Abstract Background MDR Gram-negative bacteria such as Pseudomonas aeruginosa represent the highest priority for addressing global antibiotic resistance. Moreover, selecting an appropriate empirical antibiotic treatment for MDR strains is a challenge. Cefiderocol, a novel siderophore cephalosporin, has demonstrated activity against Gram-negative strains resistant to other available antibiotics. Patient case A 58-year-old female was admitted on to the ICU with type 1 respiratory failure as a consequence of COVID-19 pneumonitis. During the course of her ICU admission she developed persistent bilateral empyema and pneumothorax which did not resolve despite the use of pleural drains. The empyema samples grew P. aeruginosa. Treatment course The patient was treated with commonly used antibiotics for P. aeruginosa, including piperacillin/tazobactam, meropenem, ceftolozane/tazobactam and ciprofloxacin. However, repeated testing of empyema fluid and respiratory secretions identified an increasingly drug-resistant P. aeruginosa strain. Following left thoracotomy and pleural decortication, cefiderocol was approved for compassionate use and the patient was treated for 14 days. The patient experienced good resolution of clinical symptoms and C-reactive protein levels and was discharged to the ward after 105 days in the ICU. The patient was briefly readmitted to the ICU with worsening type 2 respiratory failure 2 weeks later. Ceftolozane/tazobactam and colistin treatment were recommenced as a bridging measure until cefiderocol became available in the hospital. Notably, the P. aeruginosa isolated remained susceptible to cefiderocol following the first course of treatment. Cefiderocol therapy (2 g t.i.d.) was recommenced for 14 days of ward based treatment. The patient demonstrated clinical and radiographic resolution of her infection and was eventually discharged home. Conclusions This patient case describes a heavily pretreated female with a MDR P. aeruginosa strain successfully managed with cefiderocol and source control. Cefiderocol was prescribed for compassionate use for treatment of MDR P. aeruginosa. Treatment was well tolerated and led to good resolution of clinical symptoms. Cefiderocol may help address the global issue of MDR P. aeruginosa.