|Year : 2017 | Volume
| Issue : 3 | Page : 150-154
Invasive candidiasis in a neonatal intensive care unit in Lagos, Nigeria
Beatrice Nkolika Ezenwa1, Rita Okeoghene Oladele2, Patricia Eyanya Akintan1, Iretiola Bamikeolu Fajolu2, Phillip Olayiwola Oshun2, Oyinlola Omoniyi Oduyebo2, Veronica Chinyere Ezeaka1
1 Department of Paediatrics, Lagos University Teaching Hospital, Lagos, Nigeria
2 Department of Microbiology and Parasitology, Lagos University Teaching Hospital, Lagos, Nigeria
|Date of Web Publication||30-Oct-2017|
Beatrice Nkolika Ezenwa
Department of Paediatrics, Lagos University Teaching Hospital, Lagos
Source of Support: None, Conflict of Interest: None
Background: Invasive candidiasis has been identified globally as a major cause of morbidity and mortality in neonatal intensive care units (NICU). Systemic candidiasis presents like bacterial sepsis and can involve multiple organs. Objective: The objective of this study was to determine the prevalence of Candida infection in a NICU at a tertiary hospital in Nigeria and to identify its associated risk factors. Materials and Methods: The study was a retrospective descriptive study of all cases of culture-proven invasive Candida infection (ICI) in neonates admitted to the NICU over a 4-year period. The study participants were identified from microbiology records of all neonates with a positive Candida culture. Medical records of identified neonates were also reviewed, and relevant information obtained. Results: Over the 4 years, 2712 newborns were admitted to the NICU. From these, 1182 various clinical samples were collected from babies with features of sepsis and processed in the medical microbiology laboratory. Twenty-seven (2.3%) of the cultures yielded Candida organisms; fifteen of the Candida cultures were from male infants with a male:female ratio of 1.3:1. Bloodstream infection was the most frequent ICI seen in preterm babies (seven [58.3%] out of 12 babies with ICI). Nearly, all (91.7%) affected preterm infants with ICI were <1500 g in weight. All were exposed to invasive procedures and broad-spectrum antibiotics. The case fatality rate among those with ICI was 18.5%. Conclusion: There was a significant prevalence of invasive candidiasis in high-risk newborns and the incidence increases with increased practices in risk factors such as invasive procedures and antibiotic use and lower gestational age babies with very low birth weight.
Keywords: Invasive Candida infection, neonates, neonatal intensive care unit, Nigeria, risk factors
|How to cite this article:|
Ezenwa BN, Oladele RO, Akintan PE, Fajolu IB, Oshun PO, Oduyebo OO, Ezeaka VC. Invasive candidiasis in a neonatal intensive care unit in Lagos, Nigeria. Niger Postgrad Med J 2017;24:150-4
|How to cite this URL:|
Ezenwa BN, Oladele RO, Akintan PE, Fajolu IB, Oshun PO, Oduyebo OO, Ezeaka VC. Invasive candidiasis in a neonatal intensive care unit in Lagos, Nigeria. Niger Postgrad Med J [serial online] 2017 [cited 2018 Mar 21];24:150-4. Available from: http://www.npmj.org/text.asp?2017/24/3/150/217397
| Introduction|| |
Globally, invasive fungal infections are a major cause of neonatal morbidity and mortality in neonatal intensive care units (NICUs). Different species of fungi have been isolated in different studies, but the major culprit globally has been the Candida spp which account for more than one-fourth of all microbial infections in the newborn period most especially in the preterm babies. The sources of candidiasis in NICU are often endogenous following colonisation of the babies with the fungus. About 10% of these babies get colonised in the 1st week of life, and up to 64% babies get colonised by 4 weeks of hospital stay. It has been shown that Candida species rapidly colonise the skin and mucous membranes of about 40%–60% of critically ill infants and colonisation can progress to invasive infection. Invasive Candida infection (ICI) is most often associated with end-organ dissemination of disease and has high mortality. Systemic candidiasis presents like bacterial sepsis and can involve multiple organs such as the kidneys, brain, eyes, liver, spleen, bone, joints, meninges and heart. Major risk factors associated with invasive neonatal Candida infections include prematurity, vaginal delivery, prolonged central venous catheterisation and prolonged use of broad-spectrum antibacterial agents, use of H2-receptor antagonists, gastrointestinal diseases (necrotising enterocolitis [NEC], focal bowel perforation, intravenous nutrition and delayed enteral feeds).
