The efficacy of mesenchymal stem cell treatment and colistin-fosfomycin combination on colistin-resistant Acinetobacter baumannii sepsis model.

INTRODUCTION: This study examines the role of mesenchymal stem cells (MSCs) in an experimental sepsis model developed with colistin-resistant Acinetobacter baumannii (CRAB). MATERIALS AND METHODS: BALB-c mice were divided into treatment groups (MSC, MSC + colistin (C)-fosfomycin (F), and C-F and control groups (positive and negative)). CRAB was administered to mice through intraperitoneal injection. Three hours later, C, F, and MSC were given intraperitoneally to the treatment groups. Colistin administration was repeated every 12 h, F administration was done every 4 h, and the second dose of MSC was administered after 48 h. Mice were sacrificed at 24 and 72 h. The bacterial load was determined as colony-forming units per gram (cfu/g). Histopathological examination was conducted on the left lung, liver, and both kidneys. IL-6 and C-reactive protein (CRP) levels in mouse sera were determined by enzyme-linked immunosorbent assay. RESULTS: Among the treatment groups, the C-F group had the lowest colony count in the lung (1.24 ± 1.66 cfu/g) and liver (1.03 ± 1.08 cfu/g). The highest bacterial clearance was observed at 72 h compared to 24 h in the MSC-treated groups (p = 0.008). The MSC + C-F group showed the lowest histopathological score in the liver and kidney (p = 0.009). In the negative control group, the IL-6 level at the 24th hour was the lowest (p < 0.001). Among the treatment groups, the CRP level was the lowest in the MSC + C-F group at 24 and 72 h. CONCLUSION: In a CRAB sepsis model, adding MSCs to a colistin-fosfomycin treatment may be beneficial in terms of reducing bacterial loads and preventing histopathological damage.

[Domestic Malaria Cases in Kayseri Province]. / Kayseri Ilinde Görülen Yerli Sitma Olgulari.

Malaria continues to be a global public health problem considering the number of cases and death rate worldwide. There were no domestic cases reported from our country in the World Health Organization 2021 malaria report. All the 200-250 annual cases reported from our country have a history of travel to the endemic region. In this report, three malaria cases caused by Plasmodium falciparum and Plasmodium vivax in Kayseri province without a history of travel to the endemic region were presented. The first case was an 18-year-old male patient with no known chronic disease. He admitted to the hospital with the complaint of high fever reaching 40°C, which continued for two days, increased with chills and decreased with sweating. Physical examination revealed hepatosplenomegaly and laboratory results revealed thrombocytopenia. Species identification was made by real-time polymerase chain reaction (Rt-PCR) method in the patient with ring-shaped trophozoites in the peripheral smear. Artemether-lumefantrine and primaquine treatments were given to the patient with mixed parasitemia of P.falciparum and P.vivax. One and two days after the admission, the second and third cases also admitted with similar complaints. Mixed parasitemia was observed in all three patients who did not have a history of traveling abroad. After the antiparasitic treatment, the patients improved clinically and laboratory, and no recurrent parasitemia was observed. With the occurrence of these cases, efforts to combat vectors were initiated throughout the province. In conclusion, the presence of anopheles mosquitoes and imported cases still poses a risk for domestic malaria cases. In patients who do not have a history of traveling abroad, malaria should be considered in the clinical preliminary diagnosis and species identification should be made by methods such as Rt-PCR in order to give appropriate treatments.

A micro-elimination approach to addressing hepatitis C in Turkey.

BACKGROUND: In 2016, WHO passed the Global Health Sector Strategy on Viral Hepatitis (GHSS), calling for its elimination by 2030. Two years later, Turkey approved a strategy to reach the WHO targets. This study reports new national prevalence data, breaks it down by subpopulation, and models scenarios to reach HCV elimination. METHODS: Literature was reviewed for estimates of HCV disease burden in Turkey. They were discussed with stakeholders and used as inputs to develop a disease burden model. The infected population was estimated by sequelae for the years 2015-2030. Three scenarios were developed to evaluate the disease burden in Turkey: a Base 2017 scenario, representing the current standard of care in Turkey; an increased treatment scenario, representing the impact of improved access to DAAs; and a WHO targets scenario, which meet the WHO GHSS viral hepatitis targets of a 65% reduction in mortality and 90% diagnosis rate of the infected population by 2030. RESULTS: At the beginning of 2017, 271,000 viremic infections were estimated. Of these, 58,400 were diagnosed and 10,200 treated. Modelling results showed that, with the current treatment paradigm in Turkey, by 2030 the total number of viremic HCV infections would decline by 35%, while liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis would decrease by 10-25%. In the increased treatment scenario, by 2030 viremic HCV infections would decrease by 50%; liver-related deaths, HCC and decompensated cirrhosis would decrease by 45-70%. In the WHO targets scenario, HCV infections would decrease by 80%; sequelae would decrease by 80-85%. Data on disease burden in micro-elimination target subpopulations are largely unavailable. CONCLUSIONS: To meet the WHO Global Health Sector Strategy targets for the elimination of HCV, Turkey needs to increase treatment. Better data are needed as well as countrywide access to DAAs.

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.

Healthcare-Related HCV Genotype 4d Infections in Kayseri, Turkey.

BACKGROUND: The frequency of genotype 4 hepatitis C virus infection is significantly higher in a city compared to other provinces in Turkey. In this study, we aimed to investigate the epidemiology and risk factors of hepatitis C virus genotype 4 infection in Kayseri province of Turkey. METHODS: A case-control study was conducted with 61 hepatitis C virus genotype 4-infected patients and 71 controls. A questionnaire was administered to the patients and controls, asking for information about the risk factors of hepatitis C virus transmission. Core/ E1 and NS5B regions of hepatitis C virus genome were amplified and sequenced by Sanger method. Phylogenetic analysis and molecular clock analysis were performed. The risk was determined by calculating the odds ratio and 95% CI. Logistic regression analysis was performed to determine the effect of risk factors by controlling for confounding variables. RESULTS: Kayseri isolates were closely related to type 4d sequences but formed a separate cluster. According to the molecular clock analysis, hepatitis C virus genotype 4d entered Kayseri province probably between 1941 and 1988. Blood transfusion and surgical intervention were found to be significant risk factors for the infection. CONCLUSION: Epidemiological data showed that hepatitis C virus genotype 4d infections are significantly associated with unsafe medical procedures.

[Comparative evaluation of in vitro activities of carbapenems against gram-negative pathogens: Turkish data of COMPACT study]. / Karbapenemlerin Gram-Negatif Patojenlere Karsi In Vitro Aktivitelerinin Karsilastirmali Degerlendirmesi: COMPACT Çalismasi Türkiye Verisi.

The aim of this study was to determine the in vitro activities of doripenem, imipenem, and meropenem against clinical gram-negative isolates. A total of 596 clinical isolates were obtained from intensive care unit (ICU) and non-ICU patients in 10 centers over Turkey between September-December 2008. The origin of the isolates was patients with nosocomial pneumonia (42.4%), bloodstream infections (%40.4), and complicated intraabdominal infections (17.1%). Of the isolates, 51.8% were obtained from ICU patients. The study isolates consisted of Pseudomonas spp. in 49.8%, Enterobacteriaceae in 40.3%, and other gram-negative agents in 9.9%. The minimum inhibitory concentrations (MIC) for doripenem, imipenem and meropenem were determined for all isolates in each center using Etest® strips (AB Biodisk, Solna, Sweden). Of the isolates, 188 (31.5%) were resistant to at least one of the carbapenems. MIC50 of doripenem against Pseudomonas spp. Was 1 mg/L which was similar to that of meropenem and two-fold lower than imipenem. Susceptibility to carbapenems in P.aeruginosa was 64% for doripenem at an MIC level of 2 mg/L, 53.9% and 63% for imipenem and meropenem at an MIC level of 4 mg/L, respectively. Doripenem and meropenem showed similar activity with the MIC90 of 0.12 mg/L whereas imipenem was four-fold less active at 0.5 mg/L. Against other gramnegative pathogens, mostly Acinetobacter spp., MIC50 was 8 mg/L for doripenem and 32 mg/L for other two carbapenems. P.aeruginosa isolates were inhibited 84.2% with doripenem and 72.1% with meropenem at the MIC level of 8 mg/L. Doripenem generally showed similar or slightly better activity than meropenem and better activity than imipenem against pathogens collected in this study. Against Pseudomonas spp., doripenem was the most active of the three carbapenems. Doripenem and meropenem were equally active against Enterobacteriaceae and at least four-fold more active than imipenem. It was concluded that doripenem seemed to be a promising agent in the treatment of nosocomial pneumonia, blood stream infections and intraabdominal infections particularly in patients who were under risk of developing antimicrobial resistance.

