|Year : 2014 | Volume
| Issue : 2 | Page : 100-104
Clinico-epidemiological profile, risk factors, and prognosis of neonatal candidemia due to Candida parapsilosis: An emerging threat to neonates
Deepak Juyal1, Swapna Kotian1, Jyoti Sangwan1, Vyas Kumar Rathaur2, Neelam Sharma1
1 Department of Microbiology and Immunology, Veer Chandra Singh Garhwali Government Medical Sciences and Research Institute, Srinagar Garhwal, Uttarakhand, India
2 Department of Pediatrics, Veer Chandra Singh Garhwali Government Medical Sciences and Research Institute, Srinagar Garhwal, Uttarakhand, India
|Date of Web Publication||19-May-2014|
Department of Microbiology and Immunology, Veer Chandra Singh Garhwali Government Medical Sciences and Research Institute, Srinagar Garhwal 246 174, Uttarakhand
Source of Support: None, Conflict of Interest: None
Background: Candida species are the third most common blood culture isolates recovered from cases of late onset sepsis in neonatal intensive care unit (NICU). Candida parapsilosis is probably, the species that have had the largest increase in incidence since 1990, becoming the predominant agent of candidemia in certain centers. We evaluated the prevalence of neonatal candidemia due to C. parapsilosis and the main clinico-epidemiological aspects of this disease in neonates. Materials and Methods: This retrospective observational study was conducted for a period of 18 months at our rural tertiary care and referral center. Hospital records of the neonates with candidemia due to C. parapsilosis were reviewed. The Candida species isolated were identified as per standard mycological techniques. Results: Of total 163 neonates diagnosed of candidemia, 43 (26.38%) corresponded to C. parapsilosis. Failure to thrive (74.42%), abdominal distention (67.44%), and feed intolerance (65.12%) were the most common clinical presentations seen. Among the risk factors observed broad spectrum antibiotics (81.40%), total parenteral nutrition (79.07%) and indwelling catheters (79.07%) were the most common followed by prematurity (72.09%) and low birth weight (65.12%). Early mortality accounted for 20.93%, whereas late mortality accounted for 11.63% of the cases. Conclusion: Progressive shift of C. albicans to non-albicans Candida species, particularly C. parapsilosis substantiates the need of continuous monitoring of laboratory data. C. parapsilosis is an emerging fungal pathogen and the major threat for neonates in NICU. Local epidemiological knowledge is critical in terms of prevention and management of invasive Candida infections.
Keywords: Candida parapsilosis, candidemia, low birth weight, non-albicans Candida, total parenteral nutrition
|How to cite this article:|
Juyal D, Kotian S, Sangwan J, Rathaur VK, Sharma N. Clinico-epidemiological profile, risk factors, and prognosis of neonatal candidemia due to Candida parapsilosis: An emerging threat to neonates. Int J Health Allied Sci 2014;3:100-4
|How to cite this URL:|
Juyal D, Kotian S, Sangwan J, Rathaur VK, Sharma N. Clinico-epidemiological profile, risk factors, and prognosis of neonatal candidemia due to Candida parapsilosis: An emerging threat to neonates. Int J Health Allied Sci [serial online] 2014 [cited 2019 Jan 17];3:100-4. Available from: http://www.ijhas.in/text.asp?2014/3/2/100/132694
| Introduction|| |
Candida species are the leading cause of invasive fungal infections in neonatal intensive care unit (NICU) and are the third most common blood culture isolates recovered from cases of late onset sepsis in NICU. , The incidence of blood stream infections (BSIs) caused by Candida has progressively increased over the past two decades, accounting for about 9-13% of the BSI in neonates.  Although Candida albicans has historically been the most frequently isolated species, recently non-albicans Candida (NAC) have emerged as important opportunistic pathogen, notably Candida tropicalis, Candida krusei, Candida parapsilosis, and Candida glabrata, with C. parapsilosis identified as the predominant species causing BSIs among premature newborns in NICU's.  This change in most frequent cause of candidemia has been explained in part by the high affinity of C. parapsilosis for intravascular (IV) devices and parenteral nutrition and their widespread use. , The increasing use of prophylactic antifungal agents to prevent Candida infections in high-risk patients can also be one of the reasons for this epidemiological shift. 
Numerous risk factors for candidemia have been identified in NICU patients such as prematurity, low birth weight (LBW), prolonged use of broad spectrum antibiotics, indwelling central venous catheters (CVC), total parenteral nutrition (TPN), mechanical ventilation, immature skin structure, surgery, or preexisting fungal colonization.  Candida species can also spread by vertical transmission through maternal flora or through horizontal transmission from hands of health care workers (HCWs).  Nosocomial outbreaks of C. parapsilosis have also been described previously where the hands of HCW were identified as predominant environmental source. ,,
Data assessing exclusively the epidemiology and risk factors of C. parapsilosis candidemia is less. We conducted a retrospective study to evaluate the prevalence rate of C. parapsilosis candidemia and to characterize the microbiological, clinical, and epidemiological aspects of this disease among the neonates admitted to our hospital.
| Materials and methods|| |
This retrospective observational study was conducted for a period of 18 months (January 2012 to June 2013) in the Department of Microbiology and Department of Pediatrics, of our rural tertiary care and referral center in Uttarakhand state, India. Our hospital accepts babies born within the hospital as well as referred from outside the facility. Average referrals from outside sources are approximately 200-250/year. Premature infants comprise 15-20% of total number of deliveries in the hospital.
Candidemia was defined as the presence of at least one positive blood culture containing pure growth of Candida species with supportive clinical features. A case was defined as baby hospitalized in the NICU, who present with at least one positive blood culture for C. parapsilosis. Cases of candidemia caused simultaneously by different species of Candida were excluded from the analysis. We defined early mortality as death within 3-7 days after diagnosis and late mortality as death between days 8 and 30.
After the study protocol was approved by Institutional Ethics Committee, hospital records of the neonates with candidemia due to C. parapsilosis were reviewed. The demographic and clinical data evaluated were sex, birth weight, and type of delivery, underlying diseases, and use of invasive procedures such as CVC, TPN, surgery and use of broad spectrum antibiotics, or steroids. Prophylactic antifungals were not used.
Blood samples for cultures were collected (on clinical suspicion of septicemia) into Bactec Peds plus/f culture vials of an automated blood culture system (Bactec 9120, Becton Dickinson, USA). Any growth indicated was subcultured on 5% sheep blood agar, Mac Conkey agar and Sabouraud's dextrose agar (SDA) with chloramphenicol (0.05%) and incubated at 37°C. The Candida species isolated were identified as per standard mycological techniques.  The preliminary identification was done by colony morphology on SDA, chromogenic media (HiChrome, Himedia, Pvt., Ltd.), growth at 45°C, germ tube test and was confirmed by carbohydrate fermentation and assimilation tests. 
| Results|| |
During the period of months between January 2012 and June 2013, 163 neonates were diagnosed of candidemia. The characterization of various Candida species involved is shown in [Table 1]. Among the total 163 neonates with candidemia, 43 (26.38%) corresponded to C. parapsilosis.
Of the total 43 neonates with C. parapsilosis included in this study, 26 (60.47%) were females and 17 (39.53%) were males with male to female ratio was 1:1.5. The average gestational age was 32 weeks (30-39 weeks) and average birth weight was 1.25 kg (0.93-2.67 kg). [Table 2] depicts the demographic details, risk factors, and clinical characteristics of the neonates with C. parapsilosis fungemia. Failure to thrive (74.42%), abdominal distention (67.44%), and feed intolerance (65.12%) were the most common clinical presentations seen. Clinically, fever was present in 13 cases, six patients developed renal failure and five cases presented with septic shock. Four patients were documented of having infective endocarditis. Catheter removal was part of treatment in 31 (72.09%) cases.
