Empirical cefepime+vancomycin versus ceftazidime+vancomycin versus meropenem+vancomycin in the treatment of healthcare-associated meningitis: results of the multicenter ephesus study.

BACKGROUND: Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM). MATERIALS/METHODS: This retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018. RESULTS: Twenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3-5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34). CONCLUSIONS: Our study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci.

First year real life experience with tenofovir alafenamide fumarate: The pythagorean cohort.

Background and Aim: In chronic hepatitis B infection, antiviral therapy significantly reduces the incidence of complications. This study aimed to present real-life 12-month effectiveness and safety data for TAF. Materials and Methods: This Pythagoras Retrospective Cohort Study included patients from 14 centers in Turkiye. The study presents 12-month results of 480 patients treated with TAF as initial therapy or after switching from another antiviral drug. Results: The study shows treatment of about 78.1% patients with at least one antiviral agent (90.6% tenofovir disoproxil [TDF]). The rate of undetectable HBV DNA increased in both treatment-experienced and naive patients. In TDF-experienced patients, the rate of alanine transaminase (ALT) normalization increased slightly (1.6%) within 12 months, but the change was not statistically significant (p=0.766). Younger age, low albumin, and high body mass index and cholesterol were identified as risk factors for abnormal ALT after 12 months, but no linear relationship was detected. In TDF-experienced patients, renal and bone function indicators showed significant improvement three months after the transition to TAF and remained stable for 12 months. Conclusion: Real-life data demonstrated effective virological and biochemical responses with TAF therapy. After switching to TAF treatment, gains in kidney and bone functions were achieved in the early period.

Comparison of Immunological and Virological Recovery with Rapid, Early, and Late Start of Antiretroviral Treatment in Naive Plwh: Real-World Data.

Background: Rapid initiation of antiretroviral therapy (ART) reduces the transmission of HIV infection in the community. This study aimed to determine whether rapid ART initiation is effective compared to standard ART treatment in our country. Methods: Patients were grouped based on time to treatment initiation. HIV RNA levels, CD+4 T cell count, CD4/CD8 ratio, and ART regimens were recorded at baseline and follow-up visits for 12 months. Results: There were 368-ART naive adults (treatment initiated at the time of HIV diagnosis; 143 on the first day, 48 on the second-seventh day, and 177 after the seventh day). Although virological suppression rates at 12th months were higher in all groups, over 90% on average, there were no statistically significant differences in HIV-1 RNA suppression rates, CD+4 T cell count, and CD4/CD8 ratio normalization in the studied months but in multivariate logistic regression analysis; showed a significant correlation between both virological and immunological response and those with CD4+ T <350 cells/mL at 12th month in total patients. Conclusion: Our findings support the broader application of recommendations for rapid ART initiation in HIV patients.

[Comparison of Real Time PCR Cycle Threshold Values in Symptomatic and Asymptomatic COVID-19 Patients]. / Semptomatik ve Asemptomatik COVID-19 Hastalarinda Gerçek Zamanli PCR Döngü Esik Degerlerinin Karsilastirilmasi.

Patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) show different clinical courses ranging from asymptomatic to severe infection requiring intensive care treatment and death. Real-time reverse transcription polymerase chain reaction (rRT-PCR), used in the diagnosis, screening and surveillance of coronavirus-2019 (COVID-19), provides the viral load as a cycle threshold (Ct) value. It has been reported that the Ct value may be related to the course of the infection and the clinical condition of the patient. In this study, it was aimed to compare the Ct and C reactive-protein (CRP) results of symptomatic and asymptomatic patients who were found to be positive with rRT-PCR. Between 14 April and 29 August 2020, a total of 355 patients aged 18 years and older with positive SARS-CoV-2 rRT-PCR test were included in the study. The COVID-19 rRT-PCR test was performed with Bio-speedy SARS-CoV-2 rRT-PCR kit (Bioeksen, Turkey) versions, the kit targeting the RdRp gene region, and the dual gene kit versions targeting the N and ORF1ab gene regions were used. Patients were classified as symptomatic and asymptomatic according to their clinical findings. Ct and CRP results of the patients were analyzed statistically. Of the 355 patients included in the study, 237 (66.7%) were symptomatic and 118 (33.2%) were asymptomatic patients. The mean age of symptomatic patients (46.68 ± 18.03) was observed significantly higher than asymptomatic patients (38.27 ± 13.82) (p<0.001). When the patients are evaluated according to the age groups, the rate of asymptomatic patients was significantly higher in the 21-39 age group, while the rate of symptomatic patients was significantly higher in 65 years and older group (p<0.05). The rate of comorbidity was significantly higher in symptomatic patients (n= 69, 29.1%) than in asymptomatic patients (n= 11, 9.3%) (p<0.001). Hypertension (12.2%), diabetes mellitus (9.7%), chronic respiratory disease (9.3%) and cardiovascular diseases (5.5%) were the most common diseases in symptomatic patients. However, among these, hypertension and chronic respiratory disease were found significantly higher in symptomatic patients (p<0.05). Increased CRP rate in symptomatic patients (64.6%) was found significantly higher than asymptomatic patients (27.3%) (p<0.001). The median of Ct value was found significantly higher in asymptomatic patients (26.34, IQR= 19.78-35.48), than in symptomatic patients (21.77, IQR= 17.81-26.51) (p<0.001). Regarding the medians of Ct values obtained from target genes; RdRp gene Ct value was found significantly higher in asymptomatic patients than in symptomatic patients (p<0.001). However, no statistical difference was found between symptomatic and asymptomatic patients in the ORF1ab and N genes Ct value medians (p> 0.05). As a result, it was observed that SARS-CoV-2 PCR positive patients were symptomatic in the presence of advanced age and comorbidity. Increased CRP value at the time of admission to the hospital was found significantly higher in symptomatic patients. Ct value has been shown to be lower in symptomatic patients, as expected. Although Ct and CRP values are thought to be useful in monitoring the clinical course and prognosis of patients with COVID-19, more detailed studies are needed to prove their clinical value.

[Investigation of the Relationship Between TNF-α, IL-12A, IL-12B and IFN-γ Gene Polymorphisms and Chronic Hepatitis C]. / TNF-α, IL-12A, IL-12B ve IFN-γ Gen Polimorfizmleri ile Kronik Hepatit C Arasindaki Iliskinin Arastirilmasi.

Hepatitis C virus (HCV) infection is still an important public health problem worldwide. Cytokines play an important role in the prognosis of HCV infections. Polymorphisms in the cytokine genes can affect the gene expression and change the clinical course of the disease. The aim of this study was to determine the relationship between chronic hepatitis C and TNF-α rs1799964 (-1031 T/C), IL-12A rs568408 (3'UTR G/A), IL-12B rs3212227 (3'UTR A/C) and IFN-γ rs2430561 (+874 A/T) gene polymorphisms. A hundred patients with chronic hepatitis C and 100 healthy people as control group were included in the study. Approximately 2 ml peripheral blood was taken from the patient and control groups into tubes with EDTA and genomic DNA was obtained using the DNA isolation kit. Single nucleotide polymorphisms in TNF-α (rs1799964), IL-12A (rs568408), IL-12B (rs3212227) and IFN-γ (rs2430561) genes were investigated by using the real-time polymerase chain reaction (Rt-PCR) method. The data obtained were analyzed in SPSS package program. There was no statistically significant relationship between chronic hepatitis C and TNF-α and IFN-γ polymorphisms in terms of genotype and allele distributions (p> 0.05). However, it was found that the relationship between IL-12A (G/A) and IL-12B (A/C) polymorphisms was significant (p< 0.05). The frequencies of IL-12A GA (OR= 4.828, 95% CI= 1.452-16.046, p= 0.010) and AA genotypes (OR= 4.436, 95% CI= 1.398-14.077, p= 0.011) and A alele (OR= 1.602, 95% CI= 1.020-2.518, p= 0.040) were found to be higher in the patient group. When the relationship between chronic hepatitis C and IL-12B gene polymorphism was examined, it was determined that the frequencies of AC (OR= 2.060, 95% CI= 0.836-5.076, p= 0.116) and CC (OR= 3.020, 95% CI= 1.242-7.345, p= 0.015) genotypes and C allele (OR= 1.750, 95% CI= 1.152-2.659, p= 0.008) were high in the patient group. In addition, TNF-α TC/CC, IL-12A GA/AA, IL-12B AC/CC and IFN-γ TT genotypes were found to be 7.5 times higher in the patient group than the control group (OR= 7.500, 95% CI= 1.532-36.714, p= 0.013). Our results showed that IL-12A (3'UTR G/A) and IL-12B (3'UTR A/C) gene polymorphisms and TNF-α TC/CC, IL-12A GA/AA, IL-12B AC/CC and IFN-γ TT interactions may be effective in the risk of the chronicity of hepatitis C. However, further studies are needed to determine the role of polymorphisms in these cytokine genes in HCV infections.

