ArticlesAntibacterial honey for the prevention of peritoneal-dialysis-related infections (HONEYPOT): a randomised trial
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.
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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
References (33)
- et al.
Associations of dialysis modality and infectious mortality in incident dialysis patients in Australia and New Zealand
Am J Kidney Dis
(2009) - et al.
Antimicrobial agents to prevent peritonitis in peritoneal dialysis: a systematic review of randomized controlled trials
Am J Kidney Dis
(2004) - et al.
A randomized trial of Staphylococcus aureus prophylaxis in peritoneal dialysis patients: mupirocin calcium ointment 2% applied to the exit site versus cyclic oral rifampin
Am J Kidney Dis
(1996) - et al.
Mupirocin resistance after long-term use for Staphylococcus aureus colonization in patients undergoing chronic peritoneal dialysis
Am J Kidney Dis
(2002) - et al.
Global trends in rates of peritoneal dialysis
J Am Soc Nephrol
(2012) - et al.
Characteristics of dialysis important to patients and family caregivers: a mixed methods approach
Nephrol Dial Transplant
(2011) - et al.
Recent peritonitis associates with mortality among patients treated with peritoneal dialysis
J Am Soc Nephrol
(2012) - et al.
Microbiology and outcomes of peritonitis in Australian peritoneal dialysis patients
Perit Dial Int
(2011) Nasal mupirocin prevents Staphylococcus aureus exit-site infection during peritoneal dialysis
J Am Soc Nephrol
(1996)- et al.
Mupirocin for preventing exit-site infection and peritonitis in patients undergoing peritoneal dialysis
Nephrol Dial Transplant
(2010)
Prophylaxis against gram-positive organisms causing exit-site infection and peritonitis in continuous ambulatory peritoneal dialysis patients by applying mupirocin ointment at the catheter exit site
Perit Dial Int
Randomized, double-blind trial of antibiotic exit site cream for prevention of exit site infection in peritoneal dialysis patients
J Am Soc Nephrol
Evidence for peritonitis treatment and prophylaxis: prophylaxis for exit site/tunnel infections using mupirocin
Nephrology (Carlton)
ISPD–position statement on reducing the risks of peritoneal dialysis-related infections
Perit Dial Int
The effect on peritoneal dialysis pathogens of changing topical antibiotic prophylaxis
Perit Dial Int
The sensitivity to honey of Gram-positive cocci of clinical significance isolated from wounds
J Appl Microbiol
Cited by (74)
In vitro antibacterial activity of Western Australian honeys, and manuka honey, against bacteria implicated in impetigo
2022, Complementary Therapies in Clinical PracticeCitation Excerpt :However, honey has seldom been investigated in vivo for treating skin infections other than these. Investigation if topically applied honey as prophylaxis found that honey therapy did not differ significantly from standard therapy for either the time-to-infection for peritoneal dialysis patients or for skin colonisation at catheter exit sites, indicating no additional benefits over standard therapy [45,46]. In contrast, a study with healthy volunteers showed that the application of honey reduced the numbers of commensal bacteria on forearm skin by approximately 100-fold, indicating a potential benefit [47].
Trends in Adaptive Design Methods in Dialysis Clinical Trials: A Systematic Review
2021, Kidney MedicineCitation Excerpt :Tukey post hoc analysis revealed statistically significant differences between 2009 and 2013 (−5.96 [95% CI, −10.73 to −1.19]; P = 0.002); 2019 (−5.7 [95% CI, −10.36 to −1.04]; P = 0.003); 2018 (−5.62 [95% CI, −10.29 to −0.96]; P = 0.003), 2015 (−5.33 [95% CI, −10.21 to −0.45]; P = 0.02), 2020 (−5.07 [95% CI, −9.81 to −0.34]; P = 0.021]; and between 2014 and 2019 (−3.67 [95% CI, −6.69 to −0.65]; P = 0.003) and 2018 (−3.6 [95% CI, −6.62 to −0.58]; P = 0.004). Group sequential designs were the most common type of adaptive design method used; 35 (61.4%) trials (22 [71%] in dialysis populations and 13 [50%] in dialysis outcome trials; Table 124-65). The O’Brien-Fleming stopping boundary was the most common stopping rule, used in 9 trials (25.7%), followed by Lan DeMets, used in 8 trials (22.9%).
Peritoneal Dialysis Access Associated Infections
2019, Advances in Chronic Kidney DiseaseCitation Excerpt :Daily application of topical antibiotic preparations at the exit site has been associated with reduction in infection in small clinical trials.26-29 Commonly used exit site antibiotic regimens include mupirocin or gentamicin cream; polysporin and medicinal honey have similar efficacy to mupirocin, the former is associated with a higher risk of fungal exit site infection and peritonitis, and these 2 agents are not routinely recommended for use.30,31 It should be noted that a recent review and meta-analysis did not reveal strong evidence for routine antibiotic application at the exit site.12