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TABLE 149-1 Suggested Regimens for the Management of Infections TABLE 149-2 Suggested Regimens for the Management of Infections
Caused by Enterococcus faecalis Caused by Vancomycin- and Ampicillin-Resistant Enterococcus faecium
CLINICAL SYNDROME SUGGESTED THERAPEUTIC OPTIONSa CLINICAL SYNDROME SUGGESTED THERAPEUTIC OPTIONSa
Endovascular infections • Ampicillinb (12 g/d IV in divided doses q4h) plus Endovascular infections • High-dose daptomycinb plus another agentc ± an
(including endocarditis) ceftriaxone (2 g IV q12h) (including endocarditis) aminoglycosided
• Ampicillinb (12 g/d IV in divided doses q4h or by • Linezolid (600 mg IV q12h)
continuous infusion) or penicillin (18–30 mU/d IV • High-dose ampicillin (if MIC is ≤64 μg/mL) ± an
in divided doses q4h or by continuous infusion) aminoglycosided
plus an aminoglycosidec
• Ampicillin plus imipenem (if the ampicillin MIC
• Vancomycind (15 mg/kg IV per dose) plus an is ≤32 μg/mL)
aminoglycosidec
• Q/De (22.5 mg/kg per day in divided doses q8h) ±
• High-dose daptomycine ± another active agentf another active agentf
• Ampicillinb plus imipenem Nonendovascular • High-dose daptomycinb ± another agentc ± an
Nonendovascular • Ampicillin (12 g/d IV in divided doses q4h) or bacteremiag aminoglycosided
bacteremiag penicillin (18 mU/d IV in divided doses q4h) ± an • Linezolid (600 mg IV q12h)
aminoglycosidec or ceftriaxone
• Q/D (22.5 mg/kg per day in divided doses q8h) ±
• Vancomycind (15 mg/kg IV per dose) another active agentf
• High-dose daptomycine ± another active agentf Meningitis • Linezolid (600 mg IV q12h) ± another CSF-
• Linezolid (600 mg IV/PO q12h) penetrating active agenth
Meningitis • Ampicillin (20–24 g/d IV in divided doses q4h) • High-dose daptomycinb (plus intraventricular
or penicillin (24 mU/d IV in divided doses q4h) daptomycin) ± another CSF-penetrating active
plus an aminoglycosidec,h and consider adding agenth,i
ceftriaxone (2 g IV q12h) • Q/D (22.5 mg/kg per day in divided doses q8h
• Vancomycin (500–750 mg IV q6h)d plus an plus intraventricular Q/D)j ± another active
aminoglycosidec or rifampin agenth
• Linezolid Urinary tract infections • Fosfomycin (3 g PO, one dose)k
• High-dose daptomycine (plus intrathecal • Nitrofurantoin (100 mg PO q6h)
daptomycin) ± another active agentf • Ampicillin or amoxicillin (2 g IV/PO q4–6h)l

