The intramammary efficacy of first generation cephalosporins against Staphylococcus aureus mastitis in mice Dieter Demon a, *, Carolin Ludwig b , Koen Breyne a , David Gue ´ de ´ c , Julia-Charlotte Do ¨ rner b , Robrecht Froyman b , Evelyne Meyer a a Laboratory of Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium b Bayer Animal Health GmbH, Global Drug Discovery Anti-infectives, 51368 Leverkusen, Germany c ClinBAY sprl, B-1470 Baisy-Thy, Belgium 1. Introduction Mastitis provokes detrimental damage to epithelial cells. Hence, it jeopardizes milk production and entails prohibitive costs in the dairy industry (Piepers et al., 2007). Staphylococcus aureus is historically one of the most important causes of subclinical mastitis and clinical mastitis that becomes chronic (Piepers et al., 2007; Tenhagen et al., 2009). Despite intensive research and multiple preventive measures (NMC, 2006), the dairy industry has not managed to eradicate S. aureus mastitis (Zadoks and Fitzpatrick, 2009). So, antimicrobial therapy remains an essential component of staphylococcal mastitis control programs. The major concern with S. aureus infections is that once established they are extremely difficult to eradicate from the mammary gland. Although S. aureus is susceptible to numerous antibiotics in vitro (Erskine et al., 2002; EUCAST, 2011), this pathogen has Veterinary Microbiology 160 (2012) 141–150 A R T I C L E I N F O Article history: Received 4 January 2012 Received in revised form 19 March 2012 Accepted 11 May 2012 Keywords: Mastitis Mouse model Antimicrobials S. aureus Mammary gland A B S T R A C T Staphylococcus aureus-induced mastitis in cattle causes important financial losses in the dairy industry due to lower yield and bad milk quality. Although S. aureus is susceptible to many antimicrobials in vitro, treatment often fails to cure the infected udder. Hence, comprehensive evaluation of antimicrobials against S. aureus mastitis is desirable to direct treatment strategies. The mouse mastitis model is an elegant tool to evaluate antimicrobials in vivo while circumventing the high costs associated with bovine experiments. An evaluation of the antimicrobial efficacy of the intramammary (imam) applied first generation cephalosporins cefalexin, cefalonium, cefapirin and cefazolin, was performed using the S. aureus mouse mastitis model. In vivo determination of the effective dose 2log 10 (ED 2log10 ), ED 4log10 , protective dose 50 (PD 50 ) and PD 100 in mouse mastitis studies, support that in vitro MIC data of the cephalosporins did not fully concur with the in vivo clinical outcome. Cefazolin was shown to be the most efficacious first generation cephalosporin to treat S. aureus mastitis whereas the MIC data indicate that cefalonium and cefapirin were more active in vitro. Changing the excipient for imam application from mineral oil to miglyol 812 further improved the antimicrobial efficacy of cefazolin, confirming that the excipient can influence the in vivo efficacy. Additionally, statistical analysis of the variation of S. aureus-infected, excipient-treated mice from fourteen studies emphasizes the strength of the mouse mastitis model as a fast, cost-effective and highly reproducible screening tool to assess the efficacy of antimicrobial compounds against intramammary S. aureus infection. ß 2012 Elsevier B.V. All rights reserved. * Corresponding author. Tel.: +32 9 264 75 27; fax: +32 264 74 97. E-mail addresses: Dieter.Demon@ugent.be (D. Demon), Carolin.Ludwig1@bayer.com (C. Ludwig), Koen.Breyne@ugent.be (K. Breyne), David@clinbay.com (D. Gue ´de ´), Juliacharlotte.Doerner@bayer.com (J.-C. Do ¨ rner), Robrecht.Froyman@bayer.com (R. Froyman), Evelyne.Meyer@ugent.be (E. Meyer). Contents lists available at SciVerse ScienceDirect Veterinary Microbiology jo u rn al ho m epag e: ww w.els evier.c o m/lo cat e/vetmic 0378-1135/$ – see front matter ß 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.vetmic.2012.05.017