Arslankoylu et al. Italian Journal of Pediatrics 2011, 37:56 http://www.ijponline.

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ITALIAN JOURNAL OF PEDIATRICS

RESEARCH

Open Access

Symptomatic and asymptomatic candidiasis in a pediatric intensive care unit
Ali Ertug Arslankoylu1*, Necdet Kuyucu2, Berna Seker Yilmaz3 and Semra Erdogan4
Abstract
Introduction: This study aimed to examine the incidence, epidemiology, and clinical characteristics of symptomatic and asymptomatic candidiasis in a pediatric intensive care unit (PICU), and to determine the risk factors associated with symptomatic candidiasis. Methods: This retrospective study included 67 patients from a 7-bed PICU in a tertiary care hospital that had Candida-positive cultures between April 2007 and July 2009. Demographic and clinical characteristics of the patients, Candida isolates, antimicrobial and antifungal treatments, and previously identified risk factors for symptomatic candidiasis were recorded, and symptomatic and asymptomatic patients were compared. Results: In all, 36 (53.7%) of the patients with Candida-positive cultures had asymptomatic candidiasis and 31 (46.3%) had symptomatic candidiasis. Candida albicans was the most common Candida sp. in the asymptomatic patients (n = 20, 55.6%), versus Candida parapsilosis in the symptomatic patients (n = 15, 48.4%). The incidence of central venous catheter indwelling, blood transfusion, parenteral nutrition, and surgery was higher in the symptomatic patient group than in the asymptomatic patient group (P < 0.5). Surgery was the only independent predictor of symptomatic candidiasis according to forward stepwise multivariate logistic regression analysis (OR: 6.1; 95% CI: 1.798-20.692). Conclusion: Surgery was the only risk factor significantly associated with symptomatic candidiasis and non-albicans Candida species were more common among the patients with symptomatic candidiasis. While treating symptomatic candidiasis in any PICU an increase in the incidence of non-albicans candidiasis should be considered. Keywords: Candida, candidiasis, pediatric intensive care unit

Introduction Candida infections are among the major nosocomial infections associated with excessive morbidity and mortality, prolongation of hospital stay, and increased healthcare costs [1]. As the length of stay in intensive care units (ICUs) and the frequency of invasive procedures increase, the incidence of Candida colonization and Candida infection increases. Due to the severity of their primary disease and suppressed immune system patients in ICUs are at high risk of Candida infections because of invasive monitoring techniques and the specific therapeutic procedures used. Most patients suffer no ill effects due to Candida colonization because of its low-level virulence;
* Correspondence: aliertug@gmail.com 1 Department of Pediatric Intensive Care, Mersin University School of Medicine, Mersin, Turkey Full list of author information is available at the end of the article

however, in some patients with suppressed defenses the organisms invade and cause illness [2]. One study that included 20 pediatric intensive care units (PICUs) in 8 countries reported that fungi were the third most frequent infection agents, following bacteria (68%) and viruses (22%) [3]. Among fungi, Candida spp. are the most frequent causes of fungal infections in PICUs [4]. Few data exist on candidiasis in PICUs in developing countries. Most of the literature on candidiasis primarily concerns adult ICU patients, and differences in epidemiology, Candida spp., and the distribution, management, and outcome of candidiasis between adults and children limits extrapolation of the conclusions to children. The present study, therefore, aimed to determine the incidence, epidemiology, and clinical characteristics of symptomatic and asymptomatic candidiasis in a PICU, and to determine the risk factors associated with symptomatic candidiasis.

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There weren’t any differences between the symptomatic and asymptomatic patient Table 1 Descriptive statistics and demographic characteristics of the patients with Candida-positive cultures n Age (months) 0-3 4-12 13-60 60 + Culturing site Blood Urine Feces Catheter Wound CSF Pharynx Other Candida spp. Surgical procedures.0 26. The Mann-Whitney U test was used for continuous variables.5 was used for statistical analysis.9 88. Patient data were obtained from PICU records and the hospital infection committee. respiratory distress.3 31. The clinical characteristics of the symptomatic and asymptomatic patients were investigated. Descriptive statistics (median and 25th-75th quartiles) for continuous variables. corticosteroid therapy. 26 females) with Candida-positive cultures which were obtained from all sites shown in Table 1.4 6. Symptomatic candidiasis was defined as candidiasis with symptoms and signs of sepsis (fever > = 38°C. 37:56 http://www.3 68. presence of multiple-organ failure.9 67.1 29. presence of an indwelling catheter. and leukocytosis). and blood transfusion were recorded. and corticosteroid therapy.4 77.0 7.0 7.4 1. The Shapiro-Wilk test was used to determine if the continuous variables were normally distributed. included the patients who had positive cultures for Candida spp between April 2007 and July 2009. and whether or not patients were symptomatic at the time samples were obtained were noted.5 1. length of stay in the PICU. endotracheal intubation.0 97. tachypnea.8 28.ijponline. and Spearman ’ s chi-square test or the likelihood ratio test was used for categorical variables.7 11.0 3. Statistical analysis Results The study included 67 patients (41 males.5 92. surveillance cultures were sent for all patients after 5 days of stay in the PICU if the patient had any of the previously known high-risk factors for candidiasis such as broad-spectrum antibiotics.5 3. mechanical ventilation. The site from which culture samples were obtained. Italian Journal of Pediatrics 2011.1 58.2 3.0 1. either at the time sample was taken for fungal culture or anytime within 72 hrs of it.0 43.net/content/37/1/56 Page 2 of 6 Materials and methods This retrospective study. broad-spectrum antibiotic use. and the number and percentages for categorical variables are given.3 6. which was carried out in a 7bed PICU of a tertiary care hospital. or shock.9 3.0 3.8 70.6 31.0 SPSS v. In the PICU the protocols recommended by Centers for Disease Control and Prevention (CDC) are applied to prevent sepsis. Albicans Tropicalis Parapsilosis Glabrata Kefyr Sake Kefyr + albicans Albicans + tropicalis Central venous catheter No Femoral Jugular Femoral + Jugular Urinary catheterization Mechanical ventilation Parenteral nutrition Blood transfusion Corticosteroid use Surgery Broad-spectrum antibiotic use No Yes No Yes No Yes No Yes No Yes No Yes No Yes 2 29 21 15 26 19 4 9 1 1 2 5 28 5 23 4 2 2 1 2 18 45 2 2 5 62 15 52 21 46 8 59 39 28 47 20 2 65 % 3. . intravenous catheters.5 34.3 22.0 13.11. In addition.Arslankoylu et al. and the mortality rate were also recorded. Approval of the study was obtained by the local Institutional Review Board with waiver of informed consent since the sudy did not involve therapeutic interventions or potential risks to involved subjects.2 41.5 41. tachycardia. Patient demographics. Cultures were sent if infection was suspected at any time after admission to PICU.0 3. Asymptomatic patients of candisiasis were those who had no symptom or sign of sepsis but had cultures positive for Candida.8 7. Patients were categorized as symptomatic and asymptomatic. The yearly number of admissions to the PICU was 248 during the study period.4 38.5 3. clinical presentation and primary diagnosis. duration of hospitalization before the culture sample was obtained.5 22. endotracheal intubation.

