Pyelonephritis Caused by Pseudomonas aeruginosa : From Treatable Infection to Therapeutic Dead-End,Rescued by an Investigational Antibiotic

Abstract

Pseudomonas aeruginosa is a major Gram-negative pathogen causing diverse infections, including complicated urinary tract infections (cUTIs). Although such cUTIs are usually treatable with standard antipseudomonal β-lactams, the rise of carbapenem-resistant P. aeruginosa, particularly those producing New Delhi metallo-β-lactamase (NDM), has made therapeutic options extremely limited. We report a 58-year-old man with diabetes, hypertension, and ischemic heart disease who presented with pyelonephritis in the setting of a long-retained ureteric stent. Urine culture grew P. aeruginosa resistant to meropenem, and molecular testing confirmed the presence of NDM. The whole-genome sequencing revealed that the isolate belonged to high-risk sequence type 308 clone carrying NDM-1 and multiple additional resistance determinants. Given the lack of effective alternative antibiotics and the patient’s deteriorating clinical course with underlying renal impairment precluding the use of colistin, investigational drug cefepime/zidebactam (WCK 5222) was initiated under compassionate ground. The patient underwent source control with percutaneous nephrostomy and stone clearance. He received 37 days of cefepime/zidebactam, during which he showed rapid clinical improvement, resolution of pyelonephritis, and sterile urine cultures. This case underscores how infections such as cUTI or pyelonephritis, usually considered manageable, can become untreatable in NDM-endemic settings and highlights cefepime/zidebactam as a promising therapeutic option for highly resistant P. aeruginosa.