Whipple's Disease: A Case Report.

OBJECTIVE: Whipple's disease is a very rare systemic infectious disease with an annual incidence of 3 in one million, which may be fatal if not diagnosed and treated appropriately. CLINICAL PRESENTATION AND INTERVENTION: Herein we describe a 49-year-old patient admitted to the hospital with symptoms of severe malabsorption and diagnosed with Whipple's disease. The diagnosis was based on the histopathological findings of small intestine biopsies and PCR analysis. CONCLUSION: Whipple's disease should be kept in mind while dealing with patients with severe malabsorption, even in the absence of accompanying features of the disease.

Daptomycin vs. glycopeptides in the treatment of febrile neutropenia: results of the Izmir matched cohort study.

PURPOSE: In this multicentre, retrospective, matched cohort study we aimed to evaluate the outcomes of neutropenic fever cases that were treated with daptomycin or a glycopeptide (vancomycin or teicoplanin). METHODS: Data and outcomes of adult (aged > 18-years old) patients with neutropenic fever [(1) without clinical and radiological evidence of pneumonia, (2) who were treated with daptomycin or a glycopeptide (teicoplanin or vancomycin) for any reason and for at least 72 h] were extracted from the hospital databases. Matching was performed with all of the three following criteria: (1) underlying disease, (2) reason for starting daptomycin or glycopeptide (microbiologic evidence vs. microbiologic evidence, clinical infection vs. clinical infection and empirical therapy vs. empirical therapy) and (3) neutropenic status. RESULTS: Overall 128 patients [(69/123) (56.1%) in the daptomycin cohort (D) and 59/123 (48%) in the glycopeptide cohort (G)] had a resolution of fever at the end of 72 h antibiotic treatment (p = 0.25). There was no significant difference in cured, improved and (cured + improved) rates between (D) and (G) cohorts as well as fever of unknown origin cases or microbiologically confirmed infections or clinically defined infections subgroups (p > 0.05). There was also no significant difference (p > 0.05), in terms of persistent response in the (D) versus (G) cohorts, CONCLUSIONS: These findings suggest that although not better, daptomycin efficacy is comparable to vancomycin if used as empiric therapy in the treatment of adult febrile neutropenia. We conclude that daptomycin may be used at least as a salvage therapy alternative to glycopeptides in the treatment of adult febrile neutropenia cases. A large, randomized-controlled trial may further consolidate the evidence related to this question.

[Investigation of the association between chronic hepatitis B and C infections and TNF-α (-308) gene polymorphism]. / Kronik hepatit B ve C enfeksiyonlari ile TNF-α (-308) gen polimorfi zmi arasindaki iliskinin arastirilmasi.