2 96.9%).8 45. ciprofloxacin 6%.0 54.331 0.5 35.0 3. ceftriaxone 22.2 50. The patient’s descriptive statistics and demographic characteristics are given in Table 1.2 days. 38 of the patients (56.2 3. In total. 6%).8 47.2 3.9%.0 47. amphotericin-B (n = 6. In all.6 52.1 25.626 0.0 2. caspofungin (n = 8.6 0.3 ± 42.3 2. and surgery statistically differed.7 83. 17. In all.2 8.6 48.4 days.7 11.5%. 9.0 100.8 9.1 38. Mean duration of broad-spectrum antibiotic use was 28. 11.7 48.net/content/37/1/56 Page 3 of 6 groups in terms of age or gender. 36 of the patients did not receive antifungal treatment.2 6. meropenem 7.1 63. central venous catheter indwelling.0 19.0 100.4 0.5 0. parenteral nutrition.7%) survived and 29 (43.060 0. blood transfusion.4 3. The asymptomatic and symptomatic candidiasis groups were compared in terms of demographic characteristics.ijponline.111 < 0. sulperazone 19. Mean age of the patients was 36.2 41. During the study period the mortality rate of whole PICU was 14%.8 ± 23. 36 (53.2 3.011 < 0.9 ± 68. and mean length of time between admission and Candida growth in culture was 19. The percentage of patients with an indwelling catheter was significantly higher in the symptomatic group than Table 2 Comparison of the asymptomatic candidiasis and symptomatic candidiasis groups.6 ± 37.2 3.7%) of the patients with Candida-positive cultures had asymptomatic candidiasis and 31 (46.2 51.204 0.9%).6 5.3 41. 37:56 http://www.5 0.2 58.3%) died.8 64.0001 0. and voriconazole (n = 4.3 16.Arslankoylu et al.8 47.8 0. amikacin 2%.0 2.9 58.2 3.4%.5 41.4 months.1 36. vancomycin 2%.9 55.2 87.0 days.4 80.4 35.1 3.0 5.4%. Female Male Albicans Tropicalis Parapsilosis Glabrata Kefyr Sake Kefyr + Albicans Albicans + Tropicalis Central venous catheter No Femoral Jugular Femoral + Jugular Broad-spectrum antibiotic use Blood transfusion Corticosteroid use Parenteral nutrition Surgery Prognosis No Yes No Yes No Yes No Yes No Yes Survived Died 0 17 15 4 13 23 20 2 8 3 1 1 0 1 17 18 1 0 2 34 7 29 19 17 21 15 30 6 22 14 % 0. The antifungal agents used to treatment the patients with symptomatic candidiasis were fluconazole (n = 12. piperacillin tazobactam 2%. Antibiotic treatment (ampicillin sulbactam 29.8 0.6 22.434 0. Italian Journal of Pediatrics 2011.7 61.9 Symptomatic Candidiasis Number 2 12 6 11 13 18 8 3 15 1 1 1 1 1 1 27 1 2 0 31 1 30 20 11 0 31 17 14 16 15 % 6.014 P .8 2. age. in terms of demographic characteristics and P values Asymptomatic Candidiasis Number Age (months) 0-3 4-12 13-60 60+ Gender Candida spp. clarithromycin 2%) was administered to 65 (97%) of the patients.0001 0. A comparison of the asymptomatic and symptomatic candidiasis groups in terms of demographic characteristics and P values is shown in Table 2. mean length of stay in the PICU was 50.0%).7 19.5 38.3%) had symptomatic candidiasis.

