OUTCOME OF CANDIDA PARAPSILOSIS COMPLEX INFECTIONS TREATED WITH CASPOFUNGIN IN CHILDREN
Main Article Content
Keywords
Candida parapsilosis complex, caspofungin, children
Abstract
Background: We aimed to evaluate the correlation of caspofungin E-tests with the prognosis and response to caspofungin therapy of Candida parapsilosis complex bloodstream infections in children hospitalized in pediatric intensive care unit.
Methods: All children who had C.parapsilosis complex bloodstream infections and who were treated with caspofungin were included in this retrospective study. For each patient, the following parameters, including all consecutive blood and central venous catheter (CVC) cultures, duration between diagnosis and CVC removal, mortality rate, relapses of the C.parapsilosis complex infections as well as the demographic features, were recorded.
Results: The study covered 53 patients with a median age of 11 months. The median duration of C.parapsilosis complex isolation was 31 days. The CVC rescue rate was 33.3% under caspofungin treatment. In 92.4% of the patients, the negative culture was achieved within a median duration of 14 days. The rate of relapses was 18.9%. The overall mortality rate was %37.7 (20 patients) and 30-days mortality rate was 7.5% (4 patients).
Conclusions: Caspofungin is an attractive option due to its effects on biofilms in vivo, while the reflection of its affect on C.parapsilosis complex was limited in our study, but it should not be underestimated in children who strongly need the presence of central venous catheters. Moreover, in vivo susceptibility might not always guarantee good clinical response in clinical practice. The clinicians should weigh their priority for their patients and choose the optimal antifungal therapy for C.parapsilosis complex infections in children.
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References
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28. León-Gil C, Ubeda-Iglesias A, Loza-Vázquez A, et. al. Efficacy and safety of caspofungin in critically ill patients. ProCAS Study. Rev Esp Quimioter 2012; 25: 274-82.
29. Garcia-Effron G, Katiyar SK, Park S, et. al. A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility. Antimicrob Agents Chemother 2008; 52: 2305–12.
30. Pfaller MA, Diekema DJ, Andes D, et. al. Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drug Resist Updat 2011; 14: 164–76.
31. Martí-Carrizosa M, Sánchez-Reus F, March F, et. al. Fungemia in a Spanish hospital: the role of Candida parapsilosis over a 15-year period. Scand J Infect Dis 2014; 46: 454-61.
32. Lazzell AL, Chaturvedi AK, Pierce CG et. al. Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis. J Antimicrob Chemother 2009; 64: 567-70.
33. Shuford JA, Rouse MS, Piper KE, et. al. Evaluation of caspofungin and amphotericin B deoxycholate against Candida albicans biofilms in an experimental intravascular catheter infection model. J Infect Dis 2006; 194: 710-3.
34. Cateau E, Rodier MH, Imbert C. In vitro efficacies of caspofungin or micafungin catheter lock solutions on Candida albicans biofilm growth. J Antimicrob Chemother 2008; 62: 153-5.
35. Cocuaud C, Rodier MH, Daniault G, et. al. Anti-metabolic activity of caspofungin against Candida albicans and Candida parapsilosis biofilms. J Antimicrob Chemother 2005; 56: 507-12.
36. Devrim I, Yaman Y, Demira? B, et. al. A single center's experience with Candida parapsilosis related long-term central venous access device infections: the port removal decision and it’s outcomes. Pediatr Hematol Oncol 2014; 31:435-41.
37. Katragkou A1, Chatzimoschou A, Simitsopoulou M, et al. Differential activities of newer antifungal agents against Candida albicans and Candida parapsilosis biofilms. Antimicrob Agents Chemother 2008; 52(1): 357-60. Epub 2007 Oct 15.
38. Salas V, Pastor FJ, Capilla J, et. al. Evaluation of the correlation of caspofungin MICs and treatment outcome in murine infections by wild type strains of Candida parapsilosis. Diag Microbiol Infect Dis 2013; 77: 41–5.
39. Colombo AL, Ngai AL, Bourque M, et. al. Caspofungin use in patients with invasive candidiasis caused by common non-albicans Candida species: review of the caspofungin database. Antimicrob Agents Chemother 2010; 54:1864-71.
40. Fernández-Ruiz M, Aguado JM, Almirante B, et. al. Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: a propensity score analysis. Clin Infect Dis 2014; 58: 1413-21.
41. Reboli AC. Editorial commentary: Is the debate about treatment of Candida parapsilosis complex infections with echinocandins much ado about nothing? Clin Infect Dis 2014; 58: 1422-3.
