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Clin Microbiol Rev. 2019 Aug 28;32(4). pii: e00031-19. doi: 10.1128/CMR.00031-19. Print 2019 Sep 18.

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections.

Author information

1
Service of Infectious Diseases, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain jhorcajada@parcdesalutmar.cat.
2
Spanish Network for Research in Infectious Diseases (REIPI), Madrid, Spain.
3
Service of Infectious Diseases, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain.
4
Service of Microbiology, Hospital Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Palma de Mallorca, Spain.
5
Service of Infectious Diseases, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra, Barcelona, Spain.
6
Service of Pharmacy, Hospital del Mar, Infectious Pathology and Antimicrobials Research Group, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain.
7
Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

Abstract

SUMMARYIn recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR) Pseudomonas aeruginosa has become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options. In vitro and in vivo treatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Polymyxins are reviewed as an important therapeutic option, outlining dosage, pharmacokinetics and pharmacodynamics, and their clinical efficacy against MDR/XDR P. aeruginosa infections. Their narrow therapeutic window and potential for combination therapy are also discussed. Other "old" antimicrobials, such as certain β-lactams, aminoglycosides, and fosfomycin, are reviewed here. New antipseudomonals, as well as those in the pipeline, are also reviewed. Ceftolozane-tazobactam has clinical activity against a significant percentage of MDR/XDR P. aeruginosa strains, and its microbiological and clinical data, as well as recommendations for improving its use against these bacteria, are described, as are those for ceftazidime-avibactam, which has better activity against MDR/XDR P. aeruginosa, especially strains with certain specific mechanisms of resistance. A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.

KEYWORDS:

Pseudomonas aeruginosa

PMID:
31462403
PMCID:
PMC6730496
[Available on 2020-08-28]
DOI:
10.1128/CMR.00031-19

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