Abstract | BACKGROUND: RESULTS:
Gamithromycin was well absorbed and fully bioavailable (87.2-101%) after intramuscular and subcutaneous administrations. The MICs of gamithromycin for 192 clinical H. parasuis isolates ranged from 0.008 to 128 mg/L and the epidemiological cutoff (ECOFF) was calculated as 1.0 mg/L. A large potentiation effect of serum on in vitro susceptibility of gamithromycin was observed for H. parasuis, with broth/serum ratios of 8.93 for MICs and 4.46 for MBCs, respectively. The postantibiotic effects were 1.5 h (1 × MIC) and 2.4 h (4 × MIC), and the postantibiotic sub-MIC effects ranged from 2.7 to 4.3 h. Gamithromycin had rapid and concentration-dependent killing against H. parasuis, and the AUC24h/MIC ratio correlated well with ex vivo efficacy (R2 = 0.97). The AUC24h/MIC targets in serum associated with bacteriostatic, bactericidal and eradication activities were 15.8, 30.3 and 41.2, respectively. The PK/PD-based population dose prediction indicated a probability of target attainment (PTA) for the current marketed dose (6 mg/kg) of 88.9% against H. parasuis. The calculated gamithromycin dose for a PTA ≥ 90% was 6.55 mg/kg. Based on Monte Carlo simulations, the PK/PD cutoff ( COPD) was determined to be 0.25 mg/L. CONCLUSION: The determined cutoffs and PK/PD-based dose prediction will be of great importance in gamithromycin resistance surveillance and serve as an important step in the establishment of optimum dose regimen and clinical breakpoints.
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Authors | Yu-Feng Zhou, Ming-Xiao Bu, Ping Liu, Jian Sun, Ya-Hong Liu, Xiao-Ping Liao |
Journal | BMC veterinary research
(BMC Vet Res)
Vol. 16
Issue 1
Pg. 81
(Mar 05 2020)
ISSN: 1746-6148 [Electronic] England |
PMID | 32138735
(Publication Type: Journal Article)
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Chemical References |
- Anti-Bacterial Agents
- Macrolides
- gamithromycin
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Topics |
- Animals
- Anti-Bacterial Agents
(administration & dosage, pharmacokinetics, pharmacology)
- Area Under Curve
- Haemophilus Infections
(drug therapy, veterinary)
- Haemophilus parasuis
(drug effects)
- Injections, Intramuscular
(veterinary)
- Injections, Subcutaneous
(veterinary)
- Macrolides
(administration & dosage, pharmacokinetics, pharmacology)
- Male
- Microbial Sensitivity Tests
(veterinary)
- Sus scrofa
- Swine
- Swine Diseases
(drug therapy)
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