MEDICINE: INFECTIOUS DISEASES


Table 1. MIC Values for TMP-SDZ and TMP-SMZ Against Isolates of Streptococcus. equi subsp. zooepidemicus, S. equi subsp. equi, Corynebac- terial pseudotuberculosis and Actinobacillus equuli


S. zooepidemicus (282) S. equi (55)


A. equuli (46)


Organism (No. of Isolates) Antimicrobial* TMP-SDZa


TMP-SMZa TMP-SDZb TMP-SMZb


C. pseudotuberculosis (96) TMP-SDZ TMP-SMZ TMP-SDZ TMP-SMZ


0.12/2.4 101


243 21 50 95 95 43 43


No. of Isolates Susceptible at Each Antimicrobial Dilution (g/mL)* 0.25/4.75 175


0.5/9.5 4


37 33 5 1 1 2 2


1


1 1


*Mean MIC values for antimicrobials (TMP-SDZ and TMP-SMZ) identified with the same superscript letter are significantly different from each other (P  .001) for the bacterial species included in each row.


0.12/2.4 g/mL to 1/19 g/mL). For TMP-SDZ, 21 isolates had an MIC of 0.12/2.4 g/mL, 33 had an MIC of 0.25/4.75 g/mL, and 1 had an MIC of 0.5/9.5 g/mL (Table 1). For TMP-SMZ, 50 isolates had an MICof0.12/2.4g/mL and 5 had anMICof 0.25/4.75 g/mL. Twenty-three (42%) of the 55 S. equi isolates had the same MIC for both TMP-SDZ and TMP-SMZ, 33 (60%) had an MIC for TMP-SDZ that was one concentration higher than for TMP-SMZ and 1 (1.8%) had an MIC value for TMP-SMZ that was 1 concen- tration lower than for TMP-SMZ. Statistical analysis showed MIC values for TMP-SMZ to be significantly lower than those for TMP-SDZ (P  .0001). The


MIC50 and MIC90 for TMP-SDZ were both 0.25/4.75 g/mL, whereas the MIC50 and MIC90 for TMP-SMZ were both 0.12/2.4 g/mL.


A. equuli


All A. equuli isolates were highly susceptible to both TMP-SDZ and TMP-SMZ; MIC values ranged from 0.12/2.4g/mL to 0.5/9.5g/mL for both drug com- binations (Table 1). MIC values for TMP-SDZ were identical to those of TMP-SMZ. Forty-four of the 47 isolates (93.6%) had MIC values of 0.12/2.4 g/mL for both drug combinations, 2 isolates (4.3%) had MIC values of 0.25/4.75 g/mL and 1 isolate (2.1%) had an MIC value. of 0.5/9.5 g/mL. No significant differences were observed in MIC values between TMP-SDZ and TMP-SMZ.


C. pseudotuberculosis


All isolates of C. pseudotuberculosis were highly sus- ceptible to both TMP-SDZ and TMP-SMZ and the two drug combinations showed equal antimicrobial activ- ity (Table 1). The MIC value for 95 of 96 isolates was 0.12/2.4 g/mL for both TMP-SDZ and TMP-SMZ. The remaining isolate had an MIC value of 0.25/4.75


g/mL for both drug combinations. The MIC50 and MIC90 values were 0.12/2.4 g/mL for both TMP- SDZ and TMP-SMZ and no significant differences were observed between them.


4. Discussion The almost universal susceptibility of the commonly encountered equine bacterial pathogens tested in


434 2020  Vol. 66  AAEP PROCEEDINGS


this study to the potentiated sulfonamide antimicro- bials attests to their potential utility for treating a range of Gram-positive and Gram-negative bacterial infections in horses. Of the potentiated sulfon- amide antimicrobials, only the TMP-SDZ combina- tion is licensed for use in horses; the label indication being treatment of respiratory infection caused by S. zooepidemicus. In addition to the favorable pharmacokinetic profile of TMP-SDZ after oral ad- ministration to both adult horses and foals, the label indication is supported by the findings of this anti- microbial susceptibility study. Two hundred eighty-one of 282 (99.6%) S. zooepidemicus isolates were found to be susceptible to TMP-SDZ (MIC 2/38 g/mL). Of these, 276 (97.2%) were suscep- tible at concentrations  0.25/4.75 g/mL. Al- though statistical analysis using the Wilcoxon signed-rank test showed that MICs for TMP-SMZ were significantly lower than those for TMP-SDZ against S. zooepidemicus and S. equi, this difference was typically one dilution and is unlikely to be of clinical significance because the MIC was approxi- mately 10-fold lower than the cut-off for susceptibil- ity (2/38 g/mL). Additionally, those isolates that had MIC values greater than 0.25/4.75 g/mL for TMP-SDZ also had higher MIC values for TMP- SMZ. Furthermore, Diagnostic Laboratories rarely include concentrations lower than 0.5/9 g/mL in quantitative (MIC) susceptibility tests on clinical isolates or use the non-quantitative Kirby-Bauer test. Under these circumstances, reported suscep- tibility profiles for TMP-SDZ and TMP-SMZ would typically be identical. The above results do not support the extra-label


use of TMP-SMZ in preference to approved formu- lations of TMP-SDZ; in fact, such use of TMP-SMZ could be interpreted as violating the provisions of the AMDUCA and should be discouraged.


Acknowledgments


Declaration of Ethics The Authors have adhered to the Principles of Veter- inary Medical Ethics of the AVMA.


1.0/19 1


1 2.0/38


4.0/76 8.0/152 1


1


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