Compassionate use of cefiderocol for carbapenem-resistant Acinetobacter baumannii prosthetic joint infection

Abstract

Background: Cefiderocol is a recently licensed novel siderophore-conjugated cephalosporin stable to hydrolysis by serine and MBLs. It has been successfully used to treat Enterobacterales infections and is approved for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.

Objectives: To describe the compassionate use of cefiderocol and clinical outcome in a case of prosthetic joint infection due to MDR Acinetobacter baumannii.

Patients and methods: This case study follows a 66-year-old woman who sustained an open fracture of the left distal humerus in Pakistan. She underwent open reduction and internal fixation and on return to the UK presented to hospital with a discharging surgical wound.

Results: Debridement of her wound cultured NDM carbapenemase-producing A. baumannii susceptible to colistin, tobramycin and tigecycline only. She developed vomiting with acute kidney injury with colistin and tigecycline. Antimicrobial efficacy of cefiderocol was predicted from in vitro and in vivo susceptibility tests. A successful request was made to Shionogi for compassionate use of cefiderocol, which was added to tigecycline. Cefiderocol was well tolerated with no toxicity and improved renal function. In total she received 25 days of cefiderocol and continued on tigecycline for a further 6 weeks in the community. She has well-healed wounds and good range of elbow movement.

Conclusions: Cefiderocol's novel mode of cell entry is effective against MDR Gram-negative bacteria with reduced toxicity compared with other last line antibiotics. Our case demonstrates that cefiderocol may be useful as therapy for patients with limited treatment options due to antimicrobial resistance.

Figure 1.

(a) Open wound in left arm at time of presentation. (b) Plain X-ray of left arm at time of presentation. (c) Left elbow after completion of antimicrobial therapy.

Figure 2.

Efficacy of cefiderocol versus A. baumannii infection in Galleria mellonella. Survival curve over 96 h (Kaplan–Meier P < 0.05).