Antifungal susceptibility patterns of colonized Candida species isolates from immunocompromised pediatric patients in five university hospitals
AbstractBackground and Objectives: Colonization of Candida species is common in pediatric patients admitted to hematology-oncology wards. The aim of this study was to identify colonized Candida species and their susceptibility patterns in hematologic pediatric patients.Materials and Methods: Samples were collected from mouth, nose, urine and stool of the patients admitted to five university hospitals and cultured on sabouraud dextrose agar. The isolates were identified by API 20 C AUX system and their susceptibility patterns were evaluated by CLSI M27-A3 and S4. Results: From 650 patients, 320 (49.2%) were colonized with 387 Candida species. Candida albicans was the most prevalent isolated species, followed by Candida glabrata, Candida tropicalis, Candida famata, Candida kefyr and Candida kuresi. The epidemiological cut off value (ECV) for all Candida species to amphotericin B was ≤0.25 μg except C. krusei (4 μg). The resistance rate to fluconazole in this study in C. albicans was 4.9% with ECV 8 μg/ml, followed by C. tropicalis 8.8% with ECV 0.5 μg/ml. Voriconazole and posaconazole were effective antifungal agents for all Candida isolates. The ECV of C. albicans, Candida parapsilosis, C. tropicalis, C. glabrata and C. krusei for itraconazole were 0.5, 0.25, 0.5, 1 and 2 μg, respectively. The resistant and intermediate rates of Candida species to caspofungin in this study were 2.9%, 5.9%, 18.8%, 47.9%, 0.0% and 16.7% in C. tropicalis, C. glabrata and C. parapsilosis respectively.Conclusion: C. albicans was the most prevalent species in pediatric colonized patients. New azole agents like voriconazole and posaconazole are effective against non- albicans Candida species. Increase in intermediate species is alarming to future emerging resistant species.
Ghassemi A, Farhangi H, Badiee Z, Banihashem A, Mosaddegh M. Evaluation of nosocomial infection in patients at hematology-oncology ward of Dr. Sheikh children’s hospital. Iran J Ped Hematol Oncol 2015;5:179-185.
Gokcebay DG, Yarali N, Isik P, Bayram C, Ozkaya-Parlakay A, Kara A, et al. Candida associated bloodstream infections in pediatric hematology patients: a single center experience. Mediterr J Hematol Infect Dis 2016;8(1): e2016018.
Sievert DM, Ricks P, Edwards JR, Schneider A, Patel J, Srinivasan A, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections summary of data reported to the national healthcare safety network at the centers for disease control and prevention, 2009-2010. Infect Control Hosp Epidemiol 2013;34:1-14.
Badiee P, Zareifar S, Haddadi P, Jafarian H. Incidence of Fungal Infections in Pediatric Patients with Hematologic Neoplasms. Arch Pediatr Infect Dis 2017;5(3):e41317.
Hegazi M, Abdelkader A, Zaki M, El-Deek B. Characteristics and risk factors of candidemia in pediatric intensive care unit of a tertiary care children's hospital in Egypt. J Infect Dev Ctries 2014;8:624-634.
Badiee P, Alborzi A. Assessment of a real-time PCR method to detect human non-cryptococcal fungal meningitis. Arch Iran Med 2011;14:381-384.
Caggiano G, Puntillo F, Coretti C, Giglio M, Alicino I, Manca F, et al. Candida colonization index in patients admitted to an ICU. Int J Mol Sci 2011;12:7038-7047.
Eggimann P, Pittet D. Candida colonization index and subsequent infection in critically ill surgical patients: 20 years later. Intensive Care Med 2014;40:1429-1448.
Wayne P. Clinical and Laboratory Standards Institute: Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard-; CLSI document M27-A3. CLSI 2008a. 2008;28:6-12.
Wayne P. M27-S4: Reference Method for Broth Dilution antifungal susceptibility testing of yeasts; Fourth informational supplement. CLSI 2012;32(17):28.
León C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Álvarez-Lerma F, et al. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med 2006;34(3):730-737.
Badiee P, Alborzi A, Shakiba E, Farshad S, Japoni A. Susceptibility of Candida species isolated from immunocompromised patients to antifungal agents/Sensibilité aux antifongiques des espèces de Candida isolées chez des patients immunodéprimés. East Mediterr Health J 2011;17:425-430.
Haddadi P, Zareifar S, Badiee P, Alborzi A, Mokhtari M, Zomorodian K, et al. Yeast colonization and drug susceptibility pattern in the pediatric patients with neutropenia. Jundishapur J Microbiol 2014;7(9): e11858.
Salehei Z, Seifi Z, Mahmoudabadi A. Sensitivity of vaginal isolates of Candida to eight antifungal drugs isolated from Ahvaz, Iran. Jundishapur J Microbiol 2012;5(4):574-577.
Shokohi T, Bandalizadeh Z, Hedayati MT, Mayahi S. In vitro antifungal susceptibility of Candida species isolated from oropharyngeal lesions of patients with cancer to some antifungal agents. Jundishapur J Microbiol 2011;4:19-26.
Pasqualotto A, Nedel W, Machado T, Severo L. A 9-year study comparing risk factors and the outcome of paediatric and adults with nosocomial candidaemia. Mycopathologia 2005;160:111-116.
Badiee P, Alborzi A, Shakiba E, Ziyaeyan M, Rasuli M. Molecular identification and in-vitro susceptibility of Candida albicans and C. dubliniensis isolated from immu-nocompromised patients. Iran Red Crescent Med J 2009;2009:391-397.
Wisplinghoff H, Ebbers J, Geurtz L, Stefanik D, Major Y, Edmond MB, et al. Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities. Int J Antimicrob Agents 2014;43:78-81.
Moran C, Grussemeyer CA, Spalding JR, Benjamin Jr DK, Reed SD. Candida albicans and non-albicans bloodstream infections in adult and pediatric patients: comparison of mortality and costs. Pediatr Infect Dis J 2009;28:433-435.
Doi AM, Pignatari ACC, Edmond MB, Marra AR, Camargo LFA, Siqueira RA, et al. Epidemiology and microbiologic characterization of nosocomial candidemia from a Brazilian national surveillance program. PLoS One 2016;11(1):e0146909.
Jensen R, Johansen H, Søes L, Lemming L, Rosenvinge FS, Nielsen L, et al. Posttreatment antifungal resistance among colonizing Candida isolates in candidemia patients: results from a systematic multicenter study. Antimicrob Agents Chemother 2016;60:1500-1508.
Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M. Geographic variations in species distribution and echinocandin and azole antifungal resistance rates among Candida bloodstream infection isolates: report from the SENTRY Antimicrobial Surveillance Program (2008 to 2009). J Clin Microbiol 2011;49:396-399.
Taj-Aldeen S, Kolecka A, Boesten R, Alolaqi A, Almaslamani M, Chandra P, et al. Epidemiology of candidemia in Qatar, the Middle East: performance of MALDI-TOF MS for the identification of Candida species, species distribution, outcome, and susceptibility pattern. Infection 2014;42:393-404.
Zomorodian K, Rahimi MJ, Pakshir K, Motamedi M, Ghiasi MR, Rezashah H. Determination of antifungal susceptibility patterns among the clinical isolates of Candida species. J Glob Infect Dis 2011;3(4):357-360.
Won EJ, Shin JH, Choi MJ, Lee WG, Park Y-J, Uh Y, et al. Antifungal susceptibilities of bloodstream isolates of Candida species from nine hospitals in Korea: application of new antifungal breakpoints and relationship to antifungal usage. PLoS One 2015;10(2):e0118770.