3 94.001).017 0.7 21.798-20. as it comprises both symptomatic and asymptomatic candidiasis cases. The difference between the 2 groups in terms of surgery was statistically significant (P = 0. Pediatric risk of mortality score (PRISM) of the patients with symptomatic candidiasis was 44.3 13.9 71. non-candida albicans blood stream infection was significantly high (p = 0.058 0. When the risk factors for symptomatic candidiasis were analyzed surgery was the only independent predictor of symptomatic candidiasis.3% of the patients in the asymptomatic group were not administered parenteral nutrition.42 ± 17.0 0.4 28. Broad-spectrum antibiotic use was not statistically different between the groups (P = 0.8 57.1 57. indentified in the 2 groups did not statistically differ (Table 2).7 48.0 100.Arslankoylu et al.003).1 78.4 34.0 100.5 0.092).9% of PICU admissions were patients Table 3 Comparison of the patients that survived with the patients that died. Although 58.ijponline.9 0. There was a significant difference between groups (p = 0.3 5. which constitutes 12% of all PICU admissions during that period-a high percentage. The descriptive statistics for these parameters are given in Table 4. and parenteral nutrition.3 6.011).8 65.net/content/37/1/56 Page 4 of 6 in the asymptomatic group (P < 0.111).7 48.3 17.1 36.0001). 5. There was no difference in the number of patients with femoral and jugular central venous catheters between the groups.2 82. In all.0 47.09 and this value was 30. When we compared the distribution of candida species in blood stream vs non-blood stream isolates. There was no significant difference between the ventilated and non ventilated patients in terms of site of the culture (p = 0. Discussion We treated 67 patients with candidiasis in the span of 2 years and 3 months.3 Number 2 11 8 8 15 14 4 23 2 0 0 29 0 29 15 14 5 24 19 10 Died Percentage (%) 6. all the patients in the symptomatic candidiasis group received parenteral nutrition.692). whereas the Candida spp. Logistic regression was performed for mortality and risk factors.0 51. When the patients were divided into 2 groups according to prognosis their demographic characteristics were compared and there was a statistically significant difference between the patients that died and survived. period of broad-spectrum antibiotic use.6 51. in terms of central venous catheters.2 36.209 p .0001).61 ± 21.469 0. but a significant association was not noted.9 0. And the common site of isolation of candida parapsilosis was blood.2 18.05 for the patients with asymptomatic candidiasis. whereas parenteral nutrition was (P < 0.9 63.0 5. total mechanical ventilation period. The duration of stay in the PICU before Candida growth in culture. The descriptive statistics for these results are given in Table 3.6 27. in terms of demographic characteristics and P values Survived Number Age (Months) 0-3 4-12 13-60 60 + Gender Central venous catheter Female Male No Femoral Jugular Femoral + Jugular Broad-spectrum antibiotic use Blood transfusion Corticosteroid use Parenteral nutrition Surgery No Yes No Yes No Yes No Yes No Yes 0 18 13 7 11 27 14 22 0 2 2 36 8 30 24 14 16 22 28 10 %) 0.347 0.9 27.9 37. based on forward stepwise multivariate logistic regression analysis (OR: 6.030 0. blood transfusion.7 26. Italian Journal of Pediatrics 2011.9 73.502 0.8 79.5 34. 37:56 http://www.008 0. 95% CI: 1.1.0 0.8 42. and duration of hospitalization in the PICU were significantly longer in the symptomatic candidiasis group than in the asymptomatic group.

