Gürkan Mert

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.

Antistaphylococcal Activity of Dihydrophthalazine Antifolates, a Family of Novel Antibacterial Drugs

ABSTRACT For a panel of 153 Staphylococcus aureus clinical isolates (including 13 vancomycin-intermediate or heterogeneous vancomycin-intermediate and 4 vancomycin-resistant strains), MIC50s and MIC90s of three novel dihydrophthalazine antifolates, BAL0030543, BAL0030544, and BAL0030545, were 0.03 and 0.25 μg/ml, respectively, for methicillin-susceptible strains and 0.03 and ≤0.25 μg/ml, respectively, for methicillin-resistant strains. For a panel of 160 coagulase-negative staphylococci (including 5 vancomycin-intermediate and heterogeneous vancomycin-intermediate strains and 7 linezolid-nonsusceptible strains), MIC50s and MIC90s were ≤0.03 and ≤0.06 μg/ml, respectively, for methicillin-susceptible strains and 0.06 and 0.5 μg/ml, respectively, for methicillin-resistant strains. Vancomycin was active against 93.0% of 313 staphylococci examined; linezolid was active against all S. aureus strains and 95.6% of coagulase-negative staphylococcus strains, whereas elevated MICs of clindamycin, minocycline, trimethoprim, and rifampin for some strains were observed. At 4× MIC, the dihydrophthalazines were bactericidal against 11 of 12 staphylococcal strains surveyed. The prolonged serial passage of some staphylococcal strains in the presence of subinhibitory concentrations of BAL0030543, BAL0030544, and BAL0030545 produced clones for which dihydrophthalazines showed high MICs (>128 μg/ml), although rates of endogenous resistance development were much lower for the dihydrophthalazines than for trimethoprim. Single-step platings of naïve staphylococci onto media containing dihydrophthalazine antifolates indicated considerable variability among strains with respect to preexistent subpopulations nonsusceptible to dihydrophthalazine antifolates.

First molecular characterization of a Turkish orf virus strain from a human based on a partial B2L sequence

Cases of orf virus infection in human in Turkey have been reported for many years. Scab material from a man was found positive by PCR using pan-parapox-specific primers for parapoxvirus infection. The amplicon was purified and sequenced. The present study provides for the first time a phylogenetic analysis of parapoxviruses from Turkey. The partial B2L gene sequence of a Turkish orf virus from a human presented here may be useful for characterization of parapoxvirus infections in Turkey based on the phylogenetic analysis studies.

The role of human leukocyte antigen tissue groups in hepatitis B virus vaccination in Turkey

BACKGROUND/PURPOSE Between 5% and 10% of the vaccinated population responds less well to standard vaccination schedules irrespective of hepatitis B virus (HBV) vaccination. This manuscript aims at describing possible correlation of different major histocompatibility complex (MHC) Class-I and MHC Class-II haplotype to anti-HBV humoral responsiveness following HBV vaccination. MATERIALS AND METHODS The study was conducted on 944 vaccinated hospital staff members and concentrated on the 38 nonresponders as defined by enzyme-linked immunosorbent assay (ELISA) results. In order to define significance of the different haplotypes from the nonresponders, their frequency was compared to the frequency of the same haplotype in 18 randomly selected responders. Human leukocyte antigen (HLA)-A and HLA-B antigens were typed among total mononuclear cells using a standard two-stage microlymphocytotoxicity test. The typing method of HLA Class-II is based on a technique that involves amplification of the second exon of different HLA Class-II genes by PCR. RESULTS Positive correlations were found between four HLA-DR (HLA-DRB1*04X, DRB1*0401X, DRB1*11/13, and DRB1*0401X0201) haplotypes and nonresponders but there was a negative correlation with one Class-I (HLA-B13). CONCLUSION This study suggested that certain HLA types are associated with nonresponsiveness to vaccination. The different HLA of ethnic groups should also be kept in mind when evaluating the response to hepatitis vaccination. The different HLA gene frequencies of ethnic groups should be examined in further large-scale population-based studies.

