Comparative imipenem treatment of Staphylococcus aureus endocarditis in the rat

Abstract

The efficacy of imipenem alone or in association with gcntamicin against Staphylococcus aureus experimental endocarditis was compared to the efficacy of cloxacillin alone or in association with gentamicin. Parenteral treatment was started 24 h after intravenous bacterial challenge of rats with catheter-induced aortic valve vegetations. The cloxacillin MIC and MBC for Staph. aureus were 0-125 and 32 mg/1 and the imipenem MIC and MBC 0008 and 8 mg/1, respectively. In-vitro killing curves showed a synergistic effect between cloxacillin and gentamicin, and an additive effect between imipenem and gentamicin. Only large doses of cloxacillin (400 mg/kg tid) (producing serum levels above those obtained after intravenous injection of 2 g in man) achieved results comparable to those of imipenem 80 mg/kg tid (producing serum levels similar to those obtained after an intravenous dose of 750 mg in man) in reducing the bacterial numbers in vegetations after 3 and 5 days of treatment. There was a significantly greater reduction of bacterial numbers in vegetations after treatment with the association of cloxacillin and gentamicin than with cloxacillin alone. In contrast, the addition of gentamicin to imipenem did not improve significantly the results of treatment with imipenem alone, but imipenem alone was as good as the combination cloxacillin and gentamicin after 5 days of treatment. We conclude that imipenem is a highly bactericidal drug in this animal model, worth considering for clinical trials in the treatment of Staph. aureus infections.

Imipenem-cilastatin in the treatment of methicillin-sensitive and methicillin-resistant Staphylococcus aureus infections

“…However, incubation for 48 h revealed that the MIC was 50 ,ug/ml. I/C therapy was extended for another 2 weeks. Eleven days after discharge, the patient was readmitted with lumbar osteomyelitis due to MSSA.…”

Synergistic activity of ceftriaxone combined with netilmicin administered once daily for treatment of experimental streptococcal endocarditis

“…Second, the length of treatment (72 h) may have been too short. Studies with cloxacillin and imipenem showed that 5 days of treatment produced a more marked reduction in bacterial count in aortic valve vegetations than 3 days, while 10 days of treatment eliminated infection in most animals (2). Third, considering the relatively short half-life of these drugs in rats, the doses of CRO and NET may have been too low: for penicillin at least, the concentration should be maintained above the MIC throughout the dosing interval to prevent loss of efficacy as a result of bacterial regrowth (8,16).…”

Comparative efficacies of imipenem, oxacillin and vancomycin for therapy of chronic foreign body infection due to methicillin-susceptible and -resistant Staphylococcus aureus

“…In-vitro studies have reported high antimicrobial activity (Wise, Andres & Patel, 1981;Witte et al, 1982) of imipenem against methicillin-susceptible strains of S aureus and pharmacokinetic studies (Drusano, 1986;Wise et al, 1986) have shown that it is possible to achieve high levels in humans and animals, suitable for therapy of Gram-positive bacterial infections. In an experimental model of staphylococcal infection, namely aortic-valve endocarditis in rats (Baumgartner & Glauser, 1983) and rabbits (Apellaniz et al, 1991), the activity of imipenem was recorded as at least equivalent to that of the standard agent, cloxacillin, and even to that of cloxacillingentamicin combination therapy. Our results, which demonstrate significant imipenem activity against tissue cage infection by MSSA strain 120, agree with those previously reported for this antibiotic in both animals and humans.…”