Although the incidence of candidiasis in the past has been lower in pediatric departments than in adult departments [6]. Urinary catheterization and broad-spectrum antibiotic use were the most common risk factors. apart from the underlying disease [20].13 Median 25%-75%) 23 (15-37) 24 (10-44) 30 (15-45) < 0.5 (0-14) 12 (3-19. It was reported that horizontal transmission of C. Candida albicans was the most common Candida spp. especially when prolonged. observed an overall mortality rate of 41% in patients with candidemia and 71% in patients with Candida tropicalis infection [19]. however. Stamos and Rowley reported that Candida colonization was observed after ≥7 days of hospitalization.0001 < 0. observed Candida colonization in children after a median stay of 25 days [9]. parenteral nutrition. as the most frequent antifungal agent administered to our patients was fluconazole.4% of the symptomatic candidiasis group had C.28 24. reported that the presence of colonization and PRISM score were independent predictors of candidemia [17]. this emphasizes the need for a high level of suspicion of symptomatic candidiasis in patients with central venous catheters. 1-132 0-150 3-150 Mean rank 44.42 Median (25%-75%) 9 (2-16. Although these factors are common among all patients admitted to a PICU. parapsilosis has emerged as the predominant nonalbicans Candida sp. When our symptomatic and asymptomatic patients were compared for these risk factors parenteral nutrition. in recent years the proportion of cases due to species other than C. however. Italian Journal of Pediatrics 2011. was significantly associated with mortality. the most common Candida spp. Singhi et al.3%. C. Both the duration of PICU stay before Candida growth and total PICU stay were significantly longer in our symptomatic candidiasis group . which is similar to the present study’s results [5]. reported that 58% of candidemia cases in children were caused by non-albicans Candida spp [9]. On the other hand. Singhi et al. Symptomatic candidiasis is associated with a high mortality rate. increases the likelihood of fungal infection [21].13 45. C. In the present study the risk factors were compared between the symptomatic and asymptomatic groups. as a high rate of colonization has been reported in critically ill surgical patients [18].6 25. The overall mortality rate in the present study among the patients with symptomatic candidiasis was 48%. This compares well with the present results. In the present study 48.Arslankoylu et al. causing candidemia in children [10].0001 < 0.ijponline. in the present study no factor was associated with mortality [5]. central catheterization. Costa et al. and from the hands of healthcare workers to patients might contribute the high rate of C. A number of risk factors for symptomatic candidiasis in pediatric patients have been reported [13. albicans is the most common pathogen reported in most studies [5-7]. Sunit et al. and surgery rates were significantly higher in the symptomatic group. or surgery. reported that in a neonatal intensive care unit (NICU) tracheal intubation. Harvey and Myers observed that the most common risk factors in adult patients were central catheterization and blood transfusion [16]. Although the difference was not significant. The present study’s results support this hypothesis. parapsilosis from patient to patient. which is similar to the present results [6]. C. in our patients. albicans has increased markedly [8]. parapsilosis isolation [11]. Duration of stay in PICU before culturing time Duration of mechanical ventilation Duration of antibiotic treatment 1-59 0-59 0-59 Mean rank 24. in symptomatic patients was Candida parapsilosis. albicans remained the most common among the asymptomatic patients. Wey at al. Delayed diagnosis due to a lack of pathognomonic symptoms and the absence of reliable rapid diagnostic testing contributes to high mortality. reported that isolation of non-albicans Candida spp. however.14] and they were observed in our patients as well. When the patients were divided into symptomatic and asymptomatic groups. The shift in Candida spp.5) 2. to fluconazole [12]. MacDonald et al. 37:56 http://www. The median length of stay in the PICU before the development of candidemia was 16 days in Singhi et al. observed an excess mortality rate attributable to candidemia of 38%. MacDonald et al. Weese-Mayer et al. it has increased during the last decade [7]. versus 23 days in the present study [17]. It is well known that an ICU admission.’s study.0001 P with symptomatic candidiasis.92 44. isolation has also been attributed to the increased use of fluconazole and resistance of non-albicans Candida spp. Similar to the present results. and the only risk factor associated with symptomatic candidiasis was surgery.net/content/37/1/56 Page 5 of 6 Table 4 Descriptive statistics of measurements and their P values for the symptomatic and asymptomatic groups Asymptomatic Candidiasis Min-Max. central venous catheters. reported that the incidence of candidemia among all PICU admissions was 4.5) Symptomatic Candidiasis Min-Max. parapsilosis. and total parenteral nutrition were the most common risk factors [15].

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Woolson RF. risk factors. 27:781-788. 14. albicans was the most frequent Candida spp. 10. Conclusions C. 17. Mersin. parapsilosis. Singhi S. 15. Clin Infect Dis 1998. 13. 20.. Italian Journal of Pediatrics 2011 37:56. Acknowledgements The authors would like to thank the infection commitee of Mersin University School of Medicine Hospital for the records of the patients with candidiasis. should be considered. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed. Seu S. 11.com/submit . Chenoweth C: Risk factors for candidemia in a children’s hospital. Mersin University School of Medicine. Fondriest DW. Filioti J. Turkey. Rubin LG. All authors read and approved the final manuscript. Mersin University School of Medicine. and overall cost of illness. 4. Fungal Disease Registry of the Canadian Infectious Disease Society. Nicole LE. Kadiltsogluo I. were more common among the patients with symptomatic candidiasis. Author details 1 Department of Pediatric Intensive Care.1186/1824-7288-37-56 Cite this article as: Arslankoylu et al. 5:369-374. Singhi SC. Mersin University School of Medicine. Brouillette Rt. The attributable mortality and excess length of stay. Arch Intern Med 1988. Mersin. 18. 6:344-350. 4Department of Biostatistics. Suter PM. J Hosp Infect 2002. Aujard Y: Nasocomial infections in pediatric patients: a European. Received: 1 August 2011 Accepted: 21 November 2011 Published: 21 November 2011 References 1. Mori M. Spiroglou K. Rao R. Competing interests The authors declare that they have no competing interests. in the present study. Turkey.net/content/37/1/56 Page 6 of 6 than asymptomatic group. 37:56 http://www. Pediatr Crit Care Med 2004. 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