Mustafa Sunbul

Hepatitis B virus genotypes: global distribution and clinical importance.

At least 600000 individuals worldwide annually die of hepatitis B virus (HBV)-related diseases, such as chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Many viral factors, such as viral load, genotype, and specific viral mutations, are known to affect disease progression. HBV reverse transcriptase does not have a proofreading function, therefore, many HBV genotypes, sub-genotypes, mutants, and recombinants emerge. Differences between genotypes in response to antiviral treatment have been determined. To date, 10 HBV genotypes, scattered across different geographical regions, have been identified. For example, genotype A has a tendency for chronicity, whereas viral mutations are frequently encountered in genotype C. Both chronicity and mutation frequency are common in genotype D. LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes. Pathogenic differences between HBV genotypes explain disease intensity, progression to LC, and HCC. In conclusion, genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.

A national survey of surgical antibiotic prophylaxis in Turkey.

OBJECTIVE To assess the quality of antibiotic prophylaxis for clean and clean-contaminated elective surgical procedures. DESIGN A cross-sectional, country-wide survey. SETTING Thirty-six hospitals in 12 cities in Turkey. PARTICIPANTS Four hundred thirty-nine surgeons from 6 different specialties who performed selected procedures of interest. METHODS A random sample of surgeons from different hospitals was selected. A standardized data collection form was used to record the type of procedure, the names, doses, timing of the first doses, and duration of antibiotics, important decisive factors, and problems in the management of prophylactic antibiotic use for surgical procedures. RESULTS Fifty-five percent of surgeons addressed completed the survey. For clean-contaminated procedures, 6% of surgeons did not use antibiotic prophylaxis, whereas 88% used more than a single dose. Inappropriate antibiotics were chosen for 32% of procedures. In 39% of procedures, the first dose of antibiotics was not administered during induction of anesthesia. Duration of prophylaxis was longer than 24 hours in 80% and longer than 48 hours in 46% of all procedures. Only 112 surgeons (26%) were using definitely appropriate prophylaxis in all ways. Multivariate analysis revealed that surgeons in university hospitals (OR, 2.353; CI95, 1.426-3.884; P = .001) and general surgeons (OR, 4.986; CI95, 2.890-8.604; P < .001) used antibiotic prophylaxis more appropriately. Patients not covered by health insurance (OR, 0.417; CI95 0.225-0.772; P < .001) were associated with inappropriate prophylaxis. CONCLUSION Given the high frequency of antibiotics prescribed for surgical prophylaxis in Turkey, adherence to surgical prophylaxis guidelines is urgently needed.

Thwaites’ Diagnostic Scoring and the Prediction of Tuberculous Meningitis

Objective: This study was conducted to investigate the applicability of Thwaites’ diagnostic criteria in order to differentiate tuberculous from bacterial meningitis. Material and Methods: The study was done retrospectively in HIV-negative patients (n = 126) with meningitis. Of the 126 patients, 103 had bacterial meningitis and 23 patients had tuberculous meningitis. The diagnosis was confirmed microbiologically in 59 and 12 patients with bacterial and tuberculous meningitis, respectively. The prediction of tuberculous meningitis was determined by Thwaites’ diagnostic scoring using parameters such as age, history of illness, white blood cell count, total cerebrospinal fluid (CSF) white cell count and the percent of neutrophils in CSF. The diagnostic value of the model was assessed by calculating the area under the receiver operating characteristic (ROC) curves. Results: The sensitivity and the specificity of Thwaites’ diagnostic scoring were 95.6% (22/23) and 70.8% (73/103), respectively. In microbiologically proven cases the sensitivity and the specificity were 91.7% (11/12), 79.7% (57/59), respectively. The area under the ROC curve value for the diagnostic scoring was 0.92. Conclusions: Thwaites’ diagnostic score was found to be helpful in differential diagnosis of tuberculous meningitis, however, the usefulness of diagnostic scoring should be validated in large series especially in patients with viral meningitis and low CSF glucose levels.

