Feasibility of 24 h continuous-infusion cefiderocol administered by elastomeric pump in attaining an aggressive PK/PD target in the treatment of NDM-producing Klebsiella pneumoniae otomastoiditis.

Abstract

Objectives: Cefiderocol has emerged as a key treatment for managing MDR infections, and its time-dependent pharmacodynamics are optimized by prolonged infusion to maintain time above the MIC (T _> MIC). Whereas recent stability studies have shown cefiderocol remains stable up to 72 h in elastomeric pumps, its use in 24 h continuous infusions (CIs) for outpatient parenteral antibiotic therapy (OPAT) is undocumented. This case highlights its suitability for 24 h CI via elastomeric pumps in an OPAT setting, supported by therapeutic drug monitoring (TDM) to ensure optimal treatment efficacy.

Patient/case description: A 31-year-old male developed right-sided otomastoiditis caused by Klebsiella pneumoniae producing New Delhi MBL (NDM). Given the resistance profile and the need for prolonged therapy, cefiderocol was initiated at a daily dose of 6 g, administered by 24 h CI using an elastomeric pump. TDM was performed on Days 17 and 45 to assess plasma concentrations.

Results: TDM confirmed steady-state concentrations (C _ss 25.2-28.1 mg/L), achieving optimal pharmacokinetic/pharmacodynamic (PK/PD) target attainment such as 100% T _{> 4-6 MIC} (free [f]C _ss/MIC 10.58-11.80). 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 by means of an elastomeric pump and supported by real-time TDM in achieving an aggressive PK/PD target for the treatment of otomastoiditis due to NDM-producing K. pneumoniae.