[Investigation of bacterial and viral etiology in community acquired central nervous system infections with molecular methods]. / Toplum kökenli santral sinir sistemi enfeksiyonlarinda bakteriyel ve viral etiyolojinin moleküler yöntemlerle degerlendirilmesi.

In this multicenter prospective cohort study, it was aimed to evaluate the bacterial and viral etiology in community-acquired central nervous system infections by standart bacteriological culture and multiplex polymerase chain reaction (PCR) methods. Patients hospitalized with central nervous system infections between April 2012 and February 2014 were enrolled in the study. Demographic and clinical information of the patients were collected prospectively. Cerebrospinal fluid (CSF) samples of the patients were examined by standart bacteriological culture methods, bacterial multiplex PCR (Seeplex meningitis-B ACE Detection (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Group B streptococci) and viral multiplex PCR (Seeplex meningitis-V1 ACE Detection kits herpes simplex virus-1 (HSV1), herpes simplex virus-2 (HSV2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus 6 (HHV6)) (Seeplex meningitis-V2 ACE Detection kit (enteroviruses)). Patients were classified as purulent meningitis, aseptic meningitis and encephalitis according to their clinical, CSF (leukocyte level, predominant cell type, protein and glucose (blood/CSF) levels) and cranial imaging results. Patients who were infected with a pathogen other than the detection of the kit or diagnosed as chronic meningitis and other diseases during the follow up, were excluded from the study. A total of 79 patients (28 female, 51 male, aged 42.1 ± 18.5) fulfilled the study inclusion criteria. A total of 46 patients were classified in purulent meningitis group whereas 33 were in aseptic meningitis/encephalitis group. Pathogens were detected by multiplex PCR in 41 patients. CSF cultures were positive in 10 (21.7%) patients (nine S.pneumoniae, one H.influenzae) and PCR were positive for 27 (58.6%) patients in purulent meningitis group. In this group one type of bacteria were detected in 18 patients (14 S.pneumoniae, two N.meningitidis, one H.influenzae, one L.monocytogenes). Besides, it is noteworthy that multiple pathogens were detected such as bacteria-virus combination in eight patients and two different bacteria in one patient. In the aseptic meningitis/encephalitis group, pathogens were detected in 14 out of 33 patients; single type of viruses in 11 patients (seven enterovirus, two HSV1, one HSV2, one VZV) and two different viruses were determined in three patients. These data suggest that multiplex PCR methods may increase the isolation rate of pathogens in central nervous system infections. Existence of mixed pathogen growth is remarkable in our study. Further studies are needed for the clinical relevance of this result.

Comparison of the effectiveness of caspofungin and liposomal amphotericin-B for the treatment of C. tropicalis-induced peritonitis in mice.

In order to compare the effectiveness of liposomal amphotericin B (LAB) and caspofungin monotherapy in Candida tropicalis-induced peritonitis in an experimental mice model 56 healthy male BALB/c mice (10-12 weeks; 20-25 g) were divided into groups and C. tropicalis strains were intraperitoneally (IP) inoculated into mice groups except the control group. After the injection, three doses of LAB (0.5, 1.0, 2.0 mg/kg/day) and caspofungin (1.0, 2.0, 5.0 mg/kg/day) were administered to groups for five consecutive days, starting 48-h post-infection. The mice were then followed up for 14 days and killed by cervical dislocation. When their peritoneal fluid was examined, the difference in fungal growth between the treatment group and control group was significant (p <0.05). Evaluation of the treatment groups revealed that fungal growth decreased with increasing dose of the antifungal agent (p >0.05). There was no dose-related difference from mice which received LAB or those which received caspofungin in our experimental model. During our study, no death was detected despite the similar injection doses compared with other studies using Candida species. The results of this study suggest that C. tropicalis could have lower virulence, perhaps limited by natural immunity, and causes mortality at much higher doses.

Accuracy of consultations performed by infectious diseases trainees and factors associated with adherence to them.

