What are the recommended antibiotics for Gram-positive coverage?

Gram-Positive Coverage Antibiotics

First-Line Agents for Gram-Positive Coverage

For most Gram-positive infections, penicillin, cloxacillin (or other penicillinase-resistant penicillins like oxacillin/nafcillin), and erythromycin cover 90% of infections and should be used selectively to minimize resistance and adverse effects. 1

Beta-Lactam Antibiotics (Primary Options)

• Amoxicillin/clavulanate provides appropriate Gram-positive coverage for mild skin and soft tissue infections 2
• Dicloxacillin, cefuroxime, and cefalexin are recommended alternatives with appropriate Gram-positive coverage 2
• Oxacillin or nafcillin (200 mg/kg/day IV divided every 4-6 hours, up to 12 g/day) for penicillin-resistant organisms 2
• First-generation cephalosporins (cefazolin 100 mg/kg/day IV divided every 8 hours, up to 12 g daily) serve as alternatives 2
• Ampicillin (200-300 mg/kg/day IV divided every 4-6 hours, up to 12 g daily) for susceptible organisms 2

For Penicillin-Allergic Patients

• Clindamycin provides Gram-positive coverage only (78-80% clinical efficacy in children with acute bacterial rhinosinusitis) 2
• Macrolides (azithromycin, clarithromycin, erythromycin) have 78-80% clinical efficacy but carry 20-25% bacterial failure rates 2
• Respiratory fluoroquinolones (gatifloxacin, levofloxacin, moxifloxacin) are recommended for patients with beta-lactam allergies who have failed other regimens 2

Methicillin-Resistant Staphylococcus aureus (MRSA)

Vancomycin remains the first-line agent for MRSA infections (40 mg/kg/day IV divided every 8-12 hours, up to 2 g daily for those highly allergic to beta-lactams). 2

Alternative Anti-MRSA Agents

• Daptomycin (6 mg/kg IV every 24 hours; <6 years: 10 mg/kg) for right-sided endocarditis and possibly left-sided, or for vancomycin-resistant/intolerant patients 2
• Linezolid demonstrates 91% cure rates in clinically evaluable pediatric patients with Gram-positive infections, including 94% cure rate for MRSA 3
• Tedizolid (200 mg once daily for 6 days) shows non-inferiority to linezolid for acute bacterial skin and skin structure infections 4

Vancomycin-Resistant Enterococci (VRE)

• Daptomycin is the primary alternative for vancomycin-resistant or intolerant patients 2
• Linezolid achieved 75% cure rates in pediatric patients with vancomycin-resistant Enterococcus faecium 3

Severe/Complicated Infections

For serious Gram-positive infections with high bacterial load or endocarditis, combination therapy is preferred:

• Penicillinase-resistant penicillin (oxacillin/nafcillin) plus gentamicin for 3-5 days for organisms resistant to 0.1 μg/mL penicillin G 2
• Add rifampin plus gentamicin (for first 2 weeks) if prosthetic material is present 2
• Ceftriaxone plus gentamicin as an alternative (not for enterococcal endocarditis) 2

Critical Considerations

Resistance Patterns

• Approximately 30% of S. aureus isolates from skin and skin-structure infections are MRSA, making vancomycin the standard treatment 5
• Vancomycin resistance is developing in both enterococci and staphylococci, requiring judicious use 6, 7
• Higher vancomycin MICs within the susceptible range are associated with treatment failure 8

Common Pitfalls

• Do not use cephalosporins for enterococcal endocarditis 2
• Avoid aminoglycoside monotherapy—always combine with other agents for serious infections 2
• Rifampin should never be used as monotherapy due to rapid resistance development 2
• TMP/SMX, doxycycline, and macrolides have limited effectiveness against major Gram-positive pathogens with 20-25% bacterial failure rates 2