It has been observed that many resource-poor centres in developing countries encounter many of the risk factors for ICIs in their NICUs, but few consider antifungal prophylaxis in these at-risk neonates. Babies may have been lost due to lack of antifungal prophylaxis protocol or a delay in instituting treatment due to a delay in diagnosis. The diagnosis of ICI in our environment depends majorly on microbiologic cultures most especially blood cultures.,, There is a paucity of data on the prevalence of ICIs in neonates in Nigeria despite the fact that risk factors for ICIs abound in our daily practice. The present study aimed to determine the prevalence of ICIs in the newborns at the NICU of a tertiary hospital in Nigeria and to identify associated factors.
| Materials and Methods|| |
The study was a retrospective descriptive review of all cases of culture-proven invasive neonatal Candida infection admitted to the NICU of Lagos University Teaching Hospital (LUTH) between January 2012 and December 2015 (4-year period). LUTH is a tertiary hospital with an 80-bed NICU services for both referred and inborn babies. The hospital receives a referral of babies from general hospitals, maternity facilities and private hospitals, within Lagos, and its neighbouring states. The medical microbiology laboratory resides within the LUTH main laboratory and processes all the microbial cultures in the hospital.
Ethical approval was obtained from the Health Research and Ethics Committee of the LUTH Lagos with the protocol number ADM/DCST/HREC/APP/101 approved on the 10 June, 2015. The study participants were identified from microbiology records of all neonates admitted to the NICU with a positive Candida culture.
Cases of ICI were defined as those that fulfilled the following two criteria (both of which must be present): (1) A clinical picture compatible with fungal sepsis, defined by patients meeting at least five of the following parameters: admission to the NICU, history of broad-spectrum antibiotic coverage >5 days, use of a third-generation cephalosporin, negative bacterial blood culture results despite persistent features suggestive of sepsis, need for intubation and mechanical ventilation, severe cardiovascular instability, indwelling central venous catheters, delayed feeding and preterm delivery. (2) A Candida pathogen isolated from a sterile site such as blood culture; urine culture; or cerebrospinal fluid (CSF) culture.
Sample collection and processing
Blood, urine and CSF samples collected aseptically from babies with a clinical diagnosis of suspected sepsis were transported to the clinical microbiology laboratory of the hospital for immediate processing. Urine samples were collected by suprapubic tap or sterile catheterisation. Blood was cultured in the BACTEC culture system 9050 (Becton Dickinson, New Jersey, US) while urine and CSF samples were processed according to established standardised protocol. They were cultured on Sabouraud dextrose agar (Oxoid UK) and Mueller Hinton agar (Oxoid UK) to which 5-7% blood had been added. Incubation was in room air for 24 h at 35°C–37°C (Oxoid, UK). Gram stain was used to characterise isolates as yeast cells, and they were further identified using germ tube test and were categorised as Candida albicans and non-albicans spp.
Medical records of identified Candida positive neonates were retrieved and reviewed. Demographic and medical information were obtained and entered in a pre-designed pro forma. Data obtained included gestational age, age at culture which is also taken as age at diagnosis, sex, procedures done on baby, antibiotics use, day of commencing enteral feeds, other co-morbidities identified and outcome (survival or death).
Data were entered into Epi Info software version 3.4 (CDC, Atlanta GA, USA). The analysis was done with Statistical Package for Social Sciences (SPSS) software version 22.0 (SPSS Inc., Chicago, IL., USA). Data were presented using descriptive statistics. Discrete data were compared by Chi-square or Fisher's exact test and P < 0.05 was considered statistically significant for all tests.
