[Comparison of Tuberculin Skin Test (TST) and T-SPOT.TB Tests for Diagnosis of Latent Tuberculosis Infection (LTBI) in HIV-infected Patients]. / HIV ile Enfekte Hastalarda Latent Tüberküloz Enfeksiyonunu (LTBE) Belirlemede Tüberkülin Deri Testi (TDT) ve T-SPOT.TB Testlerinin Karsilastirilmasi.

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients. Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most important step in preventing the development of active TB. In our country where TB is moderately endemic, HIV-infected patients should be investigated for LTBI. Tuberculin skin test (TST) and interferongamma release assays (IGRA) are used in the diagnosis of LTBI but there isn't a standard practice. The aim of this study is to compare the TST and T-SPOT.TB test efficiency in the diagnosis of LTBI in HIVinfected patients. Patients who had no previous active TB infection, who were not treated for LTBI and who had no active tuberculosis infection at the time of admission were included in the study. A total of 100 HIV-infected patients who were admitted to the Infectious Diseases and Clinical Microbiology outpatient clinic between June 2015 and March 2016 were evaluated cross-sectionally. CD4+ T lymphocyte counts in the last one month were detected. All patients underwent chest radiography at the time of admission. Patients who are not considered as active TB infection with clinical and laboratory findings and who had no TST within the last one month were included in the study. TST was performed after the blood samples were taken for T-SPOT.TB test. In our study, 87% of the patients were male and the mean age was 40.2. The mean CD4+ T lymphocyte count was 605 cells/mm³ (26-1313). 16% of the patients had a history of encountring a person with tuberculosis and 81% had BCG vaccination scar. TST positivity and T-SPOT.TB positivity were 22.9% and 22%, respectively. The concordance between the two tests was found to be moderate (Kappa= 0.491). It was determined that BCG vaccination and the presence of a contact with a patient with TB did not affect TST and T-SPOT.TB test positivity (p> 0.05). There was a positive correlation between CD4+ T lymphocyte count and TST measurement values (r= 0.3, p= 0.003). Accordingly, as the number of CD4+ T lymphocytes increased, TST positivity increased (p= 0.007). T-SPOT.TB test was not affected by CD4+ T lymphocyte count (p= 0.289). Our study showed that TST was affected by CD4+ T lymphocyte count and patients' compliance with this test was also low. On the contrary T-SPOT.TB test was not affected by CD4+ T lymphocyte count. There was no statistically significant difference between T-SPOT.TB test positivity and CD4+ T lymphocyte count (p= 0.289). The concordance between the two tests was found to be moderate. It is thought that the main reason for the discordance between the tests is due to false negative or false positive results of TST. In conclusion, T-SPOT.TB was found more reliable in the diagnosis of LTBI in HIV-infected individuals. In the light of these findings, especially in HIV-infected patients with low CD4+ T lymphocyte counts, T-SPOT.TB test can be considered for LTBI diagnosis.

Impact of fatty liver on hepatitis B virus replication and virologic response to tenofovir and entecavir.

BACKGROUND/AIMS: We aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on viral kinetics and virologic response to tenofovir and entecavir treatment in patients with chronic hepatitis B virus (HBV) infection. MATERIALS AND METHODS: This study was designed as a retrospective multicenter cohort study. The impact of hepatosteatosis on pre-treatment serum HBV DNA levels and also on the virologic response to either tenofovir or entecavir at 6 and 12 months of therapy was investigated. RESULTS: A total of 145 cases were involved in the study [median age 40 (18-73) years, 90 (62%) males]. In multivariate analysis, it was detected that patients with NAFLD were older and had a higher body mass index (BMI) [Odds ratio (95% confidence interval) and p-value for age were 1.040 (1.003-1.079) and 0.033 and for BMI were 1.348 (1.190-1.528) and 0.0001, respectively]. When only the 43 patients who were younger than 35.5 years old and who had a BMI less than 27.59 were investigated, serum high-density lipoprotein (HDL) levels and serum HBV DNA levels were lower in patients with NAFLD in multivariate analysis [Odds ratio (95% confidence interval) and p-values for serum HDL level and HBV DNA level were 0.864 (0.061-0.980) and 0.023 and 0.995 (0.990-0.999) and 0.025, respectively]. Totally, 57 and 75 of the patients had received entecavir and tenofovir, respectively. CONCLUSION: Viral replication decreases in patients with chronic HBV infection in the presence of NAFLD, and NAFLD had no impact on the virologic response to entecavir and tenofovir treatment.

