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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 5  |  Page : 237-242

Candidemia in the pediatric intensive care unit in Eastern India


1 Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Public Health, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
3 Department of Microbiology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India

Date of Submission11-Apr-2020
Date of Decision29-Jun-2020
Date of Acceptance07-Jul-2020
Date of Web Publication14-Sep-2020

Correspondence Address:
Dr. Reshmi Mishra
Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JPCC.JPCC_38_20

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  Abstract 


Background: Nosocomial infection, due to Candida, contracted in the pediatric intensive care unit (PICU), is emerging as a significant healthcare challenge. The incidence of non-albicans Candida as a cause of candidemia is on the rise, unlike in previous decades.
Materials and Methods: All the cases of candidemia confirmed by culture, admitted to the PICU during the study period of January 2017 to December 2019, were retrospectively studied. The prevalence, speciation, sensitivity pattern and risk factors of candidemia mortality were recorded and analyzed.
Results: There were 1034 admissions to the PICU in the study period, of which 926 blood samples were sent for culture and sensitivity. A total of 31 Candida non-albicans and five Candida albican species were isolated. C. tropicalis was the most common type (44.4%) of Candida species found, followed by C. glabrata (16.7%), C. parapsilosis (16.7%) and C. krusei (5.6%). The sensitivity of all Candida isolates to Amphotericin B, Clotrimazole, Voriconazole, Itraconazole, Ketoconazole, Nystatin, and Fluconazole was 94.4%, 91.7%, 88.9%, 86.1%, 77.8%, 52.8%, and 38.9% respectively. The use of a central venous catheter was a statistically significant contributor to mortality due to candidemia.
Conclusion: Non-albican Candida species are the predominant cause of candidemia this study. They are associated with higher fatality rates. Sensitivity of the Candida spp. was more common to Amphotericin-B than azoles.

Keywords: Antifungal susceptibility, non-albicans candida, pediatric intensive care


How to cite this article:
Behera C, Mishra R, Jena PK, Mishra S, Sahoo B, Patnaik SB, Jain M. Candidemia in the pediatric intensive care unit in Eastern India. J Pediatr Crit Care 2020;7:237-42

How to cite this URL:
Behera C, Mishra R, Jena PK, Mishra S, Sahoo B, Patnaik SB, Jain M. Candidemia in the pediatric intensive care unit in Eastern India. J Pediatr Crit Care [serial online] 2020 [cited 2020 Sep 19];7:237-42. Available from: http://www.jpcc.org.in/text.asp?2020/7/5/237/295020




  Introduction Top


Millions of fungi exist in the environment as commensals. Less than 300 of these are pathogenic and usually cause opportunistic invasive fungal infections (IFIs).[1] Admission into the pediatric intensive care unit (PICU) is one of the significant risk factors for Candida IFIs.

Preexisting bacterial infection, treatment with broad-spectrum antibiotics, immunocompromised status, recent surgery, parenteral nutrition, central line, dialysis, and mechanical ventilation are some of the known risk factors for Candida IFIs.[2]

The annual incidence of candidemia is 17–100 per million population, with a higher rate of occurrence in children.[3],[4] As many as 10%–49% of the victims of candidemia run a risk of death.[5] Although Candida albicans had been traditionally found to be the usual cause of IFIs, the isolation of non-albicans Candida (NAC) such as Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei has recently been increasingly reported. C. tropicalis is the most common species among the Candida isolated in the blood. Furthermore, resistance to fluconazole and other azoles, especially NAC, has become a menace.[6],[7] This could be due to the increase in the empirical use of antifungal agents, primarily fluconazole.[8],[9]

Studies exploring the various aspects of candidemia, reported from the eastern part of India, are scarce. This study was conducted to assess the burden of candidemia, speciation, sensitivity pattern, and risk factor of candidemia-associated mortality in the PICU of the tertiary care institute of Odisha.


  Subjects and Methods Top


Study design

A retrospective observational study was carried out using medical records.

Study setting

This study was conducted in the PICU of KIMS Medical College and Hospital, Bhubaneswar, Odisha, which is a 12-bedded unit.

Study duration

This study was conducted over a period of two years (January 2017 and December 2019).

Method

A predesigned case record form was used to collect data from the case records of patients with candidemia, confirmed on blood culture. Thirty-six cases of candidemia were recruited into the study after excluding the children who were already on antifungal prophylaxis at admission. The data on demographic patterns, clinical diagnosis, Candida speciation, drug sensitivity, risk factors such as the use of broad-spectrum antibiotics, intubation, and mechanical ventilation, days of catheterization, the presence of central line, corticosteroid therapy and multiple organ dysfunction, and disease outcome were retrieved.

