Caprine abscess model of tulathromycin concentrations in interstitial fluid from tissue chambers inoculated with Corynebacterium pseudotuberculosis following subcutaneous or intrachamber administration

Abstract

Corynebacterium pseudotuberculosis causes chronic, suppurative, abscessing conditions in livestock and humans. We used an in vivo model to evaluate antimicrobial efficacy for focal abscesses caused by C. pseudotuberculosis. Tissue chambers were surgically implanted in the subcutaneous tissues of the right and left paralumbar fossa of 12 goats to serve as a model for isolated, focal abscesses. For each goat, one tissue chamber was inoculated with C. pseudotuberculosis, while the contralateral chamber served as an uninoculated control. Six goats were administered a single dose of tulathromycin at 2.5 mg/kg of body weight subcutaneously, while the other six received the same dose by injection directly into the inoculated chambers. Our objective was to compare the effects and tulathromycin concentrations in interstitial fluid (IF) samples collected from C. pseudotuberculosis-infected and control chambers following subcutaneous or intrachamber injection of tulathromycin. In addition, the effects of tulathromycin on the quantity of C. pseudotuberculosis reisolated from inoculated chambers were assessed over time. Tulathromycin IF concentrations from C. pseudotuberculosis-infected and control tissue chambers were similar to those in plasma following subcutaneous administration. Following intrachamber administration, tulathromycin IF concentrations in infected chambers were continuously above the MIC for the C. pseudotuberculosis isolate for 15 days. There were no significant differences for plasma area under the curve and elimination half-lives between subcutaneous and intrachamber administration. Six of the 12 infected chambers had no growth of C. pseudotuberculosis 15 days postadministration. Results of this study indicate that tulathromycin may be beneficial in the treatment of focal infections such as those caused by C. pseudotuberculosis.

Fig 1

(A) Unassembled and assembled tissue chambers to be surgically implanted into the paralumbar fossa of goats; (B) surgically implanted tissue chambers in the right and left paralumbar fossa serving as an abscess model.

Fig 2

Tulathromycin concentrations in plasma samples drawn from adult goats following subcutaneous administration (n = 6; SC plasma) or intrachamber (n = 6; IC plasma) injections of 2.5 mg tulathromycin/kg body weight (error bars are standard deviations).

Fig 3

Tissue chamber interstitial fluid tulathromycin concentrations following subcutaneous (n = 6 goats; SC) or intrachamber (n = 6 goats; IC) administration of 2.5 mg/kg tulathromycin to adult goats. There were 6 animals sampled for all routes and sampling sites, with the exception of s.c. right chamber, for which one outlier was removed due to unexpectedly high concentrations. All but one animal was infected on the left side prior to s.c. drug administration, and all animals were infected on the right side prior to i.c. drug administration. CBPTB, Corynebacterium pseudotuberculosis. The horizontal line represents the MIC of the strain of C. pseudotuberculosis used to induce infection.

Fig 4

Concentrations of tulathromycin in plasma and interstitial fluid collected from uninfected tissue chambers after adult goats (n = 6) were injected with tulathromycin at a dose of 2.5 mg/kg subcutaneously (SC) (error bars are standard deviations).

Fig 5

Concentrations of tulathromycin in plasma and interstitial fluid collected from uninfected tissue chambers from adult goats (n = 6) after direct injection of 2.5 mg/kg body weight of tulathromycin into surgically implanted infected tissue chambers in the paralumbar fossae of adult goats (error bars are standard deviations).

Fig 6

CFU of Corynebacterium pseudotuberculosis over time. Samples were drawn from surgically implanted infected tissue chambers following administration of 2.5 mg/kg tulathromycin subcutaneously (n = 6) or via intrachamber injection (n = 6) to adult goats (error bars are standard deviations).

Fig 7

Summary of blinded histopathology scores for Corynebacterium pseudotuberculosis-inoculated and uninoculated control chamber-associated subcutaneous tissues and draining lymph nodes from adult goats. Pathological changes in the subcutaneous tissues (A and B) and draining lymph nodes (C and D) were determined 14 days after administration of 2.5 mg/kg tulathromycin subcutaneously (A and C) or via intrachamber injection (B and D). Total bar height represents the total score of an individual tissue.