Meropenem Coverage of Staphylococcus Species
Meropenem covers methicillin-susceptible Staphylococcus aureus (MSSA) but does NOT cover methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE).
FDA-Approved Coverage
The FDA label explicitly states that meropenem is active against Staphylococcus aureus (methicillin-susceptible isolates only) for complicated skin and skin structure infections 1. The label unequivocally states: "Meropenem does not have in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE)" 1.
Mechanism and Microbiologic Activity
- Meropenem binds to penicillin-binding proteins (PBPs) 1,2, and 4 of Staphylococcus aureus to achieve bactericidal activity 1.
- Bactericidal concentrations are typically 1-2 times the bacteriostatic concentrations 1.
- The drug demonstrates excellent activity against MSSA with MICs typically in the susceptible range 2, 3.
Critical Limitation: Methicillin-Resistant Strains
Methicillin-resistant staphylococci show heteroresistance to meropenem, as is typical for all beta-lactam antibiotics 4. The biochemical correlate of methicillin resistance—penicillin-binding protein 2' (PBP2a)—shows low affinity for meropenem, similar to imipenem 4. Although MRSA strains may be inhibited by concentrations of 1-2 mg/L in agar dilution tests, they demonstrate heteroresistance in population studies 4.
Comparative Activity
- Meropenem is slightly less active than imipenem against staphylococci (imipenem is 2-4 times more active) 4.
- Compared to vancomycin or methicillin, meropenem is 10-20 times more active against susceptible strains 4.
- Meropenem demonstrates bactericidal activity comparable to imipenem in killing-curve experiments against MSSA 4.
Clinical Guidelines Context
Guidelines consistently exclude vancomycin from empiric intra-abdominal infection regimens because "while they considered it a suitable option for targeted treatment of methicillin-resistant Staphylococcus aureus infections, it was not an ideal option for empiric treatment" 5. This reinforces that when MRSA is suspected or confirmed, meropenem is inadequate and vancomycin or alternative anti-MRSA agents are required 5.
For CSF shunt infections caused by staphylococci, guidelines recommend combining vancomycin with rifampin, especially when the shunt cannot be removed—not meropenem 5.
Common Pitfalls
- Never assume meropenem covers MRSA or MRSE despite its broad-spectrum activity against other pathogens 1.
- Do not use meropenem monotherapy for suspected or confirmed MRSA infections—vancomycin, linezolid, or daptomycin are required 5.
- For severe staphylococcal infections, particularly MRSA, combination therapy with vancomycin plus rifampin may be necessary 5.
- Recent research shows that meropenem combined with piperacillin/tazobactam demonstrates synergistic activity against some MRSA strains (particularly USA300 lineage), but this triple combination is investigational and not standard practice 6.