title: High-level penicillin resistance among isolates of enterococci. Implications for treatment of enterococcal infections.
abstract: OBJECTIVE
  To determine the extent and clinical significance of high-level penicillin-resistant Enterococcus faecium at our institution.
  
  
  METHODS
  Surveillance of clinical enterococcal isolates, in-vitro susceptibility and timed survival studies, and determination of antibiotic efficacy in an experimental model of enterococcal endocarditis.
  
  
  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], greater than or equal to 200 micrograms/mL) but did not produce beta-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.
authors.affiliation: Division of Infectious Diseases, Medical College of Pennsylvania, Philadelphia.
authors.forename: L M
authors.initials: LM
authors.lastname: Bush
authors.forename: J
authors.initials: J
authors.lastname: Calmon
authors.forename: C L
authors.initials: CL
authors.lastname: Cherney
authors.forename: M
authors.initials: M
authors.lastname: Wendeler
authors.forename: P
authors.initials: P
authors.lastname: Pitsakis
authors.forename: J
authors.initials: J
authors.lastname: Poupard
authors.forename: M E
authors.initials: ME
authors.lastname: Levison
authors.forename: C C
authors.initials: CC
authors.lastname: Johnson
mesh_terms: D000818:Animals; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D004697:Endocarditis, Bacterial / Q000188:drug therapy; D005839:Gentamicins / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000627:therapeutic use; D010403:Penicillin Resistance; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013290:Streptococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013291:Streptococcus / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D005839:Gentamicins; D010400:Penicillin G