Variables determining the development of colistin-associated renal impairment.

AIM: The aim of this study was to identify the predictors of acute renal injury associated with colistin treatment. METHODS: The patients who received treatment with colistin for more than 3 days were included in this retrospective cohort study. Acute renal injury was defined by the RIFLE (Risk Injury Failure Loss End stage renal disease) criteria. Patients whose serum creatinine levels increased at least 1.5-fold compared with baseline value were considered as cases with renal injury. The independent variables determining the development of acute renal injury were investigated by survival analysis. RESULTS: A total of 112 cases [67 (59.8 %) were male, median age 64 (range: 18-93) years] were included in the study. Acute renal injury occurred in 66 (58.9 %) patients. Renal injury developed in first 7 days of the colistin therapy in 52 (78.8 %) cases and at day 8-23 in 14 (21.2 %) cases. On the day with highest levels of creatinine, 25 (22.3 %), 17 (15.2 %), and 33 (29.5 %) cases were in 'Risk', 'Injury', and 'Failure' group, respectively, according to RIFLE criteria. We identified three independent risk factors predicting acute colistin-induced renal injury: advanced age, low serum albumin levels, and high serum total bilirubin levels [odds ratio (confidence interval) = 1.022 (1.006-1.037), 0.643 (0.415-0.994), and 1.129 (1.014-1.257), respectively]. CONCLUSIONS: The advanced age, low serum albumin levels, and high serum total bilirubin levels are independent risk factors for colistin-induced nephrotoxicity.

The effect of mupirocin- and fusidic acid-nasal packings, placed after septoplasty, on the nasal bacterial profile.

AIM: To examine the effects, after septoplasty, of local antibiotic pomades as an alternative to prophylactic antibiotic use, which is a controversial matter among the otolaryngologists, on nasal flora and bacterial growth. MATERIAL AND METHOD: Nasal packings placed after septoplasty surgery to provide septal stabilization and bleeding control pose a risk in terms of infection. In this study, 106 patients, who were examined by comparing mupirocin- and fusidic acid-soaked packings and antibiotic-free packings, were divided into three groups. Nasal cultures were obtained from each patient twice, before the surgery and on the second day immediately after the packings were removed, and the culture results were statistically compared. RESULTS: In the mupirocin group (group 2), postoperative normal flora growth rate was significantly higher than in the fusidic acid group (group 3) and the antibiotic-free group (group 1) (p < 0.024). In the mupirocin group (group 2), the gram-positive growth rate in the postoperative period showed a significant decrease when compared when the preoperative period (p < 0.05) (5.7%). In the fusidic acid group (group 3), the postoperative gram-positive rate showed a significant decrease compared with the preoperative period (p < 0.05). In group 2, the postoperative methicillin-resistant Staphylococcus aureus rate showed a significant decrease than in the preoperative period (2.9%) (p < 0.05). Similarly, in group 3, the postoperative methicillin-resistant S. aureus rate showed a significant decrease compared with that of the preoperative period (11.1%) (p < 0.05). CONCLUSION: Use of mupirocin- and fusidic acid-soaked nasal packings after septoplasty significantly decreased, especially, postoperative gram-positive bacterial growth in nasal cultures. Although systemic antibiotherapy was not administered, the lack of local and systemic infection findings was an important result that we obtained in terms of clinical use. Usage advantages of mupirocin and fusidic acid soaked packings are an easily applicable, cost-effective, and safe method.

Hepatic apoptotic markers are not predictors for the virological response to interferon-based therapy in chronic hepatitis C patients.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is a major health problem worldwide. The majority of cases involving HCV infection develop into chronic hepatitis because of a failure to develop an effective immune response. Apoptosis of the hepatocytes plays a significant role in the pathogenesis of HCV infection: the interaction between the Fas antigen on hepatocytes and the Fas ligand on T cells corresponds to the main mechanism for hepatocyte damage. Interferon (IFN)-α has antiviral, immunoregulatory, and antiproliferative properties, and apoptosis seems to be a critical event in the action mechanisms of both IFNs. In this study, we aimed to detect any relationship between apoptotic markers in the liver and the response to the treatment. MATERIALS AND METHODS: The study included 180 chronic HCV patients treated with IFN and ribavirin in four centers. Apoptotic markers (Fas, Fas ligand, Fas-associated death domain, caspases 3, 8, and 9, and in-situ apoptosis) were studied in the liver. The age, sex of the patients, response to therapy, ALT level, viral load, and genotype were recorded. RESULTS: The results of the study showed that the histological activity index and fibrosis correlated with CD95 staining density, caspase-8 intensiveness, and portal and parenchymal Fas ligand scores. The apoptotic parameters of the responsive cases were not significantly different from those of the unresponsive cases. CONCLUSION: The apoptotic parameters studied in liver tissue are associated with inflammation and fibrosis; however, these parameters may not predict response to treatment.