| Results|| |
Over the 4 years' period, a total of 2,712 newborns were admitted to the NICU. There were 1,149 (42.4%) preterm and 1,563 (57.6%) term babies. From these, 1182 samples (43.6% of neonatal admissions) were collected from babies with clinical features suggestive of sepsis and processed in the medical microbiology laboratory of the hospital. Eight hundred and twenty-three (69.6%) of these were blood cultures, 252 (21.3%) were CSF cultures while 107 (9.1%) were urine cultures. There were 711 cultured samples from male and 471 from female neonates. Twenty-seven (2.3%) out of the 1182 cultures yielded fungal organisms and were identified as Candida spp. Fifteen of the positive fungal cultures were from male infants with a male:female ratio of 1.3:1. All the 27 positive Candida cultures were from neonates who met the criteria for ICI. Thus, the prevalence of ICI in this study was 2.3% of the septic neonates. There were 21 (77%) C. albicans and six non-albicans of which two were Candida krusei. Twelve (44.4%) of the 27 Candida positive neonates were preterm. Bloodstream infection was the most frequent ICI seen in preterm babies 7 (58.3%) followed by urinary tract infection four (33.3%). Only one (8.3%) CSF culture yielded Candida organism (C. krusei) and it was in a preterm baby.
The mean age at diagnosis of ICI was 9.1 ± 6.1 days in preterm babies. One baby was 3-day-old when ICI occurred. The most common co-morbidities in preterm babies with ICI was respiratory distress syndrome (66.7% of affected preterm babies) while surgical conditions were the most common underlying illness in term infants with ICI (26.7%). These surgical conditions included jejunal atresia (1), imperforate anus (1), strangulated inguinoscrotal hernia (1) and Eagle-Barrett syndrome More Details (1). [Table 1] shows the baseline demographic and clinical characteristics of the neonates with ICI. Oral feeds were commenced within 3 days of life in all the infants. Mean duration of parenteral nutrition was 7 days.
|Table 1: Baseline demographic and clinical characteristics of the neonates with invasive Candida infection|
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Treatment and outcomes
All babies with ICI had treatment doses of fluconazole at 6 mg/kg/day for at least 21 days. Overall, case fatality rate in ICI affected babies was 18.5% (five out of 27 babies), but this value increased to 33.3% when case fatality rate was calculated in preterm babies alone (four out of 12 preterm babies with ICI died). The outcome difference (in terms of survival or mortality) between term and preterm infants was not statistically significant (χ2 (1, n = 27) = 3.14, P = 0.08). There was no significant sex predilection for mortality (two females vs. three males, P = 0.83) and the source of candidal isolate was also not significant for mortality (two blood, two urine and one CSF cultures; P = 0.10). However, the only child with candidal meningitis died.
Associated factors in preterm infants with invasive Candida infection
Nearly all (91.7%) affected preterm infants with ICI were <1500 g in weight. All were exposed to invasive procedures such as umbilical venous catheterisation; parenteral nutrition; and broad-spectrum antibiotics. [Table 2] shows the recognised predisposing factors for ICI in the preterm infants.
|Table 2: Known predisposing factors for invasive Candida infection in the 12 preterm neonates (n=12)|
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| Discussion|| |
Neonatal candidaemia is a common, deadly and costly hospital-associated disease. The incidence of ICI in the present study (2.3%) was lower than the 9.0% and 13.1% documented respectively by Benjamin et al. in the USA and Shin et al. in Korea. Both studies were in low birth weight babies. A more recent report from South Africa also gave the prevalence of 24% for neonatal candidaemia  and still a higher figure (57.4%) was documented from a tertiary hospital in India. The low prevalence in this study could be due to a number of factors including the fact that most of our babies were term and bigger neonates whereas over 40% of their neonates were preterm with 91.7% being very low birth weight (VLBW). It is a well-known fact that earlier gestations and VLBW babies are more prone to fungal sepsis than term babies. Another possible cause may be the increased use of invasive procedures in their patients as they were more likely to have access to mechanical ventilators and central lines for their neonates. Furthermore, fungal sepsis is rarely suspected initially in our settings hence request for fungal cultures may not be optimal. In the present study, when the incidence of ICI is considered in septic preterm babies alone, it rose to 44.4% which is considerably higher than most of the reports mentioned above.