OBJECTIVES: Infectious diseases (ID) trainees should be familiar with duties relevant to consultation practice. In this study we aimed to analyze the ID trainee night/weekend shift consultation process in terms of consultant characteristics, types of recommendations, and compliance with recommendations. METHODS: All consultations performed by ID trainees on the night shift and at the weekends between 10 June and 10 August 2004 were recorded prospectively on standardized forms. Infectious diseases specialists assessed the appropriateness of recommendations the day after each consultation. Recommendations were considered complied with if they were carried out within 72 hours of the consultation. RESULTS: Of 440 consultations, 163 were for a clinically diagnosed infection (without specific antibiotic request) and 79 were for treatment continuation. Overall, 152 consultations were for requesting specific antibiotic(s), and 327 antibiotics were recommended or approved in 270 consultations. Eight of these recommendations were inappropriate. Overall compliance to ID recommendations was 75.3% (418/555). In univariate analysis, the compliance rate to non-treatment recommendations (microbiologic cultures, radiology, biochemistry, etc.) was found to be lower than the rate of compliance to antibiotic recommendations (186/308 vs. 232/247, p<0.05). In addition, compliance to recommendations made by the first-year trainees was lower than to the recommendations made by the other trainees. In logistic regression analysis only recommendations including antibiotic treatment was associated with higher compliance (p=0.0001, odds ratio=10.2, 95% CI=5.7-18.3). CONCLUSIONS: ID trainees are capable of evaluating patients and recommending appropriate antibiotics. Methodologies to improve the compliance to non-treatment-based recommendations and optimizing antibiotic selection seem to be necessary.

Variables determining mortality in patients with Acinetobacter baumannii meningitis/ventriculitis treated with intrathecal colistin.

AIM: To examine the variables associated with mortality in patients with Acinetobacter baumannii-related central nervous system infections treated with intrathecal colistin. MATERIALS AND METHODS: This multi-centre retrospective case control study included patients from 11 centres in Turkey, as well as cases found during a literature review. Only patients with CNS infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii treated with intrathecal colistin were included in this study. The variables associated with mortality were determined by dividing the patients into groups who died or survived during hospitalisation, and who died or survived from Acinetobacter meningitis. RESULTS: Among the 77 cases enrolled in the study, 35 were found through a literature review and 42 were cases from our centres. Forty-four cases (57.1%) were male and the median age was 48 years (range: 20-78 years). Thirty-seven patients (48%) died during hospitalisation. The variables associated with increased all-cause mortality during hospitalisation included old age (odds ratio, 1.035; 95% confidence interval (CI), 1.004-1.067; p=0.026) and failure to provide cerebrospinal fluid sterilisation (odds ratio, 0.264; 95% confidence interval, 0.097-0.724; p=0.01). There is a trend (P=0.062) towards higher mortality with using of meropenem during meningitis treatment. Fifteen cases (19%) died from meningitis. There were no significant predictors of meningitis-related mortality. CONCLUSIONS: The mortality rate for central nervous system infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii is high. Old age and failure to provide CSF sterilisation are associated with increased mortality during hospitalisation.

Colistin efficacy in the treatment of multidrug-resistant and extremelydrug-resistant gram-negative bacterial infections.

BACKGROUND/AIM: Colistin is used as a salvage therapy for multidrug-resistant and extremely drug-resistant gram-negative bacterial infections. Our aim was to evaluate colistin efficiency and toxicity in the treatment of these resistant gram-negative bacterial infections. MATERIALS AND METHODS: This is a retrospective study carried out in a tertiary care hospital during 2011-2013. Study data were collected from the medical records and consultations of the infectious diseases clinic. RESULTS: The study group included 158 patients with nosocomial infections and 136 (86.1%) of them were hospitalized in the ICU. Respiratory tract infections were the most commonly observed ones (n = 103, 65.2%). The most frequently isolated microorganism was Acinetobacter baumannii (72.2%). A total of 98 (62.0%) patients had clinical cure. There was no statistically significant difference between monotherapy (n = 3/6, 50.0%) and combination therapies (n = 95/152, 62.5%) according to clinical response. Underlying ultimately fatal disease, previous renal disease, and total parenteral nutrition were independent risk factors for poor clinical response. Nephrotoxicity developed in 80 (50.6%) patients and clinical cure was statistically unrelated with nephrotoxicity. CONCLUSION: Colistin may be used as an effective agent for multidrug-resistant and extremely drug-resistant gram-negative bacterial infections with close monitoring of renal functions, especially for older and critically ill patients.