|Table 2: Demographic details, risk factors and clinical characteristics of the neonates with Candida parapsilosis candidemia (n=43) |
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Among the risk factors observed for C. parapsilosis candidemia, broad spectrum antibiotics (81.40%), TPN (79.07%) and indwelling catheters (79.07%) were the most common followed by prematurity (72.09%) and LBW (65.12%). Early mortality accounted for 20.93% of the cases, whereas late mortality accounted for 11.63%.
| Discussion|| |
Candida parapsilosis is a ubiquitous microorganism in the natural environment and is frequently isolated from soil, water and plants.  The prevalence of C. parapsilosis fungemia has changed over the years and now in some areas C. parapsilosis is the second most common species found in patients with candidemia. , The primary reservoir of C. parapsilosis in the hospital setting is unknown, but its carriage on the skin of HCWs, particularly on hands has long been recognized ,,, as a source of outbreaks of candidemia in NICUs. , Moreover, repeated observations suggest that C. parapsilosis may gain access to the bloodstream directly from exogenous sources.  Furthermore, molecular studies substantiate that exogenous sources should be clinically suspected and epidemiologically investigated when C. parapsilosis is isolated from blood samples of infants housed in NICUs. ,
Our results showed that prevalence rate of C. parapsilosis in NICU was quite high (26.38%) and this finding was in contrast to the various other studies reported from India. Sardana et al.  reported the same in 14.5% of neonates whereas Goel et al.  and Gupta et al.  have reported it in 5.9% and 5.2% of neonates, respectively. However, reports from some researchers were in concordance to our findings. A study from Israel  reported the prevalence of C. parapsilosis in 25% of neonates, whereas another study from Kuwait  reported it to be as high as 48.2%. Dutta and Palazzi  reported C. parapsilosis (23.9%) as the most common NAC species responsible for candidemia among pediatric patients.
Our findings agree with previous epidemiological studies showing that C. parapsilosis infections are more frequent in patients with IV lines or on parenteral nutrition with catheter being the most frequent portal of entry. The predominance of C. parapsilosis in children has been reported previously and the investigations suggest that aggressive use of IV devices to treat neonates may be the reason for this. , C. parapsilosis has the capability to adhere tenaciously to the prosthetic materials and to proliferate rapidly in high concentrations of glucose.  Most experimental studies have indicated that the adherence of C. parapsilosis to acrylic is greater than that of C. albicans.  Moreover, the propensity of clinical isolates of C. parapsilosis to form extensive biofilms in glucose containing solutions suggest that this trait may contribute to its ability to adhere to plastic catheters and cause systemic infections in premature newborns receiving TPN. , Total parenteral nutrition induces gut mucosal atrophy and has immunosuppressive effects which again predisposes individual for infection. Such a route of transmission may account for the occurrence of epidemic outbreaks of C. parapsilosis BSIs when multi dose medications are used for more than one patient. ,
Preterm, very low birth weight; ≤1500 g, extremely low birth weight; ≤1000 g and critically ill infants are at highest risk of invasive Candida infections.  LBW infants can easily get colonized with C. parapsilosis. The prevalence of C. parapsilosis colonization among neonates has been described to be inversely proportional to the birth weight.  In this study, more than 70% of the neonates with C. parapsilosis candidemia were either premature or LBW infants, moreover most of the fatal cases occurred in infants <3 weeks of age and had LBW compared with the ones who survived. Given that infants of this age have decreased immunity their host response to candidemia may have contributed to mortality. Use of multiple invasive devices such as catheters, endotracheal tubes or surgery causes break in the integrity of skin/mucosa and predisposes these sites for colonization and infection by Candida spp. Studies suggest that clearance of fungemia occurs more quickly when catheters are removed and failure to remove catheter as soon as candidemia is detected is a risk factor for death.  This factor was frequent in our study and majority of neonates who died had retention of catheter for at least 48 h after diagnosis of candidemia and this may have contributed additionally to the high mortality. Although, it should not be assumed that removal of catheter alone is adequate therapy; administration of antifungal agents is also equally important as several studies have shown that early treatment with an antifungal agent is associated with enhanced survival. ,
Colonization is the precursor for clinical infection and the risk for nosocomial infection is as high as 38% with colonization by Candida.  Studies have demonstrated that a significant reduction in Candida colonization and invasive Candida infections was observed in NICU when antifungal prophylaxis was used. , Various investigators have suggested that preventive strategies in ICUs should be targeted to populations with a baseline rate of candidemia ≥10%, however, long term use of prophylactic antifungals was associated with drug resistance. , Ideally, using the lowest effective dose for the shortest length of time may be most desirable as it may limit the development of resistance. Currently, our center does not have a trend of prophylactic antifungal administration and we suggest the use of same in high risk neonates.
