Colistin: new lessons on an old antibiotic

AbstractColistin has been re-introduced into clinical practice for the treatment of carbapenem-resistant Gram-negative bacteria. Studies in the last decade attempted to reconstruct the path that present-day medications undergo prior to clinical use. In this review, we summarize the results of recent clinical studies. Colistin was associated with lower mortality than no effective treatment and higher unadjusted mortality than b-lactams in non-randomized clinical studies. However, it was administered to sicker patients with carabapenem-resistant bacteria. Overall, nephrotoxicity rates were not higher with colistin in these studies, and colistin-induced nephrotoxicity is reversible in most patients. The emergence of colistin resistance has been described in high-use settings. Synergy with carbapenem, rifampin and other antibiotics has been reported in vitro. Randomized controlled trials are ongoing or in planning to assess this and other aspects of colistin use in clinical practice

Early discontinuation of antibiotics for febrile neutropenia versus continuation until neutropenia resolution

Abstract Background: People with cancer with febrile neutropenia are at risk of severe infections and mortality and are thus treated empirically with broad-spectrum antibiotic therapy. However, the recommended duration of antibiotic therapy differs across guidelines. Objectives: To assess the safety of protocol-guided discontinuation of antibiotics regardless of neutrophil count, compared to continuation of antibiotics until neutropenia resolution in people with cancer with fever and neutropenia, in terms of mortality and morbidity. To assess the emergence of resistant bacteria in people with cancer treated with short courses of antibiotic therapy compared with people with cancer treated until resolution of neutropenia. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 10) in the Cochrane Library, MEDLINE, Embase, and LILACS up to 1 October 2018. We searched the metaRegister of Controlled Trials and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov for ongoing and unpublished trials. We reviewed the references of all identified studies for additional trials and handsearched conference proceedings of international infectious diseases and oncology and haematology conferences. Selection criteria: We included randomised controlled trials (RCTs) that compared a short antibiotic therapy course in which discontinuation of antibiotics was guided by protocols regardless of the neutrophil count to a long course in which antibiotics were continued until neutropenia resolution in people with cancer with febrile neutropenia. The primary outcome was 30-day or end of follow-up all-cause mortality. Data collection and analysis: Two review authors independently reviewed all studies for eligibility, extracted data, and assessed risk of bias for all included trials. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) whenever possible. For dichotomous outcomes with zero events in both arms of the trials, we conducted meta-analysis of risk differences (RDs) as well. For continuous outcomes, we extracted means with standard deviations (SD) from the studies and computed mean difference (MD) and 95% CI. If no substantial clinical heterogeneity was found, trials were pooled using the Mantel-Haenszel fixed-effect model. Main results: We included eight RCTs comprising a total of 662 distinct febrile neutropenia episodes. The studies included adults and children, and had variable design and criteria for discontinuation of antibiotics in both study arms. All included studies but two were performed before the year 2000. All studies included people with cancer with fever of unknown origin and excluded people with microbiological documented infections.We found no significant difference between the short-antibiotic therapy arm and the long-antibiotic therapy arm for all-cause mortality (RR 1.38, 95% CI 0.73 to 2.62; RD 0.02, 95% CI -0.02 to 0.05; low-certainty evidence). We downgraded the certainty of the evidence to low due to imprecision and high risk of selection bias. The number of fever days was significantly lower for people in the short-antibiotic treatment arm compared to the long-antibiotic treatment arm (mean difference -0.64, 95% CI -0.96 to -0.32; I² = 30%). In all studies, total antibiotic days were fewer in the intervention arm by three to seven days compared to the long antibiotic therapy. We found no significant differences in the rates of clinical failure (RR 1.23, 95% CI 0.85 to 1.77; very low-certainty evidence). We downgraded the certainty of the evidence for clinical failure due to variable and inconsistent definitions of clinical failure across studies, possible selection bias, and wide confidence intervals. There was no significant difference in the incidence of bacteraemia occurring after randomisation (RR 1.56, 95% CI 0.91 to 2.66; very low-certainty evidence), while the incidence of any documented infections was significantly higher in the short-antibiotic therapy arm (RR 1.67, 95% CI 1.08 to 2.57). There was no significant difference in the incidence of invasive fungal infections (RR 0.86, 95% CI 0.32 to 2.31) and development of antibiotic resistance (RR 1.49, 95% CI 0.62 to 3.61). The data on hospital stay were too sparse to permit any meaningful conclusions. Authors' conclusions: We could make no strong conclusions on the safety of antibiotic discontinuation before neutropenia resolution among people with cancer with febrile neutropenia based on the existing evidence and its low certainty. Results of microbiological outcomes favouring long antibiotic therapy may be misleading due to lower culture positivity rates under antibiotic therapy and not true differences in infection rates. Well-designed, adequately powered RCTs are required that address this issue in the era of rising antibiotic resistance

Full meta objects for flexible geoprocessing workflows: profiling WPS or BPMN?

