|Year : 2019 | Volume
| Issue : 3 | Page : 151-154
Systemic Candida infection in preterm babies: Experience from a tertiary care hospital of North India
Bashir Ahmad Charoo, Younis Ashraf, Javeed Iqbal Bhat, Iqbal Ahmad Qazi
Department of Pediatrics, SKIMS, Srinagar, Jammu and Kashmir, India
|Date of Web Publication||6-Aug-2019|
Dr. Javeed Iqbal Bhat
Department of Pediatrics, SKIMS, Soura, Srinagar - 190 011, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
Background: Neonatal fungal infection is an important cause of late-onset sepsis with very high mortality. The incidence is progressively increasing due to a marked improvement in the survival of low-birth weight neonates. Materials and Methods: This was a 2-year observational study. Very low-birth weight (VLBW) and extremely low-birth weight (ELBW) with suspected fungal sepsis were enrolled. All suspected neonates were evaluated for possible Candida infection. Complete clinicodemographic and laboratory profile was noted from the study participants. The main outcome measure was hospital incidence, clinical profile, and the frequency of end-organ involvement. Results: During the study, 304 ELBW and VLBW neonates were screened for invasive fungal sepsis. Sixty-four neonates were found positive for invasive Candida sepsis making the incidence of 11.6%. Majority of patients developed worsening of respiratory distress and shock. Necrotizing enterocolitis (NEC) was seen in 10 patients and disseminated intravascular coagulation (DIC) in nine patients. Nearly 7.8% had cerebrospinal fluid culture positive for Candida. Renal abscess was seen in two patients. Endohpthalmitis and endocarditis each were observed in one patient. The mortality rate in our study group was 55%. Conclusion: We found 11.9% incidence of invasive fungal incidence. Majority of neonates developed worsening of respiratory distress, shock, NEC, DIC, and thrombocytopenia. End-organ damage was noticed in 14% of patients. Mortality was around 55% in our cohort.
Keywords: Candida infection, preterm, thrombocytopenia
|How to cite this article:|
Charoo BA, Ashraf Y, Bhat JI, Qazi IA. Systemic Candida infection in preterm babies: Experience from a tertiary care hospital of North India. J Clin Neonatol 2019;8:151-4
|How to cite this URL:|
Charoo BA, Ashraf Y, Bhat JI, Qazi IA. Systemic Candida infection in preterm babies: Experience from a tertiary care hospital of North India. J Clin Neonatol [serial online] 2019 [cited 2020 May 31];8:151-4. Available from: http://www.jcnonweb.com/text.asp?2019/8/3/151/264044
| Introduction|| |
India contributes to one-fifth of global live births and more than a quarter of neonatal deaths. About 0.75 million neonates die every year in India, the highest for any country in the world. Neonatal sepsis is the second leading cause of death in this population in our country and is responsible for almost a quarter of total neonatal deaths. Most of the sepsis-related deaths are preventable by adopting standard aseptic precautions and rational use of antibiotics. Neonatal sepsis may be categorized as early onset (<72 h of life) or late onset (>72 h of life). Late-onset sepsis is commonly acquired from caregiving environment and is commonly due to Gram-negative organisms. Trends in late-onset sepsis show an increase in incidence of invasive candidiasis over the past decade. It accounts for 9%–13% of all hospital-acquired sepsis. Invasive fungal infections represent the third-leading cause of late-onset sepsis in very low-birth weight (VLBW) infants and have a high rate of infection-associated mortality. The mortality associated with invasive candidiasis can be as high as 50% in VLBW neonates and even higher in extremely low-birth weight (ELBW) infants., The most common species isolated in newborn neonates is Candida albicans. Candida parapsilosis and Candida tropicalis are other species getting notorious in neonatal intensive care unit (NICU) outbreaks. The signs and symptoms are nonspecific and include temperature instability, refusal of feeds, respiratory distress, abdominal distension, apnea, lethargy, bradycardia, decreased perfusion, or seizures. Systemic candidiasis lead more frequently to end-organ damage than other newborn infections and can involve kidneys, brain, lungs, eyes, liver spleen, bones, and joints.
