Jennifer Broom

Ethanol lock therapy to treat tunnelled central venous catheter-associated blood stream infections: Results from a prospective trial

In order to assess the efficacy of 70% ethanol locks in addition to antibiotic therapy to treat tunnelled central venous catheter-associated bloodstream infections, a pilot study of 19 patients was performed prospectively using ethanol locks for 5 d in addition to antibiotic therapy to treat tunnelled central venous catheter-associated bacteraemia. 12 patients had mono-microbial infections and 7 had polymicrobial isolates. 17 of 19 patients completed ethanol lock therapy. 15 of 17 patients completing ethanol lock therapy had no recurrence of the original organism and retained their catheter for a median of 36 and an average of 47 d following initiation of ethanol lock therapy. These results demonstrate the safety and potential efficacy of this technique against a broad range of potentially virulent organisms. The intervention was acceptable to both staff and patients with no significant side-effects. These preliminary results from our prospective pilot study suggest that ethanol lock therapy is safe and easily integrated into clinical practice, and may have utility in treating central venous catheter-associated infections, avoiding removal of catheters in patients requiring long-term venous access.

Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy

Background Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models. Methods Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models. Results The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4 = 350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment. Conclusion Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.

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

BackgroundTunnelled 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).MethodsPatients 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.ResultsObserved 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).ConclusionsCatheter 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 RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12609000493246

Immune reconstitution inflammatory syndrome producing atypical presentations of cryptococcal meningitis: case report and a review of immune reconstitution-associated cryptococcal infections.

Atypical presentations of cryptococcal infection have been described as manifestations of immune reconstitution in HIV-infected patients following introduction of antiretroviral therapy. We describe a patient presenting with cryptococcal meningitis as an immune reconstitution reaction 10 weeks after initiation of anti-retroviral therapy. Subclinical CSF cryptococcal infection was demonstrated and the serum cryptococcal antigen was negative.

What prevents the intravenous to oral antibiotic switch? A qualitative study of hospital doctors' accounts of what influences their clinical practice.

OBJECTIVES Escalating antimicrobial resistance worldwide necessitates urgent optimization of antimicrobial prescribing to preserve antibiotics for future generations. Early intravenous (iv) to oral switch campaigns are one strategy that hospital-based antimicrobial stewardship programmes can incorporate to minimize inappropriate antibiotic use. Yet, iv antibiotics continue to be offered for longer than is clinically indicated, increasing hospital length of stay, increasing costs and placing patients at risk (e.g. cannula-related infections). This study aims to identify why this inappropriate prescribing trend continues. METHODS Twenty doctors (9 females and 11 males) working at a teaching hospital in north-east England participated in semi-structured interviews about their experiences of antibiotic use. NVivo10 software was used to conduct a thematic content analysis of the full interview transcripts driven by the framework approach. Results are reported according to COREQ guidelines. RESULTS Decisions around the choice of iv over oral antibiotics were influenced by three key issues: (i) consumerism, i.e. participants were concerned about the risk of litigation or complaints if patient expectations were not met; (ii) hierarchy of the medical team structure limited opportunities for de-escalation of antibiotics; and (iii) iv antibiotics were perceived as more potent and having significant mythical qualities, which participants acknowledged were not necessarily evidence based. CONCLUSIONS The iv to oral switch interventions should tailor strategies to demystify iv versus oral antibiotic efficacy, engage consumers around the negative effects of iv antibiotic overuse and examine strategies to streamline team decision-making. Addressing these issues has the potential to reduce inappropriate antibiotic use and resistance.

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

BackgroundCatheter-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/designThe 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.DiscussionThis 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 RegistrationAustralian New Zealand Clinical Trials Registry Number: ACTRN12609000493246

What role do pharmacists play in mediating antibiotic use in hospitals? A qualitative study.

Objective To understand Australian hospital pharmacists’ accounts of antibiotic use, and the potential role of pharmacy in antibiotic optimisation within a tertiary hospital setting. Design, setting and participants Qualitative study, utilising semistructured interviews with 19 pharmacists in two hospitals in Queensland, Australia in 2014. Data was analysed using the framework approach and supported by NVivo10 qualitative data analysis software. Results The results demonstrate that (1) pharmacists’ attitudes are ambivalent towards the significance of antibiotic resistance with optimising antibiotic use perceived as low priority; (2) pharmacists’ current capacity to influence antibiotic decision-making is limited by the prescribing power of doctors and the perception of antibiotic use as a medical responsibility; and, (3) interprofessional and organisational barriers exist that prevent change in the hospital setting including medical hierarchies, limited contact with senior doctors and resource constraints resulting in insufficient pharmacy staffing to foster collaborative relationships and facilitate the uptake of their advice. Discussion While pharmacy is playing an increasingly important role in enhanced antibiotic governance and is a vital component of antimicrobial stewardship in Australia, role-based limitations, interprofessional dynamics and organisational/resource constraints in hospitals, if not urgently addressed, will continue to significantly limit the ability of pharmacy to influence antibiotic prescribing.

Nurses as Antibiotic Brokers: Institutionalized Praxis in the Hospital

We are likely moving rapidly toward a post-antibiotic era, as a result of escalating antimicrobial resistance, rapidly declining antibiotic production and profligate overuse. Hitherto research has almost exclusively focused on doctors’ prescribing, with nurses’ roles in antibiotic use remaining virtually invisible. Drawing on interviews with 30 nurses, we focus on nurses as brokers of doctors’ antibiotic decisions, nursing capacity to challenge doctors’ decisions, and, “back stage” strategies for circumnavigating organizational constraints. We argue that nurses occupy an essential and conscious position as brokers within the hospital; a subject position that is not neutral, facilitates (short-term) cohesion, and involves the pursuit of particular (preferred) nursing outcomes. Illustrating how authority can be diffuse, mediated by institutionalized praxis, and how professionals evade attempts to govern their practice, we challenge the reification of physician prescribing power, arguing that it may work against the utilization of nurses as important stakeholders in the future of antibiotics.

The social dynamics of antibiotic use in an Australian hospital

Misuse of antibiotics in hospitals in Australia and internationally is common. The combination of multi-resistant organisms and continued misuse of antibiotics is contributing to a predicted ‘antimicrobial perfect storm’ in the coming decades. Attempts to influence doctors’ use of antibiotics have seen limited success internationally, yet few studies have explored the potential social factors driving current practices within hospitals and the interpersonal processes that underpin persistent ‘suboptimal’ antibiotic use. In this qualitative study of hospital-based Australian doctors we explore some of these dynamics including: the role of clinical uncertainty and ambivalence; experiences of immediate risk; interpersonal and intra-professional pressure; and the role of localised norms and ‘craft groups’ in driving antibiotic practices. We argue that the development of a sociological understanding of antibiotic misuse in the hospital sector (and beyond) is vital for progress to be made in protecting antibiotics for future generations.

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.