Articles
Antibacterial honey for the prevention of peritoneal-dialysis-related infections (HONEYPOT): a randomised trial

https://doi.org/10.1016/S1473-3099(13)70258-5Get rights and content

Summary

Background

There is a paucity of evidence to guide the best strategy for prevention of peritoneal-dialysis-related infections. Antibacterial honey has shown promise as a novel, cheap, effective, topical prophylactic agent without inducing microbial resistance. We therefore assessed whether daily application of honey at the exit site would increase the time to peritoneal-dialysis-related infections compared with standard exit-site care plus intranasal mupirocin prophylaxis for nasal carriers of Staphylococcus aureus.

Methods

In this open-label trial undertaken in 26 centres in Australia and New Zealand, participants undergoing peritoneal dialysis were randomly assigned in a 1:1 ratio with an adaptive allocation algorithm to daily topical exit-site application of antibacterial honey plus standard exit-site care or intranasal mupirocin prophylaxis (only in carriers of nasal S aureus) plus standard exit-site care (control group). The primary endpoint was time to first infection related to peritoneal dialysis (exit-site infection, tunnel infection, or peritonitis). The trial is registered with the Australian New Zealand Clinical Trials Registry, number 12607000537459.

Findings

Of 371 participants, 186 were assigned to the honey group and 185 to the control group. The median peritoneal-dialysis-related infection-free survival times were not significantly different in the honey (16·0 months [IQR not estimable]) and control groups (17·7 months [not estimable]; unadjusted hazard ratio 1·12, 95% CI 0·83–1·51; p=0·47). In the subgroup analyses, honey increased the risks of both the primary endpoint (1·85, 1·05–3·24; p=0·03) and peritonitis (2·25, 1·16–4·36) in participants with diabetes. The incidences of serious adverse events (298 vs 327, respectively; p=0·1) and deaths (14 vs 18, respectively; p=0·9) were not significantly different in the honey and control groups. 11 (6%) participants in the honey group had local skin reactions.

Interpretation

The findings of this trial show that honey cannot be recommended routinely for the prevention of peritoneal-dialysis-related infections.

Funding

Baxter Healthcare, Queensland Government, Comvita, and Gambro.

Introduction

Peritoneal dialysis is an important treatment for individuals needing renal replacement and is used in more than 200 000 patients with end-stage kidney failure worldwide.1 An important barrier to further uptake and sustained use of peritoneal dialysis is infection, including peritonitis and exit-site and tunnel infections.2 These infections frequently complicate peritoneal dialysis and are associated with greatly increased risks of all-cause and cardiovascular mortality, catheter removal, transfer to haemodialysis, loss of residual renal function, prolonged hospital admission, and further episodes of peritoneal-dialysis-related infections.3, 4, 5

Evidence for the use of topical nasal mupirocin (particularly in individuals who are carriers of nasal Staphylococcus aureus),6, 7, 8 and exit-site mupirocin9, 10 or exit-site gentamicin application11 to prevent peritoneal-dialysis-related infections has been obtained from only a few randomised controlled trials. The guidelines of Caring for Australasians with Renal Impairment (CARI), therefore, recommend intranasal mupirocin prophylaxis for participants with nasal S aureus carriage undergoing peritoneal dialysis,12 whereas those of the International Society for Peritoneal Dialysis (ISPD) recommend use of topical antibiotics either at the catheter exit site or intranasally, or both, in all participants undergoing peritoneal dialysis.13 However, these antibiotics are only active against a narrow range of microorganisms and an increasing number of reports suggest that these agents result in the selection of resistant microorganisms and subsequent treatment failures.14, 15

Over the past decade, honey has been shown to be an inexpensive, safe, and effective antimicrobial agent, which is active against a broad range of fungi and bacteria (including multiresistant microorganisms),16, 17 prevents and disrupts formation of biofilm,18 and does not result in antimicrobial resistance even under conditions that rapidly induce resistance to antibiotics.19 The results of a meta-analysis of seven randomised controlled trials showed that honey was superior to antiseptics or systemic antibiotics, or both, for wound healing, maintenance of sterility, and eradication of infection.20 In a randomised controlled trial of participants undergoing haemodialysis, topical application of standardised antibacterial honey to haemodialysis-catheter exit sites resulted in infection rates similar to mupirocin, without the problems associated with mupirocin resistance.21 So far, there have been no other trials of honey to prevent peritoneal-dialysis-related infections.

The main objective in this trial was to assess whether daily application of honey at the exit site would increase the time to peritoneal-dialysis-related infections compared with standard exit-site care plus intranasal mupirocin prophylaxis for the carriers of nasal S aureus.

Section snippets

Study design and participants

The trial was designed and supervised by the investigators in the management committee and coordinated by the Australasian Kidney Trials Network (University of Queensland, Brisbane, QLD, Australia). The trial design and the statistical analysis plan have been reported previously.22, 23

Adults and children of all ages with end-stage kidney disease who were undergoing peritoneal dialysis were eligible for inclusion in the trial. The exclusion criteria were exit-site infection, tunnel infection, or

Results

186 of 371 participants were assigned to the honey group and 185 to the control group. Table 1 shows the two groups were well matched with respect to all baseline characteristics, including nasal carriage of S aureus. In the control group, 134 and 72 participants completed 12 months and 24 months of follow-up, respectively. At study termination, 20 participants who had not completed 24 months were censored. In the honey group, 101 and 52 participants completed 12 months and 24 months of

Discussion

Our results show that compared with standard exit-site care with additional nasal mupirocin for nasal carriage of S aureus, daily exit-site application of antibacterial honey resulted in similar rates of peritoneal-dialysis-related infections in all participants, increased risks of both infection and peritonitis related to peritoneal dialysis in participants with diabetes, and higher rates of withdrawal from the study. 6% of participants in the honey group withdrew from the study because of

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