Iatrogenic Fusarium Solani Meningitis Cases Caused Severe Injury to Brain Stem

An outbreak of iatrogenic Fusarium solani meningitis led to nine deaths resulting from “devastating” injury to the brain stem’s blood supply, a report showed.

The nine deaths occurred among 13 patients hospitalized for meningitis in southeastern Texas, who had undergone surgery with epidural anesthesia at two clinics in Matamoros, Mexico, reported Nora Strong, MD, of the McGovern Medical School at the University of Texas Health Science Center at Houston, and colleagues in the New England Journal of Medicine.

Several patients responded to variable combinations of the investigational antifungal fosmanogepix, steroids, and/or surgical interventions.

“This was really important to document because the treatment is not just antifungals and not just steroids — it was a combination of not only existing antifungals, but also novel antifungals, steroids, and advanced neurovascular procedures that ultimately was able to rescue some of these poor women,” co-author Luis Ostrosky-Zeichner, MD, also of the McGovern Medical School, told MedPage Today.

The CDC first issued a health advisory about the F. solani outbreak on May 17, 2023.

Most of the affected individuals were young, female, and otherwise healthy, and had undergone surgery at the clinics from January to May 2023. Among U.S. residents who had traveled to Mexico for surgical procedures, Mexican and U.S. authorities identified 185 people from 23 states who were potentially exposed to the fungus. Of those patients, there were nine suspected cases, 14 probable cases, and 10 confirmed cases. To date, 12 patients with probable or confirmed F. solani meningitis associated with the outbreak have died.

Iatrogenic meningitis due to fungal inoculation is not new, the authors noted. They cited a 2012 outbreak in Massachusetts involving meningitis and paraspinal and joint infections due to compounded injectable medications contaminated with Exserohilum rostratum, and another outbreak of Fusarium meningitis associated with epidural anesthesia in Durango, Mexico in 2022. The latter resulted in 41 deaths out of 80 cases.

Are these types of outbreaks becoming more common? George Thompson, MD, of the University of California Davis in Sacramento doesn’t think so. “We’re doing more interventional procedures on patients than we ever have in the past. So it would make sense that a single contamination event can lead to disastrous consequences,” he told MedPage Today.

Thompson suggested that healthcare providers maintain a high index of suspicion. “If you see an unusual infection where you don’t think it should be, those are circumstances where you should reach out to your local health agency to see if others are seeing the same thing,” he said.

That is how the current F. solani meningitis outbreak first came to attention, he noted. “Someone posted on the Emerging Infections Network and someone else said, ‘oh, I just saw a case like this.'”

Of the patients in this report, mean age was 31, and 12 of the 13 patients were women. The median time from symptom onset to hospitalization among the 13 patients was 39 days. Presenting symptoms were indicative of meningitis, and eight of 10 patients with measured opening pressures had elevated pressure.

Initial testing of cerebrospinal fluid (CSF) in two patients revealed “yeast-like” fungal forms on initial gram staining, but notably all fungal, mycobacterial, and bacterial CSF cultures were negative. Panfungal polymerase chain reaction (PCR) testing of samples from 10 patients identified five positive patients. Of these, four had gene sequencing indicative of F. solani species, and in one patient, results indicated the phylum Ascomycota, which includes F. solani.

On imaging, there were striking abnormalities in the CSF-containing structures of the skull base and fungal invasion of the vertebrobasilar arterial system. Arterial stenosis and occlusion led to subarachnoid and intraparenchymal hemorrhage, with infarction of the brain stem and cerebellum, visible on contrast MRI.

Treatment included systemic antifungal therapy in all patients, except one who presented before the identification of the outbreak. The majority of patients (10) received glucocorticoids to treat vascular stenosis and vasculitis, and nine patients received intrathecal liposomal amphotericin B.

When tissue culture from one patient at autopsy identified F. solani species, and susceptibility testing found the mold was resistant to all approved antifungals in the U.S., compassionate use of the investigational antifungal fosmanogepix was initiated in four patients, of whom three survived.

Some patients also underwent various surgical procedures, such as CSF diversion, arterial stenting, angioplasty, or intra-arterial vasodilator infusion.

Patients frequently responded initially to antifungal therapy, but later deteriorated clinically and developed vascular complications. Angiography revealed irregularities in the posterior circulation vessels that progressed over time to severe segmental stenosis, aneurysm formation, occlusion, or rupture.

“Of the four patients who were surviving at the time of this report, three continued to take fosmanogepix monotherapy, and one was no longer receiving antifungal medication because of the adverse effects of the medications,” Strong and colleagues wrote. Three of the four patients have no residual neurologic sequelae. One had a subarachnoid hemorrhage.

On autopsy, one patient had multiple vertebrobasilar thromboses and infarcts, with purulent material covering the base of the brain stem. Histopathology identified perivascular fungal hyphae around the basilar and pontine arteries, and in a perforating branch of the basilar artery. Findings in an autopsy of a second patient were similar.

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