Cefepime and Vancomycin for Gram-Positive Cocci in Chains
Yes, cefepime and vancomycin is an appropriate empirical regimen for blood cultures showing gram-positive cocci in chains, providing comprehensive coverage for the most likely pathogens including streptococci, enterococci, and potentially resistant organisms until final identification and susceptibility results are available. 1, 2
Why This Combination Works
Vancomycin provides essential coverage for potentially resistant gram-positive organisms including methicillin-resistant staphylococci, resistant pneumococci, and ampicillin-resistant enterococci that may appear as cocci in chains 1, 2. The FDA label confirms vancomycin's effectiveness against viridans streptococci, enterococci (when combined with an aminoglycoside for endocarditis), and other gram-positive cocci 3.
Cefepime contributes valuable activity against many streptococcal species, including viridans group streptococci and Streptococcus pneumoniae, which are common causes of gram-positive cocci in chains 1, 4. While cefepime is primarily selected for its anti-pseudomonal and gram-negative coverage in high-risk patients, it provides additional gram-positive activity that complements vancomycin 5, 4.
Likely Organisms and Coverage Strategy
Gram-positive cocci in chains most commonly represent:
- Streptococcus pneumoniae - covered by both agents 1
- Viridans group streptococci - excellent coverage with cefepime alone, with vancomycin as backup 1, 3
- Enterococci (including E. faecium) - requires vancomycin pending susceptibility 1, 2
Evidence Supporting Combination Therapy
Recent data suggest potential synergistic benefit when combining vancomycin with β-lactams for staphylococcal infections. A 2019 study demonstrated that vancomycin plus cefepime specifically improved microbiological clearance of MRSA bloodstream infections compared to vancomycin alone (adjusted OR 0.488 for microbiologic failure) 6. While this study focused on MRSA, the principle of combination therapy providing enhanced bacterial clearance is relevant to empirical management of unidentified gram-positive cocci 7, 6.
Critical Next Steps
Obtain additional blood cultures immediately - at least one more set from peripheral sites to confirm the finding and rule out contamination 1. If a central line is present, draw cultures from each lumen 1.
Plan for de-escalation within 48-72 hours when identification and susceptibility results become available 1, 2:
- If Streptococcus pneumoniae is identified and susceptible, narrow to appropriate β-lactam monotherapy (discontinue vancomycin) 1
- If viridans streptococci are identified, cefepime alone typically provides excellent coverage (discontinue vancomycin unless endocarditis suspected) 1, 3
- If Enterococcus faecium is identified, continue vancomycin and consider adding an aminoglycoside if endocarditis is present 1, 3
- If methicillin-susceptible Staphylococcus aureus is identified, switch to nafcillin, oxacillin, or cefazolin rather than continuing vancomycin, as vancomycin is associated with 2-3 times higher mortality for MSSA compared to β-lactams 7, 8
Common Pitfalls to Avoid
Do not continue vancomycin unnecessarily once susceptibility data show organisms are susceptible to narrower-spectrum antibiotics - this promotes resistance and is associated with worse outcomes for certain infections like MSSA 1, 2, 8.
Do not treat a single positive culture for coagulase-negative staphylococci without confirmation from a second culture set, as this likely represents contamination 1, 2.
Do not delay investigation for endocarditis if bacteremia persists beyond 48-72 hours or if viridans streptococci or enterococci are identified, as these require prolonged therapy and source control 1.
Monitor vancomycin trough levels if therapy continues beyond 72 hours, particularly in patients with renal impairment, to avoid nephrotoxicity 1, 2.