An old drug used to treat urinary tract infections may have a new trick up its sleeve. In a recent case report, doctors in California say they used it to stop a brain-eating infection caused by an amoeba. Though the infection is very rare, it’s almost always fatal.
The brain-eating bug is known as Balamuthia mandrillaris. It’s a single-celled, free-living amoeba found most everywhere in the soil and water. It likely feeds on smaller amoeba in these environments, but it was actually first discovered inside the brain of a dead mandrill monkey in the late 1980s. By 1993, it was confirmed to be a distinct species of amoeba, and one of the few that can cause serious brain infections in humans.
The amoeba can enter the body through the nose or skin wounds and eventually reach the brain through the bloodstream, causing a condition known as granulomatous amebic encephalitis, or GAE. Unlike “flesh-eating bacteria” — a misleading term — B. mandrillaris really does seem to munch on our brain matter, though a lot of the havoc it wreaks is also the result of our immune response. People might live unknowingly with the infection for years before symptoms like fever, headaches, seizures, and behavioural changes appear. But once they do, it has a fatality rate around 90%. GAE caused by B. mandrillaris is very rare, with a little more than 200 cases documented worldwide since its discovery, but it can affect anyone, including those with healthy immune systems.
The current case, detailed last month in the journal Emerging Infectious Diseases, involved a 54-year-old man who visited a hospital in Northern California after experiencing a seizure in August 2021. MRI scans soon revealed masses and swelling on the left side of his brain and, after initial treatment, he was transferred to doctors at University of California San Francisco (UCSF) Medical Centre. Initial tests ruled out culprits like bacteria or fungi, and he was eventually discharged. But upon reviewing his case again, the doctors decided to test the man’s biopsy samples for a possible amoeba infection. Finally, about a month after his initial visit, the test came back positive for B. mandrillaris, and the man was quickly readmitted to the hospital.
MRIs revealed new brain lesions, and he was placed on a lengthy combination of antimicrobials, the only known standard treatment for GAE. He initially seemed to improve, with his lesions decreasing in size, but the toxicity of the drugs was too much for the rest of his body to continue treatment as is. Though doctors tried to find an effective but safe enough mix of medications, his condition once again began to deteriorate.
Desperate, the doctors scoured the medical literature for some other option. They came across lab research from their own colleagues at USCF, which suggested that the drug nitroxoline could be an effective anti-amoeba treatment. About 100 days into the man’s care from his first hospital visit, and after obtaining permission from his family and the Food and Drug Administration, the doctors started him on nitroxoline. While he initially experienced kidney problems (possibly unrelated to the drug), he began improving. After a week of treatment, his brain lesions decreased and he was eventually discharged from the hospital.
Nitroxoline has long been approved and used as a bacteria-killing drug for urinary tract infections. But it’s not commercially available in the U.S., which is why the doctors had to secure a supply from a pharma company in China studying its potential use as a bladder cancer treatment, Science Magazine reported. Another limitation is diagnosing these rare cases early enough for the drug to still work, but new screening technologies — including those developed by some of the co-authors at UCSF — might one day make detection easier.
As for the patient, he’s had to deal with some complications along the way, but his lesions have continued to shrink and he’s largely recovered from his ordeal, the doctors say. He’s currently taking a combination of medications, including nitroxoline, though his outpatient team plans to wean him off these drugs within a year.
The USCF team says they’ve already worked with other doctors to treat a second case of brain-eating B. mandrillaris using nitroxoline, with similarly positive initial results. And they hope to convince the Centres for Disease Control and Prevention to maintain a local stockpile of the drug for emergency use.
“For every patient who exists with this disease, there’s a team of doctors where I was, which is basically desperate to find something that will help,” lead author Natasha Spottiswoode, an infectious diseases doctor and researcher at USCF, told Science.