Emel Yilmaz

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.

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.

An investigation of Candida species isolated from blood cultures during 17 years in a university hospital

Candidemia is the most frequent manifestation observed with invasive candidiasis. The aim of this study was to analyse the trends of candidemia in a large tertiary‐care hospital to determine the overall incidence during January 1996–December 2012, as well as to determine the susceptibility of 453 isolates according to the revised Clinical and Laboratory Standards Institute (CLSI) breakpoints. Candidemia episodes in adult and paediatric patients were retrospectively analysed from the laboratory data of Uludağ University Healthcare and Research Hospital. The 17‐year period studied was divided into three periods (1996–2001, 2002–2007 and 2008–2012) for better comparison, and candidemia incidence was determined by the ratio of total number of patients with candidemia per 1000 patients admitted to the hospital and per 10 000 patient days in these three periods. Redefined CLSI M27‐A3 breakpoints were used for interpretation of antifungal susceptibility results. Candidemia incidence was determined as 2.2, 1.7 and 1.5 per 1000 admitted patients during 1996–2001, 2002–2007 and 2008–2012 respectively. A significantly decreased candidemia incidence was obtained in the third period. C. albicans (43.8%) was the most common candidemia agent, followed by C.parapsilosis (26.5%) in all three periods. According to the revised CLSI breakpoints, there was fluconazole resistance in C. albicans, C.parapsilosis, C.tropicalis and C.glabrata species (1.4%, 18.2%, 2.6% and 14.3% respectively). Almost all Candida species were found susceptible to voriconazole except one C.glabrata (7.1%) isolate. Candidemia is an important health problem. Local epidemiological data are determinative in the choice of appropriate antifungal treatment agents.

Trigeminal neuralgia caused by a pontine abscess: Case report

OBJECTIVE AND IMPORTANCE:Various intracranial abnormalities, including infectious conditions, may manifest as trigeminal neuralgia. CLINICAL PRESENTATION:A 33-year-old man presented with a 15-day history of right-sided facial pain and numbness. Neurological examination revealed diminished corneal reflex and facial sensation in the right V1–V2 distribution. Magnetic resonance imaging revealed a contrast-enhancing lesion centered at the right pons with extension of the enhancement to the sphenoid sinus. INTERVENTION:Broad-spectrum antibiotics were administered for 6 weeks. This resulted in alleviation of symptoms and resolution of the lesion as revealed by repeat magnetic resonance imaging. CONCLUSION:Presentation of a pons abscess with trigeminal neuralgia is rare, and to the best of our knowledge has not been reported previously. The patient was treated successfully with antibiotics alone.

A mucormycosis case treated with a combination of caspofungin and amphotericin B

Mucormycosis is a rare, invasive and fatal disease that occurs mainly in diabetes mellitus patients with uncontrolled blood glucose levels or in immunocompromised patients. The mortality rate of this disease is as high as 25 to 80%, despite aggressive surgical treatment and antifungal therapy. This high mortality requires alternative treatment approaches. The accepted treatment modality of invasive mucormycosis are amphotericin B lipid formulations. Although echinocandins generally show no activity against Mucorales, it was shown that Rhizopus oryzae expressed the target enzyme for echinocandins, 1,3-beta-glucan synthase. Additionally, there are some experimental studies in a diabetic mouse model and case reports regarding the effects of caspofungin. In this report, we present a rhinocerebral mucormycosis case treated with liposomal amphotericin B and caspofungin. There was regression of the patients clinical and radiological condition with the addition of caspofungin, but she died due to discontinuation of her treatment and reasons other than mucormycosis.

Nosocomial Acinetobacter pneumonia: Treatment and prognostic factors in 356 cases

Acinetobacter baumannii and A. baumannii/calcoaceticus complex are commonly encountered pathogens in nosocomial infections. This study aimed to evaluate the treatment and prognostic risk factors in nosocomial pneumonia caused by these microorganisms.

Healthcare-associated Gram-negative bloodstream infections: antibiotic resistance and predictors of mortality.