Real-World Data from Turkey: Is Sofosbuvir/Ledipasvir With or Without Ribavirin Treatment for Chronic Hepatitis C Really Effective?

BACKGROUND: In this study, we aimed to investigate the efficacy and safety of sofosbuvir-based therapies in the treatment of chronic hepatitis C in real-world clinical practice. METHODS: Data from patients with chronic hepatitis C treated with SOF/LDV ± RBV or SOF/RBV in 31 centers across Turkey between April 1, 2017, and August 31, 2018, were recorded in a nationwide database among infectious disease specialists. Demographics, clinical, and virological outcomes were analyzed. RESULTS: A total of 552 patients were included in the study. The mean age of the patients was 51.28 ± 14.2, and 293 (55.8%) were female. The majority had HCV genotype 1b infection (65%), 75.04% of the patients underwent treatment, and non-cirrhosis was present at baseline in 381 patients (72.6%). SOF/LDV ± RBV treatment was given to 477 patients and 48 patients received SOF/RBV according to HCV genotype. The total SVR12 rate was 99% in all patients. Five patients experienced disease relapse during the study and all of them were genotype 2. In patients infected with HCV GT2, SVR12 was 77.3%. SVR was 100% in all patients infected with other HCV genotypes. All treatments were well tolerated by patients without causing severe adverse events. Side effects and side effects-associated treatment discontinuation rates were 28.2% and 0.4%, respectively. Weakness (13.7%) was the common side effect. CONCLUSION: The present real-world data of 525 patients with HCV genotypes 1, 1a, 1b, 3, 4, and 5 who underwent SOF/LDV ± RBV treatment in Turkey demonstrated a high efficacy and safety profile. HCV GT2 patients should be treated with more efficacious treatment.

Real-world efficacy, safety, and clinical outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin combination therapy in patients with hepatitis C virus genotype 1 or 4 infection: The Turkey experience experience.

BACKGROUND/AIMS: mbitasvir/paritaprevir/ritonavir (OMV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) combination has demonstrated excellent rates of sustained virologic response (SVR) and a very good safety profile in patients with the chronic hepatitis C virus (HCV) genotype 1 or 4 infections. We aimed to investigate the effectiveness and safety of OMV/PTV/r ± DSV ± RBV combination regimen in a real-world clinical practice. MATERIALS AND METHODS: Data from HCV genotype 1 and 4 patients treated with OMV/PTV/r ± DSV ± RBV (n=862) in 34 centers across Turkey between April 1, 2017 and August 31, 2018 were recorded in a large national database. Demographic, clinical, and virologic data were analyzed. RESULTS: The mean age of the patients was 55.63, and 430 patients (49.9%) were male. The majority had HCV genotype 1b infection (77.3%), and 66.2% were treatment-naïve. Non-cirrhosis was present at baseline in 789 patients (91.5%). SVR12 rate was 99.1% in all patients. Seven patients had virologic failure. No significant differences were observed in SVR12 according to HCV genotypes. HCV RNA was undetectable at treatment week 4 in 90.9%, at treatment week 8 in 98.5%, and at the end of treatment (EOT) in 98.9%. SVR12 ratio was significantly higher in the non-cirrhotic patients compared to that in the compensated cirrhotic patients. Rates of adverse events (AEs) in the patients was 59.7%. CONCLUSION: The present real-life data of Turkey for the OBV/PTV/r ± DSV ± RBV treatment of patients with HCV genotype 1b, 1a, or 4 infection from 862 patients demonstrated high efficacy and a safety profile.

Neurobrucellosis: an evaluation of a rare presentation of brucellosis from a tertiary care centre in Central Anatolia, Turkey.

