Bahadir Ceylan

Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study

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

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 &ggr;-glutamyl transferase and a low blood platelet count (odds ratio and P values were 1.016 and 0.004 for &ggr;-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, &ggr;-glutamyl transferase, and globulin levels and the MPV [odds ratio and P values were, respectively, 0.1001 and 0.046 for HBV DNA (×107); 1.016 and 0.004 for &ggr;-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.

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

SummaryBackgroundWe 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.MethodsPatients 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.ResultsOf 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).ConclusionsMPV 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.ZusammenfassungHintergrundWir untersuchten, ob das mittlere Thrombozytenvolumen und die Verteilung der Thrombozytenbreite Variable sind, die den Schweregrad der Leberfibrose bei Patienten mit chronischer Hepatitis B (HBV) Infektion bestimmen.MethodenDie Patienten (n = 111, davon waren 74 (66,7 %) männlich, mittleres Alter: 37,7 ± 11,6 Jahre) wurden in 2 Gruppen je nach Fibrose Score (0–2 und 3–6) eingeteilt. Verwendet wurde das Ishac Score System. Ob das mittlere Thrombozytenvolumen und die Breitenverteilung der Thrombozyten unabhängige, den Schweregrad der Leberfibrose bestimmende Variable sind, wurde durch Vergleich dieser Gruppen geprüft.ErgebnisseZweiundzwanzig (19,8 %) Patienten waren HbeAg positiv. Die Fibrose Scores waren bei 42 Patienten (37,8 %) ≥ 3 und bei den restlichen 69 (62,2 %) Patienten < 3. Folgende Parameter stellten sich als unabhängige, den Schweregrad der Leberfibrose bestimmende Variable heraus: niedrige Albumin- und niedrige mittlere Thrombozytenvolumen-Werte, sowie hohe Werte der Prothromin Zeit und der Breite der Thrombozyten (Odds ratio (95 % Konfidenz Intervalle) und p Werte waren respektive: 0,105 (0,018–0,605) und 0,012 für Albumin, 0,402 (0,234–0,692) sowie 0,001 für das mittlere Thrombozytenvolumen, 1,529 (1,183–1,975) and 0,001 für die Verteilung der Thromzytenbreite, und 0,924 (0,875–0,976) and 0,005 für die Prothrombin Zeit). Die Sensitivität, Spezifität, der positive und der negative Vorhersagewert des Regressionsmodells, das unter Verwendung der oben erwähnten Parameter etabliert wurde waren: 88,1, 75,3, 68,5, and 91.7 %, respektive (AUC = 0,886, p = 0,0001).SchlussfolgerungenDas mittlere Thrombozytenvolumen und die Verteilung der Thrombozytenbreite sind unabhängige Variable, die den Schweregrad der Leberfibrose bestimmen. Das auf Basis dieser und anderer Parameter etablierte Regressionsmodell könnte mehr Information über den Schweregrad der Leberfibrose geben.

Ribavirin is not effective against Crimean-Congo hemorrhagic fever: observations from the Turkish experience.

Summary Crimean–Congo hemorrhagic fever (CCHF) is a viral infection associated with a high mortality rate. Ribavirin is the only drug used in the treatment of this disease. Studies investigating the effectiveness of ribavirin in CCHF have been retrospective and to date have included only a small number of cases. In recent years, due to climate changes, the number of cases of CCHF in Turkey has increased, and experience in the treatment of CCHF has improved. Several studies have evaluated the efficacy of ribavirin in Turkey, including one randomized controlled trial and two studies with a large number of cases. In these studies, ribavirin therapy was not shown to decrease mortality rates; the mortality rate was 2–9% in patients treated with ribavirin and 5.6–11% in those who were not treated with this drug. These findings suggest that patients with CCHF should be followed with supportive care only until randomized controlled trials with larger groups have been conducted.

Diagnosis of chronic brucellar meningitis and meningoencephalitis: the results of the Istanbul-2 study

No detailed data exist in the literature on the accurate diagnosis of chronic brucellar meningitis or meningoencephalitis. A multicentre retrospective chart review was performed at 19 health centres to determine sensitivities of the diagnostic tests. This study included 177 patients. The mean values of CSF biochemical test results were as follows: CSF protein, 330.64 ± 493.28 mg/dL; CSF/ blood-glucose ratio, 0.35 ± 0.16; CSF sodium, 140.61 ± 8.14 mMt; CSF leucocyte count, 215.99 ± 306.87. The sensitivities of the tests were as follows: serum standard tube agglutination (STA), 94%; cerebrospinal fluid (CSF) STA, 78%; serum Rose Bengal test (RBT), 96%; CSF RBT, 71%; automated blood culture, 37%; automated CSF culture, 25%; conventional CSF culture, 9%. The clinician should use every possible means to diagnose chronic neurobrucellosis. The high seropositivitiy in brucellar blood tests must facilitate the use of blood serology. Although STA should be preferred over RBT in CSF in probable neurobrucellosis other than the acute form of the disease, RBT is not as weak as expected. Moreover, automated culture systems should be applied when CSF culture is needed.

First-line monotherapies of tenofovir and entecavir have comparable efficacies in hepatitis B treatment

Background Hepatitis B virus (HBV) infection is a health problem worldwide. Current treatment options for chronic hepatitis B (CHB) are nucleoside or nucleotide analogues and pegylated interferons. Tenofovir and entecavir are much more commonly used as they have better efficacy, tolerability, and high genetic barriers to resistance. Aim The aim of this study was to assess the efficacies of tenofovir and entecavir in previously untreated CHB patients in a treatment cohort. Patients and methods We included CHB patients in a cohort including previously untreated HBeAg-positive and HBeAg-negative patients from 10 centers in Istanbul, Turkey. The patients were compared in terms of baseline characteristics, decrease in alanine transaminase (ALT), decrease in HBV-DNA to undetectable levels, HBeAg loss and anti-HBe development (among baseline HBeAg-positive patients), interventions to therapy because of lack of efficacy, side effects, severe side effects, and side effects that required change in treatment. Results The study included 121 patients who were administered tenofovir and 130 patients who were administered entecavir. The majority of patients were men, with mild to moderate histology in both treatment groups. The mean duration of follow-up was 18 and 20 months for tenofovir and entecavir, respectively. Patients receiving both drugs showed comparable rates of HBeAg loss, rates of undetectable HBV-DNA levels, rates of ALT normalization, ALT decrease, and decrease in HBV-DNA. Both drugs were well tolerated. Conclusion This study shows that although the baseline characteristics did not match, tenofovir and entecavir sustained comparable virological efficacies. More patients discontinued entecavir during follow-up. Both drugs provided effective viral control, with few side effects.

The efficacy of ribavirin in Crimean-Congo hemorrhagic fever—randomized trials are urgently needed

The only antiviral drug used today in Crimean-Congo hemorrhagic fever (CCHF) is ribavirin; however, its efficacy is controversial due to the lack of randomized controlled trials. The studies examining the efficacy of ribavirin in CCHF have generally been retrospective studies including insufficient numbers of patients, resulting in low power. We think that ribavirin should not be used in CCHF until randomized controlled studies have been conducted, and that only supportive treatment should be used. In response to the letter from Professor Onder Ergonul suggesting that our conclusions are wrong, we provide the scientific evidence outlined below. First, Professor Ergonul suggests that a study published in 2013 showed ribavirin to decrease the mortality from CCHF. However, in that retrospective study, the patients were grouped by severity as mild, moderate, and severe cases, and ribavirin decreased mortality only in moderate cases. It was reported that two of 134 cases receiving ribavirin and three of 18 cases not receiving ribavirin died, and that this difference was statistically significant. The mortality rates were low in the ribavirin group, but because the study was not randomized, the patient selection may have been biased; for example, severe cases may not have received ribavirin if this drug was not available at the hospital of admission and then died before it became available or after just a few doses. Therefore, we believe that the study result showing the decreased mortality in the ribavirin group is due to a type 1 error. Second, Professor Ergonul suggests that some studies performed recently in Turkey have revealed as an outcome that ribavirin decreased mortality in CCHF. One of these studies is related to healthcare employees coming into contact with the CCHF virus or being infected following CCHF exposure. In that study, nine healthcare employees were administered ribavirin following injury with contaminated tools, two before any symptoms developed and seven after they had developed symptoms. It was suggested that the development of CCHFrelated symptoms was prevented in two healthcare employees coming into contact with the CCHF virus. However, CCHF is a disease with a high probability of asymptomatic presentation, thus this invalidates that comment. Additionally, stating that ribavirin is effective in CCHF based on only two cases does not coincide with scientific study principles. Further, in that study, ribavirin was administered to seven healthcare employees developing CCHF, and it was reported that only one case died. When these seven study cases are examined in detail, it is observed that four cases were of moderate severity, two of mild severity, and one was of severe grade – the healthcare worker who died was the severe grade case. Therefore, it is more probable that

Low Prevalence of Hepatitis C Virus Infection Among HIV-Positive Patients: Data From a Large-Scale Cohort Study in Istanbul, Turkey.

