In vitro susceptibility of some porcine respiratory tract pathogens to aditoprim, trimethoprim, sulfadimethoxine, sulfamethoxazole, and combinations of these agents

M. J. B. Mengelers From the Department of Toxicology, State Institute for Quality Control of Agricultural Products, Wageningen, The Netherlands (Mengelers), the Department of Chemotherapy, National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven, The Netherlands (van Klingeren), and the Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, State University of Utrecht, Utrecht, The Netherlands (van Miert).

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B. van Klingeren From the Department of Toxicology, State Institute for Quality Control of Agricultural Products, Wageningen, The Netherlands (Mengelers), the Department of Chemotherapy, National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven, The Netherlands (van Klingeren), and the Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, State University of Utrecht, Utrecht, The Netherlands (van Miert).

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A. S. J. P. A. M. van Miert From the Department of Toxicology, State Institute for Quality Control of Agricultural Products, Wageningen, The Netherlands (Mengelers), the Department of Chemotherapy, National Institute of Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven, The Netherlands (van Klingeren), and the Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, State University of Utrecht, Utrecht, The Netherlands (van Miert).

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SUMMARY

The in vitro antimicrobial activities of aditoprim (ap), a new dihydrofolate reductase (dhfr) inhibitor, trimethoprim (tmp), sulfadimethoxine (sdm), sulfamethoxazole (smx), and combinations of these drugs against some porcine respiratory tract pathogens were determined by use of an agar dilution method. The minimal inhibitory concentrations (mic) of these agents were determined twice against Bordetella bronchiseptica (n = 10), Pasteurella multocida (n = 10), and Actinobacillus pleuropneumoniae (n = 20) strains isolated from pigs suffering from atrophic rhinitis or pleuropneumonia.

All B bronchiseptica strains were resistant to ap and tmp. The mic50 values of ap and tmp for P multocida were 0.25 and 0.06 μg/ml, respectively, and for A pleuropneumoniae, 1 and 0.25 μg/ml, respectively. The mic50 values of sdm and smx for B bronchiseptica were 4 and 1 μg/ml, respectively; for P multocida, 16 and 8 μg/ml, respectively; and for A pleuropneumoniae, 16 and 8 μg/ml, respectively.

The investigated combinations of the dhfr inhibitors and the selected sulfonamides had synergism for the A pleuropneumoniae strains; the mic90 values of the combinations were ≤ 0.06 μg/ml. Potentiation was not observed for the B bronchiseptica and the P multocida isolates. The mic of the combinations against B bronchiseptica and P multocida corresponded respectively to the concentrations of the sulfonamides and the dhfr inhibitors in the combinations.

For A pleuropneumoniae, 2 types of strains were used (25% of serotype 2 and 75% of serotype 9). Type-2 strains had lower susceptibility than type - 9 strains to ap and tmp as well as to sdm and smx (at least a fourfold difference in mic between the 2 types of strains). The mic of the combinations were similar for the 2 types of strains.

SUMMARY

The in vitro antimicrobial activities of aditoprim (ap), a new dihydrofolate reductase (dhfr) inhibitor, trimethoprim (tmp), sulfadimethoxine (sdm), sulfamethoxazole (smx), and combinations of these drugs against some porcine respiratory tract pathogens were determined by use of an agar dilution method. The minimal inhibitory concentrations (mic) of these agents were determined twice against Bordetella bronchiseptica (n = 10), Pasteurella multocida (n = 10), and Actinobacillus pleuropneumoniae (n = 20) strains isolated from pigs suffering from atrophic rhinitis or pleuropneumonia.

All B bronchiseptica strains were resistant to ap and tmp. The mic50 values of ap and tmp for P multocida were 0.25 and 0.06 μg/ml, respectively, and for A pleuropneumoniae, 1 and 0.25 μg/ml, respectively. The mic50 values of sdm and smx for B bronchiseptica were 4 and 1 μg/ml, respectively; for P multocida, 16 and 8 μg/ml, respectively; and for A pleuropneumoniae, 16 and 8 μg/ml, respectively.

The investigated combinations of the dhfr inhibitors and the selected sulfonamides had synergism for the A pleuropneumoniae strains; the mic90 values of the combinations were ≤ 0.06 μg/ml. Potentiation was not observed for the B bronchiseptica and the P multocida isolates. The mic of the combinations against B bronchiseptica and P multocida corresponded respectively to the concentrations of the sulfonamides and the dhfr inhibitors in the combinations.

For A pleuropneumoniae, 2 types of strains were used (25% of serotype 2 and 75% of serotype 9). Type-2 strains had lower susceptibility than type - 9 strains to ap and tmp as well as to sdm and smx (at least a fourfold difference in mic between the 2 types of strains). The mic of the combinations were similar for the 2 types of strains.

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