Using a standardized strain of Escherichia coli 06 and a rabbit knee-joint model, we determined the following values: (1) the effective concentrations of amikacin and carbenicillin in vitro against Escherichia coli 06 when used singly or in combination; (2) the levels of each of these antibiotics in serum and synovial fluid after an intramuscular injection; (3) the effectiveness of amikacin in preventing intra-articular infection when it is administered thirty minutes before and six hours after an intra-articular inoculation of the same strain of Escherichia coli; and (4) the synergistic effects of amikacin and carbenicillin in combination both in vitro and in vivo when used together as a single dose six hours after intra-articular bacterial inoculation. Amikacin was much more effective when administered before joint inoculation and the minimum effective (inhibitory) concentrations of amikacin in vitro and in vivo were approximately the same. A synergistic effect of amikacin and carbenicillin in combination was more clearly evident in vitro than in vivo.
Clinical relevance: In vitro tests such as determinations of the minimum inhibitory concentration and the minimum bactericidal concentration, and the serum bactericidal test, can provide valuable guides for the determination of minimum goals for antibiotic therapy. These in vitro tests were related to concentrations of antibiotics in tissue assessed by in vivo bacterial challenge tests and were found to be predictive of efficacy in vivo.