Method of obtaining blood cultures

As a routine PICU protocol at KIMS, the blood samples from suspected patients with sepsis were collected in the specified bottles (BacT/Alert 3D [BioMerieux]) and sent to the central laboratory following all the standard precautions. The culture bottles were then loaded into a fully automatic BacT/Alert 3D system. Those culture bottles, which came out to be positive by this method, were further processed manually, first to get the causative organisms. A small amount of the broth from the positive bottle was inoculated into blood agar, chocolate agar, and MacConkey agar plate. The blood agar and chocolate agar plates were incubated in a carbon dioxide incubator, and the MacConkey agar plate was incubated in an ordinary incubator. After overnight incubation at 37°C, the plates were observed for any growth in a biosafety cabinet. The colonies with suspected Candida growth are usually tiny, whitish, dry, and pasty on all the culture plates. Initially, few representative colonies were used to observe the germ tube formation to know whether the colony is C. albicans or not (C. albicans only forms the germ tube). Few representative colonies were then inoculated onto CHROME agar and further incubated aerobically. The CHROME agar (HiMedia) is a novel, differential culture medium that is claimed to facilitate the isolation and presumptive identification of some clinically important yeast species. C. albicans forms greenish color colonies after an incubation of 24–48 h on CHROME agar. Thus, the colonies forming germ tube and forming greenish colonies on CHROME agar were presumptively differentiated as C. albicans, and the rest of the Candida species which were isolated were grouped under NAC. These colonies were now further evaluated for speciation and sensitivity determination using the fully automated VITEK 2 [BioMerieux] instrument which identifies the organism up to species level using its VITEK * 2YST ID card as well as gives the antifungal sensitivity pattern by minimum inhibitory concentration level.

Statistical methods

The data were processed using SPSS: IBM Corp, Armonk, NY, USA (version 25.0). Univariable analysis was presented as pie charts, bar diagrams, and tables. Categorical variables were expressed as percentage. The median and interquartile range (IQR) of age distribution were estimated. Bivariable analysis using Fisher's exact test was done to assess the factors associated with mortality due to candidemia considering various demographic and clinical characteristics. P < 0.05 (two-tailed) was considered statistically significant.


  Results Top


The total admission to PICU during the study period was 1034 cases, of which 926 blood samples were sent for microbiological assessment. Thirty-six (3.88%) cases were identified with Candida species in blood culture. The children were in the age range from 1 month to 14 years, with a median age of 4.54 years (IQR of 0.7–8 years). The majority of the children (47%) were in the age group of 6–14 years, followed by infants (36%). The male children (66.11%) were more affected than the female.

The distribution of C. albicans and non-albicans species is detailed in [Figure 1]. C. tropicalis was the most common type of Candida, followed by C. glabrata, C. parapsilosis, and C. krusei (5.6%). The only case of C. pelliculosa isolated in the study period was in a 2-month-old baby with late-onset sepsis. The isolation of NAC species was relatively higher than C. albicans (31/36 vs. 5/36).
Figure 1: Percentage-wise distribution of isolated Candida species among children

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The clinical diagnosis and outcome of children detected to be having candidemia are summarized in [Table 1]. Nearly one-third of the children had sepsis (including scrub typhus), followed by patients with central nervous system infection (encephalitis and meningitis) who accounted for 10 (27.7%). The remaining cases were pneumonia (4,11.1%), Guillain Barre syndrome (3,8.3%) and others (acute leukemia, complicated malaria, chronic liver disease, acute pancreatitis seen in one case each). Out of 36 cases 5 died (sepsis:2, encephalitis:2, acute leukemia:1).
Table 1: Distribution of underlying diseases among candidemia patients

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In this study, the presence of the central line (P = 0.047) was the only significant predictor of mortality among children with candidemia. Survival among female children was higher (92.9%) than their male (81.8%) counterparts, but it was not statistically significant. Similarly, survival among children in the age group of 1–5 years was lower than the other age groups, although it was not statistically significant. Influence of risk factors such as exposure to broad-spectrum antibiotics, fluconazole resistance, use of a mechanical ventilator, or urinary catheterization on the survival in children failed to show any statistically significant difference [Table 2].
Table 2: Factors associated with mortality among children with candidemia

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All five deaths were associated with non-albicans IFIs (C. glabrata – 2 and C. tropicalis – 3). Multiple antibiotics (≥2) were used in 19 cases (52.77%). The most common antibiotic used was beta-lactam. Meropenem, vancomycin, and linezolid were the other commonly used antibiotics [Table 3].
Table 3: Determinants influencing candidemia with albicans Vs NAC

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Most of the Candida isolates were sensitive to amphotericin B (94.44%), clotrimazole (91.67%), voriconazole (89%), and itraconazole (86%) [Figure 2]. Lower sensitivity to fluconazole (39%) and nystatin (53%) was seen. The C. albicans were less sensitive (range: 20%–60%) to antifungals than non-albicans (range: 42%–100%), except to nystatin. C. pelliculosa was sensitive to all antifungal agents, and others had varied sensitivity [Table 4].
Figure 2: Comparative sensitivity pattern of albicans and non-albicans

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Table 4: Species-wise sensitivity pattern of Candida isolates

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  Discussion Top


The prevalence of the nosocomial invasive Candida infection is on the rise, which is more or less similar to the trend of the increasing use of indwelling devices and modern medical procedures. The prevalence of candidemia in the PICU in our study was found to be 3.88%.

