antimicrobial resistance patterns of these isolates. Sixteen hospitals participated in the study and a total of 1479 isolates from 1,100 patients were collected. The isolates were tested for their susceptibility against 13 antibiotics by E-test method. Minimum inhibitory concentrations (MICs) for each isolate were determined for imipenem, ceftazidime, ceftazidime-clavulanate, cefoperazone-sulbactam, ceftriaxone, cefepime, cefuroxime, piperacillin-tazobactam, ticarcillin-clavulanate, gentamicin, amikacin and ciprofloxacin. The most common isolates were Pseudomonas spp. (28.2%), Escherichia coli (19.2%) and Klebsiella spp. (19.1%). We found very high resistance rates to all major antibiotics that are used to treat serious infections. Although imipenem is the most active agent, it had an overall susceptibility rate of 68%. Half of the tested Klebsiella spp. strains were found to produce ESBL. This is a very high rate when compared with the literature. Cross-resistance among species was also investigated. 52% of ciprofloxacin-resistant strains were also resistant to imipenem, 80% to ceftazidime, 97% to ceftriaxone, 86% to amikacin and 19% of imipenem-resistant strains were susceptible to ceftazidime and 18% to amikacin. When susceptibilities of the years 1995 and 1999 were compared, the most interesting finding was the decrease in resistance to 3rd generation cephalosporins. In conclusion, this national clinical isolate database shows that resistance rates are high, the change over years is not predictable and continuous surveillance is necessary to monitor antimicrobial resistance and to guide antibacterial therapy.

Physicians' antibiotic prescribing habits for upper respiratory tract infections in Turkey.

The aim of this study was to evaluate the antibiotic prescription rates for upper respiratory tract infections (uRTIs) by primary care physicians in Samsun, Turkey. Data were obtained from the records of 2,083 visits to 8 primary care areas. Trained research students were stationed on site at each of the 8 primary care areas during the study period. Clinical features of patients were documented on a standardized form. Patients who had acute pharyngitis, acute sinusitis, acute otitis media (AOM) and common cold were included in the study. This survey was conducted between June 1, 1999 and July 1, 1999. A total of 2,083 office visits were recorded and 502 (24.1%) of the patients had uRTIs. Physicians approached these conditions empirically, with only 2.9% of patients having a diagnostic test at initial examination. Antibiotics were prescribed for 461 patients (91.8%) with uRTIs (common cold: 41.9%, acute pharyngitis: 94.7%, acute sinusitis: 94.1% and AOM: 100%). 11.5% of the antibiotic prescriptions were inconsistent with current recommendations derived from the literature. Inadequate antibiotic prescribing was documented in 29.7% of antibiotic prescriptions. Errors were frequent in relation to dosage, dosage interval and duration of therapy. Overuse of antibiotics is widespread in our geographic area. Both administrative and educational intervention should be implemented to improve antibotic prescribing habits at the primary health care level to reduce the unnecessary use of antimicrobial agents.

The organization of hospital infection control in Turkey.

This article describes the current organization of infection control in Turkey in regard to regulations, functions and responsibilities of infection control committees and the national NosoLINE project. Also, incidence and prevalence of hospital infections and antimicrobial resistance in Turkey are reported.

Rattus norvegicus acting as reservoir of leptospira interrogans in the Middle Black Sea region of Turkey, as evidenced by PCR and presence of serum antibodies to Leptospira strain.

Leptospirosis, a common form of zoonosis, especially in rainy countries, is caused by Leptospira interrogans. In our region of Turkey this type of disease has often been encountered in connection with rice harvesting and we therefore attempted to evaluate the prevalence of L. interrogans in wild rats in our region. Fifty-nine Rattus norvegicus rats were trapped alive in different areas of an approximately 100 km stretch of seashore in the Middle Black Sea region of Turkey. L. interrogans was determined by PCR in sera, kidney and brain tissue. Sixteen (27.1%) kidney samples and 10 brain tissue samples (16.9%) were positive for L. interrogans. No PCR positivity was seen in sera samples. Five sera were positive by microagglutination test. A large proportion of wild rats in our region were found to be carriers of L. interrogans. We conclude that people who are exposed to rat urine in their daily life are at risk of acquiring L. interrogans.