This article describes the prevalence of antibiotic resistance and predictors of mortality for healthcare-associated (HA) Gram-negative bloodstream infections (GN-BSI). In total, 831 cases of HA GN-BSI from 17 intensive care units in different centres in Turkey were included; the all-cause mortality rate was 44%. Carbapenem resistance in Klebsiella pneumoniae was 38%, and the colistin resistance rate was 6%. Multi-variate analysis showed that age >70 years [odds ratio (OR) 2, 95% confidence interval (CI) 1.22-3.51], central venous catheter use (OR 2.1, 95% CI 1.09-4.07), ventilator-associated pneumonia (OR 1.9, 95% CI 1.1-3.16), carbapenem resistance (OR 1.8, 95% CI 1.11-2.95) and APACHE II score (OR 1.1, 95% CI 1.07-1.13) were significantly associated with mortality.

Comparative evaluation of galactomannan optical density indices and culture results in bronchoscopic specimens obtained from neutropenic and non‐neutropenic patients

Aspergillus infections are major causes of morbidity and mortality among immunocompromised patients. This study was designed to investigate the galactomannan assay optical density (OD) indices relative to the culture results in bronchoscopic samples obtained from neutropenic and non‐neutropenic patients. Galactomannan OD indices from 1427 samples from 2005 to 2012, which were sent from 839 patients and were composed of bronchial lavage (BL = 727) and bronchoalveolar lavage fluids (BAL = 700), were retrospectively analysed. The recovery rates of Aspergillus species from these specimens were 9.4% from the combined patient group and 13.3% from the neutropenic group. Aspergillus fumigatus complex was the most frequently isolated species. The mean and median OD indices of the positive and negative culture samples are approximately 5 and 1, respectively, and 91% of all culture‐positive samples have ≥1 OD index value. The receiver‐operating characteristics curve analysis demonstrated that the feasibility of the Aspergillus galactomannan assay and Aspergillus galactomannan test has superior accuracy in BAL compared to BL fluids, and the test is not affected by the immune status of the patient. We suggest that the Aspergillus galactomannan test, which uses bronchoscopic material, leads to an earlier diagnosis and if the OD index is found ≥1, fungal growth can be expected.

Assessment of the requisites of microbiology based infectious disease training under the pressure of consultation needs

BackgroundTraining of infectious disease (ID) specialists is structured on classical clinical microbiology training in Turkey and ID specialists work as clinical microbiologists at the same time. Hence, this study aimed to determine the clinical skills and knowledge required by clinical microbiologists.MethodsA cross-sectional study was carried out between June 1, 2010 and September 15, 2010 in 32 ID departments in Turkey. Only patients hospitalized and followed up in the ID departments between January-June 2010 who required consultation with other disciplines were included.ResultsA total of 605 patients undergoing 1343 consultations were included, with pulmonology, neurology, cardiology, gastroenterology, nephrology, dermatology, haematology, and endocrinology being the most frequent consultation specialties. The consultation patterns were quite similar and were not affected by either the nature of infections or the critical clinical status of ID patients.ConclusionsThe results of our study show that certain internal medicine subdisciplines such as pulmonology, neurology and dermatology appear to be the principal clinical requisites in the training of ID specialists, rather than internal medicine as a whole.

Diagnostic value of serum concentrations of high-mobility group-box protein 1 and soluble hemoglobin scavenger receptor in brucellosis

Both cluster of differentiation (CD)4+ and CD8+ T lymphocytes play key roles in immunity to Brucella, in part because they secrete interferon (IFN)‐γ and activate bactericidal functions in macrophages. Therefore, use of markers of macrophage activation may have diagnostic and prognostic significance. High‐mobility group‐box 1 protein (HMGB1), a late‐onset pro‐inflammatory cytokine, is secreted by activated macrophages. Soluble hemoglobin scavenger receptor (sCD163) is a specific marker of anti‐inflammatory macrophages. The aim of this study was to investigate the diagnostic value of HMGB1 and sCD163 concentrations in brucellosis and its various clinical forms. Serum HMGB1 and sCD163 concentrations in 49 brucellosis patients were compared with those in 52 healthy control subjects. Both serum HMGB1 and sCD163 concentrations were significantly higher in brucellosis patients than in healthy controls (P < 0.001). There were no statistically significant differences in serum concentrations of HMGB1 and sCD163 between cases of acute, subacute and chronic brucellosis. Additionally, serum HMGB1 concentrations were positively correlated with sCD163 concentrations, whereas neither HMGB1 nor sCD163 concentrations were correlated with C‐reactive protein concentrations, white cell counts or erythrocyte sedimentation rates. Therefore, serum concentrations of HMGB1 and sCD163 may be diagnostic markers for brucellosis, but neither can be used to differentiate the three different forms of this disease (acute, subacute and chronic).