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c 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 (E max ) 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. Streptococcus suis is an important pathogen in the swine industry and causes significant economic losses worldwide. Moreover, it is an emerging zoonotic pathogen causing severe infection in people who have close contact with diseased pigs or pork-derived products (1, 2). To date, 35 serotypes based on S. suis capsular antigens have been described. S. suis serotype 2 is the most virulent and the dominant pathogenic serotype. It has been associated with a variety of severe clinical infections such as meningitis, septicemia, pneumonia, arthritis, and endocarditis in both pigs and humans (3, 4). Significant public health concerns were raised due to large outbreaks of S. suis 2 in humans that occurred in China in 1998 and 2005 that caused high morbidity and mortality (5). Because suitable vaccines were not available, the control of S. suis 2 infections depended almost entirely on the use of antimicrobials. However, the occurrence of high levels of resistance of S. suis to certain antimicrobials (e.g., macrolides, lincosamides, tetracyclines, and sulfonamides) has limited the choice of antimicrobial agents for treatment (6). It has previously been reported that the majority of S. suis strains are susceptible to ␤-lactams (MIC of Յ0.03 g/ml). This suggested that these drugs may be efficacious in the treatment of S. suis 2 infections (7).Cefquinome (CEQ) is a fourth-generation cephalosporin developed solely for veterinary use and has been highly effective against a wide variety of Gram-positive and Gram-negative bacteria (8). CEQ has also been tested and was shown to be effective in animals using a standard thig...

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