42. Arendrup MC, Rodriguez-Tudela JL, Lass-Flo?rl C, et. al. EUCAST technical note on anidulafungin. Clin Microbiol Infect 2011; 17: 18-20.
43. Espinel-Ingroff A, Arendrup MC, Pfaller MA, et. al. Interlabo- ratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: should the clinical laboratory be testing this agent? Antimicrob Agents Chemother 2013; 57: 5836-42.
44. Shields RK, Nguyen MH, Press EG, et. al. Anidulafungin and micafungin MIC breakpoints are superior to that of caspofungin for identifying FKS mutant Candida glabrata strains and Echinocandin resistance. Antimicrob Agents Chemother 2013; 57:6361-5.
45. Eschenauer GA, Nguyen MH, Shoham S, et. al. Real-World Experience with Echinocandin MICs against Candida Species in a Multicenter Study of Hospitals That Routinely Perform Susceptibility Testing of Bloodstream Isolates. Antimicrob Agents Chemother 2014; 58: 1897-906.
2. Singhi S, Deep A. Invasive candidiasis in pediatric intensive care units. Indian J Pediatr 2009; 76: 1033-44.
3. Pfaller MA, Diekema DJ, Jones RN, et. al. International surveillance of bloodstream infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program. J Clin Microbiol 2001; 39: 3254–59.
4. Wisplinghoff H, Bischoff T, Tallent SM, et. al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004; 39: 309–17.
5. Mean M, Marchetti O, Calandra T. Bench-to-bedside review: Candida infections in the intensive care unit. Crit Care 2008; 12: 204.
6. Trofa D, Gácser A, Nosanchuk JD. Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev 2008; 21: 606-25.
7. Nakamura T, Takahashi H. Epidemiological study of Candida infections in blood: susceptibilities of Candida spp. to antifungal agents, and clinical features associated with the candidemia. J Infect Chemother 2006; 12: 132-8.
8. Nq KP, Saw TL, SL Na, et. al. Systemic Candida infection in University hospital 1997-1999: the distribution of Candida biotypes and antifungal susceptibility patterns. Mycopathologia 2001; 149: 141-6.
9. Medrano DJ, Brilhante RS, Cordeiro Rde A, et. al. Candidemia in a Brazilian hospital: the importance of Candida parapsilosis. Rev. Inst Med Trop Sao Paulo 2006; 48: 17-20.
10. Pappas PG, Kauffman CA, Andes D, et. al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 503–35.
11. Hope WW, Castagnola E, Groll AH, et. al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: prevention and management of invasive infections in neonates and children caused by Candida spp. Clin Microbiol Infect 2012; 18: 38–52.
12. Walsh TJ. Echinocandins and advance in the primary treatment of invasive candidiasis. N Engl J Med 2002; 347: 2070-2.
13. Cappelletty D, Eiselstein-McKitrick K. The echinocandins. Pharmacotherapy 2007; 27: 369–88.
14. Dodds Ashley ES, Lewis R, Lewis JS, et. al. Pharmacology of systemic antifungal agents. Clin Infect Dis 2006; 43:28-39.
15. Mora-Duarte J, Betts R, Rotstein C, et. al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002; 347: 2020-9.
16. Spellberg BJ, Filler SG, Edwards JE Jr. Current treatment strategies for disseminated candidiasis. Clin Infect Dis 2006; 42: 244-51.
17. Barchiesi F, Spreghini E, Tomassetti S, et. al. Effects of caspofungin against Candida guilliermondii and Candida parapsilosis. Antimicrob Agents Chemother 2006; 50: 2719–27.
18. FleckR, Dietz A, Hof H. Invitro susceptibility of Candida species to five antifungal agents in a German university hospital assessed by the reference broth microdilution method and E test. J Antimicrob Chemother 2007; 59: 767–71.
19. Kuhn DM, George T, Chandra J, et. al. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemother 2002; 46: 1773–80.
20. Barchiesi F, Spreghini E, Tomassetti S, et. al. Caspofungin in combination with amphotericin B against Candida parapsilosis. Antimicrob Agents Chemother 2007; 51: 941-5.
21. Kuhn DM, George T, Chandra J, et. al. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemothe. 2002; 46: 1773-80.
22. 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.
23. Kartsonis N, Killar J, Mixson L, et. al. Caspofungin susceptibility testing of isolates from patients with esophageal candidiasis or invasive candidiasis: relationship of MIC to treatment outcome. Antimicrob Agents Chemother 2005; 49: 3616- 23.
