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

Area of Science:

• Infectious Diseases
• Microbiology
• Pharmacology

Background:

• Complicated urinary tract infections (cUTIs) caused by Pseudomonas aeruginosa are typically treated with antipseudomonal β-lactams.
• The emergence of carbapenem-resistant P. aeruginosa, especially NDM producers, severely limits therapeutic choices.
• NDM-producing P. aeruginosa poses a significant challenge in managing infections like pyelonephritis.

Purpose of the Study:

• To report a case of pyelonephritis caused by NDM-producing carbapenem-resistant P. aeruginosa.
• To evaluate the efficacy of the investigational drug cefepime/zidebactam in a patient with limited treatment options.
• To highlight the challenges in treating highly resistant Gram-negative bacterial infections.

Main Methods:

• A patient with pyelonephritis due to meropenem-resistant P. aeruginosa with confirmed NDM production was identified.
• Whole-genome sequencing was performed to characterize the P. aeruginosa isolate, identifying it as ST308 clone with NDM-1.
• The patient received cefepime/zidebactam under compassionate use after other antibiotics were ineffective and colistin was contraindicated.

Main Results:

• The P. aeruginosa isolate carried NDM-1 and multiple other resistance genes.
• The patient experienced rapid clinical improvement, resolution of pyelonephritis, and sterile urine cultures after 37 days of cefepime/zidebactam treatment.
• Cefepime/zidebactam demonstrated effectiveness in treating a severe NDM-positive P. aeruginosa infection.

Conclusions:

• NDM-producing P. aeruginosa infections, even cUTIs, can become untreatable in NDM-endemic areas.
• Cefepime/zidebactam represents a potential therapeutic option for infections caused by highly resistant P. aeruginosa.
• This case underscores the need for novel antimicrobial agents to combat multidrug-resistant Gram-negative pathogens.