Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis.

Antibiotic de-escalation is an appealing strategy in antibiotic stewardship programmes. We aimed to assess its safety and effects using a systematic review and meta-analysis. We included randomized controlled trials (RCTs) and observational studies assessing adults with bacteraemia, microbiologically documented pneumonia or severe sepsis, comparing between antibiotic de-escalation and no de-escalation. De-escalation was defined as changing an initially covering antibiotic regimen to a narrower spectrum regimen based on antibiotic susceptibility testing results within 96 hours. The primary outcome was 30-day all-cause mortality. A search of published articles and conference proceedings was last updated in September 2015. Crude and adjusted ORs with 95% CI were pooled in random-effects meta-analyses. Sixteen observational studies and three RCTs were included. Risk of bias related to confounding was high in the observational studies. De-escalation was associated with fewer deaths in the unadjusted analysis (OR 0.53, 95% CI 0.39-0.73), 19 studies, moderate heterogeneity. In the adjusted analysis there was no significant difference in mortality (adjusted OR 0.83, 95% CI 0.59-1.16), 11 studies, moderate heterogeneity and the RCTs showed non-significant increased mortality with de-escalation (OR 1.73, 95% 0.97-3.06), three trials, no heterogeneity. There was a significant unadjusted association between de-escalation and survival in bacteraemia/severe sepsis (OR 0.45, 95% CI 0.30-0.67) and ventilator-associated pneumonia (OR 0.49, 95% CI 0.26-0.95), but not with other pneumonia (OR 0.97, 95% CI 0.45-2.12). Only two studies reported on the emergence of resistance with inconsistent findings. Observational studies suggest lower mortality with antibiotic susceptibility testing-based de-escalation for bacteraemia, severe sepsis and ventilator-associated pneumonia that was not demonstrated in RCTs.

In vitro elution of vancomycin from biodegradable osteoconductive calcium phosphate-polycaprolactone composite beads for treatment of osteomyelitis.

In this work, osteoconductive composite materials comprising a large volume fraction of a bioresorbable calcium phosphate ceramic (CaP) and a smaller amount of a polycaprolactone polymer (PCL) were studied as a degradable antibiotic carrier material for treatment of osteomyelitis. Beads loaded with 1 and 4wt.% vancomycin were prepared by admixing dissolved drug to an in situ synthesized dicalcium phosphate (DCP)-PCL or solution-mixed beta-tricalcium phosphate (ßTCP)-PCL composite powder followed by high pressure consolidation of the blend at room temperature. Vancomycin release was measured in phosphate-buffered saline (PBS) at 37°C. All the beads gradually released the drug over the period of 4-11weeks, depending on the composite matrix homogeneity and porosity. Mathematical modeling using the Peppas equation showed that vancomycin elution was diffusion controlled. The stability of the antibiotic after high pressure application at room temperature was demonstrated by high-performance liquid chromatography-mass spectrometry (HPLC-MS) studies and MIC testing. The preservation of the structure and activity of vancomycin during the processing of composite beads and its sustained in vitro release profile suggest that high pressure consolidated CaP-PCL beads may be useful in the treatment of chronic bone infections as resorbable delivery vehicles of vancomycin and even of thermally unstable drug substances.

Bloodstream infection as a predictor for mortality in severe burn patients: an 11-year study.

In this study we collected and analysed data of the severe burn patients at our institution over an 11-year period in order to shed light on the controversial role of bloodstream infection (BSI) as a predictive factor for mortality in this burn population. The factors examined were age, total body surface area, smoke inhalation, presence of BSI, and BSI with resistant bacteria. In total 1081 burn patients were hospitalized from 2001 to 2011, of whom 4% died. We focused here on 158 severe burn patients, 74 of whom developed BSI, and 35 who died. Using univariate analysis, it appeared that the BSI group had a threefold greater chance of mortality compared to the non-BSI group. Patients with a Ryan score 3 had a 100% chance of mortality and those with a score 0 had 0%. Thus, focusing only on Ryan score 1 and score 2 patients, BSI did not contribute to mortality, nor was it shown to contribute to mortality in a multivariate analysis in which the score and BSI were included together. When BSI did occur, it predicted longer hospitalization periods. We conclude that BSI predicts longer length of hospitalization stay but does not contribute to the prediction of mortality beyond that offered by the Ryan score in a severe burn population.

