Abstract
Introduction: Echinocandin antifungal medications including micafungin are being used more commonly in the treatment of invasive fungal infections in both pediatric and adult patients. Micafungin is also a first-line therapeutic option for candidemia and antifungal prophylaxis in a variety of clinical settings. Hypersensitivity reactions have not been well described; however, isolated cases have been reported. No cases of desensitization to echinocandins have been previously described.
Case Presentation: In this report, we described a 14-year-old female with high-risk pre-B cell acute lymphoblastic leukemia diagnosed with pulmonary aspergillosis. She developed a hypersensitivity reaction to micafungin, which was deemed first-line therapy for the infection. A rapid intravenous desensitization protocol was successfully completed without reactions. The patient completed the remaining 2 months of therapy without reactions.
Conclusion: This report outlines the first report of a successful desensitization to micafungin or any echinocandin. This is a safe method of completing antifungal therapy in a patient with echinocandin hypersensitivity and may be considered for other patients with micafungin hypersensitivities.
Keywords: desensitization, micafungin, drug allergy, hypersensitivity reaction
Introduction
Micafungin is an echinocandin antifungal medication that inhibits the synthesis of (1,3)-beta-d glucan in fungal cell walls.1,2 Owing to the evolving resistance profiles of fungi, and the favorable safety profiles of echinocandins, these antimicrobials are being used more commonly for treatment of invasive fungal infections in both adult and pediatric patients. Micafungin has emerged as a first-line therapeutic option for candidemia in a variety of clinical settings,3 and for antifungal prophylaxis in neutropenic adults and children.4,5 Hypersensitivity reactions to echinocandins have not been well described. However, isolated reactions have been reported during clinical trials, and in postmarketing experience.6,7 To our knowledge, no cases of desensitization to echinocandins have been previously reported. In this study, we present a pediatric patient with hypersensitivity to micafungin and describe the protocol implemented during her successful rapid desensitization.
Case Presentation
A 14-year-old female with high-risk pre-B cell acute lymphoblastic leukemia was diagnosed with pulmonary aspergillosis. Despite treatment with voriconazole, her respiratory symptoms worsened. Radiographic imaging was concerning for progression of fungal disease. Her antifungal therapy was changed to liposomal amphotericin B, but use of this medication was limited by renal dysfunction. Subsequently, her regimen was changed to intravenous micafungin 150 mg once daily. On the 20th day of treatment, within 15 min of starting the infusion, she acutely developed a pruritic urticarial rash that promptly resolved with administration of diphenhydramine. Despite this reaction, micafungin was deemed the first-line therapy for her aspergillus infection, with no other acceptable alternative. As her symptoms were consistent with an IgE-mediated hypersensitivity, a desensitization procedure was considered appropriate to continue optimal antifungal therapy. Owing to recent antihistamine use and urgent need for continued micafungin therapy, skin testing was deferred. The patient was admitted to the intermediate care unit with 1:1 nursing coverage for a rapid desensitization to micafungin, with goal dose of 150 mg every 24 h.
Before desensitization, informed consent was obtained. Rescue medications, including intramuscular epinephrine, intravenous diphenhydramine, normal saline, nebulized albuterol, and intravenous methylprednisolone, were available at the bedside. As given in Table 1, the patient underwent a 12-step 3-bag method desensitization protocol modified from a protocol that has been previously used successfully for desensitization to other drugs.8 No premedications were administered. The protocol started with a dose of 0.003 mg, with dose increase every 15 min until the last step to reach the cumulative dose of 150 mg. The protocol was successfully completed for 351 min without breakthrough reactions. The patient was discharged to home after tolerating her next full dose of micafungin. She completed the remaining 2 months of therapy without any reactions.
Table 1.
Desensitization Protocol for Micafungin
| Micafungin | 150 mg | IV Q24h | |||
|---|---|---|---|---|---|
| Full dose | 150 | mg | Total mg in each bag | ||
| Solution 1 | 250 | mL of | 0.006 | mg/mL | 1.500 |
| Solution 2 | 250 | mL of | 0.060 | mg/mL | 15.000 |
| Solution 3 | 250 | mL of | 0.595 | mg/mL | 148.820 |
| Step | Solution | Rate (mL/h) | Time (min) | Administered dose (mg) | Cumulative dose (mg) |
|---|---|---|---|---|---|
| 1 |
1 |
2 |
15 |
0.0030 |
0.0030 |
| 2 |
1 |
5 |
15 |
0.0075 |
0.0105 |
| 3 |
1 |
10 |
15 |
0.0150 |
0.0255 |
| 4 |
1 |
20 |
15 |
0.0300 |
0.0555 |
| 5 |
2 |
5 |
15 |
0.0750 |
0.1305 |
| 6 |
2 |
10 |
15 |
0.1500 |
0.2805 |
| 7 |
2 |
20 |
15 |
0.3000 |
0.5805 |
| 8 |
2 |
40 |
15 |
0.6000 |
1.1805 |
| 9 |
3 |
10 |
15 |
1.4882 |
2.6687 |
| 10 |
3 |
20 |
15 |
2.9764 |
5.6451 |
| 11 |
3 |
40 |
15 |
5.9528 |
11.5979 |
| 12 |
3 |
75 |
186 |
138.4021 |
150.0000 |
| Total time | 351 min | ||||
Discussion
Hypersensitivity to antifungal medications can jeopardize effective therapy for fulminant and/or disseminated fungal infections.9 In these cases, drug desensitization can be completed in situations wherein optimal alternative therapies are not available. Desensitization induces temporary tolerance to a medication as long as the drug is given at specific regular intervals, and has been shown to be safe and successful for a wide variety of medications, including antifungals, but none has been previously reported for echinocandins.8,9 A recent case report documented positive skin testing to caspofungin in a patient with suspected hypersensitivity to micafungin, but no further interventions were made.10 Skin testing before desensitization can be helpful to support an IgE-mediated mechanism; however, in our patient's case, skin testing was not possible due to recent antihistamine use and the need for urgent therapy.
In summary, we present a pediatric patient with likely IgE-mediated hypersensitivity reaction to micafungin who successfully completed a rapid desensitization followed by a full therapeutic course of micafungin for pulmonary aspergillosis. Development of a pruritic urticarial rash within minutes of the infusion is consistent with IgE-mediated hypersensitivity reaction; however, it is a limitation of this study that skin testing could not be completed before the desensitization to further support the diagnosis of micafungin allergy. To our knowledge, this is the first report of successful desensitization to micafungin or any echinocandin. This report outlines a safe method of completing antifungal therapy in a patient with echinocandin hypersensitivity and may be considered for other patients with micafungin hypersensitivities. Our protocol was successful without premedication or complications during the procedure. Future investigation, including skin testing, would further expand the knowledge of hypersensitivity to this class of antifungal agents. Our experience demonstrates that desensitization can be successfully employed to continue first-line therapy using this class of medications.
Take-home points
-
(1)
Hypersensitivity to echinocandins including micafungin has been reported.
-
(2)
Rapid desensitization to micafungin can be successfully utilized in patients with echinocandin hypersensitivities.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
This research is supported by T32 AI007512 (Maciag).
References
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