Rhizopus Oryzae Skin Infection Treated With Posaconazole in a Boy With Chronic Granulomatous Disease

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To the Editors:A 2-year-old previously healthy boy presented with a cutaneous Rhizopus oryzae infection near the right nipple. He was subfebrile (38°C). Laboratory results showed a slightly increased erythrocyte sedimentation rate (33 mm/h), C-reactive protein (24 mg/L), and white blood cell count (15.3 × 109/L).A total excision of the abscess was performed and intravenous treatment with amphotericin B lipid complex (ABLC) was started. Four days later, a re-excision was necessary and the dose of ABLC was increased.Additional testings revealed an autosomal recessive form of chronic granulomatous disease (CGD).The patient developed liver and renal toxicity (ASAT 108 U/L, ALAT 46 U/L, creatinin 60 μmol/L, BUN 10.3 μmol/L, LDH 466 U/L) that necessitated a switch in therapeutic medication to posaconazole. To allow posaconazole to reach therapeutic blood levels, ABLC was initially reduced and only stopped when posaconazol was above a trough concentration of 0.7 mg/L (Fig., Supplemental Digital Content 1 and 2, http://links.lww.com/INF/A442 and http://links.lww.com/INF/A443, respectively). At the moment of therapy, no well-defined target concentrations for efficacy were available. Based on the available knowledge, we aimed at a concentration of at least 0.7 mg/L.1After several adaptations, a dosage of 60 mg/kg/d (t.i.d.) resulted in adequate trough concentrations and ABLC was ceased. Liver and kidney function normalized. Posaconazole was successfully given during 6 months and no adverse effects were seen. The boy recovered completely.R. oryzae is a fungus of the class Zygomycetes. It causes opportunistic infections in immunocompromised hosts.2 In our patient, this infection led to the diagnosis of CGD. Infections with zygomycetes are rare in patients with CGD.3The state-of-the-art treatment of cutaneous zygomycosis consists of immediate radical surgical excision combined with high-dose amphotericin B.2Until recently, there was no good alternative for amphotericin B as treatment for infections with zygomycetes, because these fungi are generally resistant to most azoles and echinocandins. Posaconazole is an oral broad-spectrum triazole that is effective against zygomycetes, with little reported toxicity. Absorption is good when ingested with (fatty) food.1,2,4The adult dosage is 800 mg/d. In our patient, adequate posaconazole levels (>0.7 mg/L) were achieved with a dosage of 840 mg/d (60 mg/kg/d, t.i.d.). Although this is more than the adult dosage, no side effects were seen. Possible explanations for this may consist of higher clearance rates in young children and reduced intestinal absorption of posaconazole caused by difficulties of medicine intake simultaneously with food.Several other studies described the use of posaconazole in children. Sedlacek et al5 described a 15-month-old boy with leukemia who developed an invasive Rhizopus infection. Posaconazole was added to ABLC in a dosage of 18 mg/kg/d (t.i.d) for 5 months. The boy recovered completely and no side effects were seen.In a study of Krishna et al,4 12 juvenile patients (8 years and older) received adult dosages of posaconazole resulting in similar plasma concentrations, success rates, and adverse events compared with adults.In summary, we described a 2-year-old CGD patient with cutaneous zygomycosis treated successfully with posaconazole. Additional pharmacokinetic and dynamic studies are needed to evaluate different dosage regimens in children.Joanne G. Wildenbeest, MDDepartment of Pediatric Hematology,Immunology and Infectious DiseasesEmma Children's HospitalMatthijs W. Oomen, MDPediatric Surgical Center of AmsterdamEmma Children's Hospital (AMC)Free University Medical Center (VUMC)Amsterdam, The NetherlandsRoger J.

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