Ayhan Akbulut

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.

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.

Effects of Ibuprofen on the physiology and outcome of rabbit endotoxic shock

BackgroundDespite major developments in the management of septic shock, the mortality rate had progressively increased. Ibuprofen has been shown to have beneficial physiological effects when used as a treatment. However, there are conflicting results with respect to survival. This study aims to investigate the effect of ibuprofen on vital functions, various physiological parameters and survival during endotoxic shock in rabbits.MethodsTwenty-eight New Zealand rabbits were randomly separated into four groups. The first group received only saline, the second was given 2 mg/kg intravenous endotoxin at t0, the third received 30 mg/kg ibuprofen 30 minutes after endotoxin administration, whilst the fourth group received ibuprofen 30 minutes before the endotoxin. Respiratory and heart rate, mean arterial blood pressure and rectal temperature were recorded. Complete blood counts were performed and thromboxane B2 was measured every 30 minutes for the first two hours, and then hourly over the course of the experiment. Urine samples were collected at the same time points for the measurement of prostaglandin E2.ResultsIbuprofen was found to improve respiratory rate, heart rate, and arterial pressure. However, it did not improve the negative effects of endotoxin on body temperature, haematocrit values, white blood cell count, and thrombocyte number. Thromboxane B2 levels in group IV were significantly lower than in the other groups, and the increase started at a later timepoint. In ibuprofen-treated animals, Prostaglandin E2 levels stayed low for at least 90 minutes, but started to rise thereafter. While the average survival in Group II animals was 192.9 ± 46.9 minutes, those of groups III and IV were 339.1 ± 33.5 minutes (p < 0.05) and 383.0 ± 39.6 minutes (p = 0.01), respectively.ConclusionsIbuprofen appears to increase survival in endotoxic shock-induced animals. Therefore, it may be helpful for the prophylaxis and treatment of patients with, or who are likely to develop, septic shock.

Causative pathogens and antibiotic resistance in diabetic foot infections: A prospective multi-center study.

AIM Clinical practice guidelines for the management of diabetic foot infections developed by the Infectious Diseases Society of America (IDSA) are commonly used worldwide. The issue of whether or not these guidelines need to be adjusted for local circumstances, however, has seldom been assessed in large prospective trials. METHODS The Turk-DAY trial was a prospective, multi-center study in which infectious disease specialists from centers across Turkey were invited to participate (NCT02026830). RESULTS A total of 35 centers throughout Turkey enrolled patients in the trial. Overall, investigators collected a total of 522 specimens from infected diabetic foot wounds for culture from 447 individual patients. Among all isolates, 36.4% were gram-positive organisms, with Staphylococcus aureus the most common among these (11.4%). Gram-negative organisms constituted 60.2% of all the isolates, and the most commonly isolated gram-negative was Escherichia coli (15%). The sensitivity rates of the isolated species were remarkably low for several antimicrobials used in the mild infection group. CONCLUSIONS Based on our findings, several of the antimicrobials frequently used for empirical treatment, including some also recommended in the IDSA guidelines, would not be optimal for treating diabetic foot infections in Turkey. Although the IDSA guideline recommendations may be helpful to guide empiric antimicrobial therapy of DFIs, they should be adjusted to local conditions.

Effects of ibuprofen on plasma endothelin levels and some vital parameters during endotoxin shock in rabbits

BACKGROUND There is evidence that septic shock results from breakdown in the balance between vasodilators such as prostacyclin, prostaglandin E(2), and nitric oxide, and the vasoconstrictors thromboxane A(2), serotonin, and endothelin. Increased plasma endothelin (ET) concentrations during septic shock were found. Inducing phospholipase A(2), ET causes release of arachidonic acid and production of prostaglandins. Ibuprofen is nonsteroidal anti-inflammatory drug inhibiting prostaglandin synthesis. There are no any information about the effects of ibuprofen on ET production in endotoxemia. In the present study we aimed to determine the effects of ibuprofen on plasma ET concentrations in an animal model of endotoxin shock. METHODS A total of 28 rabbits were randomly allocated into four groups. The first group only received saline and served as controls. The rest of the animals (groups 2, 3, and 4) were injected intravenously with endotoxin at a dose of 2 mg/kg. To the third group, ibuprofen at 30 mg/kg dosage was given, 30 min following endotoxin administration, whereas in the fourth group animals, ibuprofen was administered 30 min before endotoxin administration. Animals were monitored through the canulation of femoral arteries and venules under the complete anaesthesia. At 0, 30, 60, 90, 120, 180, and 240 min, arterial blood pressure, heart rate, and ET determinations were carried out. RESULTS Ibuprofen before the endotoxin administration was more effective in controlling the increase in heart rate. Ibuprofen was also effective in inhibiting the sudden reductions in blood pressure if administered before endotoxin. However, if administered after endotoxin injection, ibuprofen precipitated the reduction in blood pressure further. Ibuprofen reduced the ET production which was induced by the endotoxin administration. CONCLUSIONS Ibuprofen administration during endotoxin shock seems to decrease the elevated ET concentrations, and increase the blood pressure.