Cytokines and genetic factors play important roles in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) infections. Variations in cytokine genes may effect the gene expression and may lead to changes in the clinical manifestations of diseases. One of the single nucleotide polymorphisms in the promoter region of tumor necrosis factor-alpha (TNF-α) gene is the polymorphism at -308. position which was investigated in many studies by means of its relationship between CHB and CHC infections, however their results are incompatible. Furthermore, there is no sufficient data on this subject in our country. This study was aimed to determine the relationship between TNF-α(-308) gene polymorphism with CHB and CHC infections. A total of 271 patients with chronic hepatitis and 181 healthy subjects were included in the study. Of them 167 were CHB cases (67 female, 100 male; age range 18-74 years, mean age: 40.23 ± 13.09) and 95 controls for CHB group (46 female, 49 male; mean age: 36.41 ± 15.0 years), while 104 were CHC cases (63 female, 41 male; age range: 25-79 years, mean age: 52.8 ± 12.6) and 86 controls for CHC group (41 female, 45 male; mean age: 36.4 ± 14.9 years). After the isolation of genomic DNA from blood samples of the patient and control groups, TNF-α(-308)G/A (rs 1800629) polymorphism was investigated by using the real-time polymerase chain reaction from the obtained DNAs. Among CHB group, TNF-α(-308) GG, GA, AA genotypes were detected in 126 (75.4%), 38 (22.8%) and 3 (1.8%) of the patients, respectively, while these numbers were 84 (88.4%), 11 (11.6%) and 0 (0%) in control group, respectively. Among CHC group, TNF-α(-308) GG, GA, AA genotypes were detected in 37 (35.6%), 28 (26.9%) and 39 (37.5%) of the patients, respectively, while these numbers were 38 (44.2%), 8 (9.3%) and 40 (46.5%) in control group, respectively. The frequency of GA genotype was significantly higher in both patient groups compared to the control groups (p=0.024 for CHB and p= 0.006 for CHC). When the distribution of allele frequencies of TNF-α(-308)G/A polymorphism was evaluated in the patients and control groups, it was noted that G allele was found to be high in CHB patients comparing with controls (94.2% vs 86.8%), however A allele was identified to be lower than controls (5.8% vs 13.2%) (p= 0.008). In contrast, there was no significant difference in terms of allele frequency compared with CHC patients and the control group (p= 0.969). In conclusion, our data in accordance with the results of many studies in literature, determined that TNF-α(-308) polymorphisms can influence the chronicity of hepatitis B and C infections. Further studies on this subject would contribute to the elucidation of the molecular mechanisms of chronic hepatitis B and C diseases.

Causative pathogens and antibiotic resistance in diabetic foot infections: A prospective multi-center study.

AIM: Clinical practice guidelines for the management of diabetic foot infections developed by the Infectious Diseases Society of America (IDSA) are commonly used worldwide. The issue of whether or not these guidelines need to be adjusted for local circumstances, however, has seldom been assessed in large prospective trials. METHODS: The Turk-DAY trial was a prospective, multi-center study in which infectious disease specialists from centers across Turkey were invited to participate (NCT02026830). RESULTS: A total of 35 centers throughout Turkey enrolled patients in the trial. Overall, investigators collected a total of 522 specimens from infected diabetic foot wounds for culture from 447 individual patients. Among all isolates, 36.4% were gram-positive organisms, with Staphylococcus aureus the most common among these (11.4%). Gram-negative organisms constituted 60.2% of all the isolates, and the most commonly isolated gram-negative was Escherichia coli (15%). The sensitivity rates of the isolated species were remarkably low for several antimicrobials used in the mild infection group. CONCLUSIONS: Based on our findings, several of the antimicrobials frequently used for empirical treatment, including some also recommended in the IDSA guidelines, would not be optimal for treating diabetic foot infections in Turkey. Although the IDSA guideline recommendations may be helpful to guide empiric antimicrobial therapy of DFIs, they should be adjusted to local conditions.

The incidence and risk factors of resistant E. coli infections after prostate biopsy under fluoroquinolone prophylaxis: a single-centre experience with 2215 patients.

We evaluated the incidence and risk factors of resistant Escherichia coli infections after the prostate biopsy under flouroquinolone prophylaxis. From January 2003 to December 2012, we retrospectively evaluated the records of 2215 patients. The risk factors were described for infective complications and resistant E. coli in positive cultures was calculated. Of 2215 patients, 153 had positive urine cultures, such as 129 (84·3%) E. coli, 8 (5·2%) Enterococcus spp., 6 (3·9%) Enterobacter spp., 5 (3·2%) Pseudomonas spp., 3 (1·9%) MRCNS, and 2 (1·3%) Klebsiella spp. Of the positive urine cultures which yielded E. coli, 99 (76·7%) were evaluated for fluoroquinolone resistance. Of those, 83 (83·8%) were fluoroquinolone-resistant and composed of 51 (61·4%) extended-spectrum beta-lactamase (ESBL)-positive. Fluoroquinolone-resistant E. coli ratios were 73·4 and 95·9% before 2008 and after 2008, respectively (P = 0·002). The most sensitive antibiotics for fluoroquinolone-resistant E. coli strains were imipenem (100%), amikacin (84%) and cefoperazone (83%). The use of quinolones in the last 6 months and a history of hospitalization in the last 30 days were found to be significant risk factors. We found that resistant E. coli strains might be a common microorganism in patients with this kind of complication. The risk factors for development of infection with these resistant strains were history of the use of fluoroquinolones and hospitalization.