Neisseria meningitidis Serogroup X Sequence Type 767 in Turkey

Neisseria meningitidis is a common inhabitant of the nasopharyngeal tracts of healthy humans and is a significant cause of invasive infections such as meningitis in young children and adolescents worldwide (14). N. meningitidis has been classified into 13 serogroups on the basis of antigenic variation of the capsule, but only serogroups A, B, C, Y, and W-135 have commonly caused invasive infections (8). In Turkey, W-135 has been the most frequently reported serogroup since an international outbreak was reported following the annual Hajj seasons in Saudi Arabia in 2000 and 2001 (10). During the years 2003 to 2008, 17 serogroup W-135 strains (from eight meningitis cases) were isolated from Turkish recruits vaccinated with A+C polysaccharide meningococcal vaccine (10-12). We describe here the first meningococcal meningitis case caused by a serogroup X N. meningitidis strain in Turkey. The patient was a 22-year-old male soldier, working in a military unit, who was admitted to the emergency department with complaints of a 1-week history of fever (39°C), cough, and vomiting on 10 January 2010. There was little petechiate rash on his chest and a lower leg. The laboratory evaluation at that time revealed a leukocyte count of 3,700/mm3, a hemoglobin level of 13.4 g/dl, and an erythrocyte sedimentation rate of 5 mm/h. The patient was then admitted to the infectious disease service with a diagnosis of meningococcal meningitis based on the clinical symptoms and results of confirmatory laboratory tests, including blood culture and cerebrospinal fluid analysis. He was given ceftriaxone (4 g/day) for 10 days and then discharged from the hospital in good condition. Oropharyngeal swab specimens were obtained from the patients close military personnel contacts, and one person was found to be positive for an N. meningitidis serogroup X strain. He was given a single dose of 500 mg ciprofloxacin immediately. Clinical and oropharyngeal swab specimens were inoculated immediately onto BBL-modified Thayer-Martin medium plates (MTM II; Becton Dickinson Microbiology Systems) and Thayer-Martin medium with VCAT selective supplement (SR10B; Oxoid, Hampshire, England). After incubation, suspect colonies were identified by Gram staining and oxidase reactivity testing and the identification was confirmed by the API NH system (bioMerieux) (4). An antibiotic susceptibility test was performed by the Etest method (AB BIODISK, Solna, Sweden) for ciprofloxacin, ceftriaxone, cefotaxime, penicillin, rifampin, and chloramphenicol (3). The strains were susceptible to the antibiotics tested, except penicillin, with a MIC of 0.75 μg/ml. Serogrouping of the meningococcal isolates was performed by a slide agglutination technique as recommended by Difco Laboratories (Detroit, MI). porA variant region sequencing was performed using the standard primers and identified by querying the respective databases hosted at http://neisseria.org. Multilocus sequence typing (MLST) was performed using the standard primers listed at the Neisseria MLST website (http://pubmlst.org/neisseria/). The isolates had the strain designation X: P1.5-1,10-1: sequence type 767 (ST-767) (cc167). ST-767 meningococci have been found previously among N. meningitidis serogroup A and Y strains in Europe and Africa between 1999 and 2008 (http://pubmlst.org/neisseria/). PFGE typing of NheI-digested DNA was performed by a modification of a previously described method (12). The clinical and carrier isolates had the same genotypic pattern. N. meningitidis serogroup X strains were first described in the 1960s and have been isolated from a few cases of invasive meningococcal diseases in North America, Europe, Australia, and China (2, 6, 7). Outbreaks of N. meningitidis serogroup X strains have been reported in Niger (1), western Kenya (13), and northern Ghana (5). N. meningitidis serogroup X strains were reported to be very efficient in colonization among military recruits in the United Kingdom (9). Before May 2009, eight invasive meningococcal disease cases caused by serogroup W-135 were reported in Turkish soldiers who had been vaccinated with A+C polysaccharide meningococcal vaccine; four of these were fatal. Since that time, a quadrivalent meningococcal polysaccharide vaccine (against A/C/Y/W-135) has been successfully introduced into the Turkish recruit expanded immunization program. We describe here the first meningococcal meningitis case caused by a serogroup X strain in our recruits since the introduction of the quadrivalent vaccine. It was reported that repeated mass vaccination in many African countries might have contributed to colonization by and meningococcal diseases due to serogroup X strains and might result in a changed profile of meningococcal disease (5). We suggest that comprehensive conjugate vaccines including X polysaccharides should be developed. In addition, these data highlight the need for further epidemiological surveillance to carefully monitor the pattern of incidence of meningococcal diseases caused by serogroup X strains and to inform future public health strategies.