Recommendation for treatment of hepatitis C virus infection

Address for Correspondence: Ramazan Idilman E-mail: idilman@medicine.ankara.edu.tr

Hydrocephalus and vasculitis delay therapeutic responses in tuberculous meninigitis: Results of Haydarpasa-III study

AIMS There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. MATERIALS AND METHODS This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. RESULTS In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27-86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for >9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68-19.57]). According to linear regression analysis, fever was significantly persisting (>7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. CONCLUSIONS In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.

Cutaneous anthrax: evaluation of 28 cases in the Eastern Anatolian region of Turkey

Abstract Context: Anthrax is an endemic disease in developing countries. Human cases are usually associated with animal products. About 95% of naturally acquired cases are cutaneous anthrax. Objective: In this study, cutaneous anthrax cases from the Elazig province (the Eastern Anatolian region) of Turkey seen in our hospital within a 6-year period were evaluated with respect to epidemiological and clinical features, diagnosis, treatment and outcome. Methods: Twenty-eight patients with cutaneous anthrax observed between January 2009 and December 2014 were investigated retrospectively. The diagnosis of cutaneous anthrax was based on detailed history, dermatologic findings, including painless, ulcers covered by a characteristic black eschar and/or microbiological procedures, including Gram stain and culture of materials obtained from the lesions. Results: Of the 28 patients followed up with cutaneous anthrax diagnosis, 14 (50%) were female and 14 (50%) were male. The mean age of the cases was 39.6 years (age range 17–65 years). The patients have an incubation period in the range of 1–9 days (mean 4.6 ± 0.5 days). The cases were seen between April and November of each year during the study period. Twenty-three cases (82%) had a history of contact with animals or animal products. Twenty patients (71.4%) showed malignant pustules and eight (28.6%) malignant edema. Bacillus anthracis was isolated in three cases (10.7%) and Gram stain smear were positive in five cases (17.8%). All patients were treated successfully with penicillin or ciprofloxacin. Systemic corticosteroids were added to the antibiotic treatment in six patients with malignant edema. Sepsis no developed in patients, all the cases recovered. Conclusion: Anthrax is still a serious public health problem in Turkey. Cutaneous anthrax must always be kept in mind when characteristic lesions such as a painless ulcer with vesicles, edema, and a history of contact with animals or animal products are observed in an individual. Early and correct diagnosis significantly affects course of the disease. Protective precautions such as vaccination of animals against anthrax and education of the population would reduce the incidence of the disease.

Epidemiological, Clinical, and Laboratory Evaluation of Plasmodium falciparum Malaria Cases Followed in Firat University Hospital: A 6-Year Retrospective Analysis

OBJECTIVE Malaria is an infectious disease caused by Plasmodium parasite. Sporadic cases have not been observed in Turkey since 2010, but imported malaria cases are still prevalent owing to migration. The present study aimed to evaluate Plasmodium falciparum malaria in patients hospitalized in our hospital. METHODS A total of 15 adult patients (14 males and 1 female) who were diagnosed with malaria and who were managed at our clinic between January 2011 and 2017 were evaluated retrospectively for their epidemiological, clinical, and laboratory findings; treatment; and prognosis. RESULTS Of the 15 cases, 14 (93.3%) were male and (6.7%), female. All patients had a history of travelling to endemic areas, and none of them undertook regular chemoprophylaxis. Fever (100%), splenomegaly (86.7%), hepatomegaly (26.7%), leukopenia (13.3%), thrombocytopenia (80%), elevated liver function tests (40%), and increased serum creatinine levels (13.3%) were found in the patients. CONCLUSIONS The number of import cases is increasing owing to tourism, migration, and deficiency in eradication programs. Malaria caused by P. falciparum is an import case in Turkey. The current study emphasizes on the necessity of providing proper education to Turkish individuals traveling to endemic areas for the purpose of work or travel and on the necessity of initiating chemoprophylaxis.

A Case of Severe Plasmodium falciparum Malaria Co-Infected with HIV Transmitted by Exchange Transfusion

In our country, within years, despite a dramatic drop in the number of patients with malaria, a dramatic increase in the number of patients with import malaria is noteworthy. A 32-year-old male patient presented with fever, shivering, malaise, and loss of appetite. He had travelled to West Africa. Laboratory findings were as follows: hemoglobin: 8.8 g/dL and anti-HIV: positive. Microscopic examinations of thin blood smears and thick blood preparations revealed widespread trophozoites. The presence of double-dotted ring forms and banana-shaped gametocytes resulted in Plasmodium falciparum malaria being diagnosed. The patient was started treatment with oral artemether 20 mg/ lumefantrine 120 mg 2×4 tablets and trimethoprim-sulfamethoxazole. During his follow-up, hemoglobin levels regressed to 5.8 g/dL. The patient was diagnosed as having severe malaria. He visited our hematology unit, and exchange transfusion (EET) was recommended. Using an EET apheresis device, eight units of erythrocyte suspension was transfused. The cured patient was discharged. This case was found to be interesting and reminds us the possible presence of comorbid conditions associated with malaria in patients who have a history of travelling abroad. Although its effectiveness has not been proved thus far, as a striking result, EET was used as an alternative treatment in a patient with severe malaria.