Oguz Karabay

Monotherapy versus combination therapy for sepsis due to multidrug-resistant Acinetobacter baumannii: analysis of a multicentre prospective cohort

BACKGROUND Treatment of multidrug-resistant Acinetobacter baumannii (MDRAB) infection presents a challenge because of the scarcity of available options. Even though combination therapy (CT) is frequently used in clinical practice, data are needed to support its use instead of monotherapy (MT). METHODS A prospective observational study was conducted in 28 Spanish hospitals. Patients with sepsis caused by MDRAB, defined according to strict criteria, and who received active antibiotic treatment (according to in vitro susceptibility testing) for at least 48 h, were included. The main outcome variable was all-cause 30 day mortality after initiation of targeted therapy. Multivariate analysis, including a propensity score (for receiving CT), was performed by Cox regression. RESULTS One hundred and one patients were included in the analysis; 68 (67.3%) received MT and 33 (32.7%) received CT. Pneumonia was the most common infection (50.5%), 68.6% of cases being associated with mechanical ventilation. Colistin (67.6%) and carbapenems (14.7%) were the most common drugs used in MT; colistin plus tigecycline (27.3%) and carbapenem plus tigecycline (12.1%) were the most frequent combinations. Crude 30 day mortality was 23.5% and 24.2% for the MT and CT groups, respectively (RR = 1.03; 95% CI 0.49-2.16; P = 0.94). Multivariate analysis of 30 day survival showed no trend towards reduced 30 day mortality with CT (HR = 1.35; 95% CI 0.53-3.44; P = 0.53). Subgroup analysis showed similar results. CONCLUSIONS Our data do not support an association of CT with reduced mortality in MDRAB infections. More data for specific types of infection and combinations are needed.

Effect of severe sepsis on platelet count and their indices

BACKGROUND Sepsis is a major disease affecting almost all organs and systems. OBJECTIVES To examine platelet count and indices (mean platelet volume (MPV) and platelet distribution width (PDW)) in severe sepsis. METHODS Patients with criteria for sepsis at a first examination by an Infectious Diseases specialist were selected. Consecutive patients who were admitted to the out-patient clinic and who were not diagnosed with any infectious disease were selected as the control group. RESULTS A total of 145 patients with sepsis and 143 patients as a control group were included in the study. MPV and PDW were significantly differentbetween sepsis patients and control group (P<0.05). Platelet count in sepsis patients was lower than control group but the difference was not significant. PDW was the unique significantly different parameter between survivors and non-survivors (p=0.001). CONCLUSION Platelet indices are important laboratory findings in the diagnosis of sepsis and severe sepsis. Severe sepsis patients who have greater than 18 % PDW levels have a higher risk of death. Therefore, PDW, which is part of an inexpensive, easily accessible and routinely performed test for almost all patients admitted to health facilities may be used for predicting mortality.

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

Results of a Multinational Study Suggest the Need for Rapid Diagnosis and Early Antiviral Treatment at the Onset of Herpetic Meningoencephalitis

ABSTRACT Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

Colistin nephrotoxicity increases with age.

Abstract Background: Colistin (COL) has become the backbone of the treatment of infections due to extensively drug-resistant (XDR) Gram-negative bacteria. The most common restriction to its use is acute kidney injury (AKI). Methods: We conducted a retrospective cohort study to evaluate risk factors for new-onset AKI in patients receiving COL. The cohort consisted of 198 adults admitted to 9 referral hospitals between January 2010 and October 2012 and treated with intravenous COL for ≥ 72 h. Patients with no pre-existing kidney dysfunction were compared in terms of risk factors and outcomes of AKI graded according to the RIFLE criteria. Logistic regression analysis was used to identify associated risk factors. Results: A total of 198 patients met the inclusion criteria, of whom 167 had no pre-existing kidney dysfunction; the mean patient age was 58.77 (± 18.98) y. Bloodstream infections (34.8%) and ventilator-associated pneumonia (32.3%) were the 2 most common indications for COL use. New-onset AKI developed in 46.1% of the patients, graded as risk (10%), injury (15%), and failure (21%). Patients with high Charlson co-morbidity index (CCI) scores (p = 0.001) and comparatively low initial glomerular filtration rate (GFR) estimations (p < 0.001) were more likely to develop AKI, but older age (p = 0.001; odds ratio 5.199, 95% confidence interval 2.684–10.072) was the major predictor in the multivariate analysis. In-hospital recovery from AKI occurred in 58.1%, within a median of 7 days. Conclusions: COL-induced nephrotoxicity occurred significantly more often in patients older than 60 y of age and was related to low initial GFR estimations and high CCI scores, which were basically determined by age.

Effects of Carbapenem consumption on the prevalence of Acinetobacter infection in intensive care unit patients

