From the Guidelines
Treating a Pseudomonas aeruginosa infection with ceftazidime alone can increase the risk of developing resistance to ceftazidime/avibactam. This occurs because ceftazidime/avibactam shares the same beta-lactam component (ceftazidime) as standalone ceftazidime. When P. aeruginosa is exposed to ceftazidime, it can develop resistance mechanisms such as upregulation of efflux pumps, production of AmpC beta-lactamases, or mutations in porin channels that reduce drug entry into the bacterial cell. These same mechanisms can affect the efficacy of the ceftazidime component in ceftazidime/avibactam. While avibactam provides protection against some beta-lactamases, it cannot overcome all resistance mechanisms that develop against ceftazidime.
To minimize resistance development, it's essential to use appropriate dosing of ceftazidime (typically 2g IV every 8 hours for normal renal function, adjusted for impaired renal function), ensure adequate duration of therapy without unnecessary prolongation, and consider combination therapy with other antipseudomonal agents for severe infections. Some key points to consider when treating Pseudomonas aeruginosa infections include:
- Using ceftazidime/avibactam as a first-line option for targeted treatment of invasive infections caused by Pseudomonas aeruginosa with difficult-to-treat resistance, as recommended by recent guidelines 1.
- Considering alternative treatment options, such as colistin-based therapy, ceftolozane/tazobactam, or imipenem/cilastatin–relebactam, for infections caused by carbapenem-resistant Pseudomonas aeruginosa or difficult-to-treat Pseudomonas aeruginosa, as outlined in recent recommendations 1.
- Implementing antimicrobial stewardship practices, including culture-guided therapy and de-escalation when possible, to preserve the effectiveness of both agents.
It is crucial to prioritize the most recent and highest-quality evidence when making treatment decisions, and to consider the potential risks and benefits of different treatment options in the context of individual patient needs and circumstances. In this case, the most recent evidence from 2022 1 provides guidance on the use of ceftazidime/avibactam and other treatment options for Pseudomonas aeruginosa infections.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Risk of Developing Resistance to Ceftazidime/Avibactam
- The use of ceftazidime-avibactam for the treatment of Pseudomonas aeruginosa infections may select for multidrug-resistance and prevent the design of collateral sensitivity-based therapies 2.
- However, a retrospective cohort study found that the emergence of drug resistance to ceftazidime-avibactam was not detected in patients with multidrug-resistant Pseudomonas aeruginosa infections treated with ceftazidime-avibactam 3.
- Another study found that the isolation of Pseudomonas aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems compared to ceftazidime and piperacillin-tazobactam 4.
- The addition of avibactam to ceftazidime has been shown to protect ceftazidime from degradation and restore its cidal and static activity against β-lactam-resistant Pseudomonas aeruginosa 5.
Factors Influencing Resistance Development
- The development of resistance to ceftazidime-avibactam may be influenced by factors such as the duration of treatment, the dose of ceftazidime-avibactam, and the presence of underlying resistance mechanisms in the bacterial population 2, 3.
- The use of ceftazidime-avibactam as combination therapy may also impact the development of resistance, with one study finding that combination therapy was associated with a lower risk of resistance emergence 3.
Clinical Implications
- The potential risk of developing resistance to ceftazidime-avibactam should be considered when treating Pseudomonas aeruginosa infections, particularly in patients with multidrug-resistant infections 2, 3.
- Clinicians should carefully monitor patients for signs of resistance emergence and adjust treatment regimens accordingly 3.
- Further studies are needed to fully understand the risk of resistance development associated with ceftazidime-avibactam treatment and to inform evidence-based treatment guidelines 2, 3.