Empirical Therapy for Febrile Patients with Gram-Positive Cocci on Blood Cultures

Initial Assessment and Management

For a febrile patient with gram-positive cocci on blood cultures, vancomycin should be added to the empirical antibiotic regimen until final identification and susceptibility testing is available, as recommended by the Infectious Diseases Society of America 1
At least 2 sets of blood cultures should be collected, with a set from each lumen of an existing central venous catheter if present, and from a peripheral vein site, to increase the yield of positive cultures 2
Laboratory tests should include a complete blood count with differential, serum creatinine, BUN, electrolytes, hepatic enzymes, and total bilirubin to assess the patient's overall condition and potential organ dysfunction 2

For high-risk patients, an anti-pseudomonal β-lactam agent such as cefepime, meropenem, imipenem-cilastatin, or piperacillin-tazobactam should be used as the backbone therapy, with vancomycin added for gram-positive coverage, as recommended by the Infectious Diseases Society of America 1, 2, 3
For penicillin-allergic patients, a combination of aztreonam plus vancomycin or ciprofloxacin plus clindamycin can be used as an alternative to β-lactams 2, 4

If the patient is colonized with MRSA or the institution has high rates of MRSA infections, vancomycin should be included in the initial regimen, as recommended by the Centers for Disease Control and Prevention 1, 5
For suspected Enterococcus faecium bacteremia, vancomycin should be used, and for vancomycin-resistant enterococci (VRE), linezolid, quinupristin-dalfopristin, or daptomycin can be considered 1
A single blood culture positive for coagulase-negative staphylococci should generally be considered a contaminant if a second set of blood cultures is negative, and unnecessary vancomycin use should be avoided to prevent development of resistance, as recommended by the Centers for Disease Control and Prevention 1, 6, 7

Vancomycin trough levels should be monitored in patients with impaired renal function to avoid toxicity, as recommended by the Infectious Diseases Society of America 5
Therapy should be reassessed when culture and susceptibility results become available, typically within 48-72 hours, and de-escalation from vancomycin to appropriate β-lactam therapy should be considered if gram-positive cocci are identified as susceptible 1, 8

Unnecessary continuation of vancomycin when cultures are negative for β-lactam-resistant gram-positive organisms should be avoided, as recommended by the Centers for Disease Control and Prevention 6, 7
Using vancomycin for a single positive blood culture for coagulase-negative staphylococci without confirmation from a second culture should be avoided, as recommended by the Infectious Diseases Society of America 1, 7
Delaying appropriate gram-positive coverage in a febrile patient with gram-positive cocci on blood culture can lead to increased mortality, especially with virulent organisms, and should be avoided, as recommended by the Infectious Diseases Society of America 5

The American Heart Association recommends using an anti-staphylococcal penicillin (oxacillin or nafcillin) at 200 mg/kg/day IV divided every 4-6 hours up to 12 g/day for methicillin-susceptible S. aureus (MSSA) 9, 10
The American Heart Association recommends continuing vancomycin at 40 mg/kg/day IV divided every 8-12 hours up to 2 g daily for MRSA 9, 10
The American Heart Association recommends 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 9, 10
The American Heart Association recommends penicillin G plus gentamicin for relatively resistant streptococci 9
The American Heart Association recommends ceftriaxone 100 mg/kg/day IV divided every 12 hours or 80 mg/kg/day IV every 24 hours up to 4 g daily as an alternative for streptococci 9, 10
The American Heart Association recommends ampicillin 200-300 mg/kg/day IV divided every 4-6 hours up to 12 g daily plus gentamicin for enterococci 9, 10
The American Heart Association recommends vancomycin plus gentamicin for ampicillin-resistant enterococci 9, 10

The Infectious Diseases Society of America recommends adding vancomycin empirically in patients with hemodynamic instability or severe sepsis, regardless of suspected source, due to the high risk of gram-positive infections 11, 12
The American College of Clinical Pharmacy suggests adding vancomycin when gram-positive cocci are visualized on blood culture before final identification and susceptibility results are available, to ensure appropriate coverage for serious gram-positive infections 11
Vancomycin should be added empirically in patients with clinically suspected serious catheter-related infection, as indicated by symptoms such as chills, rigors during infusion, or cellulitis around catheter entry/exit site 11
The Infectious Diseases Society of America recommends adding vancomycin in patients with radiographically documented pneumonia who have MRSA risk factors, such as prior intravenous antibiotic use or history of previous MRSA infection 11
Vancomycin should be added empirically in neutropenic or immunocompromised patients with skin or soft-tissue infection at any site, due to the high risk of gram-positive infections 11, 12

Neutropenic patients with fever require vancomycin addition when severe mucositis is present, especially if fluoroquinolone prophylaxis was given and ceftazidime is the empirical agent, as recommended by the Infectious Diseases Society of America 11
Vancomycin should be added empirically in neutropenic patients with physical findings suggesting skin or soft-tissue infection or catheter infection, as indicated by the American College of Clinical Pharmacy 12
The Infectious Diseases Society of America recommends adding vancomycin in neutropenic patients who are hemodynamically unstable, due to the high risk of gram-positive infections 13

The American College of Clinical Pharmacy recommends a vancomycin dose of 30-60 mg/kg/day in 2-4 divided doses, typically 15-20 mg/kg every 8-12 hours, to ensure adequate coverage for serious gram-positive infections 12
Target trough concentrations of 15-20 µg/mL are recommended for severe infections, as indicated by the Infectious Diseases Society of America 12, 13