Nervous system involvement is a rare manifestation of brucellosis. We describe our experience of the diagnosis, treatment and final outcome of patients with neurobrucellosis at the Erciyes University Gevher Nesibe Hospital, a tertiary referral centre in Central Anatolia, Turkey. Thirty-six adult patients were diagnosed with neurobrucellosis from January 1997 to December 2006. Headache and fever were the most common symptoms. Neck stiffness was present in 25 patients. Brucella spp was isolated from the blood of nine patients and from the cerebrospinal fluid of 11. Doxycycline (by mouth) plus rifampin (by mouth) with ceftriaxone (intravenously) were the most common treatment choices. Three patients died as a result of problems other than neurobrucellosis and relapse occurred in one patient. Neurobrucellosis presents with hetoregenous clinical signs.

Effectiveness of fixed-dose combination of paritaprevir, ritonavir, ombitasvir, and dasabuvir in patients with chronic hepatitis C virus infection and chronic kidney diseases: real-life experiences.

INTRODUCTION: Both hepatitis C virus infection (HCV) and chronic kidney disease (CKD) have been comorbid illnesses with increasing morbidity and mortality. The present study was conducted to present real-life experiences about treatment of HCV and CKD with a fixed-dose combination of paritaprevir 150 mg/day, ritonavir 100 mg/day as a booster, ombitasvir 25 mg/day, and dasabuvir 250 mg twice/day, the PROD regimen. PATIENTS AND METHODS: This was a multicenter, retrospective cohort study. Seventy-five patients with both HCV and CKD were treated with a PROD-based regimen with or without ribavirin. Fifty-three of 75 patients were on maintenance hemodialysis program. Seven patients had compensated liver cirrhosis. The patients with genotype 1a or compensated liver cirrhosis were treated with the PROD regimen and ribavirin in a dose of 200 mg every other day for 12 weeks. The patients with genotype 1b were treated with PROD for 12 weeks. The patients with genotype 4 were treated with a combination of paritaprevir, ritonavir, ombitasvir, and ribavirin 200 mg every other day. RESULTS: All patients except one were HCV-RNA negative (98.6%) at the end of treatment. One patient had decompensated after the fourth day of therapy. She stopped the treatment, and she was exitus after 2 months. Two patients died of reasons not related to the drugs 2 months after negativity of HCV-RNA. Sustained viral rate 12 weeks after treatment was found in 96% of the patients. CONCLUSION: The PROD regimen was very effective and safe for treatment in patients with HCV and CKD who were in stages 4 and 5.

Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report.

This consensus report includes expert opinions and recommendations regarding the screening, and if necessary, the follow-up, prophylaxis, and treatment of hepatitis B before the treatment in patients who will undergo immunosuppressive therapy due to an emergency risk of hepatitis B reactivation. To increase awareness regarding the risk of hepatitis B reactivation in immunosuppressive patients, academicians from several university health research and training centers across Turkey came together and discussed the importance of the subject, current status, and issues in accordance with the current literature data and presented solutions.

Sepsis and meningitis due to Listeria monocytogenes.

PURPOSE: This study focused on the effect of immuno-compromising conditions on the clinical presentation of severe listerial infection. PATIENTS AND METHODS: Nine human listeriosis cases seen from 1991-2002 were reviewed. All adult patients, from whose blood, peritoneal fluid or cerebrospinal fluid (CSF) the L. monocytogenes was isolated, were included in this retrospective study. RESULTS: Listeriosis presented as primary sepsis with positive blood cultures in 5 cases and meningitis with positive CSF cultures in 4 cases. All of these patients had at least one underlying disease, most commonly, hematologic malignancy, diabetes mellitus, amyloidosis and hepatic cirrhosis; 55.6% had received immunosuppressive or corticosteroid therapy within a week before the onset of listeriosis. The patients were adults with a mean age of 60 years. Fever, night sweats, chills and lethargy were the most common symptoms; high temperature (> 38 degrees C), tachycardia, meningeal signs and poor conditions in general were the most common findings on admission. The mortality rate was 33.3% and was strictly associated with the severity of the underlying disease. Mortality differences were significant between sepsis (20%) and meningitis (50%) patients. CONCLUSION: Listeriosis as an uncommon infection in our region and that immuno- suppressive therapy is an important pre-disposing factor of listeriosis. Sepsis and meningitis were more common in this group of patients and had the highest case-fatality rate for food-borne illnesses.