[Investigation of IL-1 beta, IL-1 receptor antagonist and IL-8 gene polymorphisms in patients with chronic hepatitis B and C]. / Kronik hepatit B ve C hastalarinda IL-1 beta, IL-1 reseptör antagonisti ve IL-8 gen polimorfizmlerinin arastirilmasi

The host immune response is closely related to the prognosis of disease and viral persistence in hepatitis B (HBV) and hepatitis C virus (HCV) infections. Although it is well known that cytokines and genetic factors play important roles in the pathogenesis of chronic HBV and HCV infections, the underlying mechanisms are not fully understood. This study was conducted to determine the role of interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1RA) and IL-8 gene polymorphisms in chronic hepatitis B and C infections. A total of 361 subjects, 171 with chronic hepatitis B (62 female, 109 male; age range: 18-74 yrs) and 104 with chronic hepatitis C (63 female, 41 male; age range: 25-79 yrs), and a control group of 86 healthy subjects (41 female, 45 male; age range: 18-72 yrs) were included in the study. Following the DNA extractions from peripheral blood leukocytes of the study groups, single nucleotide polymorphisms of IL-1ß -31, -511, +3954; IL-1RA and IL-8 -251, -353, -738, -845 gene regions were investigated by using specific primers with real-time PCR method. It was found that the genotype frequency of IL-8 -251 AT (OR: 7.895, p= 0.003) and IL-8 -738 TA (OR: 6.317, p= 0.007) in patients with chronic hepatitis B and the genotype frequency of IL-1ß-31 CT (OR: 6.757, p= 0.001), IL-1ß -511 CT (OR: 4.060, p= 0.004), IL-8 -251 AT, (OR: 13.622, p= 0.001), IL-8 -738 TA (OR: 14.058, p= 0.001), and IL-8 -845 TC (OR: 2.539, p= 0.004) in patients with chronic hepatitis C was significantly higher than the control group. When the allelic frequency was compared between chronic hepatitis B patients and the control group, it was determined that IL-1ß +3954 T allel increased the disease risk 1.5 times (p< 0.05), however, no statistically significant difference was detected for the other allels. It was also determined that IL-8 -845 C allel increased the disease risk 0.6 times in chronic hepatitis C (p< 0.05) and no statistically significant difference was detected for the other allels (p> 0.05). In conclusion, IL-1ß -31, -511 and IL-8 -251, -738, -845 gene polymorphisms may play a role in the chronicity of hepatitis B and C infection. In order to determine the importance of this cytokine polymorphisms in hepatitis B and hepatitis C virus infections, large-scale studies with different patient groups such as carriers, chronic hepatitis, cirrhosis, and hepatocellular carcinoma should be conducted to elucidate the molecular mechanisms underlying the disease process.

Chronic hepatitis B and IL28B rs12979860 polymorphism: preliminary study.

The aim of this study is to evaluate the role of IL28B rs12979860 polymorphism on pegylated interferon (peg IFN) and oral antiviral treatment in chronic hepatitis B (CHB) patients and to investigate the relationship between the severities of illness with this polymorphism. 74 CHB patients who are received treatment, 61 asymptomatic carriers and 40 healthy controls were recruited in this study. Genomic DNA of controls and patients were extracted from whole blood using High Pure PCR Template Preparation Kit (Roche, Mannheim, Germany) according to the manufacturer's instructions and stored at 4 °C. Genotype distribution of the IL-28B polymorphism at position -3176C/T (rs12979860) (LightMix Kit IL28B, Cat.-No. 40-0588-32 TIB MOLBIOL, Berlin, Germany) was detected by real time PCR (Roche Diagnostics, Manheim, Germany). Thirty of the patients with CHB received peg IFN-α treatment. There were no significant difference between groups by means of age, gender and IL28B rs12979860 polymorphism (p = 0.122, p = 0.07, p = 0.376 respectively). Patients with chronic hepatitis were categorized as grade and stage (minimal, moderate and severe) and then were analyzed for the polymorphism. There was no effect of IL28B -3176 C/T polymorphism on severity of illness (p = 0.293 for grade, p = 0.911 for stage). When the CHB treatment monitored in different time arrivals (beginning, 3th, 6th and 12th months of the treatment) in order to see if there was an effect on virological and biological response none of the genotypes of IL28B -3176C/T polymorphism altered peg IFN or oral antiviral treatment process. There are conflicting results about the role of IL28B rs12979860 polymorphism in CHB in the literature. In this preliminary study, we observed that IL28B rs12979860 polymorphism was not related with severity of illness and also was not effective on treatment response.

