Effects of clarithromycin, azithromycin and rifampicin on terbutaline‐induced sweating in foals

Stewart, Amy Stieler; Sanchez, L. Chris; Mallicote, Martha; Muniz, A. V. C. da S.; Westerterp, Marit; Burrow, J. A.; MacKay, Robert J.

doi:10.1111/evj.12677

Cited by 13 publications

(18 citation statements)

References 19 publications

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“…An additional concern about use of macrolides and azalides in foals is the induction of hyperthermia during treatment, a significant adverse effect that can lead to morbidity and mortality in already compromised and febrile foals. The mechanism of hyperthermia has been investigated, and it was found that the macrolides induce anhidrosis in foals (Stieler Stewart et al, 2016, 2017). Erythromycin is the most potent at inducing anhidrosis; however, azithromycin and clarithromycin also suppressed sweating.…”

Section: Introductionmentioning

confidence: 99%

Equine antimicrobial therapy: Current and past issues facing practitioners

Knych

Magdesian

2021

Vet Pharm & Therapeutics

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Equine antimicrobial therapy has advanced over time with the availability of increasing pharmacokinetic and pharmacodynamic studies in horses, allowing for greater evidence‐based clinical decision‐making. However, many challenges to optimal antimicrobial therapy remain and further research is needed to address these areas. There are a limited number of approved antimicrobials for use in horses, which creates a need for compounded preparations for clinicians. Extra‐label drug use is commonplace in equine practice, which warrants continual education of veterinarians about policies and updates. Performance and competitive horses have their own unique concerns when it comes to antimicrobial use and drug testing. In keeping with the use of a broader range of antimicrobials over time, antimicrobial resistance is emerging as an important issue facing veterinary medicine, including equine practice. Another challenge is that of drug interactions and adverse drug events for which there are little scientific data available for horses, especially for critically important diseases such as Rhodococcus equi infection. Finally, much progress has been made in the availability of equine‐specific antimicrobial susceptibility break points. These aid clinicians in interpreting culture and susceptibility results and antimicrobial selection. Even with these advances, continuing education and further research are needed in this area.

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Section: Introductionmentioning

confidence: 99%

Equine antimicrobial therapy: Current and past issues facing practitioners

Knych

Magdesian

2021

Vet Pharm & Therapeutics

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“…Foals with rectal temperatures above 39.4 °C were hosed down and kept under fans until their temperature dropped below 38.9 °C. It was previously noted that environmental effects did not significantly affect sweat response for different macrolide treatments [19]. Still, to decrease the odds of heat shock, ambient environmental temperature and relative humidity data were collected each time days 5 to 10-foals remain in stalls during period of hyperthermia risk; days 10 to foals and their dams taken from stalls and kept in small pasture enclosures (Figur days 1, 2, 5, 9, 24, 39-QITSTs to establish the quantitative profiles for induction of recovery from, anhidrosis.…”

Section: Experimental Animals and Designmentioning

confidence: 95%

Ion Channel and Ubiquitin Differential Expression during Erythromycin-Induced Anhidrosis in Foals

Rosa

Mallicote

MacKay

et al. 2021

Animals

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Macrolide drugs are the treatment of choice for Rhodococcus equi infections, despite severe side-effects temporary anhidrosis as a. To better understand the molecular biology leading to macrolide induced anhidrosis, we performed skin biopsies and Quantitative Intradermal Terbutaline Sweat Tests (QITSTs) in six healthy pony-cross foals for three different timepoints during erythromycin administration—pre-treatment (baseline), during anhidrosis and post-recovery. RNA sequencing of biopsies followed by differential gene expression analysis compared both pre and post normal sweating timepoints to the erythromycin induced anhidrosis episode. After Bonferroni correction for multiple testing, 132 gene transcripts were significantly differentially expressed during the anhidrotic timepoint. Gene ontology analysis of the full differentially expressed gene set identified over-represented biological functions for ubiquitination and ion-channel function, both biologically relevant to sweat production. These same mechanisms were previously implicated in heritable equine idiopathic anhidrosis and sweat gland function and their involvement in macrolide-induced temporary anhidrosis warrants further investigation.

