High-Level Penicillin Resistance among Isolates of Enterococci

Implications for Treatment of Enterococcal Infections

Abstract

Study Objective: To determine the extent and clinical significance of high-level penicillin-resistant Enterococcus faecium at our institution.

Design: Surveillance of clinical enterococcal isolates, invitro susceptibility and timed survival studies, and determination of antibiotic efficacy in an experimental model of enterococcal endocarditis.

Measurements and Main Results: For a 6-month period, 14% of enterococcal isolates (30 of 212) were identified as E. faecium. One third of the isolates were highly resistant to penicillin G (minimum inhibitory concentration [MIC], < 200 µg/mL) but did not produce β-lactamase. The findings from in-vitro survival studies showed that this high-level resistance resulted in the loss of bactericidal activity normally observed when an aminoglycoside antibiotic agent is combined with penicillin. An experimental rat model of endocarditis provided in-vivo data that confirmed our in-vitro observations. After the rats received therapy for 72 hours, penicillin G either alone or in combination with gentamicin did not significantly decrease the numbers of enterococci in vegetations on heart valves compared with untreated controls (P = 0.62 and P = 0.58, respectively).

Conclusions: Enterococcus faecium accounts for a notable proportion of clinical enterococcal isolates. Many strains from patients at our institution, as well as from patients at other institutions throughout the country, are highly resistant to penicillin. Because high-level penicillin resistance has important therapeutic implications, periodic surveillance and MIC testing of significant enterococcal isolates, especially E. faecium, are suggested.

Article and Author Information

  • From the Division of Infectious Diseases, Medical College of Pennsylvania and Veterans Administration Medical Center, Philadelphia, Pennsylvania. For current author addresses, see end of text.

  • Grant Support: Partial funding for this study was provided by a grant from Merrell Dow Pharmaceuticals.

  • Requests for Reprints: Caroline C. Johnson, MD, Division of Infectious Diseases, The Medical College of Pennsylvania, 3300 Henry Avenue, Philadelphia, PA 19129.

  • Current Author Addresses: Drs. Johnson, Levison, and Calmon: Division of Infectious Diseases, Dr. Poupard: Clinical Microbiology Laboratory; and Mr. Pitsakis, The Medical College of Pennsylvania, Philadelphia, PA 19129.

    Dr. Bush: Memorial Hospital of Burlington County, Mount Holly, NJ 08060.

    Dr. Cherney: St. Francis Medical Center, Trenton, NJ 08629. Mr. Wendeler: 2238 Longshore Avenue, Philadelphia, PA 19149.

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