24. Odds FC, Motyl M, Andrade R, et. al. Interlaboratory comparison of results of susceptibility testing with caspofungin against Candida and Aspergillus species. J Clin Microbiol 2004; 42: 3475-82.
25. Segal BH, Herbrecht R, Stevens DA, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis 2008 Sep 1;47(5):674-83.
26. Wayne PA. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard, 3rd ed., M27-A3. USA: Clinical and Laboratory Standards Institute, 2008.
27. Pfaller MA, Diekema DJ, Andes D, et. al. Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drug Resist Updat 2011; 14: 164-76.
28. León-Gil C, Ubeda-Iglesias A, Loza-Vázquez A, et. al. Efficacy and safety of caspofungin in critically ill patients. ProCAS Study. Rev Esp Quimioter 2012; 25: 274-82.
29. Garcia-Effron G, Katiyar SK, Park S, et. al. A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility. Antimicrob Agents Chemother 2008; 52: 2305–12.
30. Pfaller MA, Diekema DJ, Andes D, et. al. Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drug Resist Updat 2011; 14: 164–76.
31. Martí-Carrizosa M, Sánchez-Reus F, March F, et. al. Fungemia in a Spanish hospital: the role of Candida parapsilosis over a 15-year period. Scand J Infect Dis 2014; 46: 454-61.
32. Lazzell AL, Chaturvedi AK, Pierce CG et. al. Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis. J Antimicrob Chemother 2009; 64: 567-70.
33. Shuford JA, Rouse MS, Piper KE, et. al. Evaluation of caspofungin and amphotericin B deoxycholate against Candida albicans biofilms in an experimental intravascular catheter infection model. J Infect Dis 2006; 194: 710-3.
34. Cateau E, Rodier MH, Imbert C. In vitro efficacies of caspofungin or micafungin catheter lock solutions on Candida albicans biofilm growth. J Antimicrob Chemother 2008; 62: 153-5.
35. Cocuaud C, Rodier MH, Daniault G, et. al. Anti-metabolic activity of caspofungin against Candida albicans and Candida parapsilosis biofilms. J Antimicrob Chemother 2005; 56: 507-12.
36. Devrim I, Yaman Y, Demira? B, et. al. A single center's experience with Candida parapsilosis related long-term central venous access device infections: the port removal decision and it’s outcomes. Pediatr Hematol Oncol 2014; 31:435-41.
37. Katragkou A1, Chatzimoschou A, Simitsopoulou M, et al. Differential activities of newer antifungal agents against Candida albicans and Candida parapsilosis biofilms. Antimicrob Agents Chemother 2008; 52(1): 357-60. Epub 2007 Oct 15.
38. Salas V, Pastor FJ, Capilla J, et. al. Evaluation of the correlation of caspofungin MICs and treatment outcome in murine infections by wild type strains of Candida parapsilosis. Diag Microbiol Infect Dis 2013; 77: 41–5.
39. Colombo AL, Ngai AL, Bourque M, et. al. Caspofungin use in patients with invasive candidiasis caused by common non-albicans Candida species: review of the caspofungin database. Antimicrob Agents Chemother 2010; 54:1864-71.
40. Fernández-Ruiz M, Aguado JM, Almirante B, et. al. Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: a propensity score analysis. Clin Infect Dis 2014; 58: 1413-21.
41. Reboli AC. Editorial commentary: Is the debate about treatment of Candida parapsilosis complex infections with echinocandins much ado about nothing? Clin Infect Dis 2014; 58: 1422-3.
42. Arendrup MC, Rodriguez-Tudela JL, Lass-Flo?rl C, et. al. EUCAST technical note on anidulafungin. Clin Microbiol Infect 2011; 17: 18-20.
43. Espinel-Ingroff A, Arendrup MC, Pfaller MA, et. al. Interlabo- ratory variability of caspofungin MICs for Candida spp. using CLSI and EUCAST methods: should the clinical laboratory be testing this agent? Antimicrob Agents Chemother 2013; 57: 5836-42.
44. Shields RK, Nguyen MH, Press EG, et. al. Anidulafungin and micafungin MIC breakpoints are superior to that of caspofungin for identifying FKS mutant Candida glabrata strains and Echinocandin resistance. Antimicrob Agents Chemother 2013; 57:6361-5.
45. Eschenauer GA, Nguyen MH, Shoham S, et. al. Real-World Experience with Echinocandin MICs against Candida Species in a Multicenter Study of Hospitals That Routinely Perform Susceptibility Testing of Bloodstream Isolates. Antimicrob Agents Chemother 2014; 58: 1897-906.