Combinations of voriconazole, fluconazole, and itraconazole with caspofungin were evaluated against 50 Candida glabrata isolates by the time-kill, disk diffusion, and Etest methods. The majority of antifungal combinations were indifferent. By the time-kill method, synergistic activity was detected with eight (16%) of the caspofungin-voriconazole and seven (14%) of the caspofungin-fluconazole combinations, but synergy was not seen with the caspofungin-itraconazole combination. Further comparisons of the Etest and disk diffusion synergy techniques with the time-kill method are warranted.Candida glabrata infections are common in immunocompromised hosts and difficult to treat since they are often resistant to azole antifungal agents (2, 10, 12). The echinocandin caspofungin (CAS) inhibits the synthesis of 1,3-␤-D-glucan, an essential cell wall compound (19). Voriconazole (VORI), fluconazole (FLU), and itraconazole (ITRA) are triazole antifungal agents and inhibit the synthesis of ergosterol by inhibiting the enzyme lanosterol 14␣-demethylase (3). As these drugs act on different targets, it is important to look for combinations of drugs that might be synergistic. The main objective of our study was to test for synergistic activities of VORI, FLU, and ITRA combined with CAS against C. glabrata isolates. The other objectives were to compare results from different synergy testing methods, namely, the time-kill method, Etest, and disk diffusion method, and to evaluate the CLSI and Etest methods in terms of categorical agreement.Fifty clinical isolates were tested. Candida parapsilosis ATCC 22019 was included for quality control (6). Stock solutions of VORI (Pfizer, Barcelona, Spain), CAS (Merck & Co., Inc., West Point, PA), FLU (Pfizer, Barcelona, Spain), and ITRA (Jansen-Cilag) were prepared with the appropriate solvent (dimethyl sulfoxide for VORI and ITRA and distilled water for CAS and FLU). The final concentrations were 0.03 to16 g/ml for VORI, 0.0625 to 64 g/ml for CAS and FLU, and 0.5 to 8 g/ml for ITRA. MICs of drugs were determined by the CLSI broth microdilution method (BMD) (6) and corresponded to the lowest concentration that showed prominent (Ն50%) growth inhibition. MICs were read after 24 and 48 h of incubation and were evaluated (5, 6, 9). The Etest was performed on RPMI 1640 agar plates as recommended by the manufacturer, and MICs were compared to the reference BMD MICs (AB Biodisk, Solna, Sweden) (1).Synergy testing was performed using the time-kill, Etest, and disk diffusion methods. All testing was carried out in duplicate.For the time-kill studies, each isolate was tested against drugs alone and in combination at concentrations equal to each drug's MIC to correlate with the Etest. The numbers of CFU were determined at 0, 2, 6, and 24 h. The limit of detection was 50 CFU/ml. Synergy and antagonism were defined, respectively, as a Ն100-fold increase or decrease in killing compared with the killing of the most active single agent. If the change was less than 100-fold, the interaction was considered indi...

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with multisystem involvement. An increased incidence of cancer in SSc patients compared with the general population has been reported in several reports. Our aims in this study were to determine the most common malignancies and to investigate the possible risk factors for the development of malignancy in patients with SSc. Three hundred forty SSc patients from 13 centers were included to the study. Data of the patients were obtained by evaluating their medical records retrospectively. A total of 340 patients with SSc were evaluated. Twenty-five of the patients had 19 different types of malignancy. Bladder cancer was the most common type of cancer with four patients and was followed by breast cancer with three patients, and cervix cancer and ovarian cancer with two patients each. Other types of cancers such as squamous cell skin cancer, adenocancer with an unknown origin, multiple myeloma, chronic myeloid leukemia, papillary thyroid cancer, larynx cancer, non-small cell lung cancer, follicular type non-Hodgkin lymphoma (NHL), endometrium cancer, colon cancer, uterus cancer, neuroendocrine tumor, glioblastoma multiforme, and soft tissue sarcoma were diagnosed in one patient each. The only cancer type that showed an association with cyclophosphamide dose was bladder carcinoma. Other malignancies did not show a correlation with age, sex, smoking, type and duration of the disease, autoantibodies, organ involvement, and dose and duration of cyclophosphamide therapy. Cancer may develop in any organ in patients with SSc. Continuous screening of the patients during a follow-up period is necessary for the early detection of the tumor development.

