Imipenem was evaluated for its activity against Staphylococcus epidermidis in vitro and in a rabbit model of
endocarditis. The MBC for
imipenem of 55 methicillin-resistant S. epidermidis isolates from patients with prosthetic valve
endocarditis increased by eightfold or greater with increasing inoculum size; there was no inoculum-associated increase in the
imipenem MBC for 20
methicillin-susceptible S. epidermidis isolates.
Endocarditis was produced in rabbits with either a
methicillin-susceptible or a methicillin-resistant S. epidermidis isolate to investigate the correlation in vivo of the in vitro inoculum effect for
imipenem. Six days of
imipenem treatment eradicated
methicillin-susceptible S. epidermidis from vegetations of infected rabbits significantly better than no
therapy but was less effective against methicillin-resistant S. epidermidis in this regard. Among methicillin-resistant S. epidermidis-infected rabbits, 6 days of
imipenem therapy (i) was not significantly better than that of the control and was significantly worse than that of
vancomycin in eradicating bacteria from infected vegetations and (ii) increased the frequency of
imipenem-resistant subpopulations in infected vegetations. Resistant subpopulations were not seen in vegetations from untreated or
imipenem-treated,
methicillin-susceptible S. epidermidis-infected rabbits.
Imipenem may not be effective
therapy for serious human methicillin-resistant S. epidermidis
infections.