Haematologica, Vol 93, Issue 4, 639-640 doi:10.3324/haematol.11149
Copyright © 2008 by Ferrata Storti Foundation
Stem Cell Transplantation |
Breakthrough C. parapsilosis and C. guilliermondii blood stream infections in allogeneic hematopoietic stem cell transplant recipients receiving long-term caspofungin therapy
Nabil Kabbara1,
Claire Lacroix2,
Regis Peffault de Latour1,
Gérard Socié1,
Mahmoud Ghannoum3,
Patricia Ribaud1
1 AP-HP Service d’Hématologie-Greffe
2 Laboratoire de Mycologie-Parasitologie, Hôpital Saint-Louis, Paris, France;
3 Center for Medical Mycology, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH, USA
Correspondence: Nabil Kabbara, MD, AP-HP, Hôpital Saint Louis, Service d’Hématologie-Greffe de moelle osseuse, 1, avenue Claude Vellefaux, 75010 Paris, France. Phone: international +33.142499826. Fax: international +33.142385390. E-mail:nabil.kabbara{at}sls.aphp.fr
Key words: Candida parapsilosis, Candida guilliermondii, caspofungin, echinocandin, candidemia.
Since 2004, when caspofungin became available at our institution for empirical treatment of fever, we have been faced with the occurrence of candidemia due to unusual species, i.e. C. parapsilosis and C. guilliermondii, which have been reported to exhibit decreased susceptibility to echinocandins in vitro.1–3 While only 5 episodes of candidemia (C. glabrata n=3, C. albicans n=1, and C. krusei n=1) were observed in 487 allogeneic hematopoietic stem cell transplant (HSCT) recipients between January 2000 and December 2004, 3 cases of candidemias (C. parapsilosis n=2, C. guilliermondii n=1) occurred out of 170 HSCT recipients from January 2005 to July 2006. The 3 patients were receiving long-term caspofungin therapy. Main characteristics of the patients and of the Candida infections are shown in Table 1.
Patient #1, an 18 year-old male, underwent a first unrelated HSCT in January 2004 with no sustained engraftment. Two months post-transplant he developed a definitive lung invasive aspergillosis successfully treated with voriconazole. He received a second transplant on May 2005. On day 7 post-transplant, secondary prophylaxis was switched from voriconazole to caspofungin due to liver toxicity. There was no granulocyte recovery. On day 48, he became febrile and a blood culture was positive for C. parapsilosis. Due to the patient’s poor condition, the central venous catheter (CVC) was not removed. Skin and throat colonization with C. parapsilosis had been documented from day 39 onward.
Patient 2, a 46-year old male, underwent an allogeneic HSCT from an HLA matched sibling donor on May 2005. Antifungal prophylaxis consisted of fluconazole. Caspofungin was introduced on day 6 post-transplant as empirical treatment for a persistant fever. Granulocyte recovery occurred on day 28. He further experienced a severe acute graft-versus-host disease treated with multiple immunosuppressive regimens, and a cytomegalovirus infection. On days 58–60, three blood cultures were positive for C. parapsilosis. Skin, gastro-intestinal tract and upper respiratory airways were colonized with C. parapsilosis from day 33 onward.
