Are you for real, <i>Tsukamurella</i>? Novel <i>Tsukamurella</i> species isolated from a patient with primary myelofibrosis

Background Tsukamurella species, often considered colonizers or contaminants, are increasingly recognized as opportunistic pathogens associated with catheter-related bloodstream infections, pneumonia, meningitis, and keratitis. Diagnosis of Tsukamurella pulmonary infections can be challenging. There are no established clinical guidelines due to the rarity of such infections, and accurate species-level identification of Tsukamurella remains difficult due to high interspecies similarities. Case summary A 64-year-old man with primary myelofibrosis presented for infectious disease evaluation prior to hematopoietic cell transplant (HCT). Although he had past tuberculosis (TB) exposure, he was asymptomatic, and chest CT was normal except for two stable left lower-lobe subpleural nodules noted earlier. Multiple respiratory cultures grew a modified acid-fast positive rod identified by MALDI-TOF MS and targeted sequencing as Tsukamurella spp., but further speciation was not possible, prompting whole-genome sequencing (WGS). Comparative genomic analysis demonstrated that the isolate represented a novel Tsukamurella species, with 91.32% average nucleotide identity to its nearest relative, Tsukamurella sputi . Given the absence of clinical or radiographic disease, the findings were most consistent with colonization, and no treatment was initiated. Twenty-three days after culture collection, the patient underwent a reduced-intensity mismatched unrelated HCT without complications. Post-transplant, he showed no evidence of Tsukamurella infection. Conclusion Despite meeting microbiologic criteria for non-tuberculous mycobacteria pulmonary disease, this case underscores that clinical and radiographic context is essential when interpreting Tsukamurella isolated from respiratory sources. Accurate species identification requires a tiered approach including MALDI-TOF MS and targeted sequencing. Determination of novel species requires WGS and appropriate bioinformatic analysis.