RESUMO

We investigated the in vitro antibacterial activity of the combination rifampicin (RIF) + polymyxin B (PB) against extensively drug-resistant (XDR) Klebsiella pneumoniae isolates. We evaluated clinical isolates co-resistant to PB (non-mcr carriers; eptB, mgrB, pmr operon, and ramA mutations) and to carbapenems (KPC, CTX-M, and SHV producers; including KPC + NDM co-producer), belonging to sequence types (ST) ST16, ST11, ST258, ST340, and ST437. We used the standard broth microdilution method to determine RIF and PB minimum inhibitory concentration (MIC) and the checkerboard assay to evaluate the fractional inhibitory concentration index (FICI) of RIF + PB as well as to investigate the lowest concentrations of RIF and PB that combined (RIF + PB) had antibacterial activity. Time-kill assays were performed to evaluate the synergistic effect of the combination against selected isolates. PB MIC (32-256 µg/mL) and RIF MIC (32-1024 µg/mL) were determined. FICI (<0.5) indicated a synergistic effect for all isolates evaluated for the combination RIF + PB. Our results showed that low concentrations of PB (PB minimal effective antibiotic concentration [MEAC], ≤0.25-1 µg/mL) favor RIF (≤0.03-0.125 µg/mL) to reach the bacterial target and exert antibacterial activity against PB-resistant isolates, and the synergistic effect was also observed in time-kill results. The combination of RIF + PB showed in vitro antibacterial activity against XDR, carbapenem-, and PB-resistant K. pneumoniae and could be further studied as a potential combination therapy, with cost-effectiveness and promising efficacy.

Assuntos

RESUMO

BACKGROUND: Sensitization to house dust mites (HDMs) is frequent in patients with atopic dermatitis. OBJECTIVE: To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus extract in patients with atopic dermatitis sensitized to HDM. METHODS: In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients 3 years or older, with SCORing Atopic Dermatitis (SCORAD) score greater than or equal to 15 and positive skin test result and/or IgE to D pteronyssinus. Patients were stratified according to age (<12 and ≥12 years) to receive HDM SLIT or placebo for 18 months. Primary outcome was a greater than or equal to 15-point decrease in SCORAD score. Secondary outcomes were decreases in SCORAD and objective SCORAD, Eczema Area and Severity Index, visual analog scale for symptoms, and pruritus scale scores; Investigator's Global Assessment 0/1; and decrease greater than or equal to 4 points in Dermatology Life Quality Index. Background therapy was maintained. RESULTS: A total of 66 patients completed the study (35 HDM SLIT, 31 placebo). After 18 months, 74.2% and 58% of patients in the HDM SLIT group and the placebo group, respectively, showed greater than or equal to 15-point decrease in SCORAD score (relative risk, 1.28; 95% CI, 0.89-1.83). Significant SCORAD score decreases from baseline of 55.6% and 34.5% in HDM SLIT and placebo groups (mean difference, 20.4; 95% CI, 3.89-37.3), significant objective SCORAD score decreases of 56.8% and 34.9% in HDM SLIT and placebo groups (mean difference, 21.3; 95% CI, 0.66-41.81), and more patients with Investigator's Global Assessment 0/1 in the HDM SLIT group as compared with the placebo group (14 of 35 vs 5 of 31; relative risk, 2.63; 95% CI, 1.09-6.39) were observed at 18 months. CONCLUSIONS: Our results suggest that HDM SLIT may be effective in HDM-sensitized patients as an add-on treatment for atopic dermatitis.

Assuntos

RESUMO

BACKGROUND: Nontuberculous mycobacteria (NTM) have been identified with increasing frequency in the clinical practice. The aim of this study was to characterize NTM isolates in respiratory specimens from patients with pulmonary disease and to correlate this with clinical/radiological findings, decision to start treatment and outcomes. METHODS: A cross-sectional descriptive study was performed and included all patients who had at least one NTM isolated in respiratory specimens between 2011 and 2014. NTM culture was performed in liquid medium followed by immunochromatographic identification (anti-MPT64). Species identification was based on nucleic acid amplification followed by restriction analysis of a 441 bp fragment of the hsp65 gene (hsp65 PRA) and patients' records were reviewed. RESULTS: From 14,394 cultures in 4 years, 590 (4.10%) grew NTM and 305 (51.7%) isolates were characterized till species level, representing 290 patients including those with and without human immunodeficiency virus (HIV) infection. Two hundred and eleven non-HIV patients had NTM isolated from respiratory specimens, 49 (23.2%) had criteria for active disease based on the American Thoracic Society (ATS) 2007. The majority was men above 51 years old and M. intracellulare was detected in 59.2% (29/49), followed by M. avium 14.3% (7/49), and M. abscessus 12.2% (6/49). CONCLUSIONS: Old age, nodular and nodular/bronchiectasis radiographic pattern, previous tuberculosis (TB) treatment and M. intracellulare were more frequent among NTM-disease patients compared to those only colonized. Positive culture and maintenance of clinical symptoms (poor outcome) was a rule when M. abscessus caused NTM-disease. Positive acid-fast smear in respiratory specimen is a strong predictor of disease.