Transmission route and reasons for HIV testing among recently diagnosed HIV patients in HIV-TR cohort, 2011-2012.

INTRODUCTION: Routes of transmission and reasons for HIV testing are important epidemiologic data to analyze the epidemic and to tailor the response to AIDS. The aim of this study was to analyze reasons for testing and transmission ways of HIV among recently diagnosed HIV patients registered in the multicenter HIV-TR cohort in Turkey. METHODS: Transmission ways and reasons for testing of all patients diagnosed in 2011 and 2012 were recorded on a web-based data collection system and were analyzed retrospectively. RESULTS: The study included 693 patients (561 male, 132 female) from 24 sites. Reason for HIV testing was available in 640 patients (92%). The most common reason for HIV testing was diagnostic workout for other conditions or illness followed by patient-initiated testing. The reasons for testing were listed in Table 1. The most common routes of HIV transmission were heterosexual intercourse (62.7%) and sex among men who have sex with men (MSM) (22.6%). At the time of HIV diagnosis, the mean CD4 lymphocyte cell count was 355/mm(3) (3-1433/mm(3)). Primary HIV infection was determined in 42/693 (6%) patients and 9/693 (% 1, 2) cases were considered "probable primary HIV infection." The majority of the cases presented to a clinic for follow-up right after the diagnosis. On the other hand 32/616 (5.2%) patients delayed their presentation for more than 3 months. The longest delay was 11 months. CONCLUSIONS: The results of the database suggest that targeted testing is lacking in the country. The shift toward homosexual transmission during the last 2 years emphasizes the need for targeted interventions. Patients present relatively late and HIV infection could only be diagnosed when immunosuppression related findings appeared. Patient-initiated testing,an indicator of awareness, was very low suggesting a need to scale-up awareness raising interventions.

Outcomes of initial antiretroviral treatment (ART) among recently diagnosed HIV patients in HIV-TR cohort, 2011-2012.

INTRODUCTION: HIV-TR is a recently established (2012) multicentre cohort in Turkey. The aim of this study is to analyze epidemiological, immunologic and virologic data of recently diagnosed HIV patients. MATERIALS AND METHODS: Epidemiologic, clinical and laboratory data of all patients diagnosed in 2011 and 2012 were recorded by a web-based data collection system, retrospectively. RESULTS: A total of 693 patients (561 male, 132 female) at 24 sites were enrolled. The median age at first presentation for HIV care was 36. The proportion of patients presenting with advanced HIV disease (CD4 count<200/mm(3) or presenting with an AIDS-defining event) was 30.6%; and 52.4% of patients were late presenters (CD4 count<350/mm(3) or presenting with an AIDS-defining event). Median CD4 counts at presentation and before treatment were 344 (IQR: 175-540) and 295 (IQR: 150-430), respectively. Pretreatment CD4 count was >500 copies/mL in 18.5% of patients. Of 531 patients receiving ART, initial combinations consist of tenofovir/emtricitabine (TDF/FTC) plus efavirenz (EFV) in 48.2% and TDF/FTC plus lopinavir/ritonavir (LPV/r) in 37.5% and other combinations in 14.3% of the patients. Pre-treatment HIV-RNA was over 100.000 copies/mL in 52.3% of patients. At Weeks 24 and 48, HIV-RNA were<50 copies/mL in 63,4% of 385 patients and 82% of 311 patients reported to be still on ART and had a viral load measurement, respectively. Median pretreatment CD4 count was lower for TDF/FTC+LPV/r recipients than TDF/FTC+EFV recipients (250 vs 316) (p<0.05). The median increase from baseline CD4 cell count was 230 in TDF/FTC+LPV/r group, 193 in TDF/FTC+EFV group and 216 among all treated patients. Of 531 patients receiving ART, 11 had died and 19 were lost to follow-up. CONCLUSION: Despite 52.4% of recently diagnosed patients were late presenters; a high rate of virologic suppression was achieved in HIV-TR Cohort. A national HIV testing strategy targeting subpopulations with higher risk is urgently needed.

The effect of the different treatment protocols on virological and immunological responses in patients with HIV/AIDS.

