to establish synergy. Synergy does not exist if the enterococcus is resistant to the cell wall
active antibiotic (226).
Currently 5% ofE. faecalis and 40% ofE. faecium exhibit high-grade resistance to
gentamicin (> 2000 mg/mL) (227). Some gentamicin-resistant strains may remain sensitive to
streptomycin and vice versa (227).
Ampicillin resistance, on the basis ofb-lactamase production, has been recognized since
the 1980s. This is not usually picked up by routine sensitivity testing and requires the use of a
nitrocefin disc for detection.
When the enterococcus is sensitive to theb-lactam antibiotics, vancomycin and the
aminoglycosides, the classic combination of a cell wall active antibiotic with an aminoglycoside
remains the preferred therapeutic approach (228). Vancomycin is substituted for ampicillin in
the treatment of those individuals who are allergic to or whose infecting organism is resistant
to ampicillin.
When resistance to both gentamicin streptomycin is present, continuously infused
ampicillin to achieve a serum level of 60 mg/mL has had some success. Quinpristin/
dalfopristin and linezolid are alternative agents. They have the disadvantage of being
bacteriostatic against the enterococcus. Quinpristin/dalfopristin is only active against
E. faeciumbut not against the most commonly isolated strain of enterococcus,E. faecalis
(229–231). Daptomycin is bactericidal against these organisms. Experience with the use of this
compound against enterococcus is limited but growing. It is not synergistic with aminoglyco-
sides against enterococcal isolates (232). The combination of ampicillin and ceftriaxone does
produce synergy against enterococci both in vitro and in vivo. It appears quite effective in the
setting off enterococcal PVE (233). Tables 17 and 18 summarize the antibiotic treatment of
enterococcal NVIE.
S. Aureus
The penicillinase-resistant penicillins are the drugs of choice in treating MSSA infections,
vancomycin, is significantly less effective. It has a failure rate up to 35% in treating MSSA IE
(234). The use of vancomycin in treating MSSA infections in CCU patients should be limited to
patients with significant allergies to the penicillins. Cefazolin is used in individuals with mild
Table 16 Guidelines for Antimicrobial Therapy of Nonenterococcal Streptococcal Native Valve IEb,f
Antibiotic Dosage regimen
A. Penicillin-sensitiveStreptococcus viridansandStreptococcus bovisd
Penicillin Ga Penicillin G 20,000,000 U IV in four divided doses for 4 wk
Penicillin Gaand gentamicinc Penicillin 20,000,000 U IV in four divided doses for 2 wk gentamicin 3mg/kg given
q24h as a single dose or in divided doses q8h for 2 wk (ceftriaxone 2g IV/IM for
4 wk may be used in patients with mild reactions to penicillin)
Or
Ceftriaxone Ceftriaxone 2g IV/IM for 4 wk (may be used in patients with mild reactions to
penicillin)
B. Penicillin-resistant or tolerantS. viridansandS. bovisd,e
Penicillin Gaor ceftriaxone Penicillin G 24,000,000 U IV in four divided doses for 4 wk and ceftriaxone 2g IV/
IM for 4 wk
Gentamicin Gentamicin 3mg/kg given q24h as a single dose or in divided doses q8h for 2 wk
C.Abiotrophiaspp. and group B streptococcid
Penicillin Gaand Penicillin G 20,000,000 U IV in four divided doses for 6 wk
Gentamicin Gentamicin 3mg/kg given q24h as a single dose or in divided doses q8h for 2 wk
Drug dosages:aVancomycin 30mg/kg IV q12h in patients highly allergic to penicillin.
bFor patients with normal renal function.
cShort course therapy (see text).
dSee text for definition.
eRegimen is appropriate for treatment of prosthetic valve endocarditis with penicillin sensitive or resistant
S. viridansorS. bovis.
fUse of gentamicin is associated with increased risk of renal failure (222a).
Source: From Ref. 222.
242 Brusch