Association of insulin resistance, viral load, and adipokine levels with liver histology in patients with chronic hepatitis C: an observational, multicenter study in Turkey.

OBJECTIVE: To evaluate the association of insulin resistance (IR), viral load, and adipokine levels with liver histology in patients with chronic hepatitis C (CHC). PATIENTS AND METHODS: In this noninterventional, multicenter study carried out at 11 infectious diseases clinics in Turkey, 103 CHC patients [mean (SD) age: 50.2 (11.0) years, 60 (58.3%) women] planned to be treated by ribavirin and peginterferon-α2a were included. Data on hepatic fibrosis and steatosis, IR, viral load, and hepatitis C virus-RNA genotyping, adipokine, and cytokine levels were collected. RESULTS: The mean (SD) Knodell score was 8.1 (3.6); grade I steatosis was evident in 46 (44.7%) patients and IR was identified in 56 (54.9%). There was a significant positive correlation of the homeostasis model assessment-IR index with Knodell fibrosis (r=0.235; P=0.027) and hepatic steatosis (r=0.435; P<0.001). There was a significant positive correlation of leptin levels with Knodell fibrosis (r=0.265; P=0.013) and hepatic activity index (r=0.218; P=0.041). Hepatic steatosis was correlated negatively with adiponectin (r=-0.320; P=0.001) and positively with leptin (r=-0.368; P<0.001) levels. Logistic regression analysis showed that increase in age [odds ratio (OR), 1.056; 95% confidence interval (CI), 1.005-1.110; P=0.030] was the only significant predictor of hepatic fibrosis (OR, 1.056; 95% CI, 1.005-1.110; P=0.030), whereas increase in age (OR, 1.066; 95% CI, 1.006-1.130; P=0.030), the presence of IR (OR, 5.621; 95% CI, 1.547-20.425; P=0.009), and decrease in adiponectin levels (OR, 0.808; 95% CI, 0.682-0.957; P=0.013) were the significant predictors of hepatic steatosis. CONCLUSION: Our findings indicate a significant relationship of hepatic fibrosis and hepatic steatosis with IR and leptin levels, but not with the viral load in Turkish patients with CHC.

Correlation between intrahepatic hepatitis B virus cccDNA levels and other activity markers in patients with HBeAg-negative chronic hepatitis B infection.

OBJECTIVE: The aim of this study was to demonstrate the relation between intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) levels and the other HBV replicative intermediates and hepatocyte expression of HBV antigens. PATIENTS AND METHODS: Patients with hepatitis B surface antigen (HBsAg) positivity, hepatitis B early antigen negativity, serum HBV DNA levels 10 copies/ml or more, and constantly or intermittently increased alanine aminotransferase levels were included. RESULTS: Fifty-nine patients were included. There was a good correlation between the levels of IH HBV cccDNA and serum HBV DNA (P<0.001). Serum HBsAg levels were weakly correlated with IH HBV cccDNA levels and moderately correlated with serum HBV DNA (r=0.322, P=0.017; r=0.489, P=0.001, respectively). There were no significant correlation between serum HBsAg level and histologic activity index groups (P=0.691), but stage 0, 1, and greater than 2 fibrosis groups were positively correlated with serum HBsAg levels (P=0.019). IH cccDNA and serum HBV DNA were significantly different in hepatitis B core antigen staining groups (P=0.008 and <0.001, respectively) but there was no significant correlation between HBsAg staining groups and HBV replication markers. There was a weak correlation between serum HBsAg levels and IH HBsAg and hepatitis B core antigen levels (r=0.333, P=0.012; r=0.366, P=0.006, respectively). In multivariate analysis, alanine aminotransferase, age, fibrosis stage, and serum HBsAg quantitation were the most important factors predicting IH HBV cccDNA level. CONCLUSION: Histopathologic damage, serum HBV DNA levels, and IH HBV replication markers have a more complex and dynamic process. However, both serum and IH HBV replication markers provide important knowledge about the activity of the disease.

Effects of GSTT1, GSTM1 and GSTP1 gene polymorphism on the course of hepatitis B virus infection.

