Medical honey for canine nasal intertrigo: A randomized, blinded, placebo-controlled, adaptive clinical trial to support antimicrobial stewardship in veterinary dermatology

Abstract

Intertrigo is a skin fold dermatitis often requiring recurrent treatment with topical antiseptics or antibiotics, which can select antimicrobial resistance. To minimize this risk, we tested the effectiveness of medical-grade Manuka honey at treating intertrigo as compared to a placebo hydrogel. We additionally characterized the culturable microbial flora of intertrigo and recorded any adverse effect with either treatment. During this randomized, placebo-controlled, double-blinded, adaptive group-sequential trial, the owners washed the affected sites on their dog with water, dried and applied a thin film of either the honey or the placebo product once daily for 21 days. Cytological and lesional composite scores, owner-assessed pruritus, and microbial cultures were assessed prior to treatment and on Day-22. The fixed effects of time, treatment, and animal-related variables on the pruritus and on each composite score, accounting for random dog effect, were estimated separately with generalized linear mixed models for repeated count outcomes (α = 0.05). The null hypothesis of equal treatment effects was rejected at the first interim analysis. The placebo (n = 16 dogs) outperformed the medical honey (n = 13 dogs) at improving both the cytological score (Treatment×Time = -0.35±0.17; P = 0.04) and clinical score (Treatment×Time = -0.28±0.13; P = 0.04). A microbial burden score higher than 4 increased the severity of the cytological score (dichotomous score: 0.29±0.11; P = 0.01), which in turn increased the severity of the clinical score and pruritus score. For every unit increase in cytological score, the linear predictor of clinical score increased by 0.042±0.019 (P = 0.03), and the one of pruritus score increased by 0.12±0.05 (P = 0.01). However, medical honey outperformed the placebo at alleviating the dog’s owner-assessed pruritus after statistically controlling for masking effects (Time = -0.94±0.24; P = 0.002; and Treatment×Time = 0.80±0.36; P = 0.04). Unilateral tests of the least-square mean estimates revealed that honey only significantly improved the pruritus (Hommel-adjusted P = 0.003), while the placebo only improved the cytological and clinical scores (Hommel-adjusted P = 0.01 and 0.002, respectively). Taken together, these results question the value of Manuka honey at treating nasal intertrigo in dogs.

Design and Medical Effects of a Vaginal Cleaning Device Generating Plasma-Activated Water with Antimicrobial Activity on Bacterial Vaginosis

“…In addition, the above clinical trials revealed no adverse effects due to our device. There was no case of symptoms such as itching, flaring, and warmth of the vulva as possible adverse effects on the skin [18][19][20]. Therefore, this clinical test confirmed the stability of our device, and the above results established its validity.…”

The standards of reporting trials in pets (PetSORT): Explanation and elaboration

“…Our secondary objectives were (2) to assess how each treatment affected the culturable microbial flora of nasal intertrigo, which is currently undefined, and (3) to record any adverse effect with either treatment." (30) "The purpose of this study was to compare a [bupivacaine liposome injectable suspension] with a control protocol in cats after ovariohysterectomy (OHE). The hypothesis was that a BLIS block would provide equivalent pain relief .…”