Background: Rate of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) varies in different countries. This may be attributable to common transmission routes as well as social, economic, and cultural factors. Objectives: The purpose of this study was to investigate the prevalence and risk factors of HCV infection among HIV-positive patients in Istanbul, Turkey. Patients and Methods: Since January 2006 to November 2013, 949 HIV-positive patients that were enrolled in this study by ACTHIV-IST (Action Against HIV in Istanbul) Study Group, which consists of five centers to follow up HIV-positive patients in Istanbul. Epidemiologic and clinical data were collected retrospectively from medical records and were transferred to an HIV database system. Results: Among 949 patients, 84% were men and the mean age was 37.92 ± 11.54 years (range, 17-79). The most frequent route of transmission was heterosexual intercourse (48.8%), followed by men having sex with men (30.5%). Only nine patients (0.9%) had history of injection drug use (IDU). The prevalence of HIV/HCV coinfection was 0.9% (9:949). The IDU rate was 44.4% (4:9) in patients with HIV/HCV coinfection (three of them were not Turkish citizens), whereas this rate was only 0.6% (5:881) in patients with only HIV infection (P < 0.01). Genotypes 1b, 2a/2c, and 3 were determined in five, one, and two patients, respectively. Genotype could not be determined in one patient. History of residence in a foreign country (P < 0.01) and imprisonment (P < 0.01) were also considered as risk factors in terms of HIV/HCV coinfection. Conclusions: Prevalence of HIV/HCV coinfection is considerably low in Turkey. The extremely rare prevalence of IDU might have a role in this low prevalence.

Epidemiological Profile of Naive HIV-1/AIDS Patients in Istanbul: The Largest Case Series from Turkey

The aim of the study was to report the epidemiological profile of HIV-1 positive patients from, Istanbul, Turkey, which has one of the lowest HIV-1/AIDS prevalences in Europe. The patients were followed by ACTHIV-IST group which was established by the Infectious Diseases Departments of five teaching hospitals (three university hospitals and two public hospitals) in Istanbul, Turkey. The HIV-1 positive patients were added to the standard patient files in all of the centers; these files were then transferred to the ACTHIV-IST database in the Internet. A total of 829 naiv-untreated HIV-1 positive patients were chosen from the database. The number of male patients was 700 (84.4%) and the mean age of the patients was 37 years (range, 17-79). In our study group 348 (42%) of the patients were married and 318 (38.7%) of the patients were single. The probable route of transmission was heterosexual intercourse in 437 (52.7%) patients and homosexual intercourse in 256 (30.9%) patients. In 519 (62.6%) patients the diagnose was made due to a screening test and in 241 (29.1%) patients, the diagnose was made due to an HIV-related/non-related disease. The mean CD4+ T cell number in 788 of the patients was 357.8/mm(3) (±271.1), and the median viral load in 698 of the patients was 100,000 copies/mL (20-9,790,000). In Turkey, the number of HIV-1 positive patients is still low and to diagnose with a screening test is the most common way of diagnostic route.

Miliary tuberculosis: Epidemiologicaland clinical analysis of large-case series from moderate to low tuberculosis endemic Country

Abstract The aim of this study was to determine the clinical features, and outcome of the patients with miliary tuberculosis (TB). We retrospectively evaluated 263 patients (142 male, 121 female, mean age: 44 years, range: 16–89 years) with miliary TB. Criteria for the diagnosis of miliary TB were at least one of the followings in the presence of clinical presentation suggestive of miliary TB such as prolonged fever, night sweats, anorexia, weight loss: radiologic criterion and pathological criterion and/or microbiological criterion; pathological criterion and/or microbiological criterion. The miliary pattern was seen in 88% of the patients. Predisposing factors were found in 41% of the patients. Most frequent clinical features and laboratory findings were fever (100%), fatigue (91%), anorexia (85%), weight loss (66%), hepatomegaly (20%), splenomegaly (19%), choroid tubercules (8%), anemia (86%), pancytopenia (12%), and accelerated erythrocyte sedimentation rate (89%). Tuberculin skin test was positive in 29% of cases. Fifty percent of the patients met the criteria for fever of unknown origin. Acid-fast bacilli were demonstrated in 41% of patients (81/195), and cultures for Mycobacterium tuberculosis were positive in 51% (148/292) of tested specimens (predominantly sputum, CSF, and bronchial lavage). Blood cultures were positive in 20% (19/97). Granulomas in tissue samples of liver, lung, and bone marrow were present in 100% (21/21), 95% (18/19), and 82% (23/28), respectively. A total of 223 patients (85%) were given a quadruple anti-TB treatment. Forty-four (17%) patients died within 1 year after diagnosis established. Age, serum albumin, presence of military pattern, presence of mental changes, and hemoglobin concentration were found as independent predictors of mortality. Fever resolved within first 21 days in the majority (90%) of the cases. Miliary infiltrates on chest X-ray should raise the possibility of miliary TB especially in countries where TB is endemic. Although biopsy of the lungs and liver may have higher yield rate of organ involvement histopathologicaly, less invasive procedures including a bone marrow biopsy and blood cultures should be preferred owing to low complication rates.