ABSTRACT Background Bacteriophages (phages), viruses ubiquitous in the environment infecting bacteria, are an increasingly attractive option for adjunct therapy with conventional antibiotics in complicated, refractory multidrug-resistant infections. Bacteria (“hypermutators”) with defects in methyl-directed mismatch repair (MMR) have been described in Pseudomonas aeruginosa , with the resultant defect in DNA repair responsible for rapid development of antimicrobial resistance. Case Summary A 72-year-old male with mild chronic obstructive pulmonary disease, diagnosed with resectable, advanced right frontoethmoid adenoid cystic carcinoma, underwent endoscopic resection to remove the affected bone and tissue. The subsequent large craniofacial defect was reconstructed with non-vascularized calvarial bone grafts, rigidly fixated with titanium hardware and externally covered with a vascularized pericranial flap. He developed complete dehiscence of the skull base reconstruction, and wound cultures grew multiple susceptible P. aeruginosa isolates with distinct morphologies that became progressively drug resistant on treatment. Whole-genome sequencing of isolates showed the presence of a non-synonymous mutation in the mutS gene impacting the MMR pathway, consistent with a hypermutator. Phage therapy was pursued due to ongoing infection with retained hardware, lack of clinical response to antibiotic therapy alone, extreme antibiotic resistance, and possible surgical cure of his cancer. He received twice-daily intravenous phage therapy in combination with cefiderocol for 2 weeks with clinical and microbiological resolution of his infection. Conclusion This case suggests that phage therapy may be useful in the treatment of deep-seated hypermutator P. aeruginosa infections with retained hardware.
Ngauy et al. (Fri,) studied this question.