Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study

Reyes, Jinnethe; Komarow, Lauren; Chen, Liang; Ge, Lizhao; Hanson, Blake; Cober, Eric; Herc, Erica; Alenazi, Thamer H.; Kaye, Keith S.; Garcia‐Diaz, Julia; Li, Lanjuan; Kanj, Souha S.; Liu, Zhengyin; Oñate, Jose M; Salata, Robert A.; Marimuthu, Kalisvar; Gao, Hainv; Zong, Zhiyong; Valderrama-Beltrán, Sandra; Yu, Yunsong; Tambyah, Paul Ananth; Weston, Gregory; Salcedo, Soraya; Abbo, Lillian; Xie, Qing; Ordóñez, Karen; Wang, Minggui; Stryjewski, Martín E.; Munita, José M.; Paterson, David L.; Evans, Scott; Hill, Carol; Baum, Katherine T.; Kreiswirth, Barry N.; Villegas, María Virginia; Patel, Robin; Arias, César A.; Chambers, Henry F.; Fowler, Vance G.; Doi, Yohei; Duin, David van; Satlin, Michael J.

doi:10.1016/s2666-5247(22)00329-9

Cited by 119 publications

(100 citation statements)

References 28 publications

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“…aeruginosa, a common opportunistic pathogen, is now generally recognized as one of the most causative agents of hospital-acquired infections 1 . MDR P. aeruginosa has become more and more common in recent years, posing severe challenges to global health 1,14 . Moreover, P. aeruginosa was included in the World Health Organization's list of superbugs that urgently need novel antibiotics in 2017 1 .…”

Section: Discussionmentioning

confidence: 99%

“…MDR P. aeruginosa has become more and more common in recent years, posing severe challenges to global health 1,14 . Moreover, P. aeruginosa was included in the World Health Organization's list of superbugs that urgently need novel antibiotics in 2017 1 . The search for novel treatments for MDR P. aeruginosa has become a hot topic.…”

Section: Discussionmentioning

confidence: 99%

“…Pseudomonas aeruginosa infections are a severe concern in healthcare settings, especially for patients with compromised immune systems or those who require prolonged hospital stays 1 . The ability of P. aeruginosa to form biofilms in the lungs of patients such as cystic fibrosis (CF) is particularly concerning, as this can lead to chronic infections that are difficult to eradicate 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, bacteria within a biofilm may exhibit altered gene expression and metabolism, further complicating treatment strategies 2,3 . Furthermore, the emergence of multi-drug resistant (MDR) strains of P. aeruginosa adds another layer of difficulty in treating infections caused by this pathogen 1 . Thus, there is an urgent need for the implementation of novel antimicrobial agents to treat P. aeruginosa infections.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of a phage cocktail preparation for chronic lung infection withPseudomonas aeruginosain mice

Gao

Tan

Pan

et al. 2023

Preprint

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Pseudomonas aeruginosa is a leading cause of hospital-acquired infections, and the emergence of multi-drug resistant strains has prompted the search for alternative treatments such as phage therapy. In this study, we combined host range and genomic information to design a four-phage cocktail that effectively killed several clinical strains (79%, 23/29) of P. aeruginosa. We demonstrated that the cocktail, composed of three novel phages (PA_ZH1, PA_GL1, and PA_CQ9) and one previously characterized phage (PA_LZ7), was able to lyse P. aeruginosa both in planktonic cultures and in alginate microbeads (an in vivo-like biofilm model). Additionally, we showed that the phage cocktail administered intranasally or intraperitoneally effectively rescued mice from chronic lung infection with P. aeruginosa. Our work explores the potential use of phages as an alternative therapeutic agent against chronic lung infections caused by P. aeruginosa strains.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of a phage cocktail preparation for chronic lung infection withPseudomonas aeruginosain mice

Gao

Tan

Pan

et al. 2023

Preprint

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show abstract

“…In a 10-year program involving 76 countries, 20.5% of the 68 897 PA isolates were resistant to carbapenems (CR-PA). Carbapenemase genes were detected in 14.3% of patients infected with CR-PA, and VIM was the most prevalent [35] However, this incidence may vary according to the region [36].…”

Section: Epidemiology: When To Suspect Pseudomonas Aeruginosa Infecti...mentioning

confidence: 99%

Management strategies for severe Pseudomonas aeruginosa infections

Do Rego,

Timsit

2023

Current Opinion in Infectious Diseases

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Purpose This review focuses on the management of severe Pseudomonas aeruginosa infections in critically ill patients. Recent findings Pseudomonas aeruginosa is the most common pathogen in intensive care; the main related infections are nosocomial pneumonias, then bloodstream infections. Antimicrobial resistance is common; despite new antibiotics, it is associated with increased mortality, and can lead to a therapeutic deadlock. Summary Carbapenem resistance in difficult-to-treat P. aeruginosa (DTR-PA) strains is primarily mediated by loss or reduction of the OprD porin, overexpression of the cephalosporinase AmpC, and/or overexpression of efflux pumps. However, the role of carbapenemases, particularly metallo-β-lactamases, has become more important. Ceftolozane-tazobactam, ceftazidime-avibactam and imipenem-relebactam are useful against DTR phenotypes (noncarbapenemase producers). Other new agents, such as aztreonam-ceftazidime-avibactam or cefiderocol, or colistin, might be effective for carbapenemase producers. Regarding nonantibiotic agents, only phages might be considered, pending further clinical trials. Combination therapy does not reduce mortality, but may be necessary for empirical treatment. Short-term treatment of severe P. aeruginosa infections should be preferred when it is expected that the clinical situation resolves rapidly.

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Antimicrobial Peptides: A Promising Alternative to Conventional Antimicrobials for Combating Polymicrobial Biofilms

Roque‐Borda,

Primo,

Medina‐Alarcón

et al. 2024

Advanced Science

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Polymicrobial biofilms adhere to surfaces and enhance pathogen resistance to conventional treatments, significantly contributing to chronic infections in the respiratory tract, oral cavity, chronic wounds, and on medical devices. This review examines antimicrobial peptides (AMPs) as a promising alternative to traditional antibiotics for treating biofilm‐associated infections. AMPs, which can be produced as part of the innate immune response or synthesized therapeutically, have broad‐spectrum antimicrobial activity, often disrupting microbial cell membranes and causing cell death. Many specifically target negatively charged bacterial membranes, unlike host cell membranes. Research shows AMPs effectively inhibit and disrupt polymicrobial biofilms and can enhance conventional antibiotics' efficacy. Preclinical and clinical research is advancing, with animal studies and clinical trials showing promise against multidrug‐resistant bacteria and fungi. Numerous patents indicate increasing interest in AMPs. However, challenges such as peptide stability, potential cytotoxicity, and high production costs must be addressed. Ongoing research focuses on optimizing AMP structures, enhancing stability, and developing cost‐effective production methods. In summary, AMPs offer a novel approach to combating biofilm‐associated infections, with their unique mechanisms and synergistic potential with existing antibiotics positioning them as promising candidates for future treatments.

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Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study

Cited by 119 publications

References 28 publications

Efficacy of a phage cocktail preparation for chronic lung infection withPseudomonas aeruginosain mice

Efficacy of a phage cocktail preparation for chronic lung infection withPseudomonas aeruginosain mice

Management strategies for severe Pseudomonas aeruginosa infections

Antimicrobial Peptides: A Promising Alternative to Conventional Antimicrobials for Combating Polymicrobial Biofilms

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