Continuous intravenous versus intermittent ampicillin therapy of experimental endocarditis caused by aminoglycoside-resistant enterococci

Abstract

We studied the efficacy of continuous intravenous infusion of ampicillin compared with that of intermittent administration of ampicillin alone or in combination with gentamicin for the therapy of highly aminoglycosideresistant enterococcal experimental endocarditis. Rabbits were infected with a gentamicin-susceptible (MIC, 256 tg/ml) strain ofEnterococcusfaecalis or a strain ofE. faecalis which was highly resistant to gentamicin in vitro (MIC, >2,000 pg/mI). Administration of ampicillin by continuous intravenous infusion did not significantly enhance the killing of enterococci in vivo compared with that by intermittent administration of ampicillin for either the aminoglycoside-susceptible or the aminoglycoside-resistant strain. In combination with gentamicin, there were no significant differences in efficacies obtained with intermittent venus continuous intravenous infusion of ampicillin therapy for experimental endocarditis caused by either strain of E. faecalis.The frequency of resistance of enterococci to multiple aminoglycosides in vitro is increasing (4,12,17,18,29). Currently, approximately 15% of enterococci recovered from patients at the Mayo Clinic are highly aminoglycoside resistant. Recently, cases of infective endocarditis caused by highly aminoglycoside-resistant enterococci have been described (6, 15, 19, 21). Penicillin or vancomycin together with aminoglycosides does not act synergistically in vitro against these microorganisms (4,12,17,18,29). Continuous intravenous (i.v.) infusion of ampicillin was reportedly more effective than intermittent administration for the therapy of enterococcal experimental endocarditis (22). The purpose of this study was to evaluate the efficacy of continuous i.v. infusion of ampicillin versus that of intermittent administration of ampicillin alone or in combination with gentamicin for the therapy of experimental endocarditis caused by a strain of highly aminoglycoside-resistant Enterococcus faecalis. MATERIALS AND METHODSIn vitro studies. Two strains of E. faecalis recovered at the Mayo Clinic from patients with infective endocarditis were selected for study. One strain was susceptible in vitro to gentamicin, and the other strain was highly gentamicin resistant. Microorganisms were stored in defibrinated sheep blood at -70°C for testing. Each strain was thawed and subcultured in tryptic soy agar containing 5% sheep blood. A macrodilution method was used for susceptibility testing (24). Inocula were prepared from broth cultures in the logarithmic phase of growth to yield an inoculum size of >5.5 x 105 CFU of enterococci per ml and were inoculated in serial twofold dilutions of antimicrobial agents in MuellerHinton broth. Subcultures were made for confirmation of * Corresponding author.

Comparison of ampicillin-sulbactam with vancomycin for treatment of experimental endocarditis due to a beta-lactamase-producing, highly gentamicin-resistant isolate of Enterococcus faecalis

“…Several injection of the bacterial inoculum or removal of the catheter during infection), and, finally, the duration of therapy (4,5,20).…”

Antibiotic treatment of infective endocarditis due to viridans streptococci, enterococci, and other streptococci

“…In these patients, prolonged therapy (8 weeks) with high dosages of ampicillin or amoxycillin is recommended (Table 3 E). Alternatively, the group suggests that killing curves with multiple‐drug regimens including ampicillin, vancomycin, teicoplanin, imipenem, fluoroquinolones and other agents may be performed [38–43]. Therapy should be instituted with the most effective combination of agents for at least 8 weeks.…”

“…As for cases infected with glycopeptide‐resistant strains, the group suggests that these patients be treated in consultation with an infectious diseases specialist. Combinations of drugs and new compounds are under investigation and have shown some encouraging results [38–43]. Antimicrobial therapy alone may not result in cure, and those patients failing therapy should be considered as candidates for cardiac valve replacement surgery.…”

Enterococcal Endocarditis Revisited

“…Some studies based on animal models support continuous infusion to avoid it [18]. On the other hand, it is controversial that continuous infusion is more effective than pulses to maintain trough antibiotic concentration above the MIC [19]. Enterococcus faecium is more resistant to penicillin than E. faecalis, with MICs often between 16 and 32 μg/ml or higher [20].…”