Nail Ozgunes

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.

Mortality indicators in pneumococcal meningitis: therapeutic implications

BACKGROUND The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. METHODS This retrospective, multicenter cohort study involved a 15-year period (1998-2012). Culture-positive cases (n=306) were included solely from 38 centers. RESULTS Fifty-eight patients received ceftriaxone plus vancomycin empirically. The rest were given a third-generation cephalosporin alone. Overall, 246 (79.1%) isolates were found to be penicillin-susceptible, 38 (12.2%) strains were penicillin-resistant, and 22 (7.1%) were oxacillin-resistant (without further minimum inhibitory concentration testing for penicillin). Being a critical case (odds ratio (OR) 7.089, 95% confidence interval (CI) 3.230-15.557) and age over 50 years (OR 3.908, 95% CI 1.820-8.390) were independent predictors of mortality, while infection with a penicillin-susceptible isolate (OR 0.441, 95% CI 0.195-0.996) was found to be protective. Empirical vancomycin use did not provide significant benefit (OR 2.159, 95% CI 0.949-4.912). CONCLUSIONS Ceftriaxone alone is not adequate in the management of pneumococcal meningitis due to penicillin-resistant pneumococci, which is a major concern worldwide. Although vancomycin showed a trend towards improving the prognosis of pneumococcal meningitis, significant correlation in statistical terms could not be established in this study. Thus, further studies are needed for the optimization of pneumococcal meningitis treatment.

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.

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.

Predictors for limb loss among patient with diabetic foot infections: an observational retrospective multicentric study in Turkey

We aimed to investigate the predictors for limb loss among patients with diabetes who have complicated skin/soft-tissue infections. In this observational study, consecutive patients with diabetic foot infection (DFI) from 17 centres in Turkey, between May 2011 and May 2013 were included. The Turkish DFI Working Group performed the study. Predictors of limb loss were investigated by multivariate analysis. In total, 455 patients with DFI were included. Median age was 61 years, 68% were male, 65% of the patients were hospitalized, 52% of the patients had used antibiotics within the last month, and 121 (27%) had osteomyelitis. Of the 208 microorganisms isolated, 92 (44.2%) were Gram-positive cocci and 114 (54.8%) were Gram-negative rods (GNR). The most common GNR was Pseudomonas; the second was Escherichia coli, with extended spectrum β-lactamase positivity of 33%. Methicillin-resistant Staphylococcus species were found in 14% (29/208). Amputations were performed in 126/455 (28%) patients, 44/126 (34%) of these were major amputations. In multivariate analysis, significant predictors for limb loss were, male gender (OR 1.75, 95% CI 1.04-2.96, p 0.034), duration of diabetes >20 years (OR 1.9, 95% CI 1.18-3.11, p 0.008), infected ulcer versus cellulitis (OR 1.9, 95% CI 1.11-3.18, p 0.019), history of peripheral vascular disease (OR 2, 95% CI 1.26-3.27, p 0.004), retinopathy (OR 2.25, 95% CI 1.19-4.25, p 0.012), erythrocyte sedimentation rate >70 mm/hr (OR 1.6, 95% CI 1.01-2.68, p 0.05), and infection with GNR (OR 1.8, 95% CI 1.08-3.02, p 0.02). Multivariate analysis revealed that, besides the known risk factors such as male gender, duration of diabetes >20 years, infected ulcers, history of peripheral vascular disease and retinopathy, detection of GNR was a significant predictor of limb loss.

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.

Influence of multidrug resistant organisms on the outcome of diabetic foot infection

OBJECTIVES We described the clinical outcomes of the diabetic patients who had foot infections with multidrug resistant organisms. METHODS We included the patients with diabetic foot infections (DFI) from 19 centers, between May 2011 and December 2015. Infection was defined according to IDSA DFI guidelines. Patients with severe infection, complicated moderate infection were hospitalized. The patients were followed-up for 6 months after discharge. RESULTS In total, 791 patients with DFI were included, 531(67%) were male, median age was 62 (19-90). Severe infection was diagnosed in 85 (11%) patients. Osteomyelitis was diagnosed in 291(36.8%) patients. 536 microorganisms were isolated, the most common microorganisms were S. aureus (20%), P. aeruginosa (19%) and E. coli (12%). Methicillin resistance (MR) rate among Staphylococcus aureus isolates was 31%. Multidrug resistant bacteria were detected in 21% of P. aeruginosa isolates. ESBL (+) Gram negative bacteria (GNB) was detected in 38% of E. coli and Klebsiella isolates. Sixty three patients (8%) were re-hospitalized. Of the 791 patiens, 127 (16%) had major amputation, and 24 (3%) patients died. In multivariate analysis, significant predictors for fatality were; dialysis (OR: 8.3, CI: 1.82-38.15, p=0.006), isolation of Klebsiella spp. (OR:7.7, CI: 1.24-47.96, p=0.028), and chronic heart failure (OR: 3, CI: 1.01-9.04, p=0.05). MR Staphylococcus was detected in 21% of the rehospitalized patients, as the most common microorganism (p<0.001). CONCLUSION Among rehospitalized patients, methicillin resistant Staphylococcus infections was detected as the most common agent, and Klebsiella spp. infections were found to be significantly associated with fatality.

Predictors of response to pegylated interferon treatment in HBeAg-negative patients with chronic hepatitis B

INTRODUCTION Although pegylated interferons (pegIFNs) alpha-2a and alpha-2b have been used in chronic hepatitis B (CHB) treatment for many years, there are few studies concerning predictors of sustained virologic response (SVR) to pegIFN therapy. In this study, we aimed to investigate the predictors of response to pegIFN treatment in cases with HBeAg-negative CHB infection. METHODOLOGY Seventeen tertiary care hospitals in Turkey were included in this study. Data from consecutively treated HBeAg-negative CHB patients, who received either pegIFN alpha-2a or alpha-2b, were collected retrospectively. SVR is defined as an HBV DNA concentration of less than 2,000 IU/mL six months after the completion of therapy RESULTS SVR was achieved in 40 (25%) of the 160 HBeAg-negative CHB patients. Viral loads in patients with SVR were lower compared to those with no SVR, beginning in the third month of treatment (p < 0.05). The number of cases with a decline of 1 log10 IU/mL in viral load after the first month of treatment and with a serum HBV DNA level under 2,000 IU/mL after the third month of treatment was higher in cases with SVR (p < 0.05). The number of patients who had undetectable HBV DNA levels at week 48 among responders was significantly greater than among post-treatment virological relapsers (p < 0.05). CONCLUSIONS Detection of a 1 log10 decline in serum HBV DNA level at the first month of treatment and a serum HBV DNA level < 2000 IU/mL at the third month of therapy may be predictors of SVR.

HIV-related Eye Disease in Patients Presenting to a Tertiary Care Government Hospital in Turkey

Aim: To document the ocular involvement in HIV-infected individuals in Turkey and to compare the findings with those from other centers throughout the world. Methods: In this cross-sectional study, patients with HIV infection being monitored in a tertiary hospital in Istanbul were enrolled. Ocular examination was performed, and the prevalence of ocular manifestations determined. Results: In total, 93 patients were enrolled, of whom 37.6% had ocular pathology. HIV retinopathy was the most frequent retinal finding, affecting 8.6% of the enrolled patients, but none of the affected individuals had any ophthalmic complaints. There were no ocular lesions suggestive of cytomegalovirus (CMV) retinitis. Discussion: In contrast to the case in the developed world, sight-threatening infections are uncommon in Turkish HIV+ patients. The reasons for this are not clear, but it is possible that there are some genetic or environmental protective factors against CMV retinitis in the population studied.