Indian J Pediatr (November 2014) 81(11):1158–1162 DOI 10.1007/s12098-014-1343-5
ORIGINAL ARTICLE
Risk Factors for Candidemia in Pediatric Intensive Care Unit Patients Hasan Ağın & Ilker Devrim & Rana İşgüder & Utku Karaarslan & Esra Kanık & İlker Günay & Miray Kışla & Sultan Aydın & Gamze Gülfidan
Received: 19 September 2012 / Accepted: 6 January 2014 / Published online: 14 March 2014 # Dr. K C Chaudhuri Foundation 2014
Abstract Objectıve To determine the risk factors for developing candida infections in pediatric intensive care unit (PICU). Methods The present study was conducted as a case–control study and included the population of patients who were admitted to PICU during the period of March 2010– March 2011. Results During the study period, a total of 57 patients in PICU had candidemia, 4 cases were excluded due to their PICU stay less than 48 h and one due to the insufficient data. The most commonly isolated Candida species was C. albicans, followed by C. parapsilosis. The median duration of hospitalization in PICU was higher (22.0 d) in candidemia patients compared to control group (13.5 d) (p= 0.037). The patients with candidemia had higher rates of presence of mechanical ventilation, presence of central venous catheter, and being under total parenteral nutrition; compared to the control group. Conclusıons The longer PICU durations, mechanical ventilation, central venous catheter, total parenteral nutrition were the associated factors. Although trials for predicitive models or scoring systems for development of candidemia have been H. Ağın : R. İşgüder : U. Karaarslan : E. Kanık Department of Intensıve Care, Dr. Behcet Uz Children’s Hospital, Izmir, Turkey I. Devrim (*) Pediatric Infectious Disease Unit, Dr. Behcet Uz Children’s Hospital, Izmir 35100, Turkey e-mail: [email protected] İ. Günay : M. Kışla : S. Aydın Department of Pedıatrıcs, Dr. Behcet Uz Children’s Hospital, Izmir, Turkey G. Gülfidan Department of Clinical Microbiology, Dr. Behcet Uz Children’s Hospital, Izmir, Turkey
performed; more future studies were required for practical usage in clinics settings in order to prevent candidemia. Keywords Pediatric intensive care unit . Candida . Risk factors
Introduction Infections with Candida species are one of the most leading causes of nosocomial bloodstream infections [1]. They are also important in children, being one of the most frequent causes of healthcare associated infections [2]. Candida infections are not only associated with prolonged hospital stay and increased cost of care; but also cause mortality in children [3]. Several risk factors were reported for candidemia. One of the important risk factors for candida infections is intensive care unit stay [4, 5]. This is related with patient’s critical underlying problems, immune system malfunction and invasive procedures performed for monitoring and treatment [6]. Pediatric intensive care unit (PICU) patients with candidemia are at highest risk of death [7]. The studies concerning the risk factors for developing candidemia in PICU are limited when compared to adult group [3]. The reported risk factors for candidemia in PICU include endotracheal intubation, presence of central venous and arterial catheters (CVC) [8–10], parenteral nutrition [4, 11], prolonged ICU stay, previous broad-spectrum antibiotics [4], immunodeficiency [10], neutropenia, malignancies [4], prolonged use of antimicrobial agents [12] and vancomycin [9], mechanical ventilation [6], bone marrow transplantation and prior colonization with Candida spp. [6, 10, 11, 13]. In the present study; the authors aimed to determine the risk factors for developing candida infections in the PICU of a
Indian J Pediatr (November 2014) 81(11):1158–1162
tertiary level hospital in Turkey with a retrospective case– control study setting.
Material and Methods Dr. Behçet Uz Children’s Hospital, Izmir, Turkey is a 400-bed pediatric teaching hospital with annual outpatient visits exceeding 465,000 in 2007 and approximately 20,000 hospitalization per year. The PICU of Dr. Behçet Uz Children’s Hospital is 12-bed unit in which annual admission is about 600 patient. This retrospective case–control study included the patients who were admitted to PICU during the period of March 2010– March 2011. All patients admitted were identified using both hospital and unit-specific databases. The neonates (babies younger than 28 d of life) were not included. Inclusion Criteria 1. The patients with candidemia who were followed-up in PICU. 2. Candidemia was defined by isolation of Candida species from the blood samples of the patients hospitalized in the PICU for at least 48 h. 3. Presence of fever and signs of infection while blood culture samples were obtained. 4. For the patients with one or more positive culture for candida; the time of the first isolated culture was accepted as the date for enroling into the study.
