Ayse Seza Inal

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.

Risk factors of carbapenem-resistant Klebsiella pneumoniae infection: a serious threat in ICUs.

Background Nosocomial infections caused by Carbapenem-resistant Klebsiella pneumoniae (CRKP) are increasing. Our aim in this study was to investigate the risk factors of CRKP infections. Material/Methods A retrospective cohort study was performed between 1 January and 31 December 2012 in ICU patients. Data was taken from the hospital infection control database for CRKP. The clinical samples collected from the patients were tested by an automatized system and disk diffusion. SPSS software v11.5 was used for statistical analysis. Results Totally, 105 Klebsiella pneumoniae isolates were found in 2012 and the carbapenem resistance rate was 48%. The first episode of infection was taken into risk factor analysis. Of the 98 patients, 61 (62.2%) were male and the mean and median ages were 30.4±29.8 and 25 (0–93). The length of stay was longer in the resistant group (p=0.026). Mortality was 48% in the whole group and similar between groups (p=0.533). There was a relationship between meropenem and third-generation cephalosporin use and resistance (OR 3.244 (1.193–8.819) and OR: 3.590 (1.056–12.209). The other risk factors in univariate analysis were: Immunosuppression OR: 2.186 (1.754–2.724), nasogastric catheter OR: 3.562 (1.317–9.634), peripheral arterial catheter OR: 2.545 (1.027–6.307), and being admitted to the neurosurgical unit OR: 4.324 (1.110–16.842). The multivariate analysis showed use of third-generation cephalosporin OR: 4.699 (1.292–17.089), nasogastric catheter use OR: 3.983 (1.356–11.698), and being admitted to neurosurgical ICU OR: 4.603 (1.084–19.555) as independent risk factors. Conclusions Restriction of third-generation cephalosporin and carbapenem use and invasive procedures, along with infection control precautions and disinfection policies, may be effective in reducing the carbapenem resistance in ICUs.

The Place and the Efficacy of Infectious Disease Consultations in the Hospitals

Abstract Our study aims to determine the efficacy of infectious disease consultations and the interrelations between doctors in this social laboratory. This study was conducted at 34 centers located in 22 cities across Turkey and contributed by 210 infectious disease specialists (IDSs) and 970 non–infectious disease specialists (NIDSs), totaling 1180 medical doctors. Infectious disease specialists and NIDSs have separately contributed by responding to questionnaires designed specifically for the consultation process. It appears that a satisfactory collaboration has been established between IDSs and NIDSs during the consultation practices. There are some discrepancies in the perceptions of some of the NIDSs. These are the evaluation of patients holistically, the expectation of NIDSs in critical infection cases to start the therapy immediately, losing the support of drug companies by NIDSs, and the restriction of NIDSs in routine medical practice. On the other hand, NIDSs seem to have real problems in the diagnosis or treatment of infectious diseases. The consultation service provided by the IDSs in Turkey is widely accepted among other clinicians and appears to be of a crucial importance.

A Case of HIV Infection with Thrombocytopenia: Assosiation of HIV, Thrombotic Thrombocytopenic Purpura and Brucellosis

To report a case of HIV infection presenting with thrombotic thrombocytopenic purpura (TTP) and brucellosis that responded well to plasmapheresis and anti-infective therapy. A 64-year-old woman with moderate confusion, fever and pancytopenia was admitted. HIV infection history was taken from her family and she was not receiving antiretroviral therapy last one year. She had generalized purpuric skin lesions. Wright tube agglutination test was found positive with a 1:160 dilution and the patient was diagnosed as brucellosis. Detailed literature search showed brucellosis as a possible cause of TTP. Patient was treated by plasma exchange/fresh frozen plasma and antimicrobials and the response was excellent. Although brucellosis seems to explain the clinical picture of this patient, it is revealed that broad differential diagnosis is needed to reach uncommon diagnosis like TTP particularly in HIV infected patients.

The causes of post-operative meningitis: the comparison of gram-negative and gram-positive pathogens

AIM In this study, we aim to determine the microbiological etiology in critically ill neurosurgical patients with nosocomial meningitis (NM) and show the impact of Gram-negative rods and differences of patients characteristics, clinical and prognostic measures between Gram-negative and Gram-positive meningitis. MATERIAL AND METHODS In this prospective, one center study we reviewed all adult patients hospitalized during a 12-year period and identified pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical, and treatment characteristics were noted from the medical records. RESULTS Of the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age of 46±15.9 and median age of 50 (18-80) years. 141 strains isolated; 82 (58.2%) were Gram negative, 59 (41.8%) were Gram positive. Most common isolated microorganism was Acinetobacter baumannii (%34.8). In comparison of mortality data shows that the patients who have meningitis with Gram-negative pathogens have higher mortality than with Gram positives (p=0.034). The duration between surgery and meningitis was shorter in Gram negative meningitis cases compared to others (p=0.045) but the duration between the diagnosis and death was shorter in Gram-positive meningitis cases compared to Gram negatives (p= 0.017). CSF protein and lactate level were higher and glucose level was lower in cases of NM with Gram negatives (p value were respectively, 0.022, 0.039 and 0.049). CONCLUSION As conclusions; in NM, Gram-negative pathogens were seen more frequently; A.baumanni was the predominant pathogen; and NM caused by Gram negatives had worse clinical and laboratory characteristic and prognostic outcome than Gram positives.AIM To determine the microbiological etiology in critically ill neurosurgical patients with nosocomial meningitis (NM) and to show the impact of Gram-negative rods and the differences between patient characteristics and the clinical and prognostic measures in Gram-negative and Gram-positive meningitis. MATERIAL AND METHODS In this prospective, single-center study, we reviewed all adult patients hospitalized during a 12-year period and identified pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical, and treatment characteristics were noted from the medical records. RESULTS Of the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age of 46±15.9 and a median age of 50 (18-80) years. One hundred and forty-one strains were isolated; 82 (58.2%) were Gram-negative, 59 (41.8%) were Grampositive. The most commonly isolated microorganism was Acinetobacter baumannii (34.8%). Comparison of mortality data shows that the patients who have meningitis with Gram-negative pathogens have higher mortality than with Gram-positives (p=0.034). The duration between surgery and meningitis was shorter in Gram-negative meningitis cases compared to others (p=0.045) but the duration between the diagnosis and death was shorter in Gram-positive meningitis cases compared to Gram-negatives (p=0.017). Cerebrospinal fluid protein and lactate levels were higher and glucose level was lower in cases of NM with Gram-negatives (p values were respectively, 0.022, 0.039 and 0.049). CONCLUSION In NM, Gram-negative pathogens were seen more frequently; A. baumanni was the predominant pathogen; and NM caused by Gram-negatives had worse clinical and laboratory characteristic and prognostic outcome than Gram-positives.

