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Nanoparticles in the Treatment of Infections Caused by Multidrug-Resistant Organisms.

ABSTRACT: Nanotechnology using nanoscale materials is increasingly being utilized for clinical applications, especially as a new paradigm for infectious diseases. Infections caused by multidrug-resistant organisms (MDROs) are emerging as causes of morbidity and mortality worldwide. Antibiotic options for infections caused by MDROs are often limited. These clinical challenges highlight the critical demand for alternative and effective antimicrobial strategies. Nanoparticles (NPs) can penetrate the cell membrane of pathogenic microorganisms and interfere with important molecular pathways, formulating unique antimicrobial mechanisms. In combination with optimal antibiotics, NPs have demonstrated synergy and may aid in limiting the global crisis of emerging bacterial resistance. In this review, we summarized current research on the broad classification of the NPs that have shown in vitro antimicrobial activity against MDROs, including the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The pharmacokinetics and pharmacodynamic characteristics of NPs and bacteria-resistant mechanisms to NPs were also discussed.

SUBMITTER: Lee NY

PROVIDER: S-EPMC6787836 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Nanoparticles in the Treatment of Infections Caused by Multidrug-Resistant Organisms.

Lee Nan-Yao NY Ko Wen-Chien WC Hsueh Po-Ren PR

Frontiers in pharmacology 20191004

Nanotechnology using nanoscale materials is increasingly being utilized for clinical applications, especially as a new paradigm for infectious diseases. Infections caused by multidrug-resistant organisms (MDROs) are emerging as causes of morbidity and mortality worldwide. Antibiotic options for infections caused by MDROs are often limited. These clinical challenges highlight the critical demand for alternative and effective antimicrobial strategies. Nanoparticles (NPs) can penetrate the cell mem ...[more]

PMID: 31636564

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Project description:Appropriate antibiotic treatment for critically ill patients with serious Gram-negative infections in the intensive care unit is crucial to minimize morbidity and mortality. Several new antibiotics have shown in vitro activity against carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat resistant Pseudomonas aeruginosa. Cefiderocol is the first approved siderophore beta-lactam antibiotic with potent activity against multidrug-resistant, carbapenem-resistant, difficult-to-treat or extensively drug-resistant Gram-negative pathogens, which have limited treatment options. The spectrum of activity of cefiderocol includes drug-resistant strains of Acinetobacter baumannii, P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia spp. and CRE that produce serine- and/or metallo-carbapenemases. Phase 1 studies established that cefiderocol achieves adequate concentration in the epithelial lining fluid in the lung and requires dosing adjustment for renal function, including patients with augmented renal clearance and continuous renal-replacement therapy (CRRT); no clinically significant drug-drug interactions are expected. The non-inferiority of cefiderocol versus high-dose, extended-infusion meropenem in all-cause mortality (ACM) rates at day 14 was demonstrated in the randomized, double-blind APEKS-NP Phase 3 clinical study in patients with nosocomial pneumonia caused by suspected or confirmed Gram-negative bacteria. Furthermore, the efficacy of cefiderocol was investigated in the randomized, open-label, pathogen-focused, descriptive CREDIBLE-CR Phase 3 clinical study in its target patient population with serious carbapenem-resistant Gram-negative infections, including hospitalized patients with nosocomial pneumonia, bloodstream infection/sepsis, or complicated urinary tract infections. However, a numerically greater ACM rate with cefiderocol compared with BAT led to the inclusion of a warning in US and European prescribing information. Cefiderocol susceptibility results obtained with commercial tests should be carefully evaluated due to current issues regarding their accuracy and reliability. Since its approval, real-world evidence in patients with multidrug-resistant and carbapenem-resistant Gram-negative bacterial infections suggests that cefiderocol can be efficacious in certain critically ill patient groups, such as those requiring mechanical ventilation for COVID-19 pneumonia with subsequently acquired Gram-negative bacterial superinfection, and patients with CRRT and/or extracorporeal membrane oxygenation. In this article, we review the microbiological spectrum, pharmacokinetics/pharmacodynamics, efficacy and safety profiles and real-world evidence for cefiderocol, and look at future considerations for its role in the treatment of critically ill patients with challenging Gram-negative bacterial infections.

Dataset Information

Nanoparticles in the Treatment of Infections Caused by Multidrug-Resistant Organisms.

Publications

Nanoparticles in the Treatment of Infections Caused by Multidrug-Resistant Organisms.

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