A Case Study in Translating Scientific Discoveries into Real-World Care

Erlinda (“Chulie”) Ulloa, MD, leveraged bedside-to-bench testing to identify novel treatment options for a young woman with a life-threatening infection. The patient became the first in the U.S. to receive the investigational antibiotic cefepime–zidebactam.

What happens when a young patient with a rare, life-threatening disease has serious complications, resulting in a multidrug-resistant infection that will not respond to conventional therapies?

A new case study published in The Lancet Infectious Diseases outlines how UC Irvine researchers helped save a patient at Rady’s Children’s Hospital of Orange County (CHOC), using novel antimicrobial approaches.

“We cared for a young woman with leukemia who developed a rare condition — calciphylaxis — that caused painful skin wounds and a life-threatening infection from a bacterium that was resistant to nearly every available antibiotic,” says Erlinda (“Chulie”) Ulloa, MD, an infectious disease specialist at the UC Irvine School of Medicine and attending physician at Rady’s CHOC.

The patient became the first in the U.S. to receive the investigational antibiotic cefepime–zidebactam. She was also the first patient at CHOC to receive bacteriophage therapy, which uses viruses that specifically target bacteria.

“By combining a novel antibiotic with bacteriophage therapy, specialized wound care, and treatment of the underlying skin disease,” says Ulloa, “we were able to help the patient recover and achieve complete wound healing.”

Rapid Bedside-to-Bench Testing

The case study exemplifies how to translate scientific discoveries into real-world therapies for patients with otherwise untreatable infections.

Researchers in the Ulloa Lab conducted antibiotic susceptibility to guide precision antimicrobial therapy for the patient’s multidrug-resistant infection.

“When standard treatments failed, our team rapidly moved between the bedside and the laboratory to identify new treatment options,” says Ulloa. “Laboratory testing helped us select an investigational antibiotic and bacteriophage therapy tailored to the patient’s infection.”

Their initial testing identified cefepime–zidebactam as a potential option. The team also collaborated with the Van Tyne Laboratory at the University of Pittsburgh to pursue bacteriophage therapy. That same month, the U.S. Food and Drug Administration and CHOC’s Institutional Review Board approved emergency access to cefepime–zidebactam and bacteriophage.

Ulloa then oversaw the administration of the cefepime–zidebactam and bacteriophage therapy while also directing management of the patient’s calciphylaxis throughout her hospitalization.

The wound completely healed eight months after therapy, and the patient’s leukemia was still in remission 18 months after chemotherapy.

New Strategies for Multidrug-Resistant Infections

This experience has inspired several ongoing research efforts in the Ulloa Lab, which aims to improve patient care by informing treatment guidelines, drug repurposing and development, and antimicrobial susceptibility testing.

“We are studying how bacteriophages and novel antibiotics influence bacterial evolution and whether they can drive bacteria to become less virulent or more susceptible to existing antibiotics,” says Ulloa.

“We are also investigating the genetic mechanisms that allowed this Pseudomonas aeruginosa [bacterium] strain to develop and later lose resistance to multiple therapies,” she continues. “Ultimately, our goal is to develop more effective treatment strategies for patients with multidrug-resistant infections.”

— Shani Murray