Mucormycosis: a 10-year experience at a tertiary care center in Turkey.

BACKGROUND/AIM Mucormycosis is a rare invasive fungal infection most commonly encountered in the immunocompromised host. We analyzed 51 adult patients treated for mucormycosis between 2003 and 2013 and recorded at a tertiary university hospital in Turkey. MATERIALS AND METHODS We examined the following data for all patients: age, sex, predisposing disease, symptoms, treatment, surgical procedure, concomitant infections, intensive care requirement, and outcomes. RESULTS During the study period 51 cases of mucormycosis were documented; 54.9% of the patients were female. The mean age was 44.2 ± 18.2 years. Rhinocerebral presentation was reported in 94.1% of patients. Almost all patients (88.2%) had at least one risk factor. The common predisposing factors were hematologic malignancies (52.9%), diabetes mellitus (25.5%), and solid malignancies (5.8%). The most common initial symptoms were fever, cellulitis, and facial pain. The primary medication used was liposomal amphotericin B or conventional amphotericin B. Surgery was performed in 94.1% of patients. Mortality was 52.9%. CONCLUSION Our study revealed that mucormycosis continues to be a mortal disease in about half of the cases. Our findings indicate that treatment with L-AMB is associated with a favorable response. Also, in the case of facial pain, the low mortality rate may indicate the importance of early diagnosis.

Effects of mannose-binding lectin and mannose-binding lectin polymorphisms on treatment response in patients with chronic hepatitis C.

BACKGROUND/AIMS The natural course and clinical outcome of hepatitis C virus (HCV) infection is related to the interaction between HCV and the immune response of the host. Only a limited number of studies have investigated the role of mannose-binding lectin (MBL) levels in HCV infection. The aim of the present study was to explore the relationship between MBL levels and gene polymorphisms on treatment response in patients with chronic hepatitis C (CHC). MATERIALS AND METHODS Serum MBL levels from 50 CHC patients who completed treatment at least 24 weeks before the present study and 75 healthy HCV-negative controls were measured. In addition, the presence of codon 54 mutations was investigated. Correlational analyses were performed to determine relationships between MBL levels and treatment response. RESULTS In patients, mean serum MBL levels were lower and the rate of codon 54 mutations was higher. However, these differences were not statically significant. In both patients and controls, serum MBL levels were significantly lower in individuals with codon 54 mutations. Moreover, serum MBL levels and the rate of the codon 54 mutation were similar in patients regardless of treatment response. CONCLUSION Our findings suggest that low MBL levels do not increase the susceptibility for HCV infection. Furthermore, MBL levels were not found to have a significant effect on the course of the disease or treatment response.

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.

Telaprevir Experience From Turkey

BACKGROUND In patients with chronic hepatitis C, triple drug regimens containing a protease inhibitor, peginterferon and ribavirin were found to significantly increase sustained virologic response rates compared to dual drug regimen containing pegylated interferon and ribavirin, especially in genotype 1. OBJECTIVES In Turkey, telaprevir has been used since March 2013. We aimed to evaluate results of patients with chronic hepatitis C treated with telaprevir, peginterferon and ribavirin. PATIENTS AND METHODS We evaluated 28 patients with genotype 1 chronic hepatitis C infection treated with triple drug regimen containing telaprevir, in three medical centers in Turkey, retrospectively. Demographic data of patients, treatment indications, adverse events and outcomes were recorded. RESULTS Of 28 patients intended to treat, 25 (89.2%) patients completed the treatment. Overall, 21 (82.1%) patients had relapse and five patients were non-responder. Regarding the treatment outcomes of Telaprevir based regimen, 20/26 patients achieved sustained virological response. Pruritus, rash, dysgeusia, anorectal discomfort and anemia were main adverse effects. Blood transfusion and ribavirin dose reduction required for 7 and 11 patients, respectively. Due to several adverse effects, 10 patients were hospitalized. CONCLUSIONS Although more frequent and severe adverse effects, telaprevir has been promising for patients with treatment-experienced hepatitis C.