Efficacy of tigecycline/colistin combination in a pneumonia model caused by extensively drug-resistant Acinetobacter baumannii

Due to increasing drug resistance, available antimicrobial options are limited in the treatment of Acinetobacter baumannii infections. Particularly in cases caused by extensively drug-resistant (XDR) A. baumannii, combination regimens must also be taken into consideration. In this study, the efficacies of tigecycline, colistin and tigecycline/colistin combination on bacterial counts in lung tissue were investigated in a rat pneumonia model. One A. baumannii strain resistant to all antimicrobial agents except tigecycline and colistin was selected for the study. In vivo studies revealed a >3 log reduction in bacterial counts in the tigecycline, colistin and combination groups at 24 h and 48 h compared with the control group. No significant differences were determined between colistin, tigecycline and combination groups (P>0.05). On the other hand, differences between treatment groups and the control group were statistically significant (P=0.01). A greater reduction in bacterial counts was observed at 48 h compared with 24 h in the tigecycline group than in the colistin group (P=0.038 and P=0.139, respectively); the most significant decrease between 24 h and 48 h was observed in the combination group (P=0.014). Despite detection of in vitro synergistic activity in this study, no statistically significant differences were found between colistin, tigecycline and combination treatments in terms of efficacy on bacterial counts in lung tissue. In the treatment of infections with a high mortality rate such as pneumonia caused by XDR A. baumannii, combining tigecycline with colistin during the first 48 h and continuing treatment with one of these agents seems a rational approach.

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 ≈ 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.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.

Antibiotic prescribing and urinary tract infection.

The aim of this study was to evaluate the diagnostic and therapeutic approach to urinary tract infections (UTIs) by primary care physicians, in Samsun, Turkey. Data were obtained from the records of 2083 visits at eight primary care areas. Trained research students were stationed on site at each of the eight primary care centres between 1 June, 1999 and 1 July, 1999. Patients who had acute cystitis, recurrent UTIs, acute pyelonephritis and acute urethritis were included in the study. A total of 2083 office visits were recorded and 419 (20.1%) of the patients had UTIs and acute urethritis. Antibiotics were prescribed for 94.7% of the patients with UTIs and urethritis. Some 74% of prescriptions were consistent with current recommendation, but only 41% of the antibiotic prescriptions were rational according to dosage, dosage interval and duration of therapy. Urinary antiseptic agents were prescribed to 75% of patients with UTIs. These data indicate that polypharmacy is widespread in our region; primary care physicians need to review their knowledge about the diagnosis and treatment of UTIs and acute urethritis.

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

Weil's Disease: Report of 12 Cases

The epidemiological distribution and clinical features of 12 cases of Weils disease from Turkey, are reviewed. The disease is most common in male farmers from rural areas. Myalgia and jaundice were recorded in all patients. Signs included vomiting in 9 patients, haemorrhages in 6, and renal function was impaired in 6. Creatine phosphokinase levels were found above normal limits in 75% of the cases. Leptospires were demonstrated with dark-field microscopy in the blood of 9 and in the urine of 5 of these patients. The diagnosis was confirmed with microscopic agglutination test (MAT) as well as with ELISA. Ig M antibodies were detected in 11 (92%) of the patients and is an accurate marker for acute leptospirosis. Penicillin was used for therapy and the outcome was favorable in 10 patients. Two patients died. It should be kept in mind that leptospirosis is an extremely severe disease which requires appropriate examinations at the right moment.

Results of a Multinational Study Suggest the Need for Rapid Diagnosis and Early Antiviral Treatment at the Onset of Herpetic Meningoencephalitis

ABSTRACT 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.

Acute renal failure in leptospirosis in the black-sea region in Turkey

Leptospirosis is an infectious disease caused by pathogenic leptospires and is characterized by a broad spectrum of clinical manifestations, varying from inappearent infection to fulminant, fetal disease. Eighty-five to 90% of leptospirosis infections are self-limiting. However, 5–10% of infection by L.interrogans can cause renal tubular damage, microvascular injury, acute renal failure (ARF), and interstitial nephritis.We studied 36 patients with leptospirosis. Twenty-seven (65%) cases of 36 patients had ARF. Fourteen (51%) had nonoliguric ARF. In thirteen (48%) oliguria appeared on the third or fourth days of hospitalization. Serum BUN, creatinine, serum bilirubine, ALT, AST, potassium and thrombocytopenia levels were higher in oliguric than nonoliguric patients (p < 0.05). However, serum sodium, CPK levels were not different between oliguric and nonoliguric groups (p > 0.05). Thirteen patients (48%) needed in renal replacement therapy (RRT). 8 of them were treated by hemodialysis (HD) alone and 5 patients by HD in combination with hemoperfusion. Twenty-five patients (92%) recovered completely after 3–5 weeks. Two patients (7.4%) who had severe hepatorenal and hemorrhagic syndromes, died.We concluded that till now leptospirosis is actual problem for nephrologist in the developing countries because of very high percentage of renal disease, with good prognosis in patients without multiorgan failure and early treatment.