Efficacies of ceftobiprole medocaril and comparators in a rabbit model of osteomyelitis due to methicillin-resistant Staphylococcus aureus.

The pharmacokinetics and distribution into bone tissue of ceftobiprole in uninfected New Zealand White rabbits were determined after subcutaneous administration of the prodrug ceftobiprole medocaril. Serum exposure (maximum concentration of the drug in serum, trough concentration, area under the concentration-time curve) to ceftobiprole at 20 and 80 mg/kg was dose proportional, and there was no accumulation of ceftobiprole following repeated (every 6 h [q6h]) injections of the antibiotic. Ceftobiprole titers in the tibial matrix and marrow were 3.2 +/- 1.3 microg/g and 11.2 +/- 6.5 microg/g, respectively, in uninfected animals treated with 20 mg/kg of the antibiotic and 13.4 +/- 7.3 microg/g and 66.3 +/- 43.2 microg/g, respectively, in uninfected animals treated with 80 mg/kg of the antibiotic. No differences in ceftobiprole titers were observed between right and left tibiae for either bone matrix or marrow. The efficacies of 4 weeks of treatment with ceftobiprole (40 mg/kg administered subcutaneously [s.c.] q6h), vancomycin (30 mg/kg administered s.c. q12h), or linezolid (60 mg/kg administered orally q8h) were compared, using a rabbit model of methicillin-resistant Staphylococcus aureus tibial osteomyelitis. After treatment with ceftobiprole, the bacterial titers in all infected left tibiae from evaluable rabbits were below the level of detection, whereas only 73% of infected left tibiae from vancomycin- or linezolid-treated animals had bacterial titers below the level of detection; the mean titers of ceftobiprole were 3 to 5 times higher in infected left tibiae than in uninfected right tibiae. These results indicate that ceftobiprole provided effective parenteral treatment of osteomyelitis in this rabbit model.

The role of atopy in corneal graft survival in keratoconus.

PURPOSE: To compare the prevalence of endothelial rejection episodes and the probability of graft survival after initial and repeat penetrating keratoplasty (PK) in patients with keratoconus with and without atopy. METHODS: A retrospective review was conducted of all patients receiving PK for keratoconus at the University of Texas Southwestern Medical Center at Dallas from 1988 to 2009. Inclusion criteria involved those with both an International Classification of Diseases-9 code for keratoconus and a Current Procedural Terminology code for PK based on a computer database search. Patients younger than 18 years were excluded. These records were then reviewed for a history of atopic disorders. The main outcome measures included the prevalence of endothelial rejection episodes and the probability of graft survival. The probability of corneal graft survival in patients with and without a history of atopy was compared using the Kaplan-Meier method. RESULTS: There were 168 grafts in 122 patients. There were 66 (39.2%) and 102 (60.8%) grafts with and without a history of atopy, respectively. Bilateral first grafts were required in 32 patients, 14 and 18 patients with and without a history of atopy, respectively. The atopic and nonatopic groups had no significant differences with respect to age, preexisting ocular conditions, concomitant surgical procedures, and length of follow-up. Men received first grafts significantly more frequently than women in the nonatopic group (P = 0.029); however, there was no sex difference in repeat grafts. There were no significant differences in the prevalence of endothelial rejection episodes after the first (P = 0.716), second (P > 0.999), and third or further grafts (P > 0.999). Graft survival between the atopic and nonatopic groups did not differ significantly in the first (P = 0.881), second (P = 0.752), or third or further graft (P = 0.157). Among first grafts in the atopic group, no statistically significant difference in survival existed among patients analyzed with different manifestations of atopy (P = 0.061). One episode of allograft endothelial rejection created a statistically significant difference in ultimate graft survival probability in both the atopic (P = 0.003) and nonatopic (P = 0.002) groups. CONCLUSIONS: Among patients with keratoconus receiving PK, there is no statistically significant difference in the prevalence of endothelial graft rejection episodes or probability of graft survival between patients with and without a clinical history of atopy.