gamithromycin and tilmicosin

The objective of this project was to evaluate the effects of antimicrobials approved for parenteral metaphylactic use in feeder and stocker calves on morbidity and mortality for bovine respiratory disease with the use of a mixed treatment comparison meta-analysis. An initial literature review was conducted in April 2016 through Pubmed, Agricola, and CAB (Commonwealth Agricultural Bureau) for randomized controlled trials for metaphylaxis antimicrobial administered parentally to incoming feedlot or stocker calves within 48 h of arrival. The final list of publications included 29 studies, with a total of 37 trials. There were 8 different metaphylactic antimicrobials. Final event outcomes were categorized into bovine respiratory disease (BRD) morbidity cumulative incidence d 1 to ≤ 60 of the feeding period, BRD morbidity cumulative incidence d 1 to closeout of the feeding period, BRD mortality cumulative incidence d 1 to closeout of the feeding period, and BRD retreatment cumulative incidence morbidity d 1 to closeout of the feeding period. Network meta-analysis combined direct and indirect evidence for all the event outcomes to determine mean odds ratio (OR) with 95% credibility intervals (CrIs) for all metaphylactic antimicrobial comparisons. The "upper tier" treatment arms for morbidity d 1 to ≤ 60 included tulathromycin, gamithromycin, and tilmicosin. For BRD mortality cumulative incidence d 1 to closeout and BRD retreatment morbidity d 1 to closeout, classifying the treatment arms into tiers was not possible due to overlapping 95% CrIs. The results of this project accurately identified differences between metaphylactic antimicrobials, and metaphylactic antimicrobial options appear to offer different outcomes on BRD morbidity and mortality odds in feedlot cattle.

Topics: Animals; Anti-Bacterial Agents; Bovine Respiratory Disease Complex; Cattle; Disaccharides; Heterocyclic Compounds; Incidence; Macrolides; Tylosin

Mycoplasma mycoides mycoides Small Colony (MmmSC) is the causative agent of contagious bovine pleuropneumonia (CBPP), which is responsible for major economic losses in sub-Saharan Africa. Current control relies on live attenuated vaccines, which are of limited efficacy, and antimicrobials are now being assessed as an alternative or adjunct to vaccination. The objective of this study was to determine the in vitro effector kinetics of the macrolide antimicrobial, gamithromycin, against MmmSC in artificial medium and adult bovine serum. Furthermore, it was determined if any differences in gamithromycin activity between these two matrices were mirrored by the older macrolides, tylosin and tilmicosin. Minimum inhibitory concentrations (MICs) for gamithromycin, tylosin and tilmicosin against MmmSC strains B237 and Tan8 were determined in artificial medium and serum. Time-kill curves were constructed at concentrations corresponding to multiples of the MIC for all three macrolides in artificial medium and for gamithromycin in serum. Data were fitted to sigmoid Emax models. Post-antibiotic effects (PAE) were established by exposing strain B237 to antimicrobials at 10× MIC for 1h and monitoring mycoplasma growth thereafter. MICs for gamithromycin, tylosin and tilmicosin were 64-, 8- and 64-fold lower, respectively, in serum than in artificial medium at an inoculum size of 10(6)cfu/mL B237. A similar pattern emerged for Tan8. All three antimicrobials were mycoplasmastatic with maximum effects of -0.44, -0.32 and -0.49log10(cfu/mL) units for gamithromycin, tylosin and tilmicosin, respectively, against B237 in artificial medium. Tylosin and tilmicosin elicited longer PAEs than gamithromycin. In conclusion, gamithromycin, tylosin and tilmicosin all demonstrated in vitro efficacy against MmmSC and represent potential candidates for clinical studies to assess their therapeutic effect against CBPP.

Topics: Anti-Bacterial Agents; Culture Media; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Macrolides; Microbial Sensitivity Tests; Mycoplasma mycoides; Tylosin