Postantibiotic and physiological effects of tilmicosin, tylosin, and apramycin at subminimal and suprainhibitory concentrations on some swine and bovine respiratory tract pathogens

The antimicrobial activity of tilmicosin, tylosin, and apramycin on some im portant gram-negative swine and bovine pathogens namely, Pasteurella multoc ida, Pasteurella haemolytica, Bordetella bronchiseptica, and Actinobacillus pleuropneumoniae were studied in vitro. The effect of minimal inhibitory c oncentrations (MICs) and sub-MICs (1/4, 1/2 MIC) on bacterial growth was ev aluated. The presence of tilmicosin, tylosin and apramycin in the medium de creased the rate of growth of the bacterial strains tested using drug conce ntrations as low as 1/4 MIC. The postantibiotic effect (PAE) which is the s uppression of optimal bacterial growth that persists after a short exposure (2 h) of microorganisms to an antibiotic was studied by exposure of bacter ia to drugs at 1/4, 1/2, 1, 4 and 8 times MIC. The duration of PAEs increas ed with rising concentration for all drugs tested but at concentrations bel ow the MIC, tilmicosin showed more significant PAEs than tylosin or apramyc in against P. multocida and A. pleuropneumoniae. Tilmicosin and tylosin cau sed PAEs of up to 8 h when used at 8 times the MIC, while apramycin caused PAEs of up to 5 h when used at this concentration. Sub-MICs of either tilmi cosin. tylosin, or apramycin had no effect on P. multocida dermonecrotic to xin production. However sub-MICs of tylosin, or apramycin significantly red uced the haemolytic activity of A. pleuropneumoniae and affected the capsul ar material production of this isolate and of one isolate of P. multocida ( type A). The in vitro effect of tilmicosin, tylosin, and apramycin (even wh en used at sub-MIC levels) on growth, production of capsular material, and haemolytic activity might impair the virulence of some of the microorganism s studied. In addition to the effects of these drugs on some putative virul ence factors, we suggest that the strong PAEs caused by tilmicosin, tylosin , and apramycin may also contribute to the in vivo efficacy of these drugs. (C) 1999 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.