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Background: Clostridioides (Clostridium) difficile infection (CDI) is diagnosed using clinical signs and symptoms plus positive laboratory tests. Recurrence of CDI after treatment is common, and coinfection with other enteric pathogens may influence clinical outcomes.
Methods: We aimed to assess rates of C difficile positivity, by enzyme-linked immunosorbent assay (ELISA) toxin A/B and BioFire FilmArray, and the effect of enteric coinfection on clinical outcomes, using samples from the EXTEND study of extended-pulsed fidaxomicin (EPFX) versus standard vancomycin.
Results: All 356 randomized and treated patients tested positive for C difficile toxin A/B by local tests; a majority (225 of 356, 63.2%) also tested positive by both ELISA and BioFire. Most stool samples taken at screening tested positive for C difficile only using BioFire (EPFX: 112 of 165, 69.7%; vancomycin: 118 of 162, 72.8%). Of the 5 patients who failed treatment and had stool samples available, all (1) had tested negative for C difficile by BioFire at screening and (2) were negative by ELISA at time of treatment failure. When analyzed by BioFire results at screening, rates of sustained clinical cure at 30 days after end of treatment were numerically higher with EPFX than with vancomycin for almost all patients, except for those who tested negative for C difficile but positive for another pathogen. However, these outcome differences by presence of coinfection did not reach statistical significance. Whole-genome sequencing analysis determined that 20 of 26 paired samples from patients with recurrence were reinfections with the same C difficile strain.
Conclusions: Testing for presence of copathogens in clinical trials of antibiotics could help to explain clinical failures.
Objectives: Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups, clinical manifestation and treatment strategies of these infections.
Methods: Pediatric patients (age ≤18 years) with proven/probable Scedosporium spp. or L. prolificans infection were identified in PubMed and the FungiScope® registry. Data on diagnosis, treatment and outcome were collected.
Results: Fifty-five children (median age 9 years [IQR: 5–14]) with invasive Scedosporium spp. (n = 33) or L. prolificans (n = 22) infection were identified between 1990 and 2019. Malignancy, trauma and near drowning were the most common risk factors. Infections were frequently disseminated. Most patients received systemic antifungal therapy, mainly voriconazole and amphotericin B, plus surgical treatment.
Overall, day 42 mortality was 31%, higher for L. prolificans (50%) compared to Scedosporium spp. (18%). L. prolificans infection was associated with a shorter median survival time compared to Scedosporium spp. (6 days [IQR: 3–28] versus 61 days [IQR: 16–148]). Treatment for malignancy and severe disseminated infection were associated with particularly poor outcome (HR 8.33 [95% CI 1.35–51.40] and HR 6.12 [95% CI 1.52–24.66], respectively). Voriconazole use at any time and surgery for antifungal treatment were associated with improved clinical outcome (HR 0.33 [95% CI 0.11–0.99] and HR 0.09 [95% CI 0.02–0.40], respectively).
Conclusions: Scedosporium spp. and L. prolificans infections in children are associated with high mortality despite comprehensive antifungal therapy. Voriconazole usage and surgical intervention are associated with successful outcome.