caa a22 4500 397591551 CHVBK 20180308164940.0 cr unu---uuuuu 161202e199610 xx s 000 0 eng 10.1093/jac/38.4.655 doi (NATIONALLICENCE)oxford-10.1093/jac/38.4.655 In-vivo activity and phannacodynamics of cefotaxime in combination with vancomycin in fibrin clots infected with highly penicillin-resistant Streptococcus pneumoniae [Elektronische Daten] [Pascal Chavanet, Dominique Champliaud, André Pechinot, Marielle Buisson, Michel Duong, Catherine Neuwirth, Antoine Kazmierczak, Henri Portier] We studied the antipneumococcal efficacy of cefotaxime and vancomycin alone and a combination of cefotaxime with various dosages of vancomycin in the treatment of prolonged (48 h) experimental fibrin clot infections in rabbits. A clinical pneumococcal strain for which MICs were 2, 0.5 and 0.5 mg/L of penicillin, cefotaxime and vancomycin respectively, was used in this study. Cefotaxime was given iv at a fixed dose of 50 mg/kg and vancomycin iv at 1, 2.5, 5, 10 or 20 mg/kg. Maximal concentrations in clots were (mean ± S.D.): 2.1 ± 0.9, 1.1 ± 0.4, 1.9 ± 1, 2.3 ± 1.5, 3.6 ± 0.4 and 4 ± 0.3 mg/g, respectively. The mean half-lives of elimination from clots were 2.2 h for cefotaxime and 7 h for vancomycin. We observed the highest bacterial reductions for the highest doses of vancomycin with or without cefotaxime. The combination of intermediate doses of vancomycin with cefotaxime led to higher antibacterial effects than either monotherapy. The low dose of vancomycin gave no significant additional effect compared with cefotaxime alone. The times of regrowth were similar for cefotaxime and cefotaxime-vancomycin 1, and also for vancomycin 10 and vancomycin 20 with or without cefotaxime but were significantly delayed for the combination cefotaxime-vancomycin 2.5 and cefotaxime-vancomycin 5 as compared with vancomycin 2.5 and vancomycin 5. By using a multivariate analysis, we demonstrated that the most important parameters were Cmax (r = 0.43) and AUC (r = 0.58) for cefotaxime alone and Cmax (r = 0.70) for vancomycin alone; none of the tested parameters was found to be significantly correlated with the efficacy of the combinations of cefotaxime and vancomycin. From these findings, and under the experimental conditions used (i.e., relatively low concentrations of cefotaxime), we demonstrated that the in-vivo antibacterial efficacy of the combination of cefotaxime and vancomycin was higher than each monotherapy when the local concentrations of vancomycin were at least 1.9 mg/L. © 1995 The British Society for Antimicrobial Chemotherapy Original articles nationallicence Chavanet Pascal Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut Champliaud Dominique Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut Pechinot André Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut Buisson Marielle Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut Duong Michel Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut Neuwirth Catherine Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut Kazmierczak Antoine Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut Portier Henri Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut Journal of Antimicrobial Chemotherapy Oxford University Press 38/4(1996-10), 655-670 0305-7453 38:4<655 1996 38 jac https://doi.org/10.1093/jac/38.4.655 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/38.4.655 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chavanet Pascal Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut NATIONALLICENCE 700 1- Champliaud Dominique Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut NATIONALLICENCE 700 1- Pechinot André Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut NATIONALLICENCE 700 1- Buisson Marielle Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut NATIONALLICENCE 700 1- Duong Michel Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut NATIONALLICENCE 700 1- Neuwirth Catherine Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut NATIONALLICENCE 700 1- Kazmierczak Antoine Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut NATIONALLICENCE 700 1- Portier Henri Infectious Diseases Department, Hopital du Bocage, BP 1542, 21034 Dijon, France aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 38/4(1996-10), 655-670 0305-7453 38:4<655 1996 38 jac Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford