Candidemia profile and antifungal drugs susceptibility pattern in neonatal intensive care unit patients in a tertiary care teaching institute in Maharashtra
Keywords:
Antifungal drug resistance, AFST, Candidemia, NICU
Abstract
Background: Invasive candidiasis is one of the most commonly encountered problems in neonatal intensive care unit (NICU) leading to substantial morbidity and mortality. Recent studies show an increase in antifungal resistance of candida species. Therefore, species identification with antifungal susceptibility pattern of Candida isolates is very important and helps in the selection of appropriate antifungal agents to prevent the emergence of drug resistance and successful treatment.Methods: Seven thirty four blood culture samples from 244 patients of NICU were tested. Yeast isolates from these blood cultures were identified by conventional methods. Anti-fungal susceptibility testing was done according to CLSI M44A guidelines for Fluconazole, Voriconazole, ketoconazole, Amphotericin-B and Itraconazole.Result: From 118 isolates c. albicans were 37.28 % and remaining 62.72% were non-albicans candida species including c.glabrata (28.81%), c.parapsilosis (14.4%), c.tropicalis (12.71%) and other (6.77%). From all isolates of candida species, Fluconazole, Amphotericin B and ketoconazole were sensitive in 61.0%, 86.4% and 99.1% patients respectively. Voriconazole and Itraconazole were 100% sensitive.Conclusion: Although previously Candida albicans accounted for majority cases of candidiasis, recently NAC species have been increasingly reported in neonatal intensive care units. Amphotericin B should be reserved for life threatening conditions and extended spectrum azole drugs like Voriconazole, Itraconazole and ketoconazole can be good alternatives for treating these infections.DOI: 10.21276/APALM.2017.1000References
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7) Elguezabal N, Lopitz-Otsoa F, Lain A, Larrinoa IF, Moragues MD, Ponton J. Serodiagnosis of mycoses using recombinant antigens.Mycopathologia 2005;160:97-109.
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9) Magill SS, Shields C, Sears CL, Choti M, Merz WG. Triazole cross-resistance among Candida spp.: Case report, occurrence among bloodstream isolates, and implications for antifungal therapy. J Clin Microbiol 2006;44:529-35.
10) Lortholary O, Dupont B. Antifungal prophylaxis during neutropenia and immunodeficiency. Clin Microbiol Rev 1997;10(3):477-04.
11) Hospenthal DR, Murrey CK, Rinaldi MG. The role of antifungal susceptibility testing in the therapy of candidiasis. Diagn. Microbiol.Infect. Dis.2004;48:153-60.
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14) Verduynlunel FM, Meis JF, Voss A. Nosocomial fungal infections: candidemia. Diagnostic Microbiology and Infectious Disease 1999;34:213-220.
15) Roilides E, Farmaki E, Evdoridou J, Dotis J, Hatziioannidis E, Tsivitanidou M et al. Neonatal candidiasis: analysis of epidemiology, drug susceptibility, and molecular typing of causative isolates. European Journal of Clinical Microbiology & Infectious Diseases2004;23:745-750.
16) Onwuanak CA, Okolo SN, Ige KO, Okpe SE, Toma BO. The effects of birth weight and gender on neonatal mortality in north central Nigeria. BMC Research Notes2011;4:562.
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18) Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Donowitz GL. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med.2001;345:1660–66.
19) Hazen KC, Baron EJ, Colombo AL, Girmenia C, Sanchez-Sousa A, Palacio A et al. Comparison of the Susceptibilities of Candida spp. to Fluconazole and Voriconazole in a 4-Year Global Evaluation Using Disk Diffusion: J C M2003;41(12):5623–32.
20) Capriles CH, Essayag SM, Azpiróz A, Ponente A, Magaldi S, Pérez C, et al. Neonatal candidiasis in Venezuela: Clinical and epidemiological aspects. Rev Latinoam Microbiol 2005;47:11-20.
21) Almirante B, Rodríguez D, Cuenca-Estrella M, Almela M, Sanchez F, Ayats J, et al. Epidemiology, risk factors, and prognosis of Candida parapsilosis bloodstream infections: Case-control population-based surveillance study of patients in Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 2006;44:1681-5.
22) Trofa D, Gácser A, Nosanchuk JD. Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev 2008;21:606-25.
23) Roilides E, Farmaki E, Evdoridou J, Francesconi A, Kasai M, Filioti J, et al. Candida tropicalis in a neonatal intensive care unit: Epidemiologic and molecular analysis of an outbreak of infection with an uncommon neonatal pathogen. J Clin Microbiol 2003;41:735-41.1
24) Zaoutis TE, Foraker E, Mcgowan KL, Mortensen J, Campos J, Walsh TJ et al. Antifungal susceptibility of Candida spp. Isolated from pediatric patients: a survey of 4 children’s hospitals. Diagnostic Microbiology and Infectious Disease2005;52:295-98.
25) Healy CM, Campbell JR, Zaccaria E, Baker CJ. Fluconazole prophylaxis in extremely low birth weight neonates reduces invasive candidiasis mortality rates without emergence of fluconazoleresistant Candida species. Pediatrics.2008;121:703–10.
26) Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ, Jones RN. In vitro susceptibilities of rare Candida bloodstream isolates to ravuconazole and three comparative antifungal agents. Diagnostic Microbiology and Infectious Disease.2004;48, 101-5.
27) Avila-Aguero ML, Canas-Coto A, Ulloa-Gutierrez R, Caro MA, Alfaro B, Paris MM. Risk factors for Candida infections in a neonatal intensive care unit in Costa Rica. International Journal of Infectious Diseases. 2005;9:90-5.
28) Pfaller MA, Diekema DJ, Jones RN, Messer SA, Hollis RJ. Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY Antimicrobial Surveillance Program, 1997 to 2000. Journal of Clinical Microbiology.2002;40:852-56.
29) Kuzucu C, Durmaz R, Otlu B, Aktas E, Gulcan H, Cizmeci Z. Species distribution, antifungal susceptibility and clonal relatedness of Candida isolates from patients in neonatal and pediatric intensive care units at a medical center in Turkey. New Microbiologica.2008;31:401-8.
30) Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP. National surveillance of nosocomial bloodstream infection due to Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. Diagn Microbiol Infect Dis.1998;31:327–32.
2) Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Late-onset sepsis in very low birth weight neonates.The experience of the NICHD Neonatal Research Network. Pediatrics 2002;110:285-91.
3) Ariff S, Saleem AF, Soofi SB, Sajjad R. Clinical spectrum and outcomes of neonatal candidiasis in a tertiary care hospital in Karachi, Pakistan. J Infect Dev Ctries 2011;5:216-23.
4) Beck-sague CM, Jarvis WR. The national nosocomial infections surveillance system secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990 J. Infect Dis.1993;167:1247-51.
5) Nielsen H, Stedemp J, Buin R. Fungemia at a university hospital 1984– 1988. Scand J Infect Dis 1991;23:275–82.
6) Benjamin DK Jr, Stoll BJ, Fanaroff AA, McDonald SA, Oh W, Higgins RD et al. National Institute of Child Health and Human Development Neonatal Research Network. Neonatal candidiasis among extremely low birth weight infants: Risk factors, mortality rates, and neuro developmental outcomes at 18 to 22 months. Pediatrics 2006;117:84-92.
7) Elguezabal N, Lopitz-Otsoa F, Lain A, Larrinoa IF, Moragues MD, Ponton J. Serodiagnosis of mycoses using recombinant antigens.Mycopathologia 2005;160:97-109.
8) Prasad KN, Agarwal J, Dixit AK, Tiwari DP, Dhole TN, Ayyagiri A. Role of yeasts as nosocomial pathogens and their susceptibility to fluconazole and amphotericin B. Indian J Med Res 1999;110:11-7.
9) Magill SS, Shields C, Sears CL, Choti M, Merz WG. Triazole cross-resistance among Candida spp.: Case report, occurrence among bloodstream isolates, and implications for antifungal therapy. J Clin Microbiol 2006;44:529-35.
10) Lortholary O, Dupont B. Antifungal prophylaxis during neutropenia and immunodeficiency. Clin Microbiol Rev 1997;10(3):477-04.
11) Hospenthal DR, Murrey CK, Rinaldi MG. The role of antifungal susceptibility testing in the therapy of candidiasis. Diagn. Microbiol.Infect. Dis.2004;48:153-60.
12) National Committee for Clinical Laboratory Standards. Method for antifungal disk diffusion susceptibility for yeasts. Approved guideline M44-A. National Committee for Clinical Laboratory Standards, Wayne, Pa 2004.