This study analyzed the differences between the virological and immunological responses in patients with HIV/AIDS subjected to different treatment protocols. The cases treated with HAART were divided into groups on the basis of treatment protocols. The groups were evaluated with respect to the differences by comparing the virological and immunological responses prior to treatment and at 12 and 24 weeks of therapy. Six different treatment protocols were applied in the treated patients. As the largest clusters, the lopinavir/ritonavir-based patient group (Group 1, n = 29) and efavirenz-based patient group (Group 2, n = 18) were compared. The mean CD4 and HIV-RNA values of Groups 1 and 2 were 184 and 243 h/µl and 422,266 and 317,684 copies/ml, respectively. At 24 weeks of treatment, the HIV-RNA levels were below detectable values in 86% and 78% of the patients in Groups 1 and 2, respectively (p > 0.001). The striking outcomes observed in this study demonstrated that the pretreatment HIV-RNA level, CD4 value, gender, age, and protease inhibitor- or non-nucleoside reverse transcriptase inhibitor-based combined treatment protocols do not cause a significant difference and that patient compliance to treatment is the most important factor associated with treatment success.

[Elizabethkingia meningosepticum bacteremia in a patient with Bardet-Biedl syndrome and chronic renal failure]. / Bardet-Biedl sendromlu kronik böbrek yetmezligi olan bir hastada Elizabethkingia meningosepticum bakteriyemisi.

Elizabethkingia meningosepticum, a gram-negative opportunistic pathogen may cause life-threatening nosocomial infections especially in newborns and immunosuppressive patients. This bacterium has a peculiar antibiotic resistance profile. It is resistant to most of the antibiotics against gram-negative bacteria and susceptible to antibiotics that are used to treat gram-positive bacteria, such as vancomycin and trimethoprim-sulphamethoxazole (SXT). For this reason appropriate treatment of E.meningosepticum infections are based on the proper identification of bacteria. In this report, a case of catheter-related E.meningosepticum bacteremia in a patient with chronic renal failure due to Bardet-Biedl syndrome, a genetic disorder characterized by multiorgan dysfunction, was presented. A 25-year-old male patient with Bardet-Biedl syndrome was admitted to the emergency room with the complaints of high fever with shivers that started the day before. The patient had a femoral dialysis catheter. Venous blood samples drawn at the time of administration were cultured immediately. Two days later, blood cultures which yielded positive signals were passaged onto blood and MacConkey agar plates and after incubation at 37°C for 16 hours, wet-raised colonies with clear margin, gray colour and large size similar to gram-negative bacterial colonies were detected on blood agar medium. No growth was observed on MacConkey agar plate at the end of five days. The isolate was found positive for KOH, oxidase, catalase, urease, esculine and MOI (Motility Indole Ornithine) tests, whereas it was citrate negative. Gram staining revealed faintly stained thin gram-negative bacilli. The isolate was identified as E.meningosepticum by Vitek® 2 system (bioMérieux, USA), and confirmed by sequence analysis of 16S RNA gene region amplified with PCR method. The antibiotic susceptibility profile of the strain was detected by the Vitek 2 system, while vancomycin susceptibility was investigated by Kirby-Bauer disc diffusion method. The isolate was found resistant to ampicillin/sulbactam, piperacillin/tazobactam, ceftazidime, cefepime, meropenem, imipenem, amikacin, gentamicin, netilmicin, levofloxacin, tetracycline, colistin and rifampicin; intermediate to tigecyclin and tetracyclin; susceptible to cefoperazone/sulbactam, ciprofloxacin, levofloxacin, SXT and vancomycin. One gram vancomycin once every four days was administered to the patient, however on the ninth day of the treatment he developed fever again. Blood cultures obtained again yielded E.meningosepticum. After changing his dialysis catheter and extending the vancomycin treatment to 15 days, the patient was discharged with cure. In conclusion, clinicians should consider E.meningosepticum as a possible causative agent of bacteremia non-responsive to the empirical antibiotic regimens and when gram-negative bacteria are isolated from the blood cultures of such patients with underlying diseases. Accurate and prompt identification of E.meningosepticum will allow immediate administration of the specific antibiotic treatment, thereby decreasing the mortality and morbidity rates.

Predictors of fatality in pandemic influenza A (H1N1) virus infection among adults.

