Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C.

BACKGROUND: Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. MATERIALS AND METHODS: 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. RESULTS: In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. CONCLUSION: We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment.

Evaluation of hepatitis B virus transmission and antiviral therapy among hepatitis B surface antigen-positive pregnant women.

AIM: The aim of the present study was to assess the potential risk of hepatitis B virus (HBV) vertical transmission among Turkish parturient women and to evaluate the efficacy and safety of antiviral agents. MATERIAL AND METHODS: Data were collected retrospectively from 114 HBV-infected pregnant women and their infants in eight health institutions in Turkey. RESULTS: The baseline characteristics of the women were: mean age, 28.3 ± 5.2 years; alanine aminotransferase, 57.4 ± 139.0 U/L; aspartate aminotransferase, 56.6 ± 150.0 U/L; and HBV DNA, 8.3 × 10(7) ± 2.6 × 10(8) copies/mL. Family history of HBV infection was detected in 53.5% (n = 61). In total, 60 (52.6%) pregnant women received tenofovir (60.0%), lamivudine (33.3%) or telbivudine (6.7%) therapy at the median gestational age of 22.2 ± 8.5 (1-36) weeks. All infants were vaccinated and hepatitis B immune globulin was administered, with 81 of them (71.1%) available for follow-up. After completion of HBV vaccination course, 71 (87.7%) infants had protective anti-HBs levels, three (3.7%) were hepatitis B surface antigen-positive, and seven (8.6%) were hepatitis B surface antigen-negative with nonprotective anti-HBs levels. Five of the infants had low gestational birthweight but no other birth defects were observed. CONCLUSION: According to our results, viral load may not be the only effecting factor for transmission of HBV to children of infected mothers. Pregnant women with high viral load should be followed-up closely during pregnancy. They should begin to take tenofovir or telbivudine, which are category B drugs for pregnancy, at the beginning of the third trimester at the latest. We need new treatment strategies; and close follow-up of mothers and children is another important issue.

Risk factors for occupational brucellosis among veterinary personnel in Turkey.

Veterinarians and veterinary technicians are at risk for occupational brucellosis. We described the risk factors of occupational brucellosis among veterinary personnel in Turkey. A multicenter retrospective survey was performed among veterinary personnel who were actively working in the field. Of 712 veterinary personnel, 84 (11.8%) had occupational brucellosis. The median number of years since graduation was 7 (interquartile ranges [IQR], 4-11) years in the occupational brucellosis group, whereas this number was 9 (IQR, 4-16) years in the non-brucellosis group (p<0.001). In multivariable analysis, working in the private sector (odds ratio [OR], 2.8; 95% confidence interval [95% CI], 1.55-5.28, p=0.001), being male (OR, 4.5; 95% CI, 1.05-18.84, p=0.041), number of performed deliveries (OR, 1.01; 95% CI, 1.002-1.02, p=0.014), and injury during Brucella vaccine administration (OR, 5.4; 95% CI, 3.16-9.3, p<0.001) were found to be risk factors for occupational brucellosis. We suggest that all veterinary personnel should be trained on brucellosis and the importance of using personal protective equipment in order to avoid this infection.

The characteristics of patients with chronic hepatitis B in Turkey.

AIM: To evaluate the characteristics of patients with hepatitis B virus (HBV) infection and summarize the treatment modalities. METHODS: By September 30, 2011 the data of 7871 HBsAg (+) patients were complied and analysed according to demographic and medical records (age, sex, laboratory tests, treatment with antiviral agents) in thirty centres of Turkey. RESULTS: Of the 7871 patients 3078 (39.1%) were females; mean (standard deviation) age was 35 (14) years, 3180 (40.4%) were HBsAg positive (+) after admission to a hospital, 1488 (18.9%) after blood donation and 967 (11.9%) were found during routine screening. The HBV prevalence among relatives of HBsAg (+) patients was 1764 (22.4%), and most frequently infected family members were siblings and mothers, 4961 (63.0%) and 2149 (27.3%), respectively). Anti-HDV was negative in 7407 94.1% of patients. Three-fourths of the patients 6383 (81.1%) were HBeAg negative (-). Mean (SD) ALT was 85.8 (266.4) U/L. Majority of patients, 5588 (71.0%) were chronic hepatitis-B patients under treatment, while 2283 (29.0%) were asymptomatic carriers without treatment and only 165 (2.1%) of patients were cirrhotic and 6612 (84.0%) of those were compensated. One-third of the patients 2983 (37.9%) were under a combined treatment, while others were under monotherapy. Lamivudine, entecavir and adefovir were the most frequently used oral therapies, used for 2583 (32.8%), 11.6% and 787 (10.0%) of patients, respectively), while 2975 (37.8%) of patients were under interferon treatment. CONCLUSION: Hepatitis B is still a problem in our country. First task of the physicians and our state should be to prevent the development and spread of the disease with education and vaccination programs, safe blood transfusions, and control of barbers.