Several studies have shown Candida, particularly the albicans strain, as one of the major causes of bloodstream infection in the hospital setting.[4],[7],[10] However, gradually, there appears to be a shift toward the NAC species as a cause of candidemia. In this study, most of the isolates (86.1%) are NAC. A study by MacDonald et al.[11] found 58% of candidemia cases in children to be caused by NAC. The continuous exposure to prophylactic antifungal agents, particularly fluconazole, has led to emergence of NAC species as the predominant cause of candidemia.[12] In this study, C. tropicalis has been identified as the most prevalent Candida species (44.4%). Similar results suggesting the high prevalence of C. tropicalis in the range of 35.6% and 39.7% have been reported from South India.[13],[14] The isolation of C. glabrata (16.7%) and C. parapsilosis (16.7%) was also found to be higher than C. albicans in this study. The incidence of C. glabrata is increasing remarkably, so is its resistance to the azole group.[15]

Studies suggest central venous catheterization as an important predisposing factor for candidemia.[16],[17] In our study, the presence of a central venous line was significantly associated with high mortality in children with candidemia (19 children with P = 0.047). Considering this, the critical care society has strongly recommended removing the central line catheter as early as possible in the cases of candidemia.[18]C. parapsilosis has been particularly implicated in causing the intravascular catheter-related infection in neonates and pediatric age group.[19]

The presence of a urinary catheter is usually associated with urinary tract infection of fungal origin. Candiduria can sometimes be an indicator of impending sepsis in PICU-admitted patients.[7] The urinary catheter was present in 58.3% of the cases of candidemia in this study. Similar results have been obtained by Giri et al. (55.9%) and Xess el al. (55.6%).[7],[10] In the present study, almost all the Candida species isolated (34/36) are found to be susceptible to amphotericin B, whereas fluconazole resistance was seen in two-third of the cases, which is different from the other Indian studies reported by Bhattacharjee and Kothari and Sagar.[20],[21]

A study on 595 cases of candidemia conducted by Badiee and Alborzi[22] demonstrated C. albicans to be having highest sensitivity to caspofungin (98.2%), followed by voriconazole (94%), amphotericin B (93%), ketoconazole (90.6%), and fluconazole (89.5%). On the other hand, the NAC isolates such as C. krusei and C. glabrata strains showed only 30%–40% sensitivity to fluconazole. The sensitivity to caspofungin was the highest (96%) and that to amphotericin B, ketoconazole, and voriconazole was in the range of 85%–93%.

Another study conducted by Hii et al.[23] on the resistance rates of NAC infections showed that C. tropicalis was the predominant non-albicans candidemia pathogen (42.4%) and showed 36.3% nonsensitivity to fluconazole. These findings closely resembled the findings of our study.

In our study, the sensitivity to amphotericin, clotrimazole, and voriconazole was high. The sensitivity to amphotericin B by NAC and albicans was 94% and 60%, respectively, followed by clotrimazole 92% and 40% and voriconazole 89% and 40%. Hence, these drugs could be a better choice of antifungals when started empirically. Similar findings also have been reported by Madhavan et al. and Balaram et al.[24],[25] These findings may help in treating fluconazole-resistant strains.

As a protocol, antifungals are started in our unit in all high-risk patients including abdominal surgery, broad-spectrum antibiotic therapy, central line or urinary catheter, intensive care unit stay for more than 4 days, persistence of fever, and in cases, developing thrombocytopenia. Fluconazole is started in them empirically till the culture and sensitivity report is available.

There were five deaths (13.8%) in our study, all of which were from the non-albicans group. Dimopoulos et al.[26] similarly reported a higher mortality due to NAC candidemia than C. albicans in nonimmunosuppressed, nonneutropenic patients. Although the cause is unclear, delayed initiation of therapy or inappropriate treatment (owing to the slower growth of NAC isolates on primary culture) and severity of illness in patients with NAC candidemia may be the possible reasons. Patients on mechanical ventilation and the use of vasopressors were strongly associated with mortality in our study.

The mortality rate in this study was lower (13.8%) than that of other various other studies conducted in different parts of India.[7],[16],[25] A review article has suggested the mortality rate in the range of 10%–49%.[5]


  Conclusion Top


NAC species were the more common cause of candidemia in this study, C. tropicalis being the most common. Overall, the Candida species were more sensitive to amphotericin, clotrimazole, and voriconazole than fluconazole. Non-albicans candidemia and the use of central venous catheters were associated with higher mortality rates. However, these findings need to be validated by more extensive prospective studies, which would help in a perfect choice of antifungal therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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