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How do I manage difficult-to-treat Pseudomonas aeruginosa infections? Key questions for today's clinicians
Juan P Horcajada1, Ana Gales2, Burcu Isler3
1Department of Infectious Diseases, Hospital del Mar, Hospital del Mar Research Institute (IMIM), Universitat Pompeu Fabra (UPF), Barcelona, Spain; Center for Biomedical Research Network (CIBER) of Infectious Diseases, CIBERINFEC, Institute of Health Carlos III, Madrid, Spain.
Background:
Pseudomonas aeruginosa has a remarkable ability to develop resistance to antimicrobials in vivo, often leaving very limited therapeutic options and making treatment particularly challenging. In fact, P. aeruginosa infections with "difficult-to-treat resistance" are one of the most concerning contemporary bacterial infections. Many are hospital-acquired and frequently affect immunocompromised patients with high mortality risk.
Objectives:
In the absence of head-to-head clinical trials, we have conducted a narrative review of the current therapeutic options for these infections, addressing five key management questions.
Sources:
Pubmed, Scopus, Web od Sicence and reference lists of key articles.
Content:
Ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam, and cefiderocol are newer options, but resistance and lack of relevant data from randomized clinical trials hamper knowledge of the best way to use them.
Implications:
Ceftolozane-tazobactam and ceftazidime-avibactam are initially preferred when susceptible because they enter the market first, and there is more published evidence about them. Ceftolozane-tazobactam is preferred in P. aeruginosa pneumonia instead of ceftazidime-avibactam. Both can be equally used in other P. aeruginosa infection types. Imipenem-relebactam and cefiderocol may retain susceptibility when there is resistance to ceftolozane-tazobactam and ceftazidime-avibactam, and when metallo-beta-lactamases are not present. However, there are no head-to-head comparative studies to support a preference for one over the other. In the presence of metallo-beta-lactamases, cefiderocol is the preferred agent. Other options in this situation are aztreonam-avibactam, ceftazidime-avibactam combined with aztreonam, and polymyxins combined with meropenem, but evidence is limited. In difficult-to-treat P. aeruginosa infections, combination therapy could be an option. However, despite demonstrations of in vitro synergy and of enhanced activity in hollow fibre or animal models, there is no clinical evidence to support using combination therapy in these infections, and it is not currently recommended as a general option. The role of older antibiotics such as fosfomycin, polymyxin B, or colistin is also reviewed.
Insights
Pseudomonas aeruginosa infections are challenging due to antimicrobial resistance. Newer agents like ceftolozane-tazobactam and ceftazidime-avibactam are preferred, but resistance patterns and limited trials impact optimal use.
Area of Science:
- Infectious Diseases
- Clinical Pharmacy
- Antimicrobial Resistance
Background:
- Pseudomonas aeruginosa exhibits significant antimicrobial resistance, complicating treatment and increasing mortality risk, especially in hospital-acquired infections.
- Difficult-to-treat resistant P. aeruginosa infections pose a major public health concern, particularly for immunocompromised individuals.
Purpose of the Study:
- To review current therapeutic strategies for difficult-to-treat P. aeruginosa infections.
- To address key management questions regarding antimicrobial options in the absence of direct comparative clinical trials.
Main Methods:
- A narrative review of existing literature on P. aeruginosa treatment.
- Analysis of current and emerging antimicrobial agents and their resistance profiles.
- Evaluation of evidence for combination therapies and older antibiotics.
Main Results:
- Newer agents (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam, cefiderocol) show promise but require more clinical trial data.
- Ceftolozane-tazobactam and ceftazidime-avibactam are initial choices; cefiderocol is preferred for metallo-beta-lactamase-producing strains.
- Limited evidence supports combination therapy for P. aeruginosa infections despite in vitro synergy.
Conclusions:
- Optimal use of newer P. aeruginosa antibiotics is hindered by resistance and lack of head-to-head trials.
- Ceftolozane-tazobactam and ceftazidime-avibactam are preferred initially, with specific recommendations for pneumonia and metallo-beta-lactamase presence.
- The role of older antibiotics and combination therapies requires further investigation for difficult-to-treat P. aeruginosa infections.
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