Impact of antimicrobial drug restrictions on doctors' behaviors.

BACKGROUND/AIM: Broad-spectrum antibiotics have become available for use only with the approval of infectious disease specialists (IDSs) since 2003 in Turkey. This study aimed to analyze the tendencies of doctors who are not disease specialists (non-IDSs) towards the restriction of antibiotics. MATERIALS AND METHODS: A questionnaire form was prepared, which included a total of 22 questions about the impact of antibiotic restriction (AR) policy, the role of IDSs in the restriction, and the perception of this change in antibiotic consumption. The questionnaire was completed by each participating physician. RESULTS: A total of 1906 specialists from 20 cities in Turkey participated in the study. Of those who participated, 1271 (67.5%) had ≤5 years of occupational experience (junior specialists = JSs) and 942 (49.4%) of them were physicians. Specialists having >5 years of occupational experience in their branch expressed that they followed the antibiotic guidelines more strictly than the JSs (P < 0.05) and 755 of physicians (88%) and 720 of surgeons (84.6%) thought that the AR policy was necessary and useful (P < 0.05). CONCLUSION: This study indicated that the AR policy was supported by most of the specialists. Physicians supported this restriction policy more so than surgeons did.

Association between hematologic parameters and in-hospital mortality in patients with infective endocarditis.

Early and accurate risk prediction is an important clinical demand in patients with infective endocarditis (IE). The platelet-to-lymphocyte ratio (PLR) is an independent predictor of worse prognosis in various cardiovascular diseases. The aim of this study was to determine the value of PLR in the prediction of in-hospital mortality among IE patients. We retrospectively analyzed the clinical, laboratory, and echocardiographic data of 59 adult patients with definite IE and in 40 adult controls. In-hospital mortality occurred in 16 (27%) patients. Vegetation size, levels of high-sensitive C-reactive protein and procalcitonin, neutrophil-to-lymphocyte ratio, and PLR were significantly higher in the in-hospital-mortality-positive group than in the in-hospital-mortality-negative group (p = 0.004, p = 0.009, p = 0.030, p = 0.001, and p = 0.008, respectively). Lymphocyte count was, however, significantly lower in the in-hospital-mortality-positive group (p = 0.004). In the receiver-operating characteristic analysis, PLRs over 191.01 predicted in-hospital mortality with 56.3% sensitivity and 81.4% specificity [area under the curve 0.725, 95% confidence interval (CI) 0.594-0.833; p = 0.0027]. In the multivariate analysis, PLR was found to be an independent predictor of in-hospital mortality in patients with IE (odds ratio 1.022, 95% CI 1.003-1.042; p = 0.021). In conclusion, higher PLR may predict in-hospital mortality in patients with IE.

Comparison of brucellar and tuberculous spondylodiscitis patients: results of the multicenter "Backbone-1 Study".

BACKGROUND CONTEXT: No direct comparison between brucellar spondylodiscitis (BSD) and tuberculous spondylodiscitis (TSD) exists in the literature. PURPOSE: This study aimed to compare directly the clinical features, laboratory and radiological aspects, treatment, and outcome data of patients diagnosed as BSD and TSD. STUDY DESIGN: A retrospective, multinational, and multicenter study was used. PATIENT SAMPLE: A total of 641 (TSD, 314 and BSD, 327) spondylodiscitis patients from 35 different centers in four countries (Turkey, Egypt, Albania, and Greece) were included. OUTCOME MEASURES: The pre- and peri- or post-treatment spinal deformity and neurologic deficit parameters, and mortality were carried out. METHODS: Brucellar spondylodiscitis and TSD groups were compared for demographics, clinical, laboratory, radiological, surgical interventions, treatment, and outcome data. The Student t test and Mann-Whitney U test were used for group comparisons. Significance was analyzed as two sided and inferred at 0.05 levels. RESULTS: The median baseline laboratory parameters including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were higher in TSD than BSD (p<.0001). Prevertebral, paravertebral, epidural, and psoas abscess formations along with loss of vertebral corpus height and calcification were significantly more frequent in TSD compared with BSD (p<.01). Surgical interventions and percutaneous sampling or abscess drainage were applied more frequently in TSD (p<.0001). Spinal complications including gibbus deformity, kyphosis, and scoliosis, and the number of spinal neurologic deficits, including loss of sensation, motor weakness, and paralysis were significantly higher in the TSD group (p<.05). Mortality rate was 2.22% (7 patients) in TSD, and it was 0.61% (2 patients) in the BSD group (p=.1). CONCLUSIONS: The results of this study show that TSD is a more suppurative disease with abscess formation requiring surgical intervention and characterized with spinal complications. We propose that using a constellation of constitutional symptoms (fever, back pain, and weight loss), pulmonary involvement, high inflammatory markers, and radiological findings will help to differentiate between TSD and BSD at an early stage before microbiological results are available.

Evaluation of patients with zygomycosis.

AIM: Zygomycosis is a severe angioinvasive infection caused by Zygomycetes. We retrospectively investigated 16 cases of zygomycosis. MATERIALS AND METHODS: The data of patients, who had been followed between 2004 and 2010 in 8 tertiary-care teaching hospitals, were reviewed. Demographic characteristics, underlying diseases, and clinical signs and symptoms of the patients, as well as diagnostic methods, data obtained by radiological imaging methods, and the therapies, were recorded. Therapeutic approaches, antifungal agents and duration of use, and the characteristics of the cases were identified. RESULTS: The study included 11 female and 5 male subjects. The most common symptoms and clinical signs were fever (n = 9) and retro- orbital pain (n = 7). Rhinocerebral zygomycosis was the most common form. The mean time elapsed for diagnosis was 14.26 + 13.96 (range: 2-52) days. Antifungal therapy was given to 15 patients (94%). In addition to antifungal therapy, 12 patients underwent surgical intervention 1 to 4 times. The mean duration of receiving antifungal therapy was 61.4 + 58.02 (range: 1-180) days. The median duration of treatment was 62.5 (range: 42-180) days in survivors. CONCLUSION: Zygomycosis is an infectious disease with high mortality despite antifungal therapy and surgical interventions.

Disseminated Aspergillosis due to Aspergillus niger in Immunocompetent Patient: A Case Report.

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients. Many cases of pulmonary, cutaneous, cerebral, and paranasal sinus aspergillosis in immunocompetent patient were defined in literature but disseminated aspergillosis is very rare. Here we present an immunocompetent case with extrapulmonary disseminated aspergillosis due to Aspergillus niger, totally recovered after effective antifungal treatment with voriconazole.

Pooled analysis of 857 published adult fever of unknown origin cases in Turkey between 1990-2006.

BACKGROUND: The aim of this study was a systematic review of the literature related to adult fever of unknown origin (FUO) in Turkey. MATERIAL/METHODS: To find the published series, three national and two international databases were searched. RESULTS: Data for 857 patients with the diagnosis of fever of unknown origin were obtained from 13 articles. FUO was defined as fever over 38.3 degrees C that continues at least for three weeks with no diagnosis reached after one week of inpatient investigation in all series (Petersdorf and Beason criteria). Infections, collagen vascular diseases, and neoplasms were found to be the reason of fever in 403 (47.0%), 137 (15.9%), and 126 (14.7%) of the in all 857 patients. The most common infectious disease was tuberculosis (147/403, 36.4%) followed by brucellosis (51/403, 12.6%) and infective endocarditis (39/403, 9.6%). The most common collagen vascular disease was adult-onset Still's Disease (49/137, 35.7%), followed by systemic lupus erythematosus (23/137, 16.7%). The most common neoplasms were Hodgkin's disease (32/126, 25.3%) and non-Hodgkin's lymphoma (32/126, 25.3%). The reason of fever could not be defined in 138/857 (16.1%) patients. CONCLUSIONS: Tuberculosis and brucellosis remain common causes of FUO in Turkey. In addition, lymphomas and adult-onset Still's disease should be considered in the differential diagnosis of a patient admitted with FUO.