Nearly 58% of the Candida isolates in preterm babies in the present study were cultured from blood. This is consistent with the findings in similar studies which reported candidaemia as the most common finding in ICI.Candida isolation from other sterile sites is a known risk factor and accounts for 41.7% in this study. Research has shown that isolates of Candida in the bloodstream of neonates and the vagina of the mother share a common genotype, which provides direct evidence of the association between congenital candidiasis in the neonate and Candida vaginitis in the mother. Unfortunately, this was a retrospective study, so we are not able to determine if this was the case here. However, we did document candidaemia in a 3-day-old neonate which highly suggests a congenital origin. Nosocomial Candida colonisation is the most common source of Candida infection in neonates.
The susceptibility profiles of the Candida species were not done in this study. It would have been interesting to find out if fluconazole resistance contributed to the mortality since fluconazole is the only licensed antifungal in Nigeria available for treatment of the infection. It was interesting to note that C. krusei which had been previously reported in the study centre  as being intrinsically resistant to fluconazole was isolated in the CSF of a preterm baby in this study.
Most of the risk factors that had been identified by other researchers ,,, for invasive candidiasis were also noted in our study: low gestational age, presence of central catheters, invasive procedures and antibiotic use were common predisposing factors in our study population. Yu et al. reported that the main risk factors for invasive fungal infections in their study, were third-generation cephalosporin use, peripherally inserted central venous catheters, intubation of >6 days, prior abdominal surgery and neutropaenia (<1.5 × 109 cells/L) during the 1st week of life. Other studies have investigated the association between antibiotic use and candidemia.,, The intact gastrointestinal barrier serves a crucial function in preventing Candida species colonising the gastrointestinal tract and spreading into the blood. The destruction of the gastrointestinal barrier by gastrointestinal surgery is, therefore, a crucial risk factor for candidaemia. The only death recorded in the present study in a term baby with ICI was in a child with jejunal atresia.
The case fatality rate in babies with ICI from our study was 18.5% (five babies) which was lower than that documented in an Indian study (30.65%). However, when the analysis was done in preterm neonates alone, the mortality went up to 33.3%. A study done in another centre in Nigeria documented mortality from ICI for all patients admitted to the hospital as 91.7%, and infants made up nearly a third of the population studied. Most of the deaths in the present study occurred in preterm babies emphasising the vulnerability of this select group and the need to institute proactive preventive measures against ICI. The diagnosis of ICI depends majorly on microbiologic cultures., The blood volumes required to optimise organism recovery are large and are not easily attainable in neonates. This may cause underestimation of the incidence of ICIs. The absence of culture-proven candidal infections may lead to underdiagnosis which in turn may lead to delay in instituting appropriate treatment leading to increased short- and long-term morbidity and mortality in affected babies. In view of the fact that laboratory diagnosis of ICI can be missed in 50% of the cases  coupled with the fact that the consequences of neonatal ICI is far reaching with neurodevelopmental impairment, we recommend instituting an organised antifungal protocol in NICUs for the high risk neonates (the very preterm neonates and the surgical neonates). This may lower the incidence of candidaemia and its consequent high morbidity and mortality rates.
| Conclusion|| |
Our study documented a significant prevalence in invasive candidiasis in high-risk newborns, and the incidence increased with practices of risk factors such as invasive procedures and antibiotic use and in lower gestational age babies with VLBW. Although the retrospective nature of the present study and the small sample size limited some of the findings made, we believe the study will create awareness to neonatologists in resource poor settings on the existence of this commonly overlooked disease in our NICUs and also trigger prospective researches in ICI in our settings. It is also hoped that the findings from this study will help neonatologists in settings such as ours to have a high index of suspicion for ICI in neonates and aid them in making informed and evidence-based decisions regarding antifungal prophylaxis and treatment in at-risk newborns.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rao S, Ali U. Systemic fungal infections in neonates. J Postgrad Med 2005;51 Suppl 1:S27-9.
Parikh TB, Nanavati RN, Patankar CV, Rao S, Bisure K, Udani RH, et al.
Fluconazole prophylaxis against fungal colonization and invasive fungal infection in very low birth weight infants. Indian Pediatr 2007;44:830-7.
Cahan H, Deville JG. Outcomes of neonatal candidiasis: The impact of delayed initiation of antifungal therapy. Int J Pediatr 2011;2011:813871.
Saiman L, Ludington E, Dawson JD, Patterson JE, Rangel-Frausto S, Wiblin RT, et al.
