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 ~  Abstract
 ~  Materials and Me...
 ~  Results
 ~  Discussion
 ~  Acknowledgements
 ~  References

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Year : 2003  |  Volume : 21  |  Issue : 1  |  Page : 56-58

Neonatal systemic candidiasis in a tertiary care centre

Department of Microbiology Medical College Mumbai-400012 , India

Correspondence Address:
, India

 ~ Abstract 

The purpose of this study was to identify infections causing Candida spp. and to examine their susceptibility to antifungal drugs. The study examined 30 isolates of Candida spp. grown from blood culture samples of neonates. Clinical histories revealed that all 30 infants had received systemic broad-spectrum antibiotic therapy, 27/30 were low birth weight, 21/30 suffered from respiratory distress syndrome and 23/30 were preterm. The three species of Candida isolated were Candida albicans (16/30, 53.3%), C. tropicalis (7/30,23.3%), and C. krusei (7/30, 23.3%). Antifungal susceptibility tests against fluconazole and amphotericin B were done based on the NCCLS guidelines for antifungal susceptibility testing. The fluconazole resistance pattern was as follows: 1/16 (6.25%) strain of C. albicans was susceptible, 12/16 (75%) strains were dose dependent susceptibles, and 3/16 (18.75%) were resistant to fluconazole. Among Candida tropicalis, 2/7(29%) strains were susceptible, 4/7 (55.5%) dose dependent susceptible and 1/7 (14.5%) were resistant. All strains of C. krusei were resistant to fluconazole. There was no resistance to amphotericin B.

How to cite this article:
Narain S. Neonatal systemic candidiasis in a tertiary care centre. Indian J Med Microbiol 2003;21:56-8

How to cite this URL:
Narain S. Neonatal systemic candidiasis in a tertiary care centre. Indian J Med Microbiol [serial online] 2003 [cited 2020 Nov 24];21:56-8. Available from:

Systemic candidiasis in neonates is increasing in frequency especially since the survival of babies with low birth weight has increased. Candida spp. are the most common fungal pathogens isolated from blood cultures of neonates.[1] A number of risk factors are associated with the development of neonatal systemic candidiasis such as very low birth weight, prematurity, prolonged antibiotic therapy, prolonged use of fat emulsions in total parenteral nutrition and the use of artificial ventilation. The clinical manifestations are respiratory insufficiency, apnoea, bradycardia, temperature instability, feeding intolerance and abdominal distension.[2] Prompt treatment with antifungals is required for these babies. The emergence of resistance to fluconazole among Candida spp. and the frequent isolation of non- albicans Candida species such as C. tropicalis, C. krusei, C. parapsilosis, C. guilliermondii and C. glabrata[4] prompted us to undertake this study.

 ~ Materials and Methods Top

Thirty neonates admitted to the neonatal intensive care unit of King Edward Memorial Hospital, Mumbai, over a period of 1year (June 1998 to May 1999) were included in the study. Detailed clinical histories were taken. One to 3 mL of blood was collected from the peripheral veins of the infants using standard aseptic technique[5] and inoculated into blood culture bottles containing brain heart infusion broth. The bottles were incubated at 370C and were shaken periodically. On 3rd, 5th and 7th day, subcultures were done on Sabouraud dextrose agar slants. Candida isolates were considered clinically significant if isolated from more than one site or on two successive blood cultures.
Speciation of Candida isolates was carried out by germ tube test[5] and carbohydrate assimilation tests.[6] Antifungal susceptibility to fluconazole and amphotericin B was tested using broth microdilution technique recommended by National Committee for Clinical Laboratory Standards document M-27A. The isolates were categorised into susceptible, dose dependent susceptible (requiring higher dose of fluconazole for therapy) and resistant on the basis of minimum inhibitory concentration (MIC). The range of concentrations tested for fluconazole were 0.125 to 64 g/mL and for amphotericin B were 0.0313 to 16 g/mL. Isolates with MIC 8 g/mL were considered susceptible, values between 16 - 32 g/mL dose dependent susceptible and those 64 g/mL resistant. The end point for fluconazole was the lowest concentration in which prominent decrease in turbidity was observed and for amphotericin B was defined as the lowest concentration in which an optically clear well was observed.[7]

 ~ Results Top

[Table - 1] enumerates the predisposing factors that possibly led to neonatal systemic candidiasis based on an analysis of clinical histories. All the 30 infants received systemic broad spectrum antibiotic therapy, 27/30 were low birth weight, 21/30 suffered from respiratory distress syndrome and 23/30 were preterm.
The 30 isolates belonged to three species, namely C.albicans (16/30), C.tropicalis (7/30) and C.krusei (7/30). [Table - 2] shows the antifungal susceptibility pattern to fluconazole and amphotericin B. One out of 16 (6.25%) strains of C. albicans were susceptible, 12/16 (75%) dose dependent susceptible, 3/16 (18.75%) were resistant to fluconazole. All seven strains of C. krusei were resistant to fluconazole. 2/7(29%) strains of C. tropicalis were susceptible, 4/7 (55.5%) dose dependent susceptible and 1/7 (14.5%) were resistant to fluconazole. All the isolates were sensitive to amphotericin B as the MICs were less than 16 g/mL.