BACKGROUND/AIMS: To investigate the effects of GSTT1, GSTM1 and GSTP1 gene polymorphism on the stage of hepatitis B infection. METHODOLOGY: This study included 116 healthy controls, 56 normal carriers of hepatitis B virus, 69 chronic hepatitis B patients and 20 cirrhosis patients. The polymorphism of GSTT1, GSTM1 and GSTP1 were determined with real time PCR with LightCycler instrument using hybridization probes in combination with the LightCycler DNA Master Hybridization Probes Kit (Roche Diagnostics). Multivariate binary logistics regression analyses were used for statistical evaluation. RESULTS: GSTP1 IIe/val genotype was significantly more frequent in the patients with chronic hepatitis B infection and in the patients with cirrhosis (p=0.049 OR: 1.909, 95% CI 0.993-3.668 and p<0.001 OR: 15.238, 95% CI 1.971-117.782 respectively) than in the healthy controls. Similarly, GSTP1 val/val genotype was significantly more frequent in the patients with chronic hepatitis B infection and in the patients with cirrhosis (p=0.006 OR = 6.799, 95% CI 1.712-26.99 and p<0.001, OR: 62.857 95% CI 8.794-449.285 respectively) than in the controls. There was no significant difference in GST IIe/val frequency between the patients with chronic hepatitis B infection and normal carriers of hepatitis B virus, while GST val/val genotype was significantly more frequent in the patients with chronic hepatitis B infection (p=0.030, OR: 6.097, 95% CI 1.192-31.194). Both GST IIe/val and GST val/val genotypes were significantly more frequent in the patients with cirrhosis than in the normal carriers (p=0.001, OR: 12.160 95% CI 1.618-91.360 and p<0.001, OR: 32.154, 95% CI 4.585-225.513 respectively). In addition, there was a significant relation between GSTP1 gene polymorphism and hepatitis stage. In fact, as IIe/val and val/val genotype frequencies significantly increased so did the stage of the disease and tendency towards cirrhosis (p<0.001). The difference in the GSTP1 gene polymorphism did not significantly differ between the healthy controls and the normal carriers of hepatitis B virus. Also, none of the four groups was significantly different concerning the presence of GSTM1 and GSTT1 gene deletions. CONCLUSIONS: The results of this study suggested that GSTP1-val (105) gene polymorphism could be associated with the course of chronic hepatitis B infection.

Risk factors for infection of the diabetic foot with multi-antibiotic resistant microorganisms.

AIM: To investigate the risk factors for infection of the diabetic foot with multidrug resistant microorganisms. METHODS: Amongst 102 diabetic patients with evidence of soft tissue infection of the foot who presented to our health center over a three year period, we investigated risk factors that might be predictive of multi-antibiotic resistance of the infecting organism. RESULTS: Of 102 patients with a diabetic foot wound, bacteria were cultured from 73, yielding a total of 104 isolates. The number of multidrug resistant isolates was 42 from 36 cases and the number of isolates other than multidrug resistant ones was 62 from 37 cases. Previous antibiotic therapy (p=0.002) and its duration (p=0.0001), frequency of hospitalization for the same wound (p=0.000), duration of hospital stay (p=0.000) and osteomyelitis (p=0.001) were significant risk factors for infections with multidrug resistant microorganisms. CONCLUSION: In conclusion, an appropriate antibiotic should be initiated promptly, wound perfusion should be effective, duration of hospital stay should be as short as possible and optimum hygiene should be provided during wound care to prevent infections of diabetic foot wound with multidrug resistant microorganisms.

Clarithromycin destroys biofilms and enhances bactericidal agents in the treatment of Pseudomonas aeruginosa osteomyelitis.

