Children with Invasive Candidiasis Do Well After Switching IV Antifungal to Enteral
Children with invasive candidiasis had successful outcome whether IV antifungal treatment was completed or converted to enteral to reduce risk of infusion site infections and costs.
Robert F. T. Bucayu, MD, MPH
Image Credit: Children's Hospital of Philadelphia
Children with invasive candidiasis, a particular risk for the immunocompromised, were as likely to have a favorable outcome after transitioning antifungal treatment from IV to enteral as completing the IV course, in a secondary analysis of the multicenter Pediatric Antifungal Comparative Effectiveness (PEACE) study.1-2
Lead author Robert Bucayu, MD, MPH, Departments of Pediatrics at the University of California San Francisco and at Children's Hospital of Philadelphia, was pleased with the findings, commenting to Contagion that although the enteral route should be advantageous for children, previous evidence of comparable effectiveness to intravenous treatment is from studies with adults.
"There are many advantages," Bucayu observed, "some patients may be able to avoid having a new central venous catheter placed, and the associated risk for bloodstream infection. Being on enteral therapy often means they can go home sooner. Even if still in the hospital, they can mobilize more easily without needing long IV infusions.Enteral therapy requires less pharmacy and nursing staff time, fewer materials, lower cost, and has less environmental impact."
To ascertain outcomes with transitioning antifungal therapy from IV to enteral in children, Bucayu and colleagues analyzed data from the prospective observational cohort PEACE study, conducted with children (≥4 months to 17 years) with invasive candidiasis at 42 sites in the Pediatric Fungal Network (PFN).
Rachel Wattier, MD, MHS
Image Credit: UCSF
Principal investigator Rachel Wattier, MD, MHS, Department of Pediatrics, University of California San Francisco explained to Contagion that the PFN has been important in strengthening recommendations for pediatric invasive fungal disease that are informed by pediatric-specific data.
"To do a study of a less common disease like invasive candidiasis, we needed to coordinate across multiple centers," Wattier said. "There are also more barriers to randomized controlled trials (RCTs) in children—children are considered a vulnerable population, and there are fewer motivators from regulatory and financial perspectives to do RCTs in children. At the same time, these diseases cause a substantial burden to children's health and there are differences between pediatric and adult populations."
Of 750 episodes in the PEACE study cohort, 319 from 42 study sites met study eligibility criteria. Sixty-seven of the 319 were transitioned from intravenous to enteral antifungal (triazole).The most common causative Candida species were C albicans (35%), C parapsilosis or C ortholopsis (32%) and C tropicalis (14%). Enteral therapy was preceded by IV therapy with triazoles in 70% of participants, echinocandins in 48%, and polyenes in 31%; with some receiving multiple antifungals. Transition to enteral therapy occurred at median day 10 of study.
Patients excluded from transitioning to enteral treatment included those with infecting Candida species documented as non-susceptible to triazole; presence of endocarditis (per IDSA guidelines recommending intravenous route); and for intestinal failure, or if receiving parenteral nutrition.
In the 30 day study follow-up, the investigators considered both the feasibility of the enteral transition strategy (eg, requirement to switch back to IV for any reason or for treatment failure); and longer-term control of the invasive candidiasis.Treatment outcome was defined as successful if meeting that criteria of the Mycoses Study Group/European Organization for Research and Treatment of Cancer (MSG/EORTC) Consensus.
The investigators reported successful treatment outcome in 66 of the 67 (99%) participants who had transitioned to enteral therapy. The finding was consistent regardless of whether the transition occurred early (<7 days) in the course of antifungal treatment; although the investigators caution that the small numbers limit comparisons based on the timing of transition.
The findings also can't inform whether treatment should be initiated more often with enteral administration, Wattier pointed out."We only selected patients who received initial IV therapy, so we can't answer this specific question."
"In the PEACE parent study, there was a better early treatment response in patients who received initial therapy with an echinocandin. In general, that supports starting with an echinocandin, which is IV," she noted."There may be some situations with individualized factors that make it reasonable to start with enteral therapy, but we'd need a different study to say more."
In the present study in which selection criteria targets participants able to take enteral medications, however, Bucayu, Wattier and colleagues comment, "it is surprising that most received intravenous therapy only, especially when the duration of candidemia and baseline characteristics were similar between groups."
Bucayu elaborated on the value of the analysis in comments to Contagion, noting that it is the first systematic evaluation of the transition to enteral triazole therapy for pediatric invasive candidiasis.
"I was interested in doing the study because it provided me an opportunity to delve deeper into antimicrobial stewardship within the clinical setting," Bucayu said. "Long duration intravenous therapy for pediatric invasive candidiasis is not without risk and may not be necessary for patients who are clinically stable and can tolerate enteral therapy."
