What gram‑positive antimicrobial coverage does avibactam (in ceftazidime‑avibactam) provide?

Avibactam Gram-Positive Coverage

Avibactam provides essentially no clinically relevant gram-positive coverage—it is a β-lactamase inhibitor that restores activity of its partner β-lactam (ceftazidime) against gram-negative organisms only. 1, 2

Mechanism and Spectrum

Avibactam is a non-β-lactam β-lactamase inhibitor that works by covalently and reversibly binding to bacterial β-lactamases. 3 Its role is to inhibit Ambler class A (including ESBL and KPC), class C (AmpC), and some class D enzymes (such as OXA-48). 4, 1, 5

The key limitation: avibactam itself has no direct antibacterial activity against gram-positive organisms. 5 When combined with ceftazidime, the resulting spectrum remains focused on gram-negative pathogens because:

• Ceftazidime is a third-generation cephalosporin with inherently poor gram-positive activity 6
• Avibactam does not enhance ceftazidime's activity against gram-positive bacteria 5

Clinical Implications for Coverage Gaps

When using ceftazidime-avibactam, you must add separate agents for gram-positive coverage in specific clinical scenarios:

Hospital-Acquired/Ventilator-Associated Pneumonia

• Add vancomycin or linezolid to ceftazidime-avibactam for MRSA coverage 1
• This combination addresses both resistant gram-negative organisms and methicillin-resistant Staphylococcus aureus

Complicated Intra-Abdominal Infections

• Always combine ceftazidime-avibactam with metronidazole 1, 7, 5
• Metronidazole provides anaerobic coverage (particularly Bacteroides species), not gram-positive coverage 7
• The gram-positive cocci typically involved in intra-abdominal infections (enterococci, streptococci) may require additional consideration based on severity and source control

What Avibactam Does NOT Cover

Beyond the lack of gram-positive activity, avibactam also fails to improve ceftazidime's activity against:

• Metallo-β-lactamase producers (NDM, VIM, IMP) 4, 1, 2
• Acinetobacter species 2, 5
• Burkholderia species 2
• Stenotrophomonas maltophilia 2
• Most anaerobic bacteria (with limited exceptions for some Bacteroides fragilis, Clostridium perfringens, Prevotella spp., and Porphyromonas spp.) 5

Practical Algorithm for Coverage Decisions

When considering ceftazidime-avibactam:

1. Identify the suspected or documented gram-negative pathogen (ESBL, KPC, AmpC, OXA-48 producers, resistant Pseudomonas) 1

2. Assess need for additional coverage:

   • MRSA risk in pneumonia → add vancomycin or linezolid 1
   • Intra-abdominal source → add metronidazole 1, 7
   • Suspected enterococcal involvement → consider ampicillin or vancomycin based on local resistance patterns
   • MBL producers → switch to ceftazidime-avibactam plus aztreonam combination 1, 2

3. De-escalate when cultures return to pathogen-directed therapy if possible 1

The bottom line: never rely on ceftazidime-avibactam for gram-positive coverage—it provides none. 5