An unintended consequence: a review of iatrogenic central nervous system mold infections and outbreaks

SUMMARYIatrogenic central nervous system mold infections (ICNSMIs) are rare and occur as sporadic complications of neurosurgical procedures or device insertions. However, recent outbreaks have been reported in outpatient settings, following epidural injections with contaminated medicines. We conducted a comprehensive literature review of studies published without date restrictions through July 2025 on ICNSMIs. We identified 905 cases of such infections, with 4% occurring in non-outbreak settings and 96% associated with five documented outbreaks. In both non-outbreak and outbreak settings, infections were more common after spinal/epidural injections, with contaminated medicines or supplies being the primary source. Due to their angioinvasive tendencies, ICNSMI caused by Fusarium solani and Aspergillus species had a higher frequency of stroke/intracranial hemorrhage (P = 0.011), aneurysm formation (P = 0.012), and resulted in higher mortality compared with ICNSMI caused by other molds (P < 0.001). ICNSMI, as a result of catheter-associated fungemia, was very rare (only one case). Strategies to identify ICNSMI in exposed individuals during an outbreak have included (i) symptom-driven lumbar puncture, (ii) screening lumbar puncture regardless of symptoms, and (iii) screening brain MRI regardless of symptoms. Measurement of (1→3)-β-D-glucan in cerebrospinal fluid was a valuable tool to diagnose ICNSMI preemptively. Outcomes of ICNSMI following neurosurgical procedures were poor (90-day mortality of 35%) and depended on the route of inoculation, mold species, timing of diagnosis, and prompt initiation of appropriate antifungal therapy in combination with source control. Patients with ICNSMI often suffered long-term neurologic sequelae, even with the most optimal management strategies.