Continuous versus intermittent infusion of antibiotics in Gram-negative multidrug-resistant infections

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.

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.