Initial Antibiotic Treatment for Gram-Positive Cocci Bacteremia
Vancomycin 40 mg/kg/day IV divided every 8-12 hours (up to 2 g daily) should be initiated immediately as first-line empirical treatment for GPC bacteremia until final identification and susceptibility testing is available, with target trough concentrations of 15-20 μg/mL in severe infections. 1, 2
Empirical Regimen Selection
For critically ill patients, neutropenic patients, or those with suspected polymicrobial infections, add an anti-pseudomonal β-lactam agent (cefepime, meropenem, imipenem-cilastatin, or piperacillin-tazobactam) as backbone therapy alongside vancomycin. 1, 2
For penicillin-allergic patients, use aztreonam plus vancomycin or ciprofloxacin plus clindamycin as an alternative. 1, 2
Targeted Therapy Based on Organism Identification
Staphylococcus aureus
For MRSA (methicillin-resistant): Continue vancomycin at the same dosing. 1, 2
For MSSA (methicillin-susceptible): Switch to anti-staphylococcal penicillins (oxacillin or nafcillin) 200 mg/kg/day IV divided every 4-6 hours (up to 12 g/day) once susceptibility is confirmed. 1, 2
Streptococcal Species
For penicillin-susceptible strains: Use penicillin G 200,000-300,000 U/kg/day IV divided every 4 hours (up to 12-24 million U daily). 1, 2
For relatively resistant streptococci: Add gentamicin to penicillin G. 2
Alternative option: Ceftriaxone 100 mg/kg/day IV divided every 12 hours or 80 mg/kg/day IV every 24 hours (up to 4 g daily). 2
Enterococcal Species
For ampicillin-susceptible strains: Use ampicillin 200-300 mg/kg/day IV divided every 4-6 hours (up to 12 g daily) plus gentamicin. 1, 2
For ampicillin-resistant strains: Use vancomycin plus gentamicin. 2
For vancomycin-resistant enterococci (VRE): Linezolid 600 mg IV/PO every 12 hours is the drug of choice. 1
Coagulase-Negative Staphylococci
A single blood culture positive for coagulase-negative staphylococci should generally be considered a contaminant if a second set of blood cultures is negative—avoid unnecessary vancomycin use in this scenario. 2
Special Clinical Scenarios
Catheter-Related Infections
For suspected catheter-related GPC bacteremia, vancomycin should be included in the initial regimen, particularly if the patient is colonized with MRSA or the institution has high rates of MRSA infections. 2
For gram-negative rod catheter-related bacteremia with persistent symptoms despite therapy, remove the device and extend antibiotic duration beyond 7-14 days based on evaluation for endovascular and metastatic infection. 3
Neutropenic Patients
Initial empiric therapy must include an anti-pseudomonal β-lactam with vancomycin added for specific indications such as suspected catheter-related infections or known colonization with resistant gram-positive organisms. 1
Alternative Agents for Resistant or Refractory Infections
Daptomycin 6-8 mg/kg IV every 24 hours may be used as an alternative to vancomycin for MRSA bacteremia, particularly in cases of vancomycin treatment failure or intolerance. 1, 4
Linezolid 600 mg IV/PO every 12 hours is an alternative for MRSA and the preferred agent for VRE. 1
For enterococcal bloodstream infections when aminoglycosides are contraindicated, quinupristin-dalfopristin or daptomycin can be considered. 3
Monitoring and De-escalation Strategy
Monitor vancomycin trough levels in all patients, targeting 15-20 μg/mL for severe infections, with particular attention in patients with impaired renal function to avoid nephrotoxicity. 1, 2, 5
Reassess therapy within 48-72 hours when culture and susceptibility results become available, and de-escalate from vancomycin to appropriate β-lactam therapy if gram-positive cocci are identified as susceptible. 2
Obtain at least 2 sets of blood cultures—one from each lumen of existing central venous catheters if present, and one from a peripheral vein site—to increase diagnostic yield. 2
Critical Pitfalls to Avoid
Do not continue vancomycin unnecessarily when cultures are negative for β-lactam-resistant gram-positive organisms or when susceptibility testing reveals MSSA—this promotes resistance development. 2, 6
Do not delay appropriate gram-positive coverage in a febrile patient with GPC on blood culture, as this increases mortality, especially with virulent organisms like S. aureus. 2
For MSSA bacteremia, early transition from vancomycin to anti-staphylococcal penicillins (within 5-50 hours) significantly reduces treatment duration and improves outcomes. 6