CHAPTER 149 Enterococcal Infections

Urinary tract infections • Fosfomycin (3 g PO, one dose)i
(uncomplicated)
a
Authors’ preferences are underlined for each category; many of these regimens
• Ampicillin (500 mg IV or PO q6h) are off-label. bDaptomycin at doses of 10–12 mg/kg once daily is suggested
• Nitrofurantoin (100 mg PO q6h) (off-label). Close monitoring of creatine phosphokinase levels is recommended
throughout therapy because of possible rhabdomyolysis. cPotentially active agents
a
Authors’ preferences are underlined for each category; many of the regimens may include ampicillin or ceftaroline (even if the infecting strain is resistant in vitro)
are off-label. bIn rare cases, β-lactamase-producing isolates may be present. or tigecycline. In vitro synergism of daptomycin with ampicillin or ceftaroline has
Because these isolates are not detected by conventional determination of the been observed against some isolates that subsequently become nonsusceptible
minimal inhibitory concentration, additional tests (e.g., the nitrocefin disk) are to daptomycin during therapy. The synergism of daptomycin and β-lactams is
recommended for isolates from endocarditis. The use of ampicillin/sulbactam associated with mutations in liaFSR. Consider combination therapy if the minimal
(12–24 g/d) is suggested in these cases. cOnly if the organism does not exhibit high- inhibitory concentration (MIC) of daptomycin is ≥3 μg/mL. dOnly if the organism
level resistance (HLR) to aminoglycosides. This test is performed by the clinical does not exhibit high-level resistance to aminoglycosides (see Table 149-1, footnote
microbiology laboratory only for gentamicin or streptomycin (growth of enterococci c). eQuinupristin/dalfopristin (Q/D) lost U.S. Food and Drug Administration (FDA)
on agar containing gentamicin [500 μg/mL] or streptomycin [2000 μg/mL]). If HLR is approval for infections due to vancomycin-resistant Enterococcus. fAgents that
documented, the aminoglycoside will not act synergistically with the other agent in may be useful in combination with Q/D (if the isolate is susceptible to each agent)
the combination. However, HLR to one of these aminoglycosides does not indicate include doxycycline with rifampin (one reported case) or fluoroquinolones (one
resistance to the other agent (as reported individually). HLR to gentamicin implies reported case). gIn selected cases of catheter-associated bacteremia, removal of
lack of synergism with tobramycin and with amikacin. Gentamicin (1–1.5 mg/kg the catheter and a short course of therapy (~5–7 days) may be sufficient. A single
IV q8h) and streptomycin (15 mg/kg per day IV/IM in two divided doses) are the positive blood culture that is likely to be associated with a catheter in a patient
only two recommended aminoglycosides. dVancomycin is recommended only as who is otherwise doing well may not require therapy after removal of the catheter.
an alternative to β-lactam agents in cases of allergy or toxicity plus the inability h
Fluoroquinolones (e.g., moxifloxacin) and rifampin (if the isolate is susceptible
to desensitize. Specific pharmacologic targets for trough concentrations have to each agent) reach therapeutic levels in the cerebrospinal fluid. iIntrathecal
not been clinically evaluated in enterococcal bacteremia; trough concentrations gentamicin (2–10 mg/d) if high-level resistance is not detected. Intraventricular
of 15–20 mg/L have been associated with increased rates of nephrotoxicity. daptomycin has been used in two cases of meningitis jIntrathecal Q/D (1–5 mg/d)
Cerebrospinal fluid (CSF) concentrations in meningitis should be determined. has been used in combination with Q/D systemic therapy in meningitis. If Q/D is
Vancomycin-resistant strains of E. faecalis have been reported. eConsider doses chosen, simultaneous use of both systemic and intrathecal therapy is suggested.
of 10–12 mg/kg once daily if used in combination and 10–12 mg/kg per day if used k
Approved by the FDA only for uncomplicated urinary tract infections caused by
alone. Monitoring of creatine phosphokinase levels is recommended throughout vancomycin-susceptible E. faecalis. lConcentrations of amoxicillin and ampicillin
therapy because of possible rhabdomyolysis. fPotentially active agents may include in urine far exceed those in serum and may be potentially effective even against
an aminoglycoside (if HLR is not detected), ampicillin, ceftaroline, tigecycline, or a isolates with high MICs. Doses up to 12 g/d are suggested for isolates with MICs of
fluoroquinolone (which, if the isolate is susceptible, may be favored in meningitis). ≥64 μg/mL.
The presence of mutations in liaFSR seems to increase susceptibility to ampicillin
and ceftaroline, and combinations of daptomycin with these compounds are
bactericidal in vitro against such strains. gIn selected cases of catheter-associated
bacteremia, removal of the catheter and a short course of therapy (~5–7 days) CHOICE OF ANTIMICROBIAL AGENTS
may be sufficient. A single positive blood culture that is likely to be associated Among the β-lactams, the most active are the aminopenicillins
with a catheter in a patient who is otherwise doing well may not require therapy
after removal of the catheter. Patients at high risk for endovascular infections (ampicillin, amoxicillin) and ureidopenicillins (i.e., piperacillin);
or with severe disease may benefit from synergistic combination therapy. hThe next most active are penicillin G and imipenem. Cephalosporins,
addition of intrathecal or intraventricular therapy with gentamicin (2–10 mg/d) if the with the possible exception of ceftaroline, are not active as mono-
organism does not exhibit HLR or with vancomycin (10–20 mg/d) when the isolate
is susceptible has been suggested by some authorities. The addition of systemic therapy. For E. faecium, a combination of high-dose ampicillin (up
rifampin (a good CSF-penetrating agent) may be considered. The combination of to 30 g/d) plus an aminoglycoside has been suggested—even for
ampicillin and ceftriaxone may have clinical benefit (by analogy with endocarditis), ampicillin-resistant strains if the MIC is ≤64 μg/mL—since a plasma
but no cases treated with this combination have been reported; the authors would
use this combination. iApproved by the U.S. Food and Drug Administration only ampicillin concentration higher than this value can be achieved at
for uncomplicated urinary tract infections caused by vancomycin-susceptible E. high doses. The only two aminoglycosides recommended for syner-
faecalis. gistic therapy in severe enterococcal infections are gentamicin and
streptomycin. This is because the most common acquired enzyme
conferring high-level resistance to gentamicin also is active against
tobramycin and amikacin but not streptomycin, and the resistance
mechanisms causing streptomycin high-level resistance do not

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