Exclusion Criteria 1. Patients who had been in PICU less than 48 h before candida isolation were excluded from the study group. 2. Patients with insufficient data in his or her files were also excluded.
1159
The investigators recorded the data including age, sex, type of ICU, duration of hospitalization prior to infection, date of infection, the underlying disease and co-morbidities, indications for admission. Possible risk factors such as antimicrobial therapy, total parenteral nutrition, mechanical ventilation, insertion of central venous catheters, co-infection with other microorganisms were recorded. Also antimicrobial treatment regiments were also recorded. The co-morbidities of the patients such as malignancy, primary immunodeficiency, neutropenia (absolute neutrophil count, 0.05). In authors opinion this could be due to the patients being treated with more broad spectrum antibiotics if their hospitalizations were prolonged. In conclusion, several risk factors for candidemia in PICU had been investigated in this article. Among them, longer PICU stay, presence of central venous catheters and total parenteral nutrition were associated risk factors. Although trials for predictive models or scoring systems for development of candidemia have been performed; further prospective studies were required for risk factors for special candida species.
1161 Contribution Dr. Ilker Devrim will act as guarantor for this paper. Conflict of Interest None. Role of Funding Source None.
References 1. Pfaller MA, Diekema DJ, Jones RN, Sader HS, Fluit AC, Hollis RJ, et al. SENTRY Participant Group. International surveillance of bloodstream infections due to Candida species: Frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program. J Clin Microbiol. 2001;39:3254–9. 2. Wisplinghoff H, Seifert H, Tallent SM, Bischoff T, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in pediatric patients in United States hospitals: Epidemiology, clinical features and susceptibilities. Pediatr Infect Dis J. 2003;22:686–91. 3. Zaoutis TE, Prasad PA, Localio AR, Coffin SE, Bell LM, Walsh TJ, et al. Risk factors and predictors for candidemia in pediatric intensive care unit patients: Implications for prevention. Clin Infect Dis. 2010;51:e38–45. 4. Arslankoylu AE, Kuyucu N, Yilmaz BS, Erdogan S. Symptomatic and asymptomatic candidiasis in a pediatric intensive care unit. Ital J Pediatr. 2011;37:56. 5. Singhi S, Deep A. Invasive candidiasis in pediatric intensive care units. Indian J Pediatr. 2009;76:1033–44. 6. Filioti J, Spiroglou K, Panteliadis CP, Roilides E. Invasive candidiasis in pediatric intensive care patients: Epidemiology, risk factors, management, and outcome. Intensive Care Med. 2007;33:1272–83. 7. Zaoutis TE, Coffin SE, Chu JH, Heydon K, Zhao H, Greves HM, et al. Risk factors for mortality in children with candidemia. Pediatr Infect Dis J. 2005;24:736–9. 8. Zaoutis TE, Greves HM, Lautenbach E, Bilker WB, Coffin SE. Risk factors for disseminated candidiasis in children with candidemia. Pediatr Infect Dis J. 2004;23:635–41. 9. Zaoutis T. Candidemia in children. Curr Med Res Opin. 2010;26: 1761–8. 10. Smith MJ. Catheter-relatedbloodstreaminfections in children. Am J Infect Control. 2008;36(S173):e1–3. 11. Galal N, Badawy A, Khalaf-Allah O, Youssef A. Identification of Tlymphocyte function in healthy vs. septicpreterms and its relation to candidal infections in the hospital setting. Indian J Pediatr. 2012;79: 348–52. 12. Garcia-San Miguel L, Cobo J, Martos I, Otheo E, Muriel A, Pintado V, et al. Risk factors for candidemia in pediatric patients with congenital heart disease. Infect Control Hosp Epidemiol. 2006;27:576– 80. 13. Singhi S, Rao DS, Chakrabarti A. Candida colonization and candidemia in a pediatric intensive care unit. Pediatr Crit Care Med. 2008;9:91–5. 14. Belet N, Ciftçi E, Aysev D, Güriz H, Uysal Z, Taçyildiz N, et al. Invasive Candida infections in children: The clinical characteristics and species distribution and antifungal susceptibility of Candida spp. Turk J Pediatr. 2011;53:489–98. 15. Kuzucu C, Durmaz R, Otlu B, Aktas E, Gulcan H, Cizmeci Z. Species distribution, antifungal susceptibility and clonal relatedness of Candida isolates from patients in neonatal and pediatric intensive care units at a medical center in Turkey. New Microbiol. 2008;31:401–8. 16. Pemán J, Cantón E, Linares-Sicilia MJ, Roselló EM, Borrell N, RuizPérez-de-Pipaon MT, et al. Epidemiology and antifungal
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17.