BackgroundThe consumption of carbapenems has increased worldwide, together with the increase in resistant gram negative bacilli. Subsequently, the prevalence of carbapenem-resistant Acinetobacter infections has increased rapidly and become a significant problem particularly in intensive care unit patients. The aim of the present study was to evaluate the changes in the prevalence of Acinetobacter infection by restricting the consumption of carbapenems in intensive care unit patients.MethodsThis study was conducted between May 1, 2011 and February 28, 2013. The amount of carbapenem consumption and the number of patients with multi-drug resistant Acinetobacter baumannii (MDRAB) isolates during the study period were retrospectively obtained from the records of the patients, who were hospitalized in the intensive care unit. The study period was divided into two periods named as: Carbapenem non-restricted period (CNRP) and carbapenem-restricted period (CRP). During CNRP, no restrictions were made on the use of carbapenems. During CRP, the use of carbapenems was not allowed if there was an alternative to carbapenems. Primary Endpoint: MDRAB infection after ICU admission. The definition of nosocomial infections related to Acinetobacter spp. was based on the criteria of the Center for Disease Control (CDC). The correlation between the amount of carbapenem consumption and the number of infections with MDRAB strains between the two periods were evaluated.ResultsDuring the study period, a total of 1822 patients’ (1053 patients in CNRP and 769 patients in CRP) records were evaluated retrospectively. A total of 10.82 defined daily dose (DDD/100 ICU days) of anti-pseudomonal carbapenem were used in CNRP, and this figure decreased to 6.95 DDD/100 ICU days in CRP. In the 8-month CNRP, 42 (3.98%) MDRAB-related nosocomial infections were detected, and 14 (1.82%) infections were detected in CRP (p = 0.012).ConclusionThe prevalence of MDRAB strains isolated in the CNRP was 2.24-fold higher than the prevalence in the CRP. The prevalence of Acinetobacter infections can be reduced by taking strict isolation measures as well as by implementing good antibiotics usage policy.

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.

Comparable efficacy of tenofovir versus entecavir and predictors of response in treatment-naïve patients with chronic hepatitis B: a multicenter real-life study

OBJECTIVE To compare responses to tenofovir (TDF) and entecavir (ETV) therapy. METHODS This was a multicenter retrospective study including treatment-naïve patients with chronic hepatitis B (CHB) who received TDF or ETV. The primary end-points were undetectable HBV-DNA at 48 weeks and serological and biochemical responses. RESULTS Out of 195 CHB patients, 90 (46%) received TDF and 105 (54%) received ETV; 72% were male, their mean age was 43±12 years, and the mean duration of treatment was 30.2±15.7 months. Hepatitis B e antigen (HBeAg) seropositivity was 32% in the TDF group and 34% in the ETV group. HBeAg seroconversion rates in HBeAg-positive patients were 24% in the TDF group and 39% in the ETV group; the difference was not significant (p=0.2). The mean time to alanine aminotransferase (ALT) normalization and rates of ALT normalization at 3, 6, 12, 18, and 24 months were similar in the two groups (p > 0.05). The mean time to undetectable HBV-DNA levels in the TDF and ETV groups was 11.5±8.9 and 12.9±10.8 months, respectively (p=0.32). A significantly greater decline in HBV-DNA levels at 12 and 18 months was observed in the TDF group (p=0.02 and p=0.03, respectively). Seven (7%) patients on ETV therapy had virological breakthrough (p=0.01). Only one patient in each group had hepatitis B surface antigen (HBsAg) clearance. None of the patients developed decompensation or hepatocellular carcinoma during treatment. CONCLUSIONS The two drugs appear to have similar efficacy in CHB patients. However, 7% of patients on ETV therapy had virological breakthrough, while none of the patients on TDF therapy did.

Tetanus immunity in nursing home residents of Bolu, Turkey

BackgroundTetanus is a serious but vaccine-preventable disease and fatality rate of the disease is high in the neonates and the elderly. The aim of this study was to detect the tetanus antibody prevalence in the over sixty-year age residents of the nursing homes in Bolu.MethodsA voluntary-based study was done in the residents of two nursing homes in Bolu, Turkey. Blood samples were taken from 71 volunteers residing in there nursing homes. Tetanus IgG antibodies were measured by a commercial ELISA kit.ResultsAmong overall subjects, only 11 (15.7 %) had the protective tetanus antibody titers at the time of the study. Totally, 10 subjects were examined in emergency rooms due to trauma or accidents within the last ten years and, four (40%) of them had protective antibody levels. Of the remaining 61 subjects only 7 (11%) had protective antibody levels (p < 0.05) [Relative Risk = 3.49, 95% Confidence Interval 1.24–9.77].ConclusionsTetanus antibody level is below the protective level in the majority of the over-sixty-year-age subjects residing in the nursing homes. Each over sixty-year age person in our country should be vaccinated. Until this is accomplished, at least, nursing home residents should be vaccinated during registration.

Detection of Staphylococcal Exotoxins in Antrochoanal Polyps and Chronic Rhinosinusitis with Nasal Polyps

Objective Staphylococcal exotoxins have been reported in the pathogenesis of many chronic inflammatory diseases. Recent reports have hypothesized that staphylococcal exotoxins might be related to inflammatory mucosal changes seen in chronic sinusitis with nasal polyps (CRS-NPs). Staphylococcal exotoxins have the capacity to act as superantigens (SAgs), bypassing normal antigen processing and directly stimulating a massive inflammatory response. The objective of this study was to analyze polyp tissue samples from patients with antrochoanal polyps (ACPs) and CRS-NPs for the presence of staphylococcal exotoxins. Study Design Prospective cohort study. Setting Tertiary medical center. Subjects and Methods Tissue samples were obtained from 29 patients and 16 controls. Thirteen of 29 patients had ACPs, and 16 had CRS-NPs. Specimens were analyzed for the presence of 5 staphylococcal exotoxins (SEA, SEB, SEC, SED, and toxic shock syndrome toxin–1) using enzyme-linked immunosorbent assay (ELISA). Results At least 1 toxin was detected in 7 of 13 patients with ACPs and in 13 of 16 patients with CRS-NPs, whereas it was detected in only 4 controls. There were no statistically significant differences between ACP and control groups (P = .063). Our results showed a statistically significant association between toxin detection and patients with CRS-NPs (P = .003). Conclusion Inflammatory triggers in ACP remain a subject of debate, and this study does not support the hypothesis that staphylococcal exotoxins may play a role in ACP ethiopathogenesis. Our research is consistent with the possibility of SAgs as etiological agents in the development of bilateral nasal polyposis.