From the Guidelines
The combination of aztreonam with ceftazidime is recommended for the treatment of infections caused by OXA-48-producing organisms, as aztreonam's mechanism of action, which inhibits bacterial cell wall synthesis, is not affected by the OXA-48 carbapenemase 1.
Key Points
- Ceftazidime, a third-generation cephalosporin, is often used in combination with aztreonam at a dose of 2 grams every 8 hours, while aztreonam is administered at a dose of 2 grams every 6-8 hours, for a duration of 10-14 days 1.
- This combination therapy is effective in treating serious infections, including pneumonia and sepsis, caused by OXA-48-producing Enterobacteriaceae, with a lower 30-day mortality rate and clinical treatment failure rate compared to other antimicrobial therapies 1.
- The use of ceftazidime/avibactam plus aztreonam is strongly recommended for the treatment of infections caused by metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE), with a strength of recommendation of STRONG and a certainty of evidence of MODERATE 1.
- The combination of ceftazidime/avibactam plus aztreonam has shown in vitro synergy activities against CRE produces metallo-b-lactamases, and has been associated with lower mortality rates and clinical treatment failure rates in patients with bloodstream CRE infections 1.
Treatment Considerations
- The choice of antibiotic therapy should be guided by the results of susceptibility testing and the specific carbapenemase produced by the infecting organism 1.
- Rapid testing strategies may be crucial for starting active antibiotic therapy early and applying treatment approaches based on the specific carbapenemase 1.
- Further observational studies are needed to explore the efficacy of ceftazidime/avibactam or other new antibiotics in patients with severe CRE infections caused by OXA-48-producing organisms 1.
From the Research
Rationale for Combining Aztreonam with Ceftazidime
The combination of Aztreonam with Ceftazidime for OXA-48 infections is based on several studies that demonstrate the synergistic effects of this combination against carbapenemase-producing Enterobacteriaceae. The key points are:
- The study 2 found that the addition of Aztreonam to Ceftazidime/Avibactam potentially expands the spectrum of coverage for carbapenemase co-producers, including OXA-48-like producers.
- Another study 3 suggested that Ceftazidime-Avibactam and Aztreonam combination can be used for NDM producers, where available, and Aztreonam-Avibactam provides hope for the treatment of NDM producers.
- The use of Ceftazidime/Avibactam as a treatment option for OXA-48 producers is supported by several studies 4, 5, 6, which demonstrate its effectiveness in treating infections caused by OXA-48-producing Enterobacteriaceae.
Mechanism of Action
The mechanism of action of the combination of Aztreonam with Ceftazidime is based on the synergistic effects of the two antibiotics. Aztreonam is a monobactam antibiotic that is resistant to hydrolysis by many beta-lactamases, including OXA-48. Ceftazidime, on the other hand, is a cephalosporin antibiotic that is susceptible to hydrolysis by OXA-48. However, when combined with Avibactam, a beta-lactamase inhibitor, Ceftazidime becomes effective against OXA-48-producing Enterobacteriaceae.
Key Findings
The key findings of the studies are:
- The combination of Ceftazidime/Avibactam and Aztreonam shows synergistic effects against OXA-48-like producers 2.
- Ceftazidime-Avibactam is an effective treatment option for OXA-48 producers 4, 5, 6.
- The combination of Aztreonam with Ceftazidime/Avibactam can be used for NDM producers, where available 3.
- The use of Ceftazidime/Avibactam as a treatment option for OXA-48 producers is supported by several studies, which demonstrate its effectiveness in treating infections caused by OXA-48-producing Enterobacteriaceae 4, 5, 6.
Benefits of Combination Therapy
The benefits of combining Aztreonam with Ceftazidime for OXA-48 infections include: