Is Tazocin (piperacillin/tazobactam) effective against Enterococcus faecium infections?

Enterococcus faecium Does NOT Respond to Tazocin (Piperacillin-Tazobactam)

Tazocin should not be used for Enterococcus faecium infections due to intrinsic penicillin resistance, and its use may actually select for E. faecium over E. faecalis, worsening outcomes. 1, 2

Critical Species Distinction

The response to piperacillin-tazobactam depends entirely on which enterococcal species is present:

• E. faecalis: Susceptible to piperacillin-tazobactam (96% susceptibility) 3
• E. faecium: Intrinsically resistant to piperacillin-tazobactam due to inherent penicillin resistance 1, 2

Evidence of Intrinsic Resistance

E. faecium demonstrates intrinsic penicillin resistance that makes ampicillin and piperacillin-tazobactam ineffective as first-line therapy. 2 This is a fundamental microbiological characteristic that distinguishes it from E. faecalis, where only 43% of E. faecium strains showed susceptibility to piperacillin (with or without tazobactam) compared to 96% of E. faecalis. 4

Up to 95% of E. faecium strains express multidrug resistance to vancomycin, aminoglycosides, and penicillins. 2

Concerning Epidemiological Trend

Prior exposure to piperacillin-tazobactam is an independent risk factor for developing E. faecium bacteremia rather than E. faecalis bacteremia. 5 A recent Swedish study demonstrated that:

• The proportion of E. faecium bacteremia cases increased from 41% in 2015 to 51% in 2021 5
• This increase paralleled the dramatic expansion of piperacillin-tazobactam use 5
• Hospital-acquired infection and previous pip/taz exposure were identified as independent risk factors for E. faecium bacteremia 5

Appropriate Treatment for E. faecium

When E. faecium is identified or suspected, use these alternatives:

For Vancomycin-Susceptible E. faecium:

• Ampicillin, piperacillin-tazobactam, or vancomycin based on individual isolate susceptibility testing, with preference for ampicillin or piperacillin-tazobactam IF susceptible 1
• However, given intrinsic resistance patterns, vancomycin is typically required 1

For Vancomycin-Resistant E. faecium (VRE):

• Linezolid 600 mg IV/PO every 12 hours is first-line treatment 1, 2
• High-dose daptomycin (10-12 mg/kg/day) plus a β-lactam is the preferred alternative for bacteremia or endocarditis 1
• Standard daptomycin doses (6 mg/kg/day) are inadequate and will fail 1

Site-Specific Considerations:

• Uncomplicated UTI: Fosfomycin 3 g PO single dose, nitrofurantoin 100 mg PO every 6 hours, or high-dose ampicillin 18-30 g IV daily (if susceptible) 1
• Intra-abdominal infections: Tigecycline 100 mg IV loading then 50 mg IV every 12 hours or linezolid 600 mg IV/PO every 12 hours 1
• Endocarditis: Daptomycin 10 mg/kg/day plus ampicillin 200 mg/kg/day IV, or linezolid 600 mg IV/PO every 12 hours for ≥8 weeks 1

Critical Pitfalls to Avoid

Never assume E. faecium has the same susceptibility profile as E. faecalis—E. faecium requires different empiric coverage due to intrinsic resistance. 2 This is the single most important clinical error to avoid.

Guidelines explicitly recommend adding ampicillin when using regimens that don't cover enterococci (like ceftriaxone-metronidazole), but this only applies to E. faecalis, not E. faecium. 6 The 2017 WSES guidelines note that piperacillin-tazobactam and imipenem-cilastatin are "active against ampicillin-susceptible enterococci," which excludes most E. faecium. 6

Source control is critical—failure to remove infected devices or drain abscesses will result in treatment failure regardless of antimicrobial choice. 1

Monitoring Requirements

• Monitor CPK levels at least weekly with daptomycin due to skeletal muscle toxicity risk 1
• Monitor complete blood counts weekly with linezolid due to bone marrow suppression risk, particularly with courses >14-21 days 1
• Monitor for daptomycin resistance development by obtaining repeat cultures if clinical response is inadequate 1