The design and execution of scientific workflows is an important and necessary function within many disciplines. In the geospatial community, workflows are used to generate and quality assure new spatial datasets based on sequences of processing steps or complex modelling. Using BPMN for representing these workflows allows stakeholders to discuss the scientific conceptual approach behind this modelling whilst also being able to execute its encoding in XML. Previous research has focused on developing frameworks, including a BPMN workflow engine, capable of orchestrating OGC Web Processing Services and thus enabling construction of interoperable workflows comprised of distributed resources. These could populate, for example, the GEOSS repository. However, to date, such work has focused on executing workflows with direct access to the pre-defined data inputs and outputs, with a lack of flexibility and efficiency in semantic interoperability or data management during composition and execution. This article suggests a meta-approach based on two possible configurations that enable workflow orchestration at a meta level using a direct coupling with a metadata catalogue. The designs of a Web Processing Service profile and of a BPMN profile are presented as potential approaches to abstract the data interchange between the processing steps of a workflow. The paper concludes with a discussion of how these approaches may be extended and how complete workflows might be registered and managed using catalogues services

Association of vancomycin serum concentrations with efficacy in patients with MRSA infections: a systematic review and meta-analysis

AbstractRecent Infectious Diseases Society of America guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections recommend maintaining vancomycin trough concentrations of 15–20 mg/L for serious infections. We conducted a systematic review and meta-analysis of all studies assessing the impact of low (<15 mg/L) vs. high (≥15 mg/L) vancomycin trough level on the efficacy of MRSA infections treatment. Four prospective and 12 retrospective studies were included (2003 participants). No significant difference was demonstrated between low and high vancomycin trough level for the outcome of all-cause mortality (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.78–1.46, I2 = 28%). In studies evaluating mainly MRSA pneumonia, there was significantly higher mortality with low vancomycin level (OR 1.78, 95% CI 1.11–2.84). No significant difference was demonstrated in treatment failure rates (OR 1.25, 95% CI 0.88–1.78, I2 = 51%). However, excluding one outlier study from the analysis, treatment failure became significantly higher in patients with low vancomycin trough level (OR 1.46, 95% CI 1.12–1.91, I2 = 16%). Microbiologic failure rates were significantly higher in patients with low vancomycin levels (OR 1.56, 95% CI 1.08–2.26, I2 = 0%). Nephrotoxicity was significantly higher with vancomycin levels of ≥15 mg/L. However, no cases of irreversible renal damage were reported. Current data on the effectiveness of higher vancomycin trough levels in the treatment of MRSA infections are limited to few prospective and mainly retrospective studies. Our findings support the current recommendations for maintaining vancomycin trough levels of ≥15 mg/L in the treatment of severe MRSA infections, although no difference in all-cause mortality was observed

Prophylactic antibiotics for burns patients: systematic review and meta-analysis

Objective To assess the evidence for prophylactic treatment with systemic antibiotics in burns patients

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews

Message to complementary and alternative medicine: evidence is a better friend than power

BACKGROUND: Evidence-based medicine (EBM) is being embraced by an increasing number of practitioners and advocates of complementary and alternative medicine (CAM). A significant constituency within CAM, however, appears to have substantive doubts about EBM and some are expressly hostile. DISCUSSION: Many of the arguments raised against EBM within the CAM community are based on a caricature radically at odds with established, accepted and published principles of EBM practice. Contrary to what has sometimes been argued, EBM is not cookbook medicine that ignores individual needs. Neither does EBM mandate that only proven therapies should be used. Before EBM, decisions on health care tended to be based on tradition, power and influence. Such modes usually act to the disadvantage of marginal groups. CONCLUSION: By placing CAM on an equal footing with conventional medicine - what matters for both is evidence of effectiveness - EBM provides an opportunity for CAM to find an appropriate and just place in health care

Effects of type and level of training on variation in physician knowledge in the use and acquisition of blood cultures: a cross sectional survey

BACKGROUND: Blood culture (BCX) use is often sub-optimal, and is a user-dependent diagnostic test. Little is known about physician training and BCX-related knowledge. We sought to assess variations in caregiver BCX-related knowledge, and their relation to medical training. METHODS: We developed and piloted a self-administered BCX-related knowledge survey instrument. Expert opinion, literature review, focus groups, and mini-pilots reduced > 100 questions in multiple formats to a final questionnaire with 15 scored content items and 4 covariate identifiers. This questionnaire was used in a cross-sectional survey of physicians, fellows, residents and medical students at a large urban public teaching hospital. The responses were stratified by years/level of training, type of specialty training, self-reported practical and theoretical BCX-related instruction. Summary scores were derived from participant responses compared to a 95% consensus opinion of infectious diseases specialists that matched an evidence based reference standard. RESULTS: There were 291 respondents (Attendings = 72, Post-Graduate Year (PGY) = 3 = 84, PGY2 = 42, PGY1 = 41, medical students = 52). Mean scores differed by training level (Attending = 85.0, PGY3 = 81.1, PGY2 = 78.4, PGY1 = 75.4, students = 67.7) [p ≤ 0.001], and training type (Infectious Diseases = 96.1, Medicine = 81.7, Emergency Medicine = 79.6, Surgery = 78.5, Family Practice = 76.5, Obstetrics-Gynecology = 74.4, Pediatrics = 74.0) [p ≤ 0.001]. Higher summary scores were associated with self-reported theoretical [p ≤ 0.001] and practical [p = 0.001] BCX-related training. Linear regression showed level and type of training accounted for most of the score variation. CONCLUSION: Higher mean scores were associated with advancing level of training and greater subject-related training. Notably, house staff and medical students, who are most likely to order and/or obtain BCXs, lack key BCX-related knowledge. Targeted education may improve utilization of this important diagnostic tool