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BACKGROUND: Mold plasma cell-free DNA (cfDNA) polymerase chain reaction (PCR) is a promising noninvasive diagnostic modality for early diagnosis of invasive mold disease (IMD) in immunocompromised patients. Although mold cfDNA PCR has been shown to be highly accurate, the value of invasive procedures to collect specimens for conventional fungal diagnostics following plasma cfDNA testing remains unclear. METHODS: This retrospective single-center cohort study included patients with mold plasma cfDNA PCR performed 7 days before or 2 days after invasive specimen collection. Mold PCR detected Aspergillus species, Mucorales agents, Fusarium species, and Scedosporium species. Invasive procedures included tissue biopsy and bronchoscopy. The primary endpoint was the concordance of mold plasma cfDNA PCR results with results of conventional fungal tests performed on tissue and bronchoalveolar lavage fluid. RESULTS: Five hundred and six patients with mold plasma cfDNA PCR resulting ahead of invasive specimen (123 tissue and 426 bronchoalveolar lavage fluid) results were included, and 437 (86.4%) were immunocompromised. After adjudicating discordant results based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium definitions for IMD, mold plasma cfDNA PCR and invasive test results were 88.5% (448/506) concordant. In proven cases, 64.7% (11/17) of negative mold plasma cfDNA PCR results occurred in patients with fungal sinusitis (8) and limb infection (3). Nonhematologic malignancy and nonneutropenic state were statistically associated with negative mold plasma cfDNA PCR in patients with proven or probable IMD. CONCLUSIONS: Noninvasive mold plasma cfDNA PCR results were highly concordant with invasive specimen fungal test results, indicating risk-prone invasive specimen collection can be safely curtailed in immunocompromised patients with suspected IMD.
Lieu et al. (Fri,) studied this question.