Risk factors for Candida
species colonization of neonatal Intensive Care Unit patients. Pediatr Infect Dis J 2001;20:1119-24.
Merz W, Roberts G. Algorithms for detection and identification of fungi. In: Murrary PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH, editors. Manual of Clinical Microbiology. Washington, DC: American Society for Microbiology; 2003. p. 1668-85.
Pfaller MA, Wolk DM, Lowery TJ. T2MR and T2Candida
: Novel technology for the rapid diagnosis of candidemia and invasive candidiasis. Future Microbiol 2016;11:103-17.
Magobo RE, Naicker SD, Wadula J, Nchabeleng M, Coovadia Y, Hoosen A, et al.
Detection of neonatal unit clusters of Candida parapsilosis
fungaemia by microsatellite genotyping: Results from laboratory-based sentinel surveillance, South Africa, 2009-2010. Mycoses 2017;60:320-7.
Benjamin DK Jr., Stoll BJ, Gantz MG, Walsh MC, Sánchez PJ, Das A, et al.
Neonatal candidiasis: Epidemiology, risk factors, and clinical judgment. Pediatrics 2010;126:e865-73.
Shin HY, Park JN, Shin YH, Yun DY, Park HA, Hwang JH. The incidence, treatment and risk factors of candidiasis in very low birth weight infants. Neonatal Med 2016;23:35-42.
Hsu JL, Ruoss SJ, Bower ND, Lin M, Holodniy M, Stevens DA. Diagnosing invasive fungal disease in critically ill patients. Crit Rev Microbiol 2011;37:277-312.
Chen CJ, Weng YH, Su LH, Huang YC. Molecular evidence of congenital candidiasis associated with maternal candidal vaginitis. Pediatr Infect Dis J 2006;25:655-6.
Oladele RO, Osigwe UC, Jewoola OO, Bode-Sojobo IO, Osuagwu CS, Asuquo EE, et al
. Frequency and therapeutic outcomes of culture positive invasive fungal infections at a tertiary hospital in Lagos, Nigeria. Niger Med Pract 2014;65:31-5.
Saiman L, Ludington E, Pfaller M, Rangel-Frausto S, Wiblin RT, Dawson J, et al.
Risk factors for candidemia in Neonatal Intensive Care Unit patients. The National Epidemiology of Mycosis Survey study group. Pediatr Infect Dis J 2000;19:319-24.
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.
Yu Y, Du L, Yuan T, Zheng J, Chen A, Chen L, et al.
Risk factors and clinical analysis for invasive fungal infection in neonatal Intensive Care Unit patients. Am J Perinatol 2013;30:589-94.
Spiliopoulou A, Dimitriou G, Jelastopulu E, Giannakopoulos I, Anastassiou ED, Christofidou M. Neonatal intensive care unit candidemia: Epidemiology, risk factors, outcome, and critical review of published case series. Mycopathologia 2012;173:219-28.
Juyal D, Sharma M, Pal S, Rathaur VK, Sharma N. Emergence of non-albicans Candida
species in neonatal candidemia. N
Am J Med Sci 2013;5:541-5.
Vogiatzi L, Ilia S, Sideri G, Vagelakoudi E, Vassilopoulou M, Sdougka M, et al.
Invasive candidiasis in pediatric intensive care in Greece: A nationwide study. Intensive Care Med 2013;39:2188-95.
Klingspor L, Tortorano AM, Peman J, Willinger B, Hamal P, Sendid B, et al.
infections in surgical patients in intensive care units: A prospective, multicentre survey initiated by the European Confederation of Medical Mycology (ECMM) (2006-2008). Clin Microbiol Infect 2015;21:87.e1-87.e10.
Oladele RO, Bakare RA, Petrou MA, Oduyebo OO, Richardson M. Candidaemia in a tertiary hospital in Nigeria. Afr J Lab Med 2014;3:1-5.
Benjamin DK Jr., Stoll BJ, Fanaroff AA, McDonald SA, Oh W, Higgins RD, et al.
Neonatal candidiasis among extremely low birth weight infants: Risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics 2006;117:84-92.
Wadile RG, Bhate VM. Study of clinical spectrum and risk factors of neonatal candidemia. Indian J Pathol Microbiol 2015;58:472-4.
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[Table 1], [Table 2]