JAC Advance Access originally published online on November 16, 2007
Journal of Antimicrobial Chemotherapy 2008 61(1):219; doi:10.1093/jac/dkm453
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research letters |
Emergence of Candida tropicalis resistant to caspofungin
1 Summa Health System, 75 Arch Street, Akron, OH 44304, USA 2 University Case Medical Center, 11100 Euclid Avenue, LKS 5028, Cleveland, OH 44106, USA
* Corresponding author. Tel: +1-206-3727047; Fax: +1-330-3756608; E-mail: jonrupert{at}gmail.com
Keywords: echinocandins , invasive candidiasis , candidal oesophagitis
Candida species is the fourth leading cause of nosocomial bloodstream infection in the USA. The incidence and mortality of invasive candidiasis (IC) remain high despite new antifungal agents. Although Candida albicans remains the most common isolated species causing IC, the incidence of IC caused by non-albicans species is increasing.1 Caspofungin, an echinocandin, is approved for treatment of IC.2 Resistance to caspofungin has been rarely reported.
We admitted a 28-year-old female with acute myelogenous leukaemia (AML) for fever and otitis media. She was started on caspofungin [70 mg intravenous (iv) loading dose followed by 50 mg iv daily] on her fifth hospital day due to persistent fever despite iv broad-spectrum antibiotics. Defervescence was noted and she was started on induction chemotherapy for AML on the sixth hospital day. She again developed fever with symptoms of oesophagitis on her 21st hospital day. Oesophagogastroduodenoscopy with oesophageal biopsy was performed and showed invasive candidal oesophagitis. Caspofungin was switched to liposomal amphotericin B. Her repeat blood cultures grew Candida tropicalis susceptible to fluconazole. Amphotericin B was switched to fluconazole and the patient improved slowly. She completed 4 weeks of fluconazole treatment.
We subsequently performed additional in vitro MIC testing for echinocandins on the isolated C. tropicalis using the CLSI (formerly NCCLS) M27-A2 standard methods.3 This method has been proven to be reproducible and reliable in the study of MIC trends and patterns of antifungal medications.4 MICs of caspofungin, micafungin and anidulafungin were 4.0, 8.0 and 1.0 mg/L, respectively.
This is the first documented case of C. tropicalis infection clinically resistant to caspofungin. This suggests that all Candida species are capable of developing resistance to echinocandins. The CLSI has established an echinocandin MIC of >2 mg/L to identify ‘non-susceptible’ Candida species.5 Our isolated strain's caspofungin MIC is consistent with this breakpoint.
We also observed cross-resistance of the isolated species to micafungin. This pattern of cross-resistance is similar to the observations made by Mougdal et al.6 for Candida parapsilosis. This may suggest a similar mechanism of resistance of Candida species to echinocandins, specifically caspofungin and micafungin.
Four mechanisms of reduced susceptibility to caspofungin have been suggested: (i) fks1 gene mutation; (ii) efflux-based mechanism; (iii) Sbe2p overexpression; and (iv) paradoxical or eagle effect.1,7 Only the fks1 gene mutation, however, is proven to cause clinical failure with caspofungin therapy.1 Further investigation of the fks1 gene of our isolated strain would help support Candida species' similarity of mechanism for echinocandin resistance.
 |
Funding |
|---|
 Top Funding Transparency declarationsReferences |
|---|
None.
|
Transparency declarations |
|---|
|
TopFundingTransparency declarationsReferences |
|---|
None to declare.
|
References |
|---|
|
TopFundingTransparency declarationsReferences |
|---|
1 Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev (2007) 20:133–63.
2 Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis (2004) 38:161–89.[CrossRef][Web of Science][Medline]
3 National Committee for Clinical Laboratory Standards. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeast: Approved Standard M27-A2 (2002) Wayne, PA, USA: NCCLS.
4
Ostrosky-Zeichner L, Rex JH, Pappas PG, et al. Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States. Antimicrob Agents Chemother (2003) 47:3149–54.
5 Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated from Animals: Informational Supplement M31-S1 (2007) Wayne, PA, USA: CLSI.
6
Mougdal V, Little T, Boikov D, et al. Multiechinocandin- and multiazole-resistant Candida parapsilosis isolates serially obtained during therapy for prosthetic valve endocarditis. Antimicrob Agents Chemother (2005) 49:767–9.
7
Stevens DA, Ichinomiya M, Koshi Y, et al. Escape of Candida from caspofungin inhibition at concentrations above the MIC (paradoxical effect) accomplished by increased cell wall chitin; evidence for β-1,6-glucan synthesis inhibition by caspofungin. Antimicrob Agents Chemother (2006) 50:3160–1.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||