Periprosthetic tuberculosis of the knee joint treated with antituberculosis drugs: a case report.

We report a 55-year old man with periprosthetic tuberculosis infection following a total knee arthroplasty surgery performed during an active tuberculosis infection. The patient was conservatively treated with anti-tuberculosis drugs and retention of prosthesis. There was no recurrence during an 18-month follow-up period. Tuberculosis arthritis should be considered in the differential diagnosis in patients with osteoarthritis requiring replacement surgery. Conservative treatment with antituberculosis drugs may be an option in periprosthetic tuberculosis infections without loosening.

The activity of paraoxonase and arylesterase in patients with osteomyelitis.

BACKGROUND: The aim of this study was to evaluate oxidative stress and to determine the activity of paraoxonase and arylesterase in patients with osteomyelitis compared to healthy controls. METHOD: In total, 30 patients diagnosed with osteomyelitis and 30 healthy volunteers were enrolled in the study. Paraoxonase and arylesterase activities were measured spectrophotometrically. Serum lipid hydroperoxide (LOOH) concentrations were measured by ferrous oxidation with xylenol orange (FOX) assay as markers of oxidative stress. RESULTS: Serum paraoxonase and arylesterase activities were significantly lower in patients with osteomyelitis compared to control individuals (all p < 0.05). Serum LOOH concentrations were significantly higher in patients with osteomyelitis than those in controls (p < 0.05). Arylesterase activity was inversely correlated with triglyceride (r =- 0.49; p = 0.005) and cholesterol concentrations (r =- 0.41; p = 0.025). CONCLUSION: In light of the findings obtained from the present study, it may be assumed that decreased activity of serum paraoxonase and increased concentrations of LOOH observed in osteomyelitis patients appear to be related to the increased oxidative stress and inflammatory conditions present in these patients, and may cause a much more severe status of the disease.

Review of 17 cases of neurobrucellosis: clinical manifestations, diagnosis, and management.

BACKGROUND: Neurobrucellosis (NB) is a rare, but important complication of brucellosis. The clinical features vary greatly and, in general, tend to be chronic. Many laboratory procedures are usually employed in the diagnosis of NB. Even though the culture method is the gold standard, growth rate is low and time consuming. Thus the rate of sequelae and mortality increase in case of a delay in treatment. Therefore it is necessary to perform serological tests in both serum and cerebrospinal fluid (CSF) in suspected patients. In this study we aim to evaluate clinical features, diagnosis, and treatment of patients with NB. METHODS: We enrolled 17 patients diagnosed with NB. Clinical features, cultures, serological tests, additional laboratory findings, and CSF analyses were recorded for all patients. RESULTS: There were 14 female and 3 male patients. Ten patients presented with neuropsychiatric symptoms and signs (aphasia, diplopia, hemiparesis, facial paralysis, tremor, ataxia, depression, personality disorder, and hallucinations). Serum standard agglutination test (SAT) was negative in 4 (23.5%) patients and serum Coombs' test was negative in 2 (11.7%). CSF SAT was negative in 4 (23.5%) patients and CSF Coombs was negative in 3 (17.6%) patients. B. melitensis grew in the blood of 6 (35.2%) patients and in the CSF of 3 (17.6%). Treatment protocol for 11 patients consisted of ceftriaxone, rifampicin, and doxycyline for a period of four weeks, followed by rifampicin and doxycyline for an additional four weeks. The remaining patients were given different treatment combinations. One patient died, mild sequelae was present in another patient and the remaining patients recovered without any sequelae. CONCLUSION: NB should be considered in the differential diagnosis of neurological and psychiatric cases that are encountered in endemic areas for brucellosis. In order to prevent overlooking this diagnosis, Coombs' test should be performed in both CSF and serum.

Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results of the Istanbul study.

No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

Assessment of the requisites of microbiology based infectious disease training under the pressure of consultation needs.