 ~ Discussion Top

Neonatal systemic candidiasis occurs in the presence of predisposing factors such as broad spectrum antibiotic therapy, low birth weight, intravenous hyperalimentation, ventilator therapy and endotracheal incubation as reported in a case control study.[2] In the present study, the factors that possibly led to candidaemia were broad-spectrum antibiotic therapy, low birth weight, prematurity and ventilator therapy. Central lines were not a very important factor because they were given in only 3 babies. Parenteral nutrition was not common, as the babies were breast-fed.
Earlier studies have found C.albicans as the most common isolate from neonates followed by C.parapsilosis and C.tropicalis.[8] In our study, C.albicans was found to be the most common isolate. A striking feature of our study was the isolation of C.krusei, a species known for its innate resistance to fluconazole.[7] This could be a result of the practice in our hospital to administer fluconazole for the treatment of neonatal systemic candidiasis, which might have led to a selection of such innately resistant species. Drug resistance seen in our study is high but we do not have any previous data for internal comparison, as this is the first study in our hospital. The higher proportion of dose dependent susceptible strains (requiring higher doses of fluconazole for therapy) in comparison to susceptible strains shows either a trend towards increasing fluconazole resistance or perhaps the trailing effect seen while testing fluconazole resistance.[7] Narang et al,[9] in a study of neonatal systemic candidiasis found fluconazole to be a useful antifungal agent with 24% resistance. But they have not reported any innately resistant species. Candida spp are important pathogens in neonatal bloodstream infections. Their speciation as well as antifungal susceptibility patterns need to be studied especially in light of increasing drug resistance. Alternatives to fluconazole such as other azoles, 5-FU and amphotericin B need to be evaluated for therapy.

 ~ Acknowledgements Top

The authors acknowledge the help extended by Dr. Neelima Kshirsagar, Head of Clinical Pharmacology, GS Medical College and KEM Hospital for providing pure powder of amphotericin B and her laboratory support. The authors also acknowledge the support provided by the staff of Neonatal Intensive Care Unit of KEM Hospital in obtaining clinical histories. 

 ~ References Top

1.Weese-Mayer DE, Fondriest DW, Brouillette RT, Shulman ST. Risk Factors associated with Candidemia in the neonatal intensive care unit: a case control study. Pediatr Infect Dis J 1987;6:190-196.  Back to cited text no. 1    
2.Nelson WE. Nelsons textbook of Pediatrics. 15th edition, (Prism Books Pvt. Ltd.), 1996:536-537.  Back to cited text no. 2    
3.Price MF, La Rocco Mt, Gentry LO. Fluconazole susceptibility of Candida species and distribution of species recovered from blood culture over a 5 year period. Antimicrob Agents chemother 1994;38:1422-1424.  Back to cited text no. 3    
4.Forbed BA. Bailey and Scotts Diagnostic Microbiology, 10th edition, (CV Mosby Company, St. Louis) 1998:870-951.  Back to cited text no. 4    
5.Warren NG, Hazen KC. Candida, Cryptococcus and other yeasts of Medical importance. Chaper 61. In: Manual of Clinical Microbiology, 6th ed. Murray PR, Baron ES, Pfaller MA, Tenover FC, Yolken RH, Eds. (ASM Press, Washington DC) 1995:723.  Back to cited text no. 5    
6.National committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A. NCCLS, Wayne,Pa, USA, 1997.  Back to cited text no. 6    
7.Roy A, Maiti PK, Adhya S, Bhattacharya A, Chakraborty G, Ghosh E, Chakraborty P. Neonatal Candidemia. Indian Pediatrics, 1993;60(6):799-801.  Back to cited text no. 7    
8.Narang A, Agarwal PR, Chakrabarti A, Kumar P. Epidemiology of systemic candidiasis in a tertiary care neonatal unit. J Trop pediatrics 1998;44(2):104-108.  Back to cited text no. 8    
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