The in vitro activities of caspofungin plus amphotericin B against 50 Candida glabrata isolates were evaluated by the time-kill, disk diffusion, and Etest methods. In vitro experiments showed a positive interaction. Even though each of these methods uses different conditions and endpoints, the results of the different methods frequently agreed.Candida glabrata is an opportunistic pathogen that mainly affects severely immunocompromised patients, causing disseminated and frequently fatal infections (9). Many isolates of C. glabrata have shown innate resistance to fluconazole, and treatment often fails. Combined therapy could be a therapeutic alternative, but it has been poorly explored (7).Caspofungin (CAS), an echinocandin, inhibits fungal cell wall synthesis. Amphotericin B (AMB) targets fungal ergosterol, the main component of the fungal cell membrane (5). With their different mechanisms of action, these two drugs could be effective in combination. In this study, we hypothesized that the combination of CAS with AMB could have an advantage against C. glabrata over monotherapy with either drug.Fifty strains of C. glabrata were isolated from clinical samples at our laboratory. Candida parapsilosis ATCC 22019 was included for quality control (4). Antifungal susceptibility testing was performed, following both the broth microdilution (4) and Etest (Etest technical guide 4; AB Biodisk, Solna, Sweden) methods. The final concentrations were 0.03 to 2.0 g/ml of AMB and 0.0625 to 64 g/ml of CAS. MICs were read after 48 h of incubation. The Etest was performed on RPMI 1640 agar plates as recommended (Etest technical guide 4) (1). For CAS, an 80% inhibition in growth was used as the MIC endpoint (microcolonies were ignored), and for AMB, the MIC endpoint was defined as the lowest concentration with complete (100%) growth inhibition (1).For the time-kill studies, the drugs alone and in combination were used at 1ϫ MIC (1.0 g/ml for both drugs). The numbers of CFU were determined at 0, 2, 6, and 24 h. The limit of detection was 50 CFU/ml. Fungicidal activity was considered to have been achieved when the number of CFU per milliliter was Ͻ99.9% compared with the initial inoculum size. Synergy and antagonism were defined, respectively, as a Ն100-fold increase or decrease in killing compared with that achieved with the most active single agent. If there was less than a 100-fold change, the interaction was considered indifferent (3). For the antifungal combination studies, two types of Etest methods were used. For the first method (Etest-1; described in reference 5), synergy was defined as a decrease of Ն3 dilutions, indifference as a decrease of Ͻ2 dilutions, and antagonism as an increase of Ն3 dilutions, respectively, in the resultant MIC. The second method (Etest-2) was carried out as described in a previous study (10). The fractional inhibitory concentration (FIC) index was calculated as follows: ⌺FIC ϭ FIC A ϩ FIC B, where FIC A is the MIC of the combination/the MIC of drug A alone, and FIC B is the MIC of the combination/the...

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The aim of this study was to determine the frequency of tinea pedis and manuum (dermatophyte infections of the hands and feet) in adults in rural areas of Turkey, the risk factors and self-administered treatment options. A total of 2,574 people living in a rural area were enrolled in the study. Participants were asked demographic data, hygienic habits in a questionnaire. KOH preparations and culture were performed from suspicious lesions. Medical and alternative therapy methods and former dermatophytosis diagnosis history were taken from the respondents with suspicious lesions. Microbiological samples were taken from 285 (11.1%) participants. Culture was positive in 109 (4.2%) of those. The most common agent was Trichophyton rubrum. The predisposing factors were found as age older than 40, male gender and obesity. Forty-nine (44.9%) of patients had taken a medical therapy, 56 (51.4%) had performed non-medical methods (cologne, Lawsonia inermis-Henna and softener creams). Patient's education about the treatment compliance is important.

An increase in the prevalence of tuberculosis (TB) in recent years has accelerated the search for novel tools for the rapid diagnosis of TB infection. This study evaluated the GenoType Mycobacteria Direct (GTMD) assay (Hain Lifescience) for direct detection of the Mycobacterium tuberculosis complex (MTBC) from sputum samples and compared it with conventional methods. The GTMD test is a commercial assay produced using strip techniques and works based on a nucleic acid sequence-based amplification technique. This test allows 23S rRNA amplificationbased detection of MTBC, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium kansasii and Mycobacterium malmoense directly from decontaminated clinical samples within 6 h. In the present study, 115 sputum samples were processed to detect acid-fast bacilli (AFB) using two microscopy methods (carbol fuchsin and fluorescent staining), two culture methods [Lö wenstein-Jensen (LJ) and BACTEC 12B media] and the GTMD test. The results showed that 86 of the samples were positive by direct microscopy, 84 were positive by BACTEC 12B culture, 73 were positive by LJ culture and 95 were positive by the GTMD test. All of the isolates turned out to be MTBC. Moreover, the sensitivity and specificity of the GTMD test for MTBC in patients were 97 and 58 %, respectively, taking the culture combination as the gold standard. When the test was compared with culture of samples from anti-TB-treated patients, the sensitivity and specificity for the test were 100 and 15 %, respectively. Low specificity in treated people might arise from depressed proliferation of AFB. As the two methods target the same living bacilli, the difference is obviously notable. When the culture results and clinical findings of the patients were evaluated together (true-positive specimens), the sensitivity and specificity values of the GTMD test for all patients were 97 and 90 %, respectively. However, both of these values increased to 100 % for the patients receiving anti-TB treatment. These results implied that, to determine whether the patient's sputum contains living AFB, more sensitive techniques should be employed during the follow-up of the patients. These observations suggest that the GTMD method can be useful for early diagnosis of clinically and radiologically suspicious TB cases where smears are negative for Mycobacterium. In addition, the use of a GTMD test in smear-positive cases is helpful and practical in order to identify MTBC quickly. This allows more rapid treatment decisions and infection control precautions.

CMV DNAemia was significantly higher in allogeneic transplant recipients than in autologous transplant patients. End-organ disease could be prevented with appropriate pre-emptive therapy.