BACKGROUND: Training of infectious disease (ID) specialists is structured on classical clinical microbiology training in Turkey and ID specialists work as clinical microbiologists at the same time. Hence, this study aimed to determine the clinical skills and knowledge required by clinical microbiologists. METHODS: A cross-sectional study was carried out between June 1, 2010 and September 15, 2010 in 32 ID departments in Turkey. Only patients hospitalized and followed up in the ID departments between January-June 2010 who required consultation with other disciplines were included. RESULTS: A total of 605 patients undergoing 1343 consultations were included, with pulmonology, neurology, cardiology, gastroenterology, nephrology, dermatology, haematology, and endocrinology being the most frequent consultation specialties. The consultation patterns were quite similar and were not affected by either the nature of infections or the critical clinical status of ID patients. CONCLUSIONS: The results of our study show that certain internal medicine subdisciplines such as pulmonology, neurology and dermatology appear to be the principal clinical requisites in the training of ID specialists, rather than internal medicine as a whole.

Serum paraoxonase and arylesterase activities in various forms of hepatitis B virus infection.

The aim of this study was to determine and evaluate the activity of paraoxonase and arylesterase enzymes in various clinical forms of hepatitis B infection and to investigate the correlation between these parameters and chronic disease course/fibrosis. Overall, 40 patients diagnosed as hepatitis B carriers (CIHBV), 40 chronic active hepatitis B (CAHBV) patients, and 40 healthy adults (control group) between 18 and 65 years of age were enrolled the study. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. Their activities were significantly lower in patients with CAHBV compared with CIHBV patients or with control group patients (P<0.001). There was a negative correlation between alanine aminotransferase levels and the activity of paraoxonase and arylesterase (r = -0.38, P = 0.001 and r = -0.28, P = 0.002, respectively). A statistically significant negative correlation was found between arylesterase activity in the sera of CAHBV patients and HBV DNA levels (ρ = -0.33, P = 0.03). On the contrary, no correlation was found between paraoxonase levels and HBV DNA levels (P>0.05). The histology activity index of CAHBV patients did not correlate with paraoxonase and arylesterase activities (P>0.05). In light of these findings, it may be assumed that during the progression of an inactive hepatitis B carrier to being actively infected, reduced paraoxonase and arylesterase activities may be observed.

A rare case of seronegative neurobrucellosis.

Neurobrucellosis is one of the complications of brucellosis. We report a rare case of a 17-year-old girl with seronegative neurobrucellosis and depression and diplopia. Results of agglutination tests for Brucella both in serum and CSF were negative. Diagnosis was made only by positive culture of Brucella mellitensis with inoculation of the patient's cerebrospinal fluid in a BACTEC 9050 System. The patient was successfully treated using ceftriaxone, doxycycline and rifampicin therapy for six months.

[Post-operative bacteremia caused by multidrug-resistant Aerococcus viridans in a patient with gall bladder cancer]. / Safra kesesi kanseri olan bir hastada operasyon sonrasi gelisen cok ilaca dirençli Aerococcus viridans bakteriyemisi.

Aerococcus viridans is a gram-positive, catalase and oxidase negative, microaerophylic and non-motile coccus which is rarely associated with human infections such as endocarditis, meningitis, artritis and bacteremia. We report a case of bacteremia due to A. viridans in a 61-years-old man with malignant gall bladder neoplasm. The patient underwent a surgical operation and on the 5th day of operation he had severe abdominal pain, vomiting, high fever and discharge from operation site. He was transferred to intensive care unit and blood cultures were obtained. Piperacillin-tazobactam was initiated as empirical therapy. Blood cultures performed in Bactec system (Becton Dickinson, USA) yielded catalase negative, gram-positive cocci in tetrads. The isolate was pyrrolidonyl aminopeptidase (PYR) positive and produced alfa-hemolysis on sheep blood agar. These cocci were identified as A. viridans by Vitek 2 Compact System (BioMerieux, France) and identification was confirmed by using mini API System (BioMerieux, France). Antibiotic susceptibility testing performed with Kirby-Bauer disk diffusion method revealed that the isolate was susceptible to trimethoprim-sulfamethoxazole, tigecycline and vancomycin and resistant to penicillin, ampicillin, piperacillin-tazobactam, ceftriaxone, erythromycin, clindamycin and amikacin. The patient was successfully treated with vancomycin (2 x 1 g/day) and completely recovered without complication. In conclusion, A. viridans should be suspected as an opportunistic pathogen in immunocompromised patients and these patients should be treated according to the antibiotic susceptibility test results.