We observed that broad spectrum antibiotics two to four in number were being administered to most of the neonates (81.40%) in this study. Antibiotics promote fungal overgrowth at the expense of normal bacterial flora and encourage translocation of yeast across the intact mucosa. The risk of candidemia is also known to increase exponentially with each class of antimicrobial used.  Recent reports have suggested that the use of third generation cephalosporins was strongly associated with candidemia.  In our center, an empiric antibiotic regime is initiated based on high perinatal risk factors for early onset sepsis. The current hospital antibiotic policy recommends initial empiric use of ampicillin-gentamicin for neonates born within the facility and cefotaxime-amikacin for neonates referred from elsewhere. Probably, the long-term use of these broad spectrum antibiotics must have created a negative pressure and a favorable environment for Candida species to flourish. This further substantiates the need of prophylactic antifungals to be used in a set up where continuous upsurge in the incidence of candidemia is seen. Anecdotally, NICUs have observed decreasing rates of candidemia by implementing wise antimicrobial stewardship strategies and improving infection control practices. 
In this study, the associated mortality to C. parapsilosis candidemia was 32.6% which was quite high in comparison of studies conducted by Kossoff et al.  and Roilides et al.  who reported the same as 4% and 11.1%. Although, systemic infections caused by C. parapsilosis are less virulent than the one caused by C. albicans, but still it significantly increases the morbidity and mortality of severely ill infants who require care in NICU.  Trofa et al. have documented C. parapsilosis as emerging fungal pathogen and the major threat for neonates in NICU.  The incidence and associated mortality due to candidemia can be influenced by several factors including characteristic of the population at risk, health care facility standards and Candida species involved.  Due to considerable regional variability, the local epidemiological knowledge is critical in terms of prevention and management of invasive Candida infections. Moreover progressive shift of C. albicans to NAC species, particularly C. parapsilosis substantiates the need of continuous monitoring of laboratory data. We believe that epidemiological data of our study will be helpful in better understanding the importance of previously established risk factors for the development of potential preventive strategies.
| Conclusion|| |
We observed that the prevalence rate of C. parapsilosis in our NICU was quite high and so was the mortality in comparison to the other studies reported elsewhere. One must understand the clinico-epidemiological aspects and risk factors of C. parapsilosis candidemia in a NICU particularly in a rural set up with reduced availability of resources. Based on the available data and the previous studies premature LBW neonates, presenting with known risk factors for candidemia and a NAC species involved should raise a high index of suspicion for C. parapsilosis candidemia. Our results can serve as a template for the development of local guidelines for prevention and appropriate treatment of neonatal candidemia. Preventive measures such as use of filters for parenteral nutrition, prophylactic antifungal use, and restrictive policy of antibiotic use to decrease Candida colonization/infection rates should be implemented to reduce the morbidity and mortality associated with neonatal candidemia due to C. parapsilosis.
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[Table 1], [Table 2]