18.
19.
20.
21.
22.
susceptibility of bloodstream fungal isolates in pediatric patients: A Spanish multicenter prospective survey. J Clin Microbiol. 2011;49: 4158–63. Singhi SC, Reddy TC, Chakrabarti A. Oral itraconazole in treatment of candidemia in a pediatric intensive care unit. Indian J Pediatr. 2004;71:973–7. Çelebi S, Hacımustafaoğlu M, Özdemir Ö, Özkaya G. Nosocomial candidaemia in children: Results of a 9-year study. Mycoses. 2007;51:248–57. Blyth CC, Chen SC, Slavin MA, Serena C, Nguyen Q, Marriott D, et al. Not just little adults: Candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients. Pediatrics. 2009;123:1360–8. Nucci M, Anaissie E. Should vascular catheters be removed from all patients with candidemia? An evidence-based review. Clin Infect Dis. 2002;34:591–9. Ayala-Gaytán JJ, Alemán-Bocanegra MC, Guajardo-Lara CE. Valdovinos-Chávez SB [Catheter-associated bloodstream infections. Review of five-year surveillance among hospitalized patients]. Rev Med Inst Mex Seguro Soc. 2010;48:145–50. Levin AS, Costa SF, Mussi NS, Basso M, Sinto SI, Machado C, et al. Candida parapsilosis fungemia associated with implantable and semi-implantable central venous catheters and
Indian J Pediatr (November 2014) 81(11):1158–1162
23.
24.
25.
26.
27. 28.
29.
the hands of healthcare workers. Diagn Microbiol Infect Dis. 1998;30:243–9. Dotis J, Prasad PA, Zaoutis T, Roilides E. Epidemiology, risk factors and outcome of candida parapsilosis bloodstream infection in children. Pediatr Infect Dis J. 2012;31:557–60. Bonassoli LA, Bertoli M, Svidzinski TI. High frequency of Candida parapsilosis on the hands of healthy hosts. J Hosp Infect. 2005;59: 159–62. Yapar N, Pullukcu H, Avkan-Oguz V, Sayin-Kutlu S, Ertugrul B, Sacar S, et al. Evaluation of species distribution and risk factors of candidemia: A multicenter case–control study. Med Mycol. 2011;49:26–31. Cano MV, Perz JF, Craig AS, Liu M, Lyon GM, Brandt ME, et al. Candidemia in pediatric outpatients receiving home total parenteral nutrition. Med Mycol. 2005;43:219–25. Vollaard EJ, Clasener HA. Colonization resistance. Antimicrob Agents Chemother. 1994;38:409–14. van der Waaij D. Colonization resistance of the digestive tract: clinical consequences and implications. J Antimicrob Chemother. 1982;10:263–70. Samonis G, Gikas A, Anaissie EJ, Vrenzos G, Maraki S, Tselentis Y, et al. Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans. Antimicrob Agents Chemother. 1993;37:51–3.
ORIGINAL ARTICLE
Risk Factors for Candidemia in Pediatric Intensive Care Unit Patients Hasan Ağın & Ilker Devrim & Rana İşgüder & Utku Karaarslan & Esra Kanık & İlker Günay & Miray Kışla & Sultan Aydın & Gamze Gülfidan
Received: 19 September 2012 / Accepted: 6 January 2014 / Published online: 14 March 2014 # Dr. K C Chaudhuri Foundation 2014
Abstract Objectıve To determine the risk factors for developing candida infections in pediatric intensive care unit (PICU). Methods The present study was conducted as a case–control study and included the population of patients who were admitted to PICU during the period of March 2010– March 2011. Results During the study period, a total of 57 patients in PICU had candidemia, 4 cases were excluded due to their PICU stay less than 48 h and one due to the insufficient data. The most commonly isolated Candida species was C. albicans, followed by C. parapsilosis. The median duration of hospitalization in PICU was higher (22.0 d) in candidemia patients compared to control group (13.5 d) (p= 0.037). The patients with candidemia had higher rates of presence of mechanical ventilation, presence of central venous catheter, and being under total parenteral nutrition; compared to the control group. Conclusıons The longer PICU durations, mechanical ventilation, central venous catheter, total parenteral nutrition were the associated factors. Although trials for predicitive models or scoring systems for development of candidemia have been H. Ağın : R. İşgüder : U. Karaarslan : E. Kanık Department of Intensıve Care, Dr. Behcet Uz Children’s Hospital, Izmir, Turkey I. Devrim (*) Pediatric Infectious Disease Unit, Dr. Behcet Uz Children’s Hospital, Izmir 35100, Turkey e-mail: [email protected] İ. Günay : M. Kışla : S. Aydın Department of Pedıatrıcs, Dr. Behcet Uz Children’s Hospital, Izmir, Turkey G. Gülfidan Department of Clinical Microbiology, Dr. Behcet Uz Children’s Hospital, Izmir, Turkey
performed; more future studies were required for practical usage in clinics settings in order to prevent candidemia. Keywords Pediatric intensive care unit . Candida . Risk factors
