Abstract
Pseudomonas aeruginosa is a major opportunistic pathogen, causing a wide range of acute and chronic infections. β-lactam antibiotics including penicillins, carbapenems, monobactams, and cephalosporins play a key role in the treatment of P. aeruginosa infections. However, a significant number of isolates of these bacteria are resistant to β-lactams, complicating treatment of infections and leading to worse outcomes for patients. In this review, we summarize studies demonstrating the health and economic impacts associated with β-lactam-resistant P. aeruginosa. We then describe how β-lactams bind to and inhibit P. aeruginosa penicillin-binding proteins that are required for synthesis and remodelling of peptidoglycan. Resistance to β-lactams is multifactorial and can involve changes to a key target protein, penicillin-binding protein 3, that is essential for cell division; reduced uptake or increased efflux of β-lactams; degradation of β-lactam antibiotics by increased expression or altered substrate specificity of an AmpC β-lactamase, or by the acquisition of β-lactamases through horizontal gene transfer; and changes to biofilm formation and metabolism. The current understanding of these mechanisms is discussed. Lastly, important knowledge gaps are identified, and possible strategies for enhancing the effectiveness of β-lactam antibiotics in treating P. aeruginosa infections are considered.
Highlights
Pseudomonas aeruginosa is a Gram-negative bacillus that is found in many environments including water and soil, and in association with animals [1]
Conclusions and Prospects for the Future β-lactam antibiotics are a key tool in the treatment of P. aeruginosa infections and will remain so for the foreseeable future
Clinical isolates that have acquired carbapenemases are a serious problem as carbapenems are one of the last lines of defence against P. aeruginosa [211]
Summary
Pseudomonas aeruginosa is a Gram-negative bacillus that is found in many environments including water and soil, and in association with animals [1]. Examples of P. aeruginosa infections that have been intensively studied include chronic infections in people with CF and acute infections in burns patients. Initial treatment with antibiotics to which the bacteria were resistant was associated with a mortality rate of 40.6%, emphasising the importance of early treatment with antibiotics that are effective against the infecting P. aeruginosa [23]. In one study of hospitalised patients, 37% of 826 P. aeruginosa isolates from a CF unit, and 49% of 224 isolates from an intensive care unit were antibiotic-resistant [64] These isolates were resistant to a wide variety of antibiotics, including gentamicin (58%), carbapenems (55%), and colistin (6%) [65]. Analysis of wastewater from a burns hospital found that out of 100 P. aeruginosa isolates 66% were MDR [64], illustrating how antibiotic-resistant isolates can be spread into the general environment
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