What antibiotic should we start if the blood cultures come back with gram-positive coccus in a patient with a suspected bacterial infection?

Empirical Antibiotic Therapy for Gram-Positive Cocci on Blood Cultures

Start vancomycin immediately when blood cultures show gram-positive cocci, before final identification and susceptibility results are available. 1

Initial Empirical Regimen

Add vancomycin to your empirical antibiotic regimen as soon as gram-positive cocci are visualized on blood culture Gram stain. This recommendation applies regardless of whether the organisms appear in clusters (suggesting staphylococci) or chains (suggesting streptococci or enterococci). 2, 1

Combination Therapy Approach

• Combine vancomycin with an anti-pseudomonal β-lactam (cefepime, piperacillin-tazobactam, or a carbapenem) for broad empirical coverage until organism identification is complete. 1
• This dual approach covers both gram-positive and gram-negative pathogens while awaiting final culture results. 1
• For penicillin-allergic patients, use aztreonam plus vancomycin as an alternative. 1

Vancomycin Dosing

• Dose vancomycin at 15-20 mg/kg every 8-12 hours (typically 30-60 mg/kg/day in divided doses). 1
• Target trough concentrations of 15-20 mcg/mL for serious infections. 1, 3
• Monitor trough levels, especially in patients with renal impairment, to prevent nephrotoxicity. 1, 3

Critical De-escalation Strategy (48-72 Hours)

Plan to reassess and narrow therapy within 48-72 hours when identification and susceptibility results become available. 1

If Methicillin-Susceptible S. aureus (MSSA):

• Switch from vancomycin to nafcillin, oxacillin, or cefazolin (200 mg/kg/day IV divided every 4-6 hours, up to 12 g/day). 1
• β-lactams are superior to vancomycin for MSSA. 1

If Methicillin-Resistant S. aureus (MRSA):

• Continue vancomycin at 40 mg/kg/day IV divided every 8-12 hours (up to 2 g daily). 1

If Streptococcal Species:

• Discontinue vancomycin and switch to penicillin G (200,000-300,000 U/kg/day IV divided every 4 hours, up to 12-24 million U daily) for penicillin-susceptible streptococci. 1
• Ceftriaxone (100 mg/kg/day IV) is an acceptable alternative. 1

If Enterococcal Species:

• For E. faecalis: Switch to ampicillin (200-300 mg/kg/day IV divided every 4-6 hours, up to 12 g daily) plus gentamicin. 1
• For E. faecium or ampicillin-resistant enterococci: Continue vancomycin plus gentamicin. 1

Special Situations Requiring Vancomycin

The following clinical scenarios mandate vancomycin inclusion in the initial regimen: 2, 1

• Hemodynamic instability or severe sepsis (high risk of virulent gram-positive infections)
• Radiographically documented pneumonia (especially with MRSA risk factors)
• Clinically suspected serious catheter-related infection (chills, rigors during infusion, cellulitis around catheter site)
• Skin or soft-tissue infection at any site
• Known colonization with MRSA or institution with high MRSA prevalence
• Neutropenic patients with fever and severe mucositis

Critical Pitfalls to Avoid

Single Positive Blood Culture for Coagulase-Negative Staphylococci

Do NOT start vancomycin for a single positive blood culture showing coagulase-negative staphylococci if other simultaneously drawn cultures are negative. 2, 4

• This represents contamination in >90% of cases. 4
• Require at least 2 positive blood cultures within 48-72 hours before treating as true bacteremia. 4
• Unnecessary vancomycin use promotes resistance development. 2

Continuation Beyond 72 Hours Without Positive Cultures

Discontinue vancomycin after 2-3 days if cultures remain negative for β-lactam-resistant gram-positive organisms. 2

• Prolonged empirical vancomycin without documented resistant organisms drives resistance. 2
• This applies even in neutropenic patients unless clinical deterioration occurs. 2

Delayed Gram-Positive Coverage

Do not delay vancomycin in hemodynamically unstable patients or those with positive gram-positive cocci on blood culture. 1

• Delayed appropriate coverage increases mortality, particularly with virulent organisms like S. aureus or viridans streptococci in neutropenic patients. 1

Alternative Agents (When Vancomycin Cannot Be Used)

• Linezolid is FDA-approved for vancomycin-resistant E. faecium, MRSA, and resistant S. pneumoniae. 5
• Daptomycin is an alternative for complicated skin/soft-tissue infections and S. aureus bacteremia, but NOT for pneumonia (inactivated by surfactant). 6
• These agents should be reserved for documented resistant organisms or vancomycin intolerance, not routine empirical use. 2

Monitoring Requirements

• Draw at least 2 sets of blood cultures (one from peripheral vein, one from each catheter lumen if present) before starting antibiotics. 1
• Monitor vancomycin trough levels if therapy continues beyond 72 hours. 1, 3
• Repeat blood cultures to document clearance of bacteremia. 4
• Monitor renal function (serum creatinine, BUN) during vancomycin therapy. 1