Does Ampicillin Cover Coagulase-Negative Staphylococci?
No, ampicillin does not provide reliable coverage for coagulase-negative staphylococci (CoNS) and should not be used empirically for these infections. Almost all staphylococci, including CoNS, are highly resistant to penicillin G and ampicillin due to β-lactamase production 1.
Resistance Patterns in CoNS
- The vast majority of CoNS produce β-lactamase enzymes that inactivate ampicillin, making it ineffective for treatment 1.
- Research demonstrates that 42.9% of CoNS isolates test positive for β-lactamase production, with many carrying plasmid-mediated resistance 2.
- Only rare strains that are definitively susceptible to penicillin (confirmed by a highly qualified laboratory) would respond to ampicillin or penicillin 1.
Appropriate Antibiotic Selection
For Methicillin-Susceptible CoNS
- β-lactamase-resistant penicillins (nafcillin or oxacillin) are the drugs of choice, not ampicillin 1.
- First-generation cephalosporins like cefazolin are acceptable alternatives in patients with non-immediate penicillin allergies 1.
For Methicillin-Resistant CoNS
- Vancomycin is the standard treatment, as most CoNS causing healthcare-associated infections are methicillin-resistant 1.
- Approximately 68% of CoNS blood stream isolates demonstrate oxacillin resistance 3.
- Methicillin-resistant CoNS are also clinically resistant to all cephalosporins despite in vitro susceptibility results 1.
Clinical Context Matters
Native Valve Endocarditis
- For the rare ampicillin-susceptible CoNS strain, ampicillin could theoretically be used, but this requires definitive susceptibility testing by a qualified laboratory 1.
- Most experts recommend β-lactamase-resistant penicillins based on susceptibility profiles rather than ampicillin 1.
Prosthetic Valve Endocarditis
- Vancomycin combined with rifampin and gentamicin is the recommended regimen for methicillin-resistant CoNS prosthetic valve endocarditis 1.
- Treatment duration is minimum 6 weeks for vancomycin and rifampin, with gentamicin limited to the first 2 weeks 1.
Important Exception: Ampicillin-Sulbactam
- Ampicillin-sulbactam (which combines ampicillin with the β-lactamase inhibitor sulbactam) demonstrates efficacy against β-lactamase-producing CoNS in experimental models 4.
- This combination was equivalent to vancomycin for prophylaxis and effective for therapy of CoNS endocarditis when combined with vancomycin 4.
- However, ampicillin alone (without sulbactam) remains ineffective 4.
Critical Pitfall to Avoid
Never assume ampicillin will cover staphylococci empirically. The American Heart Association explicitly states that "almost all staphylococci are highly resistant to penicillin G and ampicillin" 1. Empiric use of ampicillin for suspected CoNS infection will result in treatment failure and potentially worse patient outcomes including increased mortality from untreated infection.