The Alliance for the Prudent Use of Antibiotics (APUA), an independent nonprofit organization dedicated to improving public health through more appropriate use of antibiotics and reduction of antibiotic resistance, commends the Center for Veterinary Medicine (CVM) on the Guidance for Industry and its efforts to protect the effectiveness of antibiotics for the treatment of human disease.
In the APUA FAAIR Report “The Need to Improve Antimicrobial Use in Agriculture: Ecological and Human Health Consequences,” published on June 1, 2002 as a Supplement to the journal Clinical Infectious Diseases, a panel of experts convened by APUA demonstrated that nontherapeutic use of antimicrobials in agriculture contributes to the emergence and spread of antimicrobial resistance in environmental bacteria, which can negatively impact human health. For this reason, APUA and its FAAIR Scientific Advisory Panel recommended that the use of antimicrobials for economic purposes such as growth promotion or feed efficiency should be discontinued (with the exception of ionophores and coccidiostats).
The impact of therapeutic and nontherapeutic antibiotic use can be direct, as in the case of transmission of resistant pathogens through the food supply, or indirect, as in the case of environmentally-mediated transfer of resistance elements to human pathogens. Risk assessment procedures should account for both direct and indirect human health effects of agricultural antimicrobial use.
Published risk assessments of antimicrobial use in agriculture are likely to underestimate risk to human health because they are subject to multiple limitations in scope, including a failure to consider ecological dimensions such as the cumulative nature of the selective pressure for resistance and cross-species plasmid transfer complicate the situation. The risk assessment process is also hampered by a lack of information on many crucial factors, most notably quantitative estimates of antimicrobial usage in agriculture as well as human and veterinary medicine.
APUA supports the ecological perspective demonstrated in this guidance document by consideration of resistance transfer as part of the assessment procedure. APUA also appreciates the conservative treatment of insufficient or unavailable information regarding a factor in the qualitative risk assessment. APUA would like to suggest that the CVM extend this conservative approach to proposed refinement of ‘medium’ risk estimations and the possible approval of ‘high’ risk drugs for NADA use. Considering that the indirect pathways for human exposure to resistance determinants or resistant bacteria that have emerged as a consequence of antimicrobial drug use in animals are not being considered in the proposed risk assessment, a conservative approach to any refinements of ‘medium’ or ‘high’ risks should be practiced in order to account for any uncertainties present in the underestimated risk estimations. APUA would also recommend a conservative integration of release, exposure, and consequence assessments for the risk estimation, particularly in cases where a high consequence assessment exists (see Table 3). APUA seeks further clarification on the categorization of antimicrobial drugs in terms of both their risk classification and risk management.
The qualitative approach to risk assessment described in this guidance document is less burdensome to industry than a quantitative approach, and it also allows for non-quantitative factors to play a role. Maintaining a consistently conservative approach to the qualitative estimates of risk will strengthen the assessment model by maintaining the importance of previous release and exposure assessments and accounting for any underestimation of risk. This would also be consistent with both the CVM’s stance on insufficient or unavailable information and its consideration of risk management steps for drugs of medium importance.
APUA values the ongoing efforts of CVM to consider potential effects on microbial ecology in assessing human health risk from antimicrobial use in agriculture. APUA will provide detailed comments in written form on Guidance #152 within the 75-day period of availability.