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“…Oral macrolide administration, particularly with erythromycin, has reported adverse side effects such as diarrhoea, and hyperthermia due to induced anhidrosis. Clarithromycin and azithromycin have also been found to suppress sweating, albeit to a lesser degree than erythromycin, in a quantitative terbutaline sweat test challenge in normal foals . The sweat suppressing effects of these macrolides was not substantially affected by concurrent administration of rifampicin .…”

Section: Judicious Use Of Macrolide Antibioticsmentioning

confidence: 95%

“…Clarithromycin and azithromycin have also been found to suppress sweating, albeit to a lesser degree than erythromycin, in a quantitative terbutaline sweat test challenge in normal foals . The sweat suppressing effects of these macrolides was not substantially affected by concurrent administration of rifampicin . Future considerations for decreasing antimicrobial use for the treatment of R. equi in foals may involve passive or active immune stimulation.…”

Section: Judicious Use Of Macrolide Antibioticsmentioning

confidence: 98%

Clinical insights: Antimicrobials in an age of resistance

Mercer

Davis

2019

Equine Veterinary Journal

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Antimicrobial-resistant bacteria cause at least 700,000 human deaths per year according to the World Health Organization [1]. The veterinary field remains a relatively minor contributor to the development of antimicrobial resistance, and significant morbidity and mortality associated with antimicrobial resistance remains relatively limited in companion and food animals. However, the risk of antimicrobial-resistant determinants travelling among bacteria, animals and humans through the food chain, direct contact and environmental contamination has made the issue of judicious antimicrobial use in the veterinary field a trending topic both among lawmakers and human healthcare professionals. Reliable estimates for equine morbidity and mortality relating to infection with antimicrobial-resistant bacteria are not yet available. However, cases doubtless occur and the most significant threat to both human and equine populations is multidrug-resistant (MDR) pathogens, including methicillin resistant Staphylococcus aureus (MRSA), extended spectrum betalactamase (ESBL) producing Escherichia coli, MDR Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, and rising MDR strains of Salmonella spp. and Clostridium difficile. Veterinarians and their staff carry a higher risk of MRSA colonisation compared to the general population, and nosocomial MRSA infections have been reported in equine hospitals resulting in patient morbidity and significant financial losses [2]. In an analysis of 12,695 antibiograms in France between 2012 and 2016, the highest proportion (22.5%) of MDR-resistant isolates was S. aureus [3]. Carriage and isolation of ESBL E. coli strains that are resistant to all available antimicrobial classes has increased markedly in horses, and are being seen as a rising cause of nosocomial disease in equine hospitals [2]. In a sampling of healthy adult horses at 41 premises in France in 2015, 44% of horses sampled shed MDR-resistant E. coli, with 29% of premises shedding ESBL isolates [4]. Resistance to even 'reserved' classes of antimicrobials has been reported in equine and canine Salmonella isolates, such as the fluoroquinolone-resistant serovar ST198 as well as ESBL and ceftiofur-resistant strains [2]. Macrolide and rifampicin-resistant strains of R. equi have been demonstrated in farms in the United States, and an increasing prevalence has been noted in Kentucky over the period of 2007-2017 compared with the period 1995-2006 [5]. Antimicrobial use is critical to the practice of veterinary medicine and safeguarding animal welfare; however, inappropriate antimicrobial use in equine and companion animal practice may lead the industry to face legislative regulations on par with food animal practices. The World Health Organization has identified five classes of antimicrobials, later generation cephalosporins, glycopeptides, macrolides, polymyxins and quinolones, as being critically important, and therefore reserved, antimicrobials in human medicine [1]. In a recent review of prescribing behaviour of three '...

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Effects of clarithromycin, azithromycin and rifampicin on terbutaline‐induced sweating in foals

Abstract: All macrolides commonly used to treat R. equi pneumonia, i.e. ERY, AZI and CLA, induce anhidrosis in foals. The potent anti-sudorific effect of ERY is delayed, but not substantially affected by concurrent RIF administration.

Cited by 13 publications

References 19 publications

Equine antimicrobial therapy: Current and past issues facing practitioners

Equine antimicrobial therapy: Current and past issues facing practitioners

Ion Channel and Ubiquitin Differential Expression during Erythromycin-Induced Anhidrosis in Foals

Clinical insights: Antimicrobials in an age of resistance

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