Aims and objective
The aim and objective of this study is to determine the incidence, clinical spectrum, organism profile, and clinical outcome of invasive candidiasis in ELBW and VLBW neonates in a neonatal ICU.
| Materials and Methods|| |
This was a prospective cohort study performed in a NICU of a tertiary care hospital of North India. The study was conducted over 2 years from June 2016 to May 2018. Study participants included VLBW neonates and ELBW neonates presented or developed signs of sepsis in NICU. All these neonates underwent full septic workup, which included complete hemogram, C-reactive protein, blood culture, urine culture, and cerebrospinal fluid (CSF) culture. Patients received treatment as per unit protocol and were followed till discharged from hospital or death. Complications if appeared such as respiratory distress, necrotizing enterocolitis (NEC), shock, disseminated intravascular coagulation (DIC), and apnea were noted. Besides septic workup, all patients positive for fungal workup underwent echocardiography for infective endocarditis, ultrasonography (USG) of the abdomen for hepatic and/or renal mycetoma, and retinal examination to rule out endophthalmitis.
Blood culture and CSF culture were done using the BACT/ALERT® automatic culture system, and urine culture was done on HiCrome UTI Agar. Identification and susceptibility were done on VITEK® 2 compact system. Urine sampling was done under aseptic condition by suprapubic aspiration and sent to laboratory for routine microscopy, culture, and sensitivity. In all the patients who showed Candida growth, lumbar puncture was also performed and CSF sample was sent for routine cytology, biochemistry, and culture.
Data were entered in a predesigned format which included variables such as gestational age, postnatal age, place of delivery (outborn/inborn), gender, duration of hospitalization, maternal risk factors for sepsis, history of prior antibiotics, relevant symptoms, and anthropometry. Vitals, such as heart rate, respiratory rate capillary refill time, and blood pressure, were also noted in all studied patients. All relevant investigations were documented in studied patients which included complete blood count, blood culture, CSF culture, CSF biochemistry and cytology, urine examination and culture if done, chest X-ray, echocardiography, and USG abdomen.
A case of invasive candidiasis was defined as positive blood culture and/or CSF culture and/or urine culture by suprapubic tap of pure growth of Candida species with clinical features supportive of Candida sepsis. The study is cleared by the Institutional Ethics Committee.
Statistical analysis was performed using the SPSS version 20 (IBM, NY, USA). Normality of data continuous data was checked by the Shapiro–Wilk test. Parametric data are expressed as mean ± standard deviation. Discrete data are expressed as a percentage.
| Results|| |
During the study, there were a total of 551 VLBW and ELBW infants admitted in our NICU, and 304 ELBW and VLBW neonates were screened for invasive fungal sepsis. Sixty-four neonates were found positive for invasive Candida sepsis making the incidence of 11.6% in our cohort. Thirty-six were male neonates and 28 were female neonates. Thirty-nine patients were outborn and were referred from neighboring hospitals, and 25 neonates were inborn. Forty-one (64%) neonates were ELBW and 23 (36%) neonates were VLBW. The demographic and laboratory profiles of the study patients are shown in [Table 1].
A total of five species of Candida were isolated from the study population, which included C. albicans (27), C. tropicalis (18), C. parapsilosis (9), Candida krusei (6), and Candida glabrata (4). Candida was grown from blood in 84.3% of patients. Urine culture and CSF culture showed positive fungal growth in 22.1% and 7.8% of patients respectively. The clinical spectrum and frequency of end-organ damage of cases are shown in [Table 2].