Doxycycline plus streptomycin versus ciprofloxacin plus rifampicin in spinal brucellosis [ISRCTN31053647].

BACKGROUND: The optimal treatment regimen and duration of the therapy is still controversial in spinal brucellosis. The aim of this study is to compare the efficacy, adverse drug reactions, complications and cost of ciprofloxacin plus rifampicin versus doxycycline plus streptomycin in the treatment of spinal brucellosis. METHODS: The patients diagnosed as spinal brucellosis between January 2002 to December 2004 were enrolled into the study. Patients were enrolled into the two antimicrobial therapy groups (doxycycline plus streptomycin vs. ciprofloxacin plus rifampicin) consecutively. For the cost analysis of the two regimens, only the cost of antibiotic therapy was analysed for each patient. RESULTS: During the study period, 31 patients with spinal brucellosis were enrolled into the two antimicrobial therapy groups. Fifteen patients were included in doxycycline plus streptomycin group and 16 patients were included in ciprofloxacin plus rifampicin group. Forty-two levels of spinal column were involved in 31 patients. The most common affected site was lumbar spine (n = 32, 76%) and involvement level was not different in two groups. Despite the disadvantages (older age, more prevalent operation and abscess formation before the therapy) of the patients in the ciprofloxacin plus rifampicin group, the duration of the therapy (median 12 weeks in both groups) and clinical response were not different from the doxycycline plus streptomycin. The cost of ciprofloxacin plus rifampicin therapy was 1.2 fold higher than the cost of doxycycline plus streptomycin therapy. CONCLUSION: Classical regimen (doxycycline plus streptomycin), with the appropriate duration (at least 12 weeks), is still the first line antibiotics and alternative therapies should be considered when adverse drug reactions were observed.

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 Dual Therapy in Real Life Setting in Treatment-Naïve Turkish Patients with HCV Infection: A Multicenter, Retrospective Study.

BACKGROUND: Before the introduction of direct-acting antivirals in the treatment of chronic hepatitis C patients, the combination of peginterferon alpha and ribavirin was the standard therapy. Observational studies that investigated sustained virological response (SVR) rates by these drugs yielded different outcomes. AIMS: The goal of the study was to demonstrate real life data concerning SVR rate achieved by peginterferon alpha plus ribavirin in patients who were treatment-naïve. STUDY DESIGN: A multicenter, retrospective observational study. METHODS: The study was conducted retrospectively on 1214 treatment naïve-patients, being treated with peginterferon alpha-2a or 2b plus ribavirin in respect of the current guidelines between 2005 and 2013. The patients' data were collected from 22 centers via a standard form, which has been prepared for this study. The data included demographic and clinical characteristics (gender, age, body weight, initial Hepatitis C virus RNA (HCV RNA) level, disease staging) as well as course of treatment (duration of treatment, outcomes, discontinuations and adverse events). Renal insufficiency, decompensated liver disease, history of transplantation, immunosuppressive therapy or autoimmune liver disease were exclusion criteria for the study. Treatment efficacy was assessed according to the patient's demographic characteristics, baseline viral load, genotype, and fibrosis scores. RESULTS: The mean age of the patients was 50.74 (±0.64) years. Most of them were infected with genotype 1 (91.8%). SVR was achieved in 761 (62.7%) patients. SVR rate was 59.1% in genotype 1, 89.4% in genotype 2, 93.8% in genotype 3, and 33.3% in genotype 4 patients. Patients with lower viral load yielded higher SVR (65.8% vs. 58.4%, p=0.09). SVR rates according to histologic severity were found to be 69.3%, 66.3%, 59.9%, 47.3%, and 45.5% in patients with fibrosis stage 0, 1, 2, 3 and 4, respectively. The predictors of SVR were male gender, genotype 2/3, age less than 45 years, low fibrosis stage, low baseline viral load and presence of early virological response. SVR rates to each peginterferon were found to be similar in genotype 1/4 although SVR rates were found to be higher for peginterferon alpha-2b in patients with genotype 2/3. The number of patients who failed to complete treatment due to adverse effects was 33 (2.7%). The number of patients failed to complete treatment due to adverse effects was 33 (2.7%). CONCLUSION: Our findings showed that the rate of SVR to dual therapy was higher in treatment-naïve Turkish patients than that reported in randomized controlled trials. Also peginterferon alpha-2a and alpha-2b were found to be similar in terms of SVR in genotype 1 patients.

