Renal and neurological side effects of colistin in critically ill patients

Colistin is a complex polypeptide antibiotic composed mainly of colistin A and B. It was abandoned from clinical use in the 1970s because of significant renal and, to a lesser extent, neurological toxicity. Actually, colistin is increasingly put forward as salvage or even first-line treatment for severe multidrug-resistant, Gram-negative bacterial infections, particularly in the intensive care setting. We reviewed the most recent literature on colistin treatment, focusing on efficacy and toxicity issues. The method used for literature search was based on a PubMed retrieval using very precise criteria

Interferon-Inducible CXC Chemokines Directly Contribute to Host Defense against Inhalational Anthrax in a Murine Model of Infection

Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms

Treatment considerations in vancomycin-resistant enterococcal bacteremia: daptomycin or linezolid? A review

Background Vancomycin resistant enterococcal bloodstream infections are an important cause of morbidity and mortality in hospitalized patients. Aim of the Review A search of the literature was undertaken to determine the optimal antimicrobial therapy for the management of vancomycin resistant enterococcal bloodstream infections. Method MEDLINE, EMBASE, and the Cochrane Library (unrestricted to time or language) were searched for studies of vancomycin resistant enterococcal bloodstream infections in adults reporting outcomes of direct comparisons of linezolid versus daptomycin on November 26, 2012. Studies of basic science, reviews, commentaries, pharmacologic, epidemiologic, or pediatric studies, and those studies examining conditions other than enterococcal bacteremia, a single antimicrobial agent or other antimicrobials were excluded. Results 226 studies were screened for eligibility and yielded eight studies evaluating a total of 807 patients. Inter-rater agreement was 100 %. Qualitative evaluation of the studies was performed using the Newcastle–Ottawa scale. No randomized controlled trials were identified. All studies were retrospective cohorts and non-randomized. 458 (57 %) patients treated with linezolid and 349 (43 %) with daptomycin were analyzed. Variable comorbidities and severity of illness were described in the included studies and reported here for comparison. Conclusion The optimal treatment of vancomycin resistant enterococcal bloodstream infections is yet to be determined. Well-designed prospective studies are needed to lend more convincing evidence regarding choice of antimicrobial therapy for this important multidrug resistant organism