Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

BACKGROUND: The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. METHODS: The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. RESULTS: Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). CONCLUSIONS: Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

The effects of creatine monohydrate supplementation with and without D-pinitol on resistance training adaptations.

Coingestion of D-pinitol with creatine (CR) has been reported to enhance creatine uptake. The purpose of this study was to evaluate whether adding D-pinitol to CR affects training adaptations, body composition, whole-body creatine retention, and/or blood safety markers when compared to CR ingestion alone after 4 weeks of resistance training. Twenty-four resistance trained males were randomly assigned in a double-blind manner to creatine + pinitol (CRP) or creatine monohydrate (CR) prior to beginning a supervised 4-week resistance training program. Subjects ingested a typical loading phase (i.e., 20 g/d-1 for 5 days) before ingesting 5 g/d-1 the remaining 23 days. Performance measures were assessed at baseline (T0), week 1 (T1), and week 4 (T2) and included 1 repetition maximum (1RM) bench press (BP), 1RM leg press (LP), isokinetic knee extension, and a 30-second Wingate anaerobic capacity test. Fasting blood and body composition using dual-energy x-ray absorptiometry (DEXA) were determined at T1 and T3. Data were analyzed by repeated measures analysis of variance (ANOVA). Creatine retention increased (p < 0.001) in both groups as a result of supplementation but was not different between groups (p > 0.05). Significant improvements in upper- and lower-body strength and body composition occurred in both groups. However, significantly greater increases in lean mass and fat-free mass occurred in the CR group when compared to CRP (p <0.05). Adding D-pinitol to creatine monohydrate does not appear to facilitate further physiological adaptations while resistance training. Creatine monohydrate supplementation helps to improve strength and body composition while resistance training. Data from this study assist in determining the potential role the addition of D-pinitol to creatine may aid in facilitating training adaptations to exercise.