Macrolide antibiotics (kitasamycin, oleandomycin and tylosin) chemical review

In September 1999, selected macrolide antibiotics (kitasamycin, oleandomycin and tylosin) were nominated for review because of concerns about their efficacy and their possible contribution to the development of antibiotic resistance in human medicine. This action was based on advice from the Joint Expert Advisory Committee on Antibiotic Resistance, which identified antibiotics used as growth promotants and for prophylactic purposes in food-producing animals as warranting review.

In December 2001, the APVMA began a review of selected macrolide antibiotics because of concerns about the potential risk to human health. 

The reconsideration will focus on the use of macrolide antibiotic growth promotants in relation to their possible contribution to the development of antibiotic resistance in human medicine, as recommended by the Joint Expert Advisory Committee on Antibiotic Resistance (JETACAR).

The work plan is available in the publication archive tab.

The APVMA sent Notices of reconsideration of macrolide antibiotics in 2001 to the registration holders of the affected products. Additional Notices sent to registration holders on 16 August 2017 and 9 November 2017 to include all registered products in the review.

The APVMA also published a Notice for the reconsideration of the macrolide antibiotics kitasamycin, oleandomycin and tylosin calling for public submissions to the review.

Public health assessment

In 2003 the APVMA commissioned a review of publicly available scientific literature relating to antimicrobial resistance and macrolides. This assessment found that although there was qualitative evidence that antimicrobial use in animals can lead to resistance in bacteria or to their resistance genes being passed to humans via the food chain, there were no reports recording the specific transfer of macrolide resistance, from animals to humans, in Campylobacter spp. and Enterococci spp., two food-borne bacterial genera of concern in the context of macrolide antibiotics.

 The APVMA also reviewed a quantitative risk assessment of tylosin prepared by a registrant in 2005. The risk assessment was not comprehensive enough to determine that the likelihood of developing resistance to macrolide was very low, as concluded in the risk assessment report.

In 2013 the APVMA commissioned an assessment of sub-therapeutic administration of tylosin to food-producing animals and its impact on antimicrobial resistance. This concluded that the sub-therapeutic use of tylosin will encourage the emergence and maintenance of resistant strains not only to tylosin but also to the more important related veterinary macrolides.

Efficacy

APVMA commissioned an assessment of the efficacy studies submitted to the review. This assessment concluded that kitasamycin is efficacious in improving average daily weight gain in pigs between 4.7 kg and 35 kg. Tylosin has been shown to be effective in improving average weight gain in pigs under a range of conditions, although its effect on food conversion efficiency appears to be more variable. Tylosin, at labelled doses, has a significant effect on susceptible disease agents including Brachyspira hyodysentriae, Lawsonia intracellularis, Mycoplasma hyopneumoniae, Erysipelothrix rhusiopathiae and Actinobacillus pleuropneumoniae, which may explain the positive effect of tylosin on weight gain and food conversion efficiency. Tylosin has also been shown to control liver abscessation in feedlot cattle. No data supporting the claims of efficacy of oleandomycin were provided for this review.

Scheduling committee decision

At the commencement of the review in 2001, products containing 50 ppm or less of tylosin were classified in Schedule 5 of the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) and could be sold in retail outlets without a veterinary prescription. From 1 June 2014, all registered macrolide products were classified in Schedule 4 of the SUSMP, meaning that such products can only be supplied through veterinary prescription.

On 30 November 2017 the macrolide antibiotics (kitasamycin, oleandomycin and tylocin) Proposed Regulatory Decisions report was published for a consultation period of three months (refer to Phase 7 Consultation for more information).

The APVMA invited comment on the macrolide antibiotics (kitasamycin, oleandomycin and tylocin) Proposed Regulatory Decisions report from 30 November 2017 to 28 February 2018. Submissions closed COB Wednesday 28 February 2018.

A total of eight submissions were received. The information in these submissions has been assessed by the APVMA and considered as part of the final decisions for the review of macrolide antibiotics.

The review of product registrations and label approvals of the macrolide antibiotics kitasamycin, oleandomycin and tylosin was completed on 28 March 2018. The APVMA published the macrolide antibiotics regulatory decisions report on 6 April 2018.

The APVMA has:

1. Varied relevant particulars of registrations and label approvals of selected products to:

• Delete product claims and associated use instructions for growth promotion and improved feed conversion efficiency (in pigs)
• Add a restraint statement to require the prudent use of the antimicrobials

1. Affirmed these product registrations and label approvals
2. Cancelled all previous product label approvals that are not consistent with the review outcomes and
3. Cancelled the registrations and associated label approvals of the product VET ONLY TRUBIN L-50 GROWTH PROMOTANT FOR PIGS (35806).

The review of macrolide antibiotics has been completed.

The APVMA has determined that one-year period ending 29 March 2019 is appropriate for the continued supply and use of registered products bearing cancelled labels, as well as the supply and use of product being cancelled. During this period, products may continue to be used according to the earlier approved label instructions. After this period all products supplied should bear a currently approved label.