Impact of carbapenem resistance on the outcome of patients' hospital-acquired bacteraemia caused by Klebsiella pneumoniae.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae, especially Klebsiella spp., have become a major health problem recently worldwide. Since 2006 the incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections has increased substantially in Israel. Bloodstream infections (BSIs) caused by these strains have been associated with high rates of treatment failure and mortality. AIM: This study was designed to identify risk factors for carbapenem resistance among patients with healthcare-related (HCR) K. pneumoniae bacteraemia and predictors of mortality associated with HCR-CRKP bacteraemia compared with carbapenem-susceptible K. pneumoniae (CSKP). METHODS: In this retrospective case-control study, all cases of K. pneumoniae bacteraemia during 2006-2008 were identified. Resistance patterns, underlying morbidities, risk factors for drug resistance and mortality rates were compared for patients with CRKP and CSKP bacteraemia. FINDINGS: Two hundred and fourteen patients with CSKP bacteraemia were compared with 103 patients with CRKP bacteraemia. Severe, chronic comorbidities and prior antibiotic use were more frequent among patients with CRKP bacteraemia. On multivariate analysis prior use of macrolides and antibiotic exposure for ≥14 days remained the only independent factors associated with CRKP bacteraemia. Mortality rates of CRKP patients were significantly higher than those of CSKP patients. On multivariate analyses: bedridden status, chronic liver disease, Charlson comorbidity index ≥5, mechanical ventilation, and haemodialysis remained independently associated with mortality among patients with K. pneumoniae bacteraemia. Carbapenem resistance was not a risk factor for mortality. CONCLUSIONS: Previous antibiotic exposure is a risk factor for CRKP-BSI. Mortality among patients with K. pneumoniae bacteraemia is associated with serious comorbidities, but not with carbapenem resistance.

In vitro antimicrobial activity of vancomycin-eluting bioresorbable ß-TCP-polylactic acid nanocomposite material for load-bearing bone repair.

Release of antimicrobial agents from bone healing devices can dramatically reduce the risk of implant-associated infection. Here we report the fabrication and antimicrobial activity of a multifunctional load-bearing bioresorbable material that can provide mechanical support to the healing bone all while slowly releasing an antibiotic drug. Dense beta-tricalcium phosphate (ß-TCP)-40 vol% polylactic acid (PLA) nanocomposite containing 1 wt% vancomycin (VH) was high pressure consolidated at 2.5 GPa, at room temperature, or at 120 °C. Over the course of 5 weeks in TRIS solution, the ß-TCP-PLA-VH nanocomposite released approximately 90 % of its drug load. Specimens consolidated at 120 °C had the highest initial mechanical properties and maintained 85 % of their compressive strength and 30 % of their bending strength after 5 weeks release. In vitro growth inhibition study showed significant antimicrobial efficacy of VH-impregnated ß-TCP-PLA against methicillin-resistant Staphylococcus aureus when exposed to both high (2 × 10(5) CFU/mL) and very high (1 × 10(8) CFU/mL) bacterial concentrations. After 1 week, total eradication of the microorganisms was achieved. The results suggest that the developed high-strength antibiotic-eluting ß-TCP-PLA nanocomposite can be a promising material for orthopedic surgical devices.

The pathogenesis of Candida infections in a human skin model: scanning electron microscope observations.

Cutaneous candidiasis is an opportunistic infection that arises, in most cases, from endogenous, saprophytic candidal blastospores that selectively colonize oral, gastrointestinal, vaginal, and cutaneous epithelium. Candida albicans has been regarded as the most common causative agent in human fungal infections. However, other Candida species have become a significant cause of infection. Scanning electron microscope (SEM) observations were used to analyze the capability of C. albicans, C. tropicalis, and C. parapsilosis to adhere to human skin model, used in this study, which was found to mimic the human skin in vivo. The skin sections were inoculated with low and high concentration of the yeasts and followed for 1 and 5 days; then they were viewed by SEM. The electron microscopy observations revealed that all three yeasts tested adhered to the skin but C. albicans covered the entire skin model to a higher extent than C. tropicalis or C. parapsilosis. Mucin-like material coated the blastoconidia mainly in C. albicans. All Candida species have shown characteristics resembling biofilm formation. The use of human skin sections for ex vivo evaluation of adherence of various yeasts may partially explain the predominance of C. albicans in cutaneous pathogenicity.