Journal
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
Volume 21, Issue 2, Pages 149-166Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14787210.2023.2169131
Keywords
DTR Gram-negative infections; critically ill patients; PK; PD dosing optimization; personalized antimicrobial therapy; ceftolozane-tazobactam; ceftazidime-avibactam; meropenem-vaborbactam; imipenem-relebactam; cefiderocol
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This review evaluates the role of pharmacokinetic/pharmacodynamic (PK/PD) optimization of novel beta-lactams in the management of difficult-to-treat resistance (DTR) Gram-negative infections. The findings suggest that optimizing antimicrobial therapy with novel beta-lactams based on PK/PD concepts can maximize clinical efficacy and prevent resistance emergence. Establishing a coordinated multidisciplinary team and implementing personalized antimicrobial exposure optimization can be crucial for the management of DTR Gram-negative infections.
IntroductionThe choice of best therapeutic strategy for difficult-to-treat resistance (DTR) Gram-negative infections currently represents an unmet clinical need.Areas coveredThis review provides a critical reappraisal of real-world evidence supporting the role of pharmacokinetic/pharmacodynamic (PK/PD) optimization of novel beta-lactams in the management of DTR Gram-negative infections. The aim was to focus on prolonged and/or continuous infusion administration, penetration rates into deep-seated infections, and maximization of PK/PD targets in special renal patient populations. Retrieved findings were applied to the three most critical clinical scenarios of Gram-negative resistance phenotypes (i.e. carbapenem-resistant Enterobacterales; difficult-to-treat resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii).Expert opinionSeveral studies supported the role of PK/PD optimization of beta-lactams in the management of DTR Gram-negative infections for both maximizing clinical efficacy and preventing resistance emergence. Optimizing antimicrobial therapy with novel beta-lactams based on the so called 'antimicrobial therapy puzzle' PK/PD concepts may represent a definitive jump into the future toward a personalized patient management of DTR Gram negative infections. Establishing a dedicated and coordinated multidisciplinary team and implementing a real-time TDM-guided personalized antimicrobial exposure optimization of novel beta-lactams based on expert clinical pharmacological interpretation, could represent crucial cornerstones for the proper management of DTR Gram-negative infections.
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