Antifungal therapy may alter epidemiology of invasive mold infections
Treatment with antifungal therapy prior to diagnosis may change the epidemiology of invasive mold infections, according to study findings in The Journal of the Pediatric Infectious Diseases Society.
Rachel L. Wattier, MD, of the University of California San Francisco, and colleagues assessed mold infections among 131 children (median age 10.6 years) from 22 sites in the International Pediatric Fungal Network. Ten of the sites were international.
The most common underlying condition among study participants was hematologic malignancy, which occurred in 56% of children. Forty-nine percent of children had proven invasive mold infections and 51% had probable invasive mold infections. Seventy-five percent of patients had invasive aspergillosis; 13% had mucormycosis; and 17% had other invasive mold infections. Multiple mold species were found in eight children.
Overall, underlying conditions and risk factors were similar among patients with invasive aspergillosis and other invasive mold infections. However, those with non-Aspergillus invasive mold infections were more likely to have received antifungal agents with mold activity prior to diagnosis than those with invasive aspergillosis (67% vs. 40%).
Children with invasive mold infections were significantly more likely to have received voriconazole (Vfend, Roerig), posaconazole (Noxafil, Merck) or an echinocandin within 2 weeks prior to diagnosis. Children with mucormycosis and those with other non-Aspergillus invasive mold infections were more likely to have greater exposure to mold therapy prior to diagnosis compared with children with invasive aspergillosis.
The most commonly used antifungals for initial monotherapy were voriconazole (34%) and polyenes (31%). One-quarter of study participants received primary combination therapy.
More than half of children received combination therapy with two or more concurrent agents within the 12 weeks after diagnosis. Combination therapy was administered for a median of 25 days. Combinations of triazole and polyene agents were used most frequently (28%). Among children with invasive aspergillosis, the most frequently used regimens were triazoles and echinocandins (32%) and triazoles and polyenes (28%).
There were 47 adverse events during therapy for invasive mold infections, including five severe events. Adverse events were most frequently reported with voriconazole (47%) and liposomal amphotericin B (36%). Children who received any type of combination therapy within 12 weeks after diagnosis were more likely to experience adverse events than children who did not receive combination therapy.
Sixty percent of patients had a complete or partial response to therapy.
“Our findings highlight a critical need to better understand the benefits and risks of combination antifungal therapy. Robust comparative studies with defined criteria for use of combination therapy, standardized regimens, and rigorous assessment of toxicity are needed to define the role of combination therapy in management of [invasive mold infections] in children,” the researchers concluded.
Disclosure: Some of the researchers have financial ties with Astellas Pharma, Cephalon, Gilead Sciences, Merck, Pfizer, Schering-Plough, Vicuron Pharmaceuticals, and Cubist.