title: In Vivo Pharmacodynamics of Cefquinome in a Neutropenic Mouse Thigh Model of Streptococcus suis Serotype 2 at Varied Initial Inoculum Sizes.
abstract: Streptococcus suis serotype 2 is an emerging zoonotic pathogen and causes severe disease in both pigs and human beings. Cefquinome (CEQ), a fourth-generation cephalosporin, exhibits broad-spectrum activity against Gram-positive bacteria such as S. suis. This study evaluated the in vitro and in vivo antimicrobial activities of CEQ against four strains of S. suis serotype 2 in a murine neutropenic thigh infection model. We investigated the effect of varied inoculum sizes (10(6) to 10(8) CFU/thigh) on the pharmacokinetic (PK)/pharmacodynamic (PD) indices and magnitudes of a particular PK/PD index or dose required for efficacy. Dose fractionation studies included total CEQ doses ranging from 0.625 to 640 mg/kg/24 h. Data were analyzed via a maximum effect (Emax) model using nonlinear regression. The PK/PD studies demonstrated that the percentage of time that serum drug levels were above the MIC of free drug (%ƒT>MIC) in a 24-h dosing interval was the primary index driving the efficacy of both inoculum sizes (R(2) = 91% and R(2) = 63%). CEQ doses of 2.5 and 40 mg/kg body weight produced prolonged postantibiotic effects (PAEs) of 2.45 to 8.55 h. Inoculum sizes had a significant influence on CEQ efficacy. Compared to the CEQ exposure and dosages in tests using standard inocula, a 4-fold dose (P = 0.006) and a 2-fold exposure time (P = 0.01) were required for a 1-log kill using large inocula of 10(8) CFU/thigh.
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Chunna
authors.initials: C
authors.lastname: Guo
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, People's Republic of China Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liao
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Mingru
authors.initials: M
authors.lastname: Wang
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Yan
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, People's Republic of China Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Sun
authors.affiliation: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, People's Republic of China Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China Jiangsu Co-Innovation Centre for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, People's Republic of China lyh@scau.edu.cn.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000188:drug therapy / Q000382:microbiology*; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D017011:Streptococcus suis / Q000187:drug effects / Q000472:pathogenicity*; D013848:Thigh / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C068212:cefquinome