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.

A case of mucosal leishmaniasis: Mimicking intranasal tumor with perforation of septum

A 79-year-old male suffering from nasal congestion was referred to our hospital. Endoscopic examination revealed a hyperemic mass obstructing the left nasal passage. The lesions surface was smooth. The findings of imaging studies were consistent with a benign tumor despite the erosion and perforation of the septum. The lesion originated from the middle concha and was attached to it with a thin stalk. It was removed easily by endoscopic resection. Histopathology revealed significant infiltration of mononuclear inflammatory cells, mostly lymphocytes and histiocytes, into the edematous subepithelial connective tissue. High-power magnification showed numerous Leishmania amastigotes in the cytoplasm of the histiocytes. A polymerase chain reaction experiment for Leishmania also confirmed the morphological diagnosis. No relapse was observed in the 12 months after surgery and the patient was doing well.

Oropharyngeal tularemia cases admitted to a military hospital in Ankara, Turkey.

INTRODUCTION This study aimed to review the possible sources of infection of 16 oropharyngeal tularemia hospital cases, and to document their epidemiological and demographical characteristics, laboratory findings, treatment methods, and treatment results. METHODOLOGY Sixteen cases from a Turkish military hospital between January 2011 and December 2012 were retrospectively evaluated. The age, sex, occupation, place of residence, symptoms, duration of symptoms, laboratory results, treatment and duration, and treatment results were recorded. Tularemia was diagnosed through tularemia-specific tests once the other conditions that may have caused lymphadenopathy were excluded. RESULTS Twelve of the patients included in this study were males. The average age of the patients was 32.1 ± 17.2 years. Sore throat, fatigue, and fever were the most frequent symptoms. The mean duration of symptoms was 21.6 ± 6.9 days. All the patients had been treated for tonsillopharyngitis in primary healthcare institutions previously. However, despite the treatment, cervical lymphadenopathy had developed in these cases. Patients were given streptomycin, doxycycline, and ciprofloxacin monotherapy or in combination. Ten of the cases fully recovered, while five required surgical lymph node drainage. Spontaneous drainage occurred in the single remaining case. CONCLUSIONS Turkey is considered to be an endemic country with regards to tularemia. Prompt diagnosis and proper treatment of the disease is imperative in providing cure. Since it can be potentially confused with tuberculous lymphadenitis, differential diagnosis is vital. Patients presenting with a condition of tonsillopharyngitis in endemic areas must be carefully monitored.

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.

Hepatitis B Prevalance in Young Adult Men Commando Candidates Applying for a Public Hospital

Our country is in the median endemicity belt in terms of hepatitis B virus infection. This study was performed in the commando candidates who came from all over Turkey to a military division/brigade, between January 2007 and December 2009, 20.681 commando candidates were checked for HBsAg positivity and these data were investigated retrospectively. In our study, hepatitis B virus carriage among young men as the Turkey\s average was 3.3%. This data was lower than those reported previously. We attribute this positive trend to the dissemination of immunization programs, the increase of births in the hospitals rather than home delivery, and the widespread use of HBsAg screening tests before marriage