Compassionate Use of Cefiderocol in the Treatment of an Intraabdominal Infection Due to Multidrug‐Resistant Pseudomonas aeruginosa: A Case Report

Abstract

Multidrug‐resistant (MDR) Pseudomonas aeruginosa infections often represent a therapeutic challenge requiring utilization of older, more toxic antibiotics, or new agents with limited data. Once susceptibility to β‐lactam and fluoroquinolone antibiotics has been lost, other therapeutic options such as aminoglycoside or polymyxin antibiotics carry significant adverse effects such as nephrotoxicity, neurotoxicity, and ototoxicity. A novel cephalosporin, cefiderocol, lacks gram‐positive and anaerobic activity but offers broad coverage of gram‐negative bacteria, including P. aeruginosa. A unique catechol side chain gives it activity as a siderophore, thereby increasing bacterial uptake and decreasing efflux. Additionally, cefiderocol is stable against a wide array of β‐lactamases. Despite these promising characteristics, there are minimal data currently available in the literature detailing the use of cefiderocol in the treatment of MDR P. aeruginosa infections. We present a case of a 46‐year‐old man who developed an MDR P. aeruginosa intraabdominal infection where serious and life‐threatening toxicities to aminoglycosides and polymyxin antibiotics led to the utilization of cefiderocol on compassionate use approval. The isolate was susceptible to cefiderocol, and the patient was treated for 28 days of therapy. He demonstrated clinical and radiographic resolution of his infection and was discharged to home.

In Vitro Activity of Cefiderocol, a Siderophore Cephalosporin, against Multidrug-Resistant Gram-Negative Bacteria

“…21 These breakpoint issues become particularly pertinent for bacteria with NDM carbapenemases as the MICs of cefiderocol for these mostly were higher than those infections involving difficult extremely resistant pathogens. [28][29][30] Ultimately, accumulating clinical experience will determine cefiderocol's utility against carbapenemase-producing gram-negative bacteria. Given the drug's unusual mode of uptake this utility may depend on the degree of iron starvation applies at a particular infection site.…”

Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms

“…Cefiderocol was also used to successfully treat a 46-year-old patient with MDR P. aeruginosa intra-abdominal infection susceptible only to amikacin, cefiderocol, colistin, and gentamicin. After 28 days of cefiderocol and metronidazole therapy, CT of the abdomen demonstrated complete resolution of the intra-abdominal abscess and the patient was ultimately discharged to independent living [44]. Lastly, cefiderocol treatment for 14 weeks resulted in clinical and radiological cure in a 15-year-old male with chronic osteomyelitis caused by XDR P. aeruginosa carrying bla NDM-1 and ESBL K. pnemoniae.…”

In vivo emergence of resistance to cefiderocol in an XDR Pseudomonas aeruginosa and an MDR Citrobacter koseri after prolonged therapy: a case report.

“…Ce derocol has been used for a longer period in some compassionate treatments like osteomyelitis (14 weeks), intra-abdominal (28 days) and endovascular infections (30 days) due to XDR germs. All three patients recovered and no emergence of resistance to ce derocol was reported (10,11,12).…”