Ceftazidime-Avibactam Coverage for Streptococcus and MSSA
Ceftazidime-avibactam provides limited and unreliable coverage for Streptococcus species and MSSA, and should not be used as primary therapy for these pathogens.
Gram-Positive Coverage Profile
Streptococcus Species Coverage
- Ceftazidime alone has poor activity against streptococci, which is a well-established limitation that has made it unreliable for empirical monotherapy in settings where streptococcal coverage is needed 1
- The addition of avibactam (a beta-lactamase inhibitor) does not meaningfully improve activity against Streptococcus species, as these organisms do not produce the beta-lactamases that avibactam targets 2
- In vitro surveillance data from China showed that ceftazidime-avibactam demonstrated no significant activity changes against Streptococcus pneumoniae or β-hemolytic Streptococcus compared to ceftazidime alone 2
MSSA Coverage
- Ceftazidime has limited activity against MSSA with an MIC90 of 4 mcg/mL, which is substantially higher than preferred antistaphylococcal agents 3
- The FDA label for ceftazidime lists Staphylococcus aureus as a covered organism, but this does not reflect optimal clinical efficacy compared to standard antistaphylococcal beta-lactams 4
- Avibactam does not enhance activity against MSSA, as methicillin-susceptible strains do not produce the beta-lactamases inhibited by avibactam 5, 2
- In vitro studies confirm that no significant changes in activity were observed for Staphylococcus species when avibactam was added to ceftazidime 2
Clinical Implications and Preferred Alternatives
When Gram-Positive Coverage is Required
- If aztreonam replaces a beta-lactam in empiric regimens (such as in penicillin allergy), specific MSSA coverage must be added, typically with levofloxacin or another fluoroquinolone, because aztreonam lacks gram-positive activity 6
- This same principle applies to ceftazidime-avibactam: when used for gram-negative coverage, a separate agent is required for adequate gram-positive coverage 6
Preferred Agents for MSSA
- Nafcillin, oxacillin, or cefazolin are the preferred antibiotics for proven MSSA infections, with antistaphylococcal penicillins being first-line due to superior efficacy 7
- For empiric coverage in hospital-acquired pneumonia, antipseudomonal beta-lactams like piperacillin-tazobactam, cefepime, or carbapenems provide better gram-positive coverage than ceftazidime-avibactam while also covering gram-negatives 1
Preferred Agents for Streptococcus
- Ceftaroline (a fifth-generation cephalosporin) provides excellent activity against MSSA and drug-resistant Streptococcus pneumoniae, making it a superior choice when both gram-positive and gram-negative coverage is needed 1
- For community-acquired pneumonia with streptococcal coverage needs, respiratory fluoroquinolones (levofloxacin, moxifloxacin) or ceftriaxone are preferred over ceftazidime-based regimens 1
Common Pitfalls to Avoid
- Do not rely on ceftazidime-avibactam for empiric coverage when Streptococcus species or MSSA are likely pathogens 1, 2
- Do not assume that avibactam addition improves gram-positive coverage—avibactam specifically targets beta-lactamases produced by gram-negative organisms and some carbapenem-resistant Enterobacteriaceae 8, 5
- Always add specific gram-positive coverage (vancomycin, linezolid, or a fluoroquinolone) when using ceftazidime-avibactam empirically in settings where MRSA or streptococcal infections are possible 6
- Ceftazidime-avibactam should be reserved for multidrug-resistant gram-negative pathogens, particularly ESBL-producing Enterobacteriaceae and Pseudomonas aeruginosa, not for gram-positive coverage 1, 8