How do professional relationships influence surgical antibiotic prophylaxis decision making? A qualitative study.

BACKGROUND: Surgical antibiotic prophylaxis (SAP) is a critical area to optimize to reduce the escalation of antimicrobial resistance. This article explores the ways by which interpersonal relationships influence SAP decision making. METHODS: Twenty surgeons and anesthetists participated in in-depth semistructured interviews on SAP prescribing. Results were analyzed using the framework approach. RESULTS: Analysis revealed 3 ways by which interpersonal relationships influence SAP: relationship dynamics between the surgeon and the anesthetist determine appropriateness of SAP, particularly operative risk ownership; perceived hierarchies within, and between, surgical and anesthetist specialties influence antibiotic prescribing decisions; and surgical distance from the antimicrobial stewardship team, which influences use of antimicrobial stewardship principles. CONCLUSIONS: Interventions to optimize SAP are more likely to be effective in enacting sustained change if they consider the interpersonal and social contexts, including issues of familiarity and cohesiveness, hierarchical patterns, and sense of place within a team. Significant relational dynamics in SAP decision making are centered around risk; that is, personal/reputational risk to different professional groups and ownership of risk for individual patient outcomes. Risk must therefore be considered for sustainable SAP optimization interventions.

Clinical and social barriers to antimicrobial stewardship in pulmonary medicine: A qualitative study.

BACKGROUND: The treatment of pulmonary infections is one of the largest indications for antibiotics in human health care, offering significant potential for antibiotic optimization internationally. This study explores the perspectives of pulmonary clinicians on antibiotic use in hospital pulmonary infections. METHODS: Twenty-eight pulmonary doctors and nurses from 2 hospitals participated in semi-structured interviews focusing on their experiences of antibiotic use. RESULTS: Barriers to antibiotic optimization in pulmonary infections were identified. Clinical barriers are as follows. The first is differentiating pneumonia vs chronic obstructive pulmonary disease: differentiating pulmonary diagnoses was reported as challenging, leading to overtreatment. The second is differentiating viral vs bacterial: diagnostic differentiation was perceived to contribute to excess antibiotic use. The third is differentiating colonization vs pathogen: the interpretation of ambiguous results was reported to lead to under- or overprescribing depending on the perspective of the treating team. Social barriers are as follows. The first is the perception of resistance: antibiotic resistance was not perceived as an immediate threat. The second is the perceived value of antibiotic clinical guidelines: there was mistrust in antibiotic guidelines. The third is hospital hierarchies: hierarchical structures had a significant influence on prescribing. CONCLUSIONS: Substantial barriers to antibiotic optimization in pulmonary infections were identified. To facilitate change in antibiotic use there must be a systematic understanding and interventions to address specific clinical issues. In the case of pulmonary medicine, significant identified issues, such as mistrust in clinical guidelines and diagnostic challenges, need to be addressed.

A randomised controlled trial of Heparin versus EthAnol Lock THerapY for the prevention of Catheter Associated infecTion in Haemodialysis patients--the HEALTHY-CATH trial.

BACKGROUND: Tunnelled central venous dialysis catheter use is significantly limited by the occurrence of catheter-related infections. This randomised controlled trial assessed the efficacy of a 48 hour 70% ethanol lock vs heparin locks in prolonging the time to the first episode of catheter related blood stream infection (CRBSI). METHODS: Patients undergoing haemodialysis (HD) via a tunnelled catheter were randomised 1:1 to once per week ethanol locks (with two heparin locks between other dialysis sessions) vs thrice per week heparin locks. RESULTS: Observed catheter days in the heparin (n=24) and ethanol (n=25) groups were 1814 and 3614 respectively. CRBSI occurred at a rate of 0.85 vs. 0.28 per 1000 catheter days in the heparin vs ethanol group by intention to treat analysis (incident rate ratio (IRR) for ethanol vs. heparin 0.17; 95%CI 0.02-1.63; p=0.12). Flow issues requiring catheter removal occurred at a rate of 1.6 vs 1.4 per 1000 catheter days in the heparin and ethanol groups respectively (IRR 0.85; 95% CI 0.20-3.5 p =0.82 (for ethanol vs heparin). CONCLUSIONS: Catheter survival and catheter-related blood stream infection were not significantly different but there was a trend towards a reduced rate of infection in the ethanol group. This study establishes proof of concept and will inform an adequately powered multicentre trial to definitively examine the efficacy and safety of ethanol locks as an alternative to current therapies used in the prevention of catheter-associated blood stream infections in patients dialysing with tunnelled catheters. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609000493246.

Antigen-specific CD4 cells assist CD8 T-effector cells in eliminating keratinocytes.

Keratinocytes expressing tumor or viral antigens can be eliminated by antigen-primed CD8 cytotoxic T cells. CD4 T-helper cells help induction of CD8 cytotoxic T cells from naive precursors and generation of CD8 T-cell memory. In this study, we show, unexpectedly, that CD4 cells are also required to assist primed CD8 effector T cells in rejection of skin expressing human growth hormone, a neo-self-antigen, in keratinocytes. The requirement for CD4 cells can be substituted by CD40 costimulation. Rejection of skin expressing ovalbumin (OVA), a non-self-antigen, by primed CD8 cytotoxic T cells can in contrast occur without help from antigen-specific CD4 T cells. However, rejection of OVA expressing keratinocytes is helped by antigen-specific CD4 T cells if only low numbers of primed or naive OVA-specific CD8 T cells are available. Effective immunotherapy directed at antigens expressed in squamous cancer may therefore be facilitated by induction of tumor antigen-specific CD4 helper T cells, as well as cytotoxic CD8 T cells.

Rationale and design of the HEALTHY-CATH trial: a randomised controlled trial of Heparin versus EthAnol Lock THerapY for the prevention of Catheter Associated infecTion in Haemodialysis patients.

BACKGROUND: Catheter-related bacteraemias (CRBs) contribute significantly to morbidity, mortality and health care costs in dialysis populations. Despite international guidelines recommending avoidance of catheters for haemodialysis access, hospital admissions for CRBs have doubled in the last decade. The primary aim of the study is to determine whether weekly instillation of 70% ethanol prevents CRBs compared with standard heparin saline. METHODS/DESIGN: The study will follow a prospective, open-label, randomized controlled design. Inclusion criteria are adult patients with incident or prevalent tunneled intravenous dialysis catheters on three times weekly haemodialysis, with no current evidence of catheter infection and no personal, cultural or religious objection to ethanol use, who are on adequate contraception and are able to give informed consent. Patients will be randomized 1:1 to receive 3 mL of intravenous-grade 70% ethanol into each lumen of the catheter once a week and standard heparin locks for other dialysis days, or to receive heparin locks only. The primary outcome measure will be time to the first episode of CRB, which will be defined using standard objective criteria. Secondary outcomes will include adverse reactions, incidence of CRB caused by different pathogens, time to infection-related catheter removal, time to exit site infections and costs. Prospective power calculations indicate that the study will have 80% statistical power to detect a clinically significant increase in median infection-free survival from 200 days to 400 days if 56 patients are recruited into each arm. DISCUSSION: This investigator-initiated study has been designed to provide evidence to help nephrologists reduce the incidence of CRBs in haemodialysis patients with tunnelled intravenous catheters. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12609000493246.