[Salmonella enteritidis: an unusual meningitis agent in an adult patient]. / Salmonella enteritidis: eriskin hastada nadir bir menenjit etkeni.

Salmonella species may cause wide spectrum of infections changing from enterocolitis to sepsis. However, Salmonella meningitis in adults is a rare but important clinical condition with a high mortality rate. In this report, a 71 years old male patient with Salmonella enteritidis meningitis who was followed-up with the diagnosis of immune thrombocytopenic purpura and had been administered azothioprin and prednisolone, has been presented and similar cases in the literature have been reviewed. The cerebrospinal fluid culture yielded S. enteritidis, and the isolate was intermediate susceptible to ampicillin, susceptible to cefotaxime, trimethoprim-sulphametoxasole, ciprofloxacin and chloramphenicol. Our patient was successfully treated with ceftriaxone (2 x 2 gr i.v.) and discharged with total cure.

Characterization of the Interleukin-28B Gene rs12979860 C/T Polymorphism in Turkish Chronic Hepatitis C Patients and Healthy Individuals.

BACKGROUND: Host genetic factors can affect the progress of hepatitis-C virus (HCV) infection. Interleukin-28B (IL28B) single nucleotide polymorphisms may play an important role in the clearance of HCV spontaneously or with treatment. AIMS: The aim of our study was to evaluate the rate of IL28B genotypes in patients with Chronic Hepatitis-C (CHC) and healthy control subjects and to examine the characteristics of patients in each IL28B subgroup. STUDY DESIGN: Case-control study. METHODS: IL28B polymorphisms were genotyped by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) in all subjects. RESULTS: The mean age was 52.3±10.9 years (33% female) in the CHC patients and 52.5±11.5 years (39.1% female) in the healthy controls. The percentage of patients with a high baseline viral load (≥400,000 IU/mL) was higher in the CT group (69.8%) compared to the C/C (44.4%) and T/T (50%) groups (p=0.021). There was no significant difference in liver fibrosis and liver necroinflammation distribution among the CC, CT and TT genotypes with mild, moderate and severe groups (p=0.058 and p=0.791, respectively). Mean age, gender ratio, body mass index, viral load at baseline, rate of HCV genotypes, baseline ALT levels were not significantly different among the three IL28B subgroups (p>0.05). A significant increase was observed in the frequencies of IL28B rs12979860 TT genotypes in the CHC patients (20.6%) compared to the healthy control group (8.7%) (p=0.033). CONCLUSION: In the patients with chronic HCV-genotype 1b and 4 infections, the IL28B rs12979860 (C>T) gene polymorphism frequency of the TT genotype and T allele was higher than in healthy control subjects. This result indicates that the TT genotype may be more effective in the progression of HCV infection than other genotypes.

Retreatment of Chronic Hepatitis C Infection with Telaprevir: Preliminary Results in Turkey.

BACKGROUND: The use of pegylated interferon alpha and ribavirin (PegIFN/RBV) for the retreatment of chronic hepatitis C virus (HCV) infection without a sustained virological response (SVR) prior to PegIFN/RBV treatment has resulted in low success rates. AIMS: To investigate the efficacy and safety of telaprevir (TVR) in combination with PegIFN/RBV in patients infected with HCV genotypes 1 and 4 who were previously treated with PegIFN/RBV and failed to achieve SVR. STUDY DESIGN: Multi-center, retrospective, cross-sectional study. METHODS: The study included 111 patients: 80 prior relapsers, 25 prior null responders, and six prior partial responders to PegIFN/RBV treatment. The patients were given TVR/PegIFN/RBV for 12 weeks, followed by a 12-week PegIFN/RBV treatment; virological response results were assessed at weeks 4, 12, and 24. Treatment was discontinued in patients with HCV RNA >1000 IU/mL at week 4 or with negative RNA results at week 4 but >1000 IU/mL at week 12. Rapid virological response (RVR), early virological response (EVR), extended rapid virological response (eRVR), and virological response at 24th week of treatment were evaluated. The side effects of combination therapy and the rates of treatment discontinuation were investigated. RESULTS: The mean age of the patients was 56.02±9.96 years and 45.9% were male. Ninety-one percent of the patients were infected with viral genotype 1, 69.6% with the interleukin (IL) 28B genotype CT and 20.2% were cirrhotic. The RVR rate was 86.3% in prior relapsers, 56% in prior null responders, and 50% in prior partial responders (p=0.002). EVR rates in those groups were 91.3%, 56%, and 83.3%, respectively (p<0.001). eRVR rates were 83.8% in prior relapsers, 48% in prior null responders, and 50% in prior partial responders (<0.001). The virological response at the 24th week of treatment was found to be the highest in prior relapsers (88.8%); it was 56% in prior null responders and 66.7% in prior partial responders (p<0.001). Common side effects were fatigue, headache, anorexia, malaise, anemia, pruritus, dry skin, rash, dyspepsia, nausea, pyrexia, stomachache, and anorectal discomfort. All treatments were discontinued due to side effects in 9.9% of patients. CONCLUSION: High virological response rates were obtained with TVR/PegIFN/RBV treatment. Although side effects were frequently observed, the discontinuation rate of combination therapy was low.

