Feasibility of 24 h Continuous Infusion of Cefiderocol Administered by Elastomeric Pump in Attaining an Aggressive Pharmacokinetic/Pharmacodynamic (PK/PD) Target in the Treatment of NDM-Producing Klebsiella Pneumoniae Otomastoiditis

Introduction: Cefiderocol, a siderophore cephalosporin, has emerged as a key treatment for managing multidrug-resistant (MDR) infections, with its time-dependent pharmacodynamics optimized by prolonged infusion to maintain effective concentrations (fT>MIC). While current technical data sheets recommend reconstitution and use within 6 hours, due to limited stability data, recent findings suggest cefiderocol concentrations remain stable for up to 72 hours at 25°C in elastomeric pumps. Despite its potential, the application in 24-hour continuous infusions (CIs) in an outpatient parenteral antibiotic therapy (OPAT) setting remains undocumented. This case highlights the successful use of cefiderocol via 24-hour CI in an elastomeric pump, supported by therapeutic drug monitoring (TDM), achieving effective serum levels in an OPAT setting.

Methods: A 31-year-old virologically suppressed male, with a prior history of AIDS (cryptococcal meningitis) in 2023, presented with right-sided otomastoiditis caused by Klebsiella pneumoniae producing New Delhi metallo-beta-lactamase (NDM). Given the resistance profile and the need for prolonged therapy, cefiderocol was initiated at 6 g/day via a 24-hour CI using an elastomeric pump (Baxter Infusor LV 10 mL/h). TDM was performed on days 17 and 45 to assess plasma concentrations and ensure pharmacokinetic/pharmacodynamic (PK/PD) target attainment.

Results: TDM confirmed steady-state concentrations (Css 25.2–28.1 mg/L), achieving optimal PK/PD target attainment, such as 100%t>4-6 MIC (fCss/MIC 11.8–12.1). Significant clinical improvement avoided the need for planned surgery, with no adverse events reported from the venous catheter, antibiotic therapy, or elastomeric pump.

Conclusions: This approach underscores the feasibility and efficacy of cefiderocol administered by 24 h CI using elastomeric pumps, supported by real-time TDM to achieve an aggressive PK/PD target for the treatment of otomastoiditis due to NDM-producing Klebsiella pneumoniae. By minimizing hospitalization and enabling outpatient care, this strategy also significantly enhances the patient’s quality of life.