Journal
CURRENT OPINION IN INFECTIOUS DISEASES
Volume 34, Issue 6, Pages 737-747Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QCO.0000000000000755
Keywords
ceftazidime-avibactam; ceftolozane-tazobactam; multidrug resistance gram-negative infections; novel beta-lactams; prolonged infusion
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Real-world evidence suggests that novel beta-lactams administered via prolonged infusion are more effective than intermittent infusion in achieving aggressive PK/PD targets and suppressing resistance development. Prolonged infusion may be beneficial in specific scenarios to optimize the efficacy of novel agents.
Purpose of review The aim of this review was to perform a critical reappraisal of the real-world evidence supporting administration by prolonged infusion of novel beta-lactams for the management of multidrug-resistant Gram-negative infections. Recent findings Real-world evidence support the use of novel beta-lactams by prolonged infusion over intermittent infusion in terms of achieving aggressive pharmacokinetic/pharmacodynamic (PK/PD) target for either maximizing efficacy and clinical outcome or suppressing the emergence of resistance development. Continuous infusion of ceftolozane-tazobactam showed a marked superiority toward both intermittent and extended infusion (EI) in achieving a PK/PD target of 100%fT(> 4 X MIC) in infections caused by less-susceptible Pseudomonas aeruginosa isolates. No resistance development was found in critically ill or immunocompromised patients treated with EI ceftolozane-tazobactam compared to intermittent infusion. Prolonged infusion of ceftazidime-avibactam was negatively associated with mortality in patients affected by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae infections. Different challenging scenarios (patients showing augmented renal clearance of affected by deep-seated infections) could benefit from prolonged infusion to optimize the efficacy of novel agents. Although available data are still limited, real-world evidence regarding mainly ceftolozane-tazobactam and ceftazidime-avibactam could support the administration of novel beta-lactams by prolonged infusion in some specific scenarios in which achievement of aggressive PK/PD target is quite challenging.
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