Majority of patients developed worsening of respiratory distress (64%) and shock (46.9). NEC was seen in 10 patients and DIC was seen in nine patients in our series. Thrombocytopenia was the most common laboratory finding in the studied population. All studied patients had received broad-spectrum antibiotics before the development of invasive fungal sepsis. Nearly 7.8% of patients had CSF culture positive for Candida. Renal abscess was seen in two patients. Endophthalmitis and endocarditis each were observed in one patient. The mortality rate in our study group was 55%. None of our patients were on prior fluconazole prophylaxis.
| Discussion|| |
Invasive fungal sepsis is a common cause of late-onset sepsis, especially in preterm neonates. It is a serious disease with very high mortality. We conducted 2-year prospective study to find the incidence of invasive Candida sepsis among high-risk VLBW and ELBW neonates in a tertiary care neonatal ICU, the clinical spectrum of the disease, organism profile, antifungal sensitivity, and its outcome. During the study, 3200 newborn neonates were admitted in our center, of which 551 neonates belonged to VLBW and ELBW category. Sixty-four neonates were diagnosed as invasive Candida infection making the incidence of 2% of total admissions and 11.6% of total VLBW and ELBW admissions. The incidence of invasive Candida sepsis was inversely related to birth weight. The high incidence of disease among the most premature neonates has been described in other studies also., It is because of profound immaturity of immune system, prolonged NICU stay, and greater requirement of invasive procedures such as central venous lines, invasive ventilation, and frequent use of broad-spectrum antibiotics in this population. All these factors place them at high risk for fungal infection. C. albicans was the most commonly isolated species in our series followed by C. tropicalis, C. parapsilosis, and C. krusei., Same trend is seen in many studies across different regions of the world. However, some recent studies in different parts of the world have detected a shift toward nonalbicans Candida (NAC) infection,, a worrying trend, as it is associated with higher mortality and poor antifungal susceptibility., Similar trend has been detected in our country. Basu et al., in their study, from Central India also found shift to NAC infection with higher mortality than albicans subgroup. We did not see this change in our study, possible reason being less use of central lines in our study patients, which was found as an independent risk factor for the higher prevalence of nonalbicans Candidiasis. The clinical spectrum of systemic candidemia in our study was worsening of respiratory distress (64%), shock (46.4%), DIC (31%), and NEC (15.6%). All patients who developed NEC in our study had Grade IIb or III NEC, and the mortality rate was 100%. Candida induces severe NEC as its presence in the bowel produces endothelial damage, blood stagnation, and platelet (PLT) aggregation, and it causes necrosis of gut with very peculiar features. Multiple studies have reported that the PLT count has a correlation with fungal infections., Torres Claveras et al. studied 42 VLBW infants with late-onset sepsis and found Gram-positive, Gram-negative, and fungal sepsis accounted for 47.6%, 33%, and 19% of the cases, respectively. The incidence of thrombocytopenia was significantly higher in Candida sepsis than bacterial sepsis (100% vs. 5.9%). Therefore, thrombocytopenia is believed to be a surrogate marker for neonatal invasive candidiasis. In this study, thrombocytopenia was the most common laboratory finding and was seen in 89% of patients. Based on our observation, we suggest thrombocytopenia be taken as a surrogate marker for invasive fungal sepsis in high-risk low-birth weight population, as the delay in treatment can have adverse impact on neonatal survival. We also found 7.8% prevalence of fungal meningitis in our cohort. Similarly, the renal abscess was seen in two patients. Endophthalmitis and endocarditis each were observed in one patient. We recommend complete evaluation for end-organ damage once invasive Candidemia is diagnosed with delay in treatment may worsen the patient and will lead to a poor outcome. The patient may need upfront another form of therapy for a better outcome like surgery/drainage in case of fungal endocarditis and renal/liver abscess.
