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Antimicrobial Agents and Chemotherapy, October 2007, p. 3775, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00890-07

LETTER TO THE EDITOR

Maintenance of Therapeutic Concentrations of Caspofungin after Temporary Treatment Interruption (48 Hours) in a Child with Invasive Aspergillosis{triangledown}


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LETTER
 
Caspofungin is an antifungal drug active as a rescue treatment for invasive aspergillosis in cancer patients (4), with a MIC level of 0.5 mg/liter (2) and a minimum target concentration of 1 mg/liter (5, 6). In adults, these levels are achieved after a loading dose of 70 mg on the first day, followed by 50 mg once a day in the following days (5), while in children, a dose of 50 mg/m2 without a loading dose is required (6).

We observed an 8-year-old girl with a previous pulmonary aspergillosis following allogeneic hemopoietic stem cell transplant for Pearson's syndrome that relapsed concomitant with the development of posttransplant acute myeloblastic leukemia (1). The infection relapsed during liposomal amphotericin B secondary prophylaxis; voriconazole treatment was not feasible because of concomitant barbiturate therapy (3), and therefore, caspofungin at 50 mg/m2 (5) (i.e., 30 mg/day) was administered.

The patient was in poor clinical and psychological condition and refused any hospital stay; therefore, after 8 days of in-hospital treatment, the patient was discharged for the weekend. No antifungal treatment was administered for two days, and then the patient was admitted again to restart therapy.

Blood samples for the determination of caspofungin blood concentrations were taken on the last day of treatment (Friday) and the first day of restarting treatment (Monday), before (through) and 30 min after the end (peak) of caspofungin infusion. The samples were stored at –80°C and sent to the Department of Pharmacology of the University of Florence for the determination of caspofungin blood levels.

Caspofungin concentrations were determined by high-pressure liquid chromatography (lowest sensitivity limit, 0.125 mg/liter). A Chromsep C8 4.6-by-250-mm 5-µm column preceded by an adequate precolumn was used for the analysis; a flow rate of 1.3 ml/min was used. The fluorescence detector excitation and emission wavelengths were set at 220 and 304 nm, respectively. The drug was isolated from the plasma by solid-phase extraction (5). The caspofungin levels that resulted were 6.7 mg/liter through and 11.5 mg/liter peak on the last day of treatment and 1.9 mg/liter through and 5.6 mg/liter peak on the first day of resumption of therapy.

Even after a 48-h interruption, the caspofungin blood concentration was above the required target concentration for the treatment of invasive aspergillosis (2, 5, 6).

Even if further studies are needed to confirm this observation, our experience suggests that the administration of caspofungin for 5 days/week, after an adequate period (at least 1 week) of daily therapy, may be a possible approach for children with invasive aspergillosis who cannot receive other antifungal drugs and may not be hospitalized for some reason.


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FOOTNOTES
 
{triangledown} Published ahead of print on 23 July 2007. Back


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REFERENCES
 
    1
  1. Faraci, M., D. Cuzzubbo, C. Micalizzi, E. Lanino, G. Morreale, S. Dallorso, E. Castagnola, M. C. Schiaffino, C. Bruno, A. Rossi, G. Dini, and B. Cappelli. 2007. Allogeneic bone marrow transplantation for Pearson's syndrome. Bone Marrow Transplant. 39:563-565.[CrossRef][Medline]
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  2. Isham, N., and M. A. Ghannoum. 2006. Determination of MICs of aminocandin for Candida spp. and filamentous fungi. J. Clin. Microbiol. 44:4342-4344.[Abstract/Free Full Text]
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  3. Johnson, L. B., and C. A. Kauffman. 2003. Voriconazole: a new triazole antifungal agent. Clin. Infect. Dis. 36:630-637.[CrossRef][Medline]
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  4. Maertens, J., I. Raad, G. Petrikkos, M. Boogaerts, D. Selleslag, F. B. Petersen, C. A. Sable, N. A. Kartsonis, A. Ngai, A. Taylor, T. F. Patterson, D. W. Denning, and T. J. Walsh. 2004. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin. Infect. Dis. 39:1563-1571.[CrossRef][Medline]
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  5. Stone, J. A., S. D. Holland, P. J. Wickersham, A. Sterrett, M. Schwartz, C. Bonfiglio, M. Hesney, G. A. Winchell, P. J. Deutsch, H. Greenberg, T. L. Hunt, and S. A. Waldman. 2002. Single- and multiple-dose pharmacokinetics of caspofungin in healthy men. Antimicrob. Agents Chemother. 46:739-745.[Abstract/Free Full Text]
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  6. Walsh, T. J., P. C. Adamson, N. L. Seibel, P. M. Flynn, M. N. Neely, C. Schwartz, A. Shad, S. L. Kaplan, M. M. Roden, J. A. Stone, A. Miller, S. K. Bradshaw, S. X. Li, C. A. Sable, and N. A. Kartsonis. 2005. Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents. Antimicrob. Agents Chemother. 49:4536-4545.[Abstract/Free Full Text]
Elio Castagnola*
Infectious Diseases Unit
Department of Hematology and Oncology
G. Gaslini Children's Hospital
Genoa, Italy

Barbara Cappelli
Maura Faraci
Department of Hematology and Oncology
G. Gaslini Children's Hospital
Genoa, Italy

Stefania Fallani
Maria Iris Cassetta
Andrea Novelli
Department of Pharmacology
University of Florence
Florence, Italy

* Phone: 39.010.5636.428, E-mail: eliocastagnola{at}ospedale-gaslini.ge.it

Antimicrobial Agents and Chemotherapy, October 2007, p. 3775, Vol. 51, No. 10
0066-4804/07/$08.00+0     doi:10.1128/AAC.00890-07





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