Regimens for treatment of bacteremia due to susceptible enterococci in adults

IV: intravenously; IM: intramuscular; AUC: area under the 24-hour time-concentration curve; MIC: minimum inhibitory concentration.

* Daptomycin, telavancin, tigecycline, and linezolid are also approved for use in complicated skin and skin structure infections due to vancomycin-susceptible Enterococcus faecalis; in addition, tigecycline has approval for complicated intraabdominal infections associated with E. faecalis.

¶ If using a beta-lactam antibiotic other than ampicillin (ie, penicillin or piperacillin) in treating severe enterococcal infections, verification of isolate susceptibility to penicillin should be performed by the clinical microbiology lab.

Δ Confirm susceptibility to penicillin prior to use.

◊ Teicoplanin (where available) may be used in place of vancomycin for treatment of infection due to isolates with minimum inhibitory concentration (MIC) ≤2 mg/L; for vancomycin-resistant strains (very common with Enterococcus faecium), teicoplanin should not be used (even if susceptible in vitro) because of concern about emergence of resistance. Teicoplanin loading and maintenance doses vary depending on the site and severity of infection. Loading doses range from 400 mg (approximately 6 mg/kg per dose) intravenously every 12 hours for 3 doses to 800 mg (approximately 12 mg/kg per dose) every 12 hours for 3 to 5 doses; maintenance doses range from 6 to 12 mg/kg/day. Therapeutic drug monitoring may be warranted; refer to local product information.

§ There is limited information on pharmacologic targets for vancomycin dosing in vancomycin susceptible enterococcal infections. An AUC/MIC_Etest ratio of ≥389 was associated with reduced mortality in one small single-center study^[1], but not another^[2]. Vancomycin trough levels above 15 mg/L are likely excessive for enterococci and have been associated with higher rates of acute kidney injury. The authors generally aim for a trough of 10 to 15 mg/L. Refer to the UpToDate topic on vancomycin dosing for discussion of AUC-guided and trough-guided vancomycin dosing.

¥ Many favor use of daptomycin for treatment of infections due to isolates that are resistant to approved agents (including vancomycin-resistant E. faecium) or patients unable to tolerate alternate therapies. Higher doses of daptomycin (10 to 12 mg/kg) have been associated with increased probability of achieving pharmacodynamic targets (free drug AUC/MIC ratio) and improved clinical outcomes in large retrospective studies, especially with E. faecium, and could be considered for life-threatening enterococcal infections with high MICs. High-dose daptomycin was not associated with dose-dependent increases in myopathy from these retrospective studies, however serial measurements of serum creatinine kinase should be monitored on daptomycin therapy.

‡ For treatment of invasive infection (such as endocarditis and bacteremia in the setting of valvulopathy and/or critical illness), bactericidal activity is recommended. This may be achieved via synergistic activity of a cell wall-active agent (such as ampicillin) in combination with ceftriaxone, gentamicin or streptomycin (if there is no high level aminoglycoside resistance). Ceftriaxone is preferred by many as the second agent to add to ampicillin for synergism. A loading dose and/or higher pharmacologic targets may be considered as guided by the overall condition of the patient or a concern for concurrent infection due to another pathogen (e.g., methicillin-resistant Staphylococcus aureus). (Refer to the UpToDate topic on antimicrobial therapy of native valve endocarditis, section on Enterococcus spp.)

† In patients with normal renal function, gentamicin dosing should be adjusted to achieve a one-hour post-dose serum concentration of 3 mcg/mL and a trough concentration of <1 mcg/mL.