In this study, the effect of clarithromycin on the destruction of bacterial biofilm in Pseudomonas aeruginosa osteomyelitis was investigated. Foreign body-related osteomyelitis caused by ceftazidime-sensitive Pseudomonas aeruginosa was produced in the tibias of 26 rats. After osteomyelitis was verified on Day 14, 10 rats had ceftazidime (1500 mg/kg/day) given subcutaneously, and 10 rats had ceftazidime given subcutaneously and clarithromycin (100 mg/kg/day, two 50-mg/kg doses every 12 hours) given orally; three rats formed the control group. After a treatment period of 20 days, the tibias and the foreign bodies were removed, cultured, and examined by electron microscopy. The number of microorganisms growing on the bone tissue in the group receiving combined treatment was significantly lower than in the other groups. The number of microorganisms growing on the foreign body in the group receiving only ceftazidime was significantly higher than that of the group receiving combined treatment. Electron microscope examination revealed that the biofilm layer was eradicated in the group that had combined therapy; however, biofilm formation was evident on the foreign body in the group receiving only ceftazidime. Clarithromycin enhanced the activity of concomitantly used bactericidal agents by destroying biofilm on the surface of the materials.

Fibronectin levels in chronic viral hepatitis and response of this protein to interferon therapy.

BACKGROUND/AIMS: In this study, the plasma fibronectin levels in the cases of chronic hepatitis B and C infection and this protein's response to the interferon therapy were examined. METHODOLOGY: Totally, 38 patients with chronic hepatitis, 21 of them being hepatitis B, 17 of them being hepatitis C; and 24 healthy blood donors, as the control group, took part in this study. The quantitative determinations of fibronectin in plasma samples were performed with the Bohring Nephelometer BN 100 (N Antiserum to Human Fibronectin, code no OUND, Dade Behring Marburg GmbH, Marburg Germany). RESULTS: It was observed that the fibronectin plasma levels of the control group were significantly higher than those of the patient group before the therapy (p=0.043). After the interferon therapy of six months, the difference between the fibronectin levels of 16 examined patients before and after the treatment was found to be significant (p=0.001). A negative correlation was detected between the fibronectin levels before the therapy and the inflammatory grade as far as the histopathology of the illness was concerned (r=-0.49), which is a statically significant value (p=0.002). The correlation between the levels of fibronectin and the stage of the fibrosis was found to be insignificant statistically (p=0.225). When comparing the levels before and after the therapy, as far as ALT and AST values were concerned, it was observed that both parameters fell significantly after the therapy (p=0.002). However, no correlation was observed between the fibronectin levels and ALT, AST before and after the therapy. CONCLUSIONS: Fibronectin can be a useful marker for showing the hepatic inflammation and damage in the cases of chronic hepatitis, and can also be used in the evaluation of the response to the interferon therapy like other biochemical parameters (ALT, prothrombin activity etc.).

Comparison of the accelerated and classic vaccination schedules against Hepatitis B: three-week Hepatitis B vaccination schedule provides immediate and protective immunity.

BACKGROUND: Hepatitis B virus infection although preventable by vaccination remains an important health issue throughout the world due to its morbidity, mortality and economical losses. Early seroprotection is desirable for people at high risk of exposure. The aim of this study was to determine whether three-week hepatitis B vaccination (on days 0, 10 and 21) provide seroprotection or not. METHODS: The 120 subjects enrolled into the study were divided into two groups and vaccinated by the classic (months 0, 1, and 2) or the accelerated (days 0, 10, and 21) schedules and antibody response determined on days 30, 60, and 90 and, if below 10 mIU/ml(-1), again on day 180. For each individual in the classic group (B) three subjects were enrolled in the accelerated group (A). Recombinant hepatitis B vaccine (Gen-Hevac B, Pasteur) was given as 20 micrograms intramuscular injections via the deltoid muscle. A booster dose on day 365 was administered for each group. Family members of hepatitis B carriers and volunteer health personnel were enrolled into group A. To the B group only volunteers who wanted vaccination against hepatitis B were included. RESULTS: After three doses of vaccine, Anti-HBs titers reached protective levels in both groups. The number of vaccinees with seroprotective levels of Anti-HBs (> or =10 mIU/ml(-1)) on day 30 was 53 (58.9%) in group A and 9 (30.0%) in group B (p < 0.05). On day 60, there was no difference between group A and B, with response rates of 84.4% (n = 76) and 80.0% (n = 24) respectively (p > 0.05). On day 90 there was no difference between group B and group A; with 26 (86.7%) and 79 (87.7%) responders respectively. In both groups those with Anti-HBs levels <10 mIU/ml(-1) attained protective levels by day 180. CONCLUSION: In this study, the three-week vaccination provided protective antibody titers within a shorter time compared to the classic schedule. Therefore, in order to provide rapid antibody production against hepatitis B virus, the accelerated vaccination schedule seems to be a good preference.