Patient #3, a 32-year old male, underwent an unrelated HSCT on November 2005. Antifungal prophylaxis consisted of fluconazole. Granulocyte recovery occurred on day 21. He experienced recurrent episodes of acute graft-versus-host disease treated with multiple immunosuppression regimens. He developed several episodes of cytomegalovirus infections and bacteremia. Antifungal prophylaxis was switched to caspofungin on day 95 because of liver toxicity. On day 118, he became febrile and a blood culture was positive for C. guilliermondii. The gastro-intestinal and the respiratory tracts were colonized with C. parapsilosis from day 116 to day 123. We report here the emergence of C. parapsilosis and C. guilliermondii fungemia in 3 immunocompromised patients receiving long-term caspofungin therapy. From January 2005 to July 2006, 170 patients were recipients of HSCT in our unit of whom 103 (61%) received at least one day of caspofungin therapy. The overall incidence was 1/1,000 patient-days exposure to the drug. Caspofungin is an effective treatment of candidiasis and has been shown to be as effective as amphotericin B for the treatment of candidemia whatever the species involved.4 Recent reports on another echinocandin, micafungin, in the treatment of candidemia and invasive candidiasis showed an identical response among patients with C. parapsilosis infections as compared with other species and no inferior result as compared with liposomal amphotericin B.5,6 However, echinocandins are known to have less intrinsic in vitro activity against C. parapsilosis and C. guilliermondii than against the other Candida species. The MICs obtained with our isolates showed values comparable to those reported for other C. parapsilosis or C. guilliermondii isolates1,2 (Table 2). The clinical studies together with the in vitro susceptibility results confirmed the unrealibility of these tests when considering echinocandin drugs.7 However, Reboli et al. observed a markedly reduced response rate to anidulafungin (63.6%) compared with fluconazole (83.3%) in 11 and 12 patients with invasive candidiasis due to C. parapsilosis.8 Recently, Cheung et al. reported a case of C. parapsilosis candidemia in a patient on caspofungin therapy which was explained by the co-administration of phenytoin. A decrease in caspofungin serum levels cannot explain our 3 cases of candidemia since these levels were between 2 and 4 mg/L (Table 2).
In conclusion, we would like to warn physicians to the fact that, in deeply immunocompromised patients treated with caspofungin, breakthrough candidemia with organisms known to have a reduced susceptibility to this drug may occur. Persisting colonization with such Candida spp. may be an indication for switching to an alternative anti-fungal drug.
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Acknowledgments
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we are indebted with Dr. Sophie Touratier (Pharmacy, Hôpital Saint Louis) for providing us the data on caspofungin delivery, and to Dr Christophe Padoin (Pharmacy, Hôpital Avicenne, Bobigny) for performing determination of serum levels of caspofungin
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References
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- Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. In vitro susceptibilities of Candida spp. to caspofungin: four years of global surveillance. J Clin Microbiol 2006;44:760-3.[Abstract/Free Full Text]
- Barchiesi F, Spreghini E, Tomassetti S, Della Vittoria A, Arzeni D, Manso E, et al. Effects of caspofungin against Candida guilliermondii and Candida parapsilosis. Antimicrob Agents Chemother 2006;50:2719-27.[Abstract/Free Full Text]
- Canton E, Peman J, Sastre M, Romero M, Espinel-Ingroff A. Killing kinetics of caspofungin, micafungin, and amphotericin B against Candida guilliermondii. Antimicrob Agents Chemother 2006;50:2829-32.[Abstract/Free Full Text]
- Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002;347:2020-9.[Abstract/Free Full Text]
- Kuse ER, Chetchotisakd P, Arns da Cunha C, Ruhnke M, Barrios M, Raghunadharao D, et al. Micafungin versus iposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet 2007;369:1519-27.[CrossRef][ISI][Medline]
- Arrieta AC, Telles Filho F, Berezin E, Freire A, Diekemann-Berndt H. A randomized, double-blind trial comparing micafungin (MCFG) and liposomal amphotericin B (LAMB) in pediatric patients with invasive candidiasis (IC) (Abstract). Paper presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Fransisco 2006; M-1308b.
- Kartsonis N, Killar J, Mixson L, Hoe CM, Sable C, Bartizal K, et al. Caspofungin susceptibility testing of isolates from patients with oesophageal candidiasis or invasive candidiasis: relationship of MICs to treatment outcome. Antimicrob Agents Chemother 2005;49:3616-23.[Abstract/Free Full Text]
- Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007;356:2472-82.[Abstract/Free Full Text]
- Cheung C, Guo Y, Gialanella P, Feldmesser M. Development of candidemia on caspofungin therapy: a case report. Infection 2006;34:345-8.[CrossRef][ISI][Medline]
- Clinical Laboratory Standards institute. Reference method for broth dilution antifungal susceptibility testing of yeasts - Approved standard-2nd edition document M27-A2. 2002. CLSI/NCCLS, Wayne, PA, USA.
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References