13) Chandar J. textbook of medical mycology. 13th ed. New Delhi: Mehta publishers. 2012 p.522-530.
14) Verduynlunel FM, Meis JF, Voss A. Nosocomial fungal infections: candidemia. Diagnostic Microbiology and Infectious Disease 1999;34:213-220.
15) Roilides E, Farmaki E, Evdoridou J, Dotis J, Hatziioannidis E, Tsivitanidou M et al. Neonatal candidiasis: analysis of epidemiology, drug susceptibility, and molecular typing of causative isolates. European Journal of Clinical Microbiology & Infectious Diseases2004;23:745-750.
16) Onwuanak CA, Okolo SN, Ige KO, Okpe SE, Toma BO. The effects of birth weight and gender on neonatal mortality in north central Nigeria. BMC Research Notes2011;4:562.
17) Sardana V, Pandey A, Madan M, Goel SP, Asthana AK. Neonatal candidemia: A changing trend. Indian J Pathol Microbiol 2012;55:132-3.
18) Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Donowitz GL. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med.2001;345:1660–66.
19) Hazen KC, Baron EJ, Colombo AL, Girmenia C, Sanchez-Sousa A, Palacio A et al. Comparison of the Susceptibilities of Candida spp. to Fluconazole and Voriconazole in a 4-Year Global Evaluation Using Disk Diffusion: J C M2003;41(12):5623–32.
20) Capriles CH, Essayag SM, Azpiróz A, Ponente A, Magaldi S, Pérez C, et al. Neonatal candidiasis in Venezuela: Clinical and epidemiological aspects. Rev Latinoam Microbiol 2005;47:11-20.
21) Almirante B, Rodríguez D, Cuenca-Estrella M, Almela M, Sanchez F, Ayats J, et al. Epidemiology, risk factors, and prognosis of Candida parapsilosis bloodstream infections: Case-control population-based surveillance study of patients in Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 2006;44:1681-5.
22) Trofa D, Gácser A, Nosanchuk JD. Candida parapsilosis, an emerging fungal pathogen. Clin Microbiol Rev 2008;21:606-25.
23) Roilides E, Farmaki E, Evdoridou J, Francesconi A, Kasai M, Filioti J, et al. Candida tropicalis in a neonatal intensive care unit: Epidemiologic and molecular analysis of an outbreak of infection with an uncommon neonatal pathogen. J Clin Microbiol 2003;41:735-41.1
24) Zaoutis TE, Foraker E, Mcgowan KL, Mortensen J, Campos J, Walsh TJ et al. Antifungal susceptibility of Candida spp. Isolated from pediatric patients: a survey of 4 children’s hospitals. Diagnostic Microbiology and Infectious Disease2005;52:295-98.
25) Healy CM, Campbell JR, Zaccaria E, Baker CJ. Fluconazole prophylaxis in extremely low birth weight neonates reduces invasive candidiasis mortality rates without emergence of fluconazoleresistant Candida species. Pediatrics.2008;121:703–10.
26) Pfaller MA, Diekema DJ, Messer SA, Boyken L, Hollis RJ, Jones RN. In vitro susceptibilities of rare Candida bloodstream isolates to ravuconazole and three comparative antifungal agents. Diagnostic Microbiology and Infectious Disease.2004;48, 101-5.
27) Avila-Aguero ML, Canas-Coto A, Ulloa-Gutierrez R, Caro MA, Alfaro B, Paris MM. Risk factors for Candida infections in a neonatal intensive care unit in Costa Rica. International Journal of Infectious Diseases. 2005;9:90-5.
28) Pfaller MA, Diekema DJ, Jones RN, Messer SA, Hollis RJ. Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY Antimicrobial Surveillance Program, 1997 to 2000. Journal of Clinical Microbiology.2002;40:852-56.
29) Kuzucu C, Durmaz R, Otlu B, Aktas E, Gulcan H, Cizmeci Z. Species distribution, antifungal susceptibility and clonal relatedness of Candida isolates from patients in neonatal and pediatric intensive care units at a medical center in Turkey. New Microbiologica.2008;31:401-8.
30) Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP. National surveillance of nosocomial bloodstream infection due to Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. Diagn Microbiol Infect Dis.1998;31:327–32.
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2017-02-24
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