Neonatal candidiasis is associated with 20% mortality, and 50% of survivors have a severe neurodevelopmental impairment. The mortality rate in VLBW babies may be as high as 50%., In our study, mortality was 55%, which was higher than other studies. One of the reasons for higher mortality in our series could be because of higher referrals to our NICU from other neighboring hospitals. Multiple studies have found outborn babies have higher than average mortality due to multitude of reasons.,
| conclusion|| |
We found 11.6% incidence of invasive fungal sepsis among total VLBW and ELBW admissions in our NICU. The incidence was higher among outborn neonates possibly because of high-broad-spectrum antibiotic use in this subgroup. Majority of neonates developed worsening of respiratory distress, shock, NEC, DIC, and thrombocytopenia. Mortality was around 55% in our cohort, it was higher among outborn neonates.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al.
Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: An updated systematic analysis. Lancet 2015;385:430-40.
Million Death Study Collaborators, Bassani DG, Kumar R, Awasthi S, Morris SK, Paul VK, et al.
Causes of neonatal and child mortality in India: A nationally representative mortality survey. Lancet 2010;376:1853-60.
Aggarwal R, Sarkar N, Deorari AK, Vinod K. Sepsis in the newborn. Indian J Pediatr 2001;68:1143-51.
Leibovitz E. Strategies for the prevention of neonatal candidiasis. Pediatr Neonatol 2012;53:83-9.
Stoll BJ, Gordon T, Korones SB, Shankaran S, Tyson JE, Bauer CR, et al.
Late-onset sepsis in very low birth weight neonates: A report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr 1996;129:63-71.
Baley JE, Kliegman RM, Fanaroff AA. Disseminated fungal infections in very low-birth-weight infants: Clinical manifestations and epidemiology. Pediatrics 1984;73:144-52.
Rao S, Ali U. Systemic fungal infections in neonates. J Postgrad Med 2005;51 Suppl 1:S27-9.
Al-Tawfiq JA. Distribution and epidemiology of Candidaspecies causing fungemia at a Saudi Arabian hospital, 1996-2004. Int J Infect Dis 2007;11:239-44.
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.
Fridkin SK, Kaufman D, Edwards JR, Shetty S, Horan T. Changing incidence of Candida bloodstream infections among NICU patients in the United States: 1995-2004. Pediatrics 2006;117:1680-7.
Steinbach WJ, Roilides E, Berman D, Hoffman JA, Groll AH, Bin-Hussain I, et al.
Results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates. Pediatr Infect Dis J 2012;31:1252-7.
Pammi M, Holland L, Butler G, Gacser A, Bliss JM. Candida parapsilosis
is a significant neonatal pathogen: A systematic review and meta-analysis. Pediatr Infect Dis J 2013;32:e206-16.
Basu S, Kumar R, Tilak R, Kumar A. Candida blood stream infection in neonates: Experience from A tertiary care teaching hospital of central India. Indian Pediatr 2017;54:556-9.
Bond S, Stewart DL, Bendon RW. Invasive Candida enteritis of the newborn. J Pediatr Surg 2000;35:1496-8.
Del Bono V, Delfino E, Furfaro E, Mikulska M, Nicco E, Bruzzi P, et al.
Clinical performance of the (1,3)-β-D-Glucan Assay in early diagnosis of nosocomial Candidabloodstream infections. Clin Vaccine Immunol 2011;18:2113-7.
Mavrommatis AC, Theodoridis T, Orfanidou A, Roussos C, Christopoulou-Kokkinou V, Zakynthinos S. Coagulation system and platelets are fully activated in uncomplicated sepsis. Crit Care Med 2000;28:451-7.
Torres Claveras S, Dupla Arenaz M, Pérez Delgado R, Aliaga Mazas Y, Rebage Moisés V. Nosocomial Candidainfections and thrombocytopenia in very low birth weight newborns. An Pediatr (Barc) 2007;67:544-7.
Jajoo M, Manchanda V, Chaurasia S, Sankar MJ, Gautam H, Agarwal R, et al.
Alarming rates of antimicrobial resistance and fungal sepsis in outborn neonates in North India. PLoS One 2018;13:e0180705.
Elwan A. Mortality among outborn versus inborn neonates: A retrospective comparative study. Med J Cairo Univ 2009;77:209-17.
[Table 1], [Table 2]