BACKGROUND: The fatality attributed to pandemic influenza A H1N1 was not clear in the literature. We described the predictors for fatality related to pandemic influenza A H1N1 infection among hospitalized adult patients. METHODS: This is a multicenter study performed during the pandemic influenza A H1N1 [A(H1N1)pdm09] outbreak which occurred in 2009 and 2010. Analysis was performed among laboratory confirmed patients. Multivariate analysis was performed for the predictors of fatality. RESULTS: In the second wave of the pandemic, 848 adult patients were hospitalized because of suspected influenza, 45 out of 848 (5.3%) died, with 75% of fatalities occurring within the first 2 weeks of hospitalization. Among the 241 laboratory confirmed A(H1N1)pdm09 patients, the case fatality rate was 9%. In a multivariate logistic regression model that was performed for the fatalities within 14 days after admission, early use of neuraminidase inhibitors was found to be protective (Odds ratio: 0.17, confidence interval: 0.03-0.77, p=0.022), nosocomial infections (OR: 5.7, CI: 1.84-18, p=0.013), presence of malignant disease (OR: 3.8, CI: 0.66-22.01, p=0.133) significantly increased the likelihood of fatality. CONCLUSIONS: Early detection of the infection, allowing opportunity for the early use of neuraminidase inhibitors, was found to be important for prevention of fatality. Nosocomial bacterial infections and underlying malignant diseases increased the rate of fatality.

A new model using platelet indices to predict liver fibrosis in patients with chronic hepatitis B infection.

BACKGROUND: We aimed to investigate whether mean platelet volume (MPV) and platelet distribution width (PDW) are variables determining the severity of liver fibrosis in patients with chronic HBV infection. METHODS: Patients were divided into two groups with fibrosis scores of 0-2 and 3-6 (according to Ishac scoring system). Whether MPV and PDW were independent variables determining the severity of liver fibrosis score or not was investigated by comparing these groups. RESULTS: Of the 111 cases, 74 (66.7 %) were male (mean age 37.7 ± 11.6 years). Twenty-two of the cases (19.8 %) were HBeAg-positive. Fibrosis scores of 42 cases (37.8 %) were ≥ 3 and the remaining 69 cases had fibrosis scores < 3 (62.2 %). Independent variables determining the severity of fibrosis score were low levels of albumin and mean platelet volume, and high levels of prothrombin time and PDW (Odds ratio (95 % confidence interval) and p values were 0.105 (0.018-0.605) and 0.012 for albumin, 0.402 (0.234-0.692) and 0.001 for mean platelet volume, 1.529 (1.183-1.975) and 0.001 for PDW, and 0.924 (0.875-0.976) and 0.005 for prothrombin time, respectively). The sensitivity, specificity, positive predictive value and negative predictive value of regression model that is established using above mentioned parameters were 88.1, 75.3, 68.5, and 91.7 %, respectively (AUC = 0.886, p = 0.0001). CONCLUSIONS: MPV and PDW are independent variables determining the severity of liver fibrosis, and the regression model that is established using these parameters along with other markers, may give more information about the severity of liver fibrosis.

Can mean platelet volume determine the severity of liver fibrosis or inflammation in patients with chronic hepatitis B?

AIMS: We aimed to determine whether mean platelet volume (MPV) is one of the variables that determine the severity of liver fibrosis and inflammation. MATERIALS AND METHODS: Patients with chronic hepatitis B virus (HBV) infection were divided into two groups: patients with fibrosis scores of 0-3 and 4-6 and patients with histologic activity index scores of 0-9 and 10-18 (according to the Ishak Scoring System). The independent variables determining the severity of liver fibrosis and inflammation were investigated. RESULTS: Two hundred and thirty-eight patients were included in this retrospective study. The fibrosis scores of 29 patients (12.2%) were higher than 3. The independent variables that determined the severity of the fibrosis score were a high level of serum γ-glutamyl transferase and a low blood platelet count (odds ratio and P values were 1.016 and 0.004 for γ-glutamyl transferase, and 0.986 and 0.002 for blood platelet count). The histologic activity indexes of 38 patients (16%) were higher than 9. The independent variables determining the severity of liver inflammation were serum HBV DNA, γ-glutamyl transferase, and globulin levels and the MPV [odds ratio and P values were, respectively, 0.1001 and 0.046 for HBV DNA (×10); 1.016 and 0.004 for γ-glutamyl transferase; 2.247 and 0.039 for globulin; and 1.488 and 0.004 for the MPV]. The sensitivity, specificity, and positive predictive value and negative predictive value of the model predicting the severity of liver inflammation were 60.5, 83, 40.3, and 91.7%, respectively (area under the receiver-operating characteristic curve=0.775, P=0.0001). CONCLUSION: MPV may provide useful information to predict the degree of liver inflammation along with other markers.