Antibiotic Treatment for Gram-Positive Cocci Bacteremia
Vancomycin 40 mg/kg/day IV divided every 8-12 hours (up to 2 g daily) with target trough concentrations of 15-20 μg/mL is the recommended first-line empirical treatment for gram-positive cocci bacteremia until organism identification and susceptibility results are available. 1, 2
Empirical Treatment Strategy
Initial Regimen Selection
Vancomycin should be initiated immediately for all patients with gram-positive cocci bacteremia, particularly those with hemodynamic instability, severe sepsis, suspected catheter-related infection, or risk factors for resistant organisms. 1, 3
Add an anti-pseudomonal β-lactam agent (cefepime, meropenem, imipenem-cilastatin, or piperacillin-tazobactam) as backbone therapy for critically ill patients, neutropenic patients, or those with suspected polymicrobial infections. 1, 2
For penicillin-allergic patients, use aztreonam plus vancomycin or ciprofloxacin plus clindamycin as an alternative regimen. 1, 2
Vancomycin Dosing and Monitoring
Target vancomycin trough levels of 15-20 μg/mL for severe infections, with careful monitoring in patients with impaired renal function to avoid nephrotoxicity. 1, 2
Adjust dosing in renal impairment to prevent accumulation and toxicity, as vancomycin at higher doses or prolonged use with trough levels >15 mcg/mL increases renal toxicity risk. 4
Targeted Therapy Based on Organism Identification
Staphylococcus aureus
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, 5
For MRSA (methicillin-resistant): Continue vancomycin at the same dosing, or consider daptomycin 6-8 mg/kg IV every 24 hours as an alternative, particularly for vancomycin treatment failure or intolerance. 1, 5
Cefazolin is preferred over vancomycin for MSSA once susceptibility is confirmed, as β-lactams demonstrate superior bactericidal activity. 5
Streptococcal Species
For penicillin-susceptible streptococcal strains: Switch to penicillin G 200,000-300,000 U/kg/day IV divided every 4 hours (up to 12-24 million U daily). 1
For relatively resistant streptococci: Add gentamicin to penicillin G for synergistic activity. 1
Enterococcal Species
For ampicillin-susceptible enterococcal strains: Use ampicillin 200-300 mg/kg/day IV divided every 4-6 hours (up to 12 g daily) plus gentamicin. 1, 6
For vancomycin-resistant enterococci (VRE): Linezolid 600 mg IV/PO every 12 hours is the drug of choice. 1, 7
Empiric anti-enterococcal therapy is recommended for health care-associated intra-abdominal infection, postoperative infection, patients who have previously received cephalosporins, immunocompromised patients, and those with valvular heart disease or prosthetic intravascular materials. 6
Quinupristin-dalfopristin or daptomycin can be considered for enterococcal bloodstream infections when aminoglycosides are contraindicated, though quinupristin-dalfopristin has no activity against E. faecalis. 6, 7
Special Clinical Scenarios
Catheter-Related Bacteremia
Vancomycin should be included in the initial regimen for suspected catheter-related gram-positive cocci bacteremia, particularly if the patient is colonized with MRSA or the institution has high rates of MRSA infections. 1
Remove long-term catheters if severe sepsis, persistent bacteremia >72 hours despite appropriate antibiotics, or evidence of endocarditis or suppurative thrombophlebitis is present. 3
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. 1
Neutropenic Patients
Initial empiric therapy must include an anti-pseudomonal β-lactam with vancomycin added for specific indications such as suspected catheter-related infections, known colonization with resistant gram-positive organisms, or severe mucositis with prior fluoroquinolone prophylaxis. 1, 3
Avoid ceftazidime as monotherapy due to its lack of adequate gram-positive coverage. 3
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, and has demonstrated noninferiority to vancomycin in phase 3 trials. 1, 5
Linezolid 600 mg IV/PO every 12 hours is an alternative for MRSA and the preferred agent for VRE, with particular utility in hospital-acquired pneumonia where it may be superior to vancomycin. 1, 8
Ceftobiprole has demonstrated noninferiority to daptomycin in phase 3 trials for S. aureus bacteremia. 5
De-escalation Strategy
Reassess therapy within 48-72 hours when culture and susceptibility results become available. 1, 2
De-escalate from vancomycin to appropriate β-lactam therapy if gram-positive cocci are identified as susceptible, as this prevents unnecessary vancomycin exposure and resistance development. 1
Discontinue empirical vancomycin beyond 48 hours if cultures are negative for resistant organisms. 3
Duration of Therapy
Treat uncomplicated bacteremia with source control for 7-14 days, and complicated infections (persistent bacteremia, endocarditis, suppurative thrombophlebitis) for 4-6 weeks. 3
Enterococcal bacteremia that persists for >4 days has been independently associated with mortality and warrants extended therapy and evaluation for endocarditis. 6
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, as this promotes resistance development and exposes patients to unnecessary toxicity. 1, 6
Do not delay appropriate gram-positive coverage in a febrile patient with gram-positive cocci on blood culture, as treatment delays increase mortality, especially with virulent organisms like S. aureus. 1, 5
Do not use vancomycin for routine surgical prophylaxis or empiric therapy in febrile neutropenic patients unless initial evidence indicates gram-positive infection and the prevalence of MRSA is substantial. 6
Do not treat single positive blood cultures for coagulase-negative staphylococci if other cultures are negative, as contamination is likely. 6
Do not forget to adjust vancomycin and other renally cleared antibiotics in patients with renal impairment to prevent toxicity. 3