Incidence, risk factors and mortality of nosocomial pneumonia in intensive care units: a prospective study.

To determine the frequency, risk factors and mortality of nosocomial pneumonia a prospective study was conducted in the intensive care units. In the study period, 2402 patients were included. The nosocomial pneumonia was defined according to the Centers for Disease Control Criteria. Overall, 163 (6.8%) of the patients developed nosocomial pneumonia and 75.5% (n = 123) of all patients with nosocomial pneumonia were ventilator-associated pneumonia. 163 patients who were admitted to the intensive care unit during the same period but had no bacteriologic or histologic evidence of pneumonia were used as a control group. The APACHE II score, coma, hypoalbuminemia, mechanical ventilation, tracheotomy, presence of nasogastric tube were found as independent risk factors. Crude and attributable mortality were 65% and 52.6%, respectively. The mortality rate was five times greater in the cases (OR: 5.2; CI 95%: 3.2-8.3). The mean length of stay in the intensive care unit and hospital in the cases were longer than controls (p < 0.0001). Patients requiring mechanical ventilation have a high frequency of nosocomial pneumonia.

Impact of Interleukin 28B Genotype on the Virological Responses in Chronic Hepatitis C Treatment.

BACKGROUND: Interleukin (IL) 28B single nucleotide polymorphisms may play a role in the clearance of hepatitis C virus (HCV). We aimed to evaluate the treatment response of chronic HCV infection patients to pegile interferon (pegIFN) and ribavirin treatment with regard to IL28B rs12979860 C/T polymorphism. METHODS: A total of 186 patients (mean age, 55.6 ± 10 years; 65.1% female) who underwent pegIFN and ribavirin treatment for chronic HCV infection were studied. We analyzed demographics, HCV genotype, baseline alanine aminotransferase (ALT) levels, histopathological data, viral load before treatment and at 4, 12, 24, 48, and 72 weeks from the treatment start, and IL28B genotype. IL28B polymorphism was genotyped using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in all the subjects. RESULTS: One hundred forty-five (86.8%) patients were infected with viral genotype 1b, and 13.2% were infected with viral genotype 4. The rates of C/C, C/T, and T/T genotypes were 22.6%, 52.7%, and 24.7% respectively. The percentage of patients with a viral load over 400,000 IU/mL was higher in the C/T group (P = 0.020). Of the patients, 44.6% provided sustained virological response (SVR) to pegIFN and ribavirin combination treatment. The frequency of T allele was 41% in patients with SVR, whereas 59% patients provided no response (P < 0.001). SVR was obtained in 66.7%, 42.9%, and 28.3% of CC, CT, and TT groups (P = 0.001). The rates of rapid virological response (RVR), early virological response (EVR), end-of-treatment response (ETR), and SVR were higher in the CC group than other groups (P = 0.216, P < 0.001, P = 0.001, P = 0.001, respectively). The relapse and null response (NR) rates were higher in TT group and partial response rate (PR) was higher in CT group. CONCLUSIONS: IL28B rs12979860 C/T gene polymorphism affects the response to antiviral treatment in the patients with chronic HCV genotypes 1b and 4 infections.