Salvage therapy with sulbactam/durlobactam against cefiderocol-resistant Acinetobacter baumannii in a critically ill burn patient: clinical challenges and molecular characterization

Giusy Tiseo; Cesira Giordano; Alessandro Leonildi; Niccolò Riccardi; Valentina Galfo; Federica Limongi; Manuela Nicastro; Simona Barnini; Marco Falcone

doi:10.1093/jacamr/dlad078

Salvage therapy with sulbactam/durlobactam against cefiderocol-resistant Acinetobacter baumannii in a critically ill burn patient: clinical challenges and molecular characterization

JAC Antimicrob Resist. 2023 Jun 14;5(3):dlad078. doi: 10.1093/jacamr/dlad078. eCollection 2023 Jun.

Authors

Giusy Tiseo¹, Cesira Giordano², Alessandro Leonildi², Niccolò Riccardi¹, Valentina Galfo¹, Federica Limongi³, Manuela Nicastro³, Simona Barnini², Marco Falcone¹

Affiliations

¹ Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.
² Microbiology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
³ Department of Anaesthesia and Critical Care Medicine, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.

Abstract

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with high mortality rates. The optimal treatment regimen for CRAB has not been defined. Cefiderocol has been recently introduced in the armamentarium against CRAB but there is concern about treatment-emergent resistance. Since mortality rates in CRAB infections remain high, further antibiotic options are needed.

Methods: We report a case of severe infection by CRAB resistant to both colistin and cefiderocol treated with sulbactam/durlobactam and describe the molecular features of the strain. Susceptibility to cefiderocol was detected by disc diffusion according to EUCAST breakpoints. Susceptibility to sulbactam/durlobactam was determined by Etest according to preliminary breakpoints provided by Entasis Therapeutics. Whole Genome Sequencing (WGS) of the CRAB isolate was performed.

Results: A burn patient with ventilator-associated pneumonia by CRAB resistant to colistin and cefiderocol received sulbactam/durlobactam as compassionate use. She was alive after 30 days from the end of therapy. Complete microbiological eradication of CRAB was achieved. The isolate harboured bla_ADC-30, bla_OXA-23 and bla_OXA-66. A missense mutation in PBP3 was detected. The isolate harboured a mutation in the TonB-dependent siderophore receptor gene piuA that showed a frameshift mutation causing a premature stop codon (K384fs). Moreover, the fepA gene, which is orthologous to pirA, was interrupted by a transposon insertion P635-ISAba125 (IS30 family).

Conclusions: Further treatment options for severe infections by CRAB resistant to all available antibiotics are urgently needed. Sulbactam/durlobactam may be a future option against MDR A. baumannii.