Introduction Infections with Candida species are one of the most leading causes of nosocomial bloodstream infections [1]. They are also important in children, being one of the most frequent causes of healthcare associated infections [2]. Candida infections are not only associated with prolonged hospital stay and increased cost of care; but also cause mortality in children [3]. Several risk factors were reported for candidemia. One of the important risk factors for candida infections is intensive care unit stay [4, 5]. This is related with patient’s critical underlying problems, immune system malfunction and invasive procedures performed for monitoring and treatment [6]. Pediatric intensive care unit (PICU) patients with candidemia are at highest risk of death [7]. The studies concerning the risk factors for developing candidemia in PICU are limited when compared to adult group [3]. The reported risk factors for candidemia in PICU include endotracheal intubation, presence of central venous and arterial catheters (CVC) [8–10], parenteral nutrition [4, 11], prolonged ICU stay, previous broad-spectrum antibiotics [4], immunodeficiency [10], neutropenia, malignancies [4], prolonged use of antimicrobial agents [12] and vancomycin [9], mechanical ventilation [6], bone marrow transplantation and prior colonization with Candida spp. [6, 10, 11, 13]. In the present study; the authors aimed to determine the risk factors for developing candida infections in the PICU of a
Indian J Pediatr (November 2014) 81(11):1158–1162
tertiary level hospital in Turkey with a retrospective case– control study setting.
Material and Methods Dr. Behçet Uz Children’s Hospital, Izmir, Turkey is a 400-bed pediatric teaching hospital with annual outpatient visits exceeding 465,000 in 2007 and approximately 20,000 hospitalization per year. The PICU of Dr. Behçet Uz Children’s Hospital is 12-bed unit in which annual admission is about 600 patient. This retrospective case–control study included the patients who were admitted to PICU during the period of March 2010– March 2011. All patients admitted were identified using both hospital and unit-specific databases. The neonates (babies younger than 28 d of life) were not included. Inclusion Criteria 1. The patients with candidemia who were followed-up in PICU. 2. Candidemia was defined by isolation of Candida species from the blood samples of the patients hospitalized in the PICU for at least 48 h. 3. Presence of fever and signs of infection while blood culture samples were obtained. 4. For the patients with one or more positive culture for candida; the time of the first isolated culture was accepted as the date for enroling into the study.
Exclusion Criteria 1. Patients who had been in PICU less than 48 h before candida isolation were excluded from the study group. 2. Patients with insufficient data in his or her files were also excluded.
1159
The investigators recorded the data including age, sex, type of ICU, duration of hospitalization prior to infection, date of infection, the underlying disease and co-morbidities, indications for admission. Possible risk factors such as antimicrobial therapy, total parenteral nutrition, mechanical ventilation, insertion of central venous catheters, co-infection with other microorganisms were recorded. Also antimicrobial treatment regiments were also recorded. The co-morbidities of the patients such as malignancy, primary immunodeficiency, neutropenia (absolute neutrophil count, 0.05). In authors opinion this could be due to the patients being treated with more broad spectrum antibiotics if their hospitalizations were prolonged. In conclusion, several risk factors for candidemia in PICU had been investigated in this article. Among them, longer PICU stay, presence of central venous catheters and total parenteral nutrition were associated risk factors. Although trials for predictive models or scoring systems for development of candidemia have been performed; further prospective studies were required for risk factors for special candida species.
1161 Contribution Dr. Ilker Devrim will act as guarantor for this paper. Conflict of Interest None. Role of Funding Source None.
References 1. Pfaller MA, Diekema DJ, Jones RN, Sader HS, Fluit AC, Hollis RJ, et al. SENTRY Participant Group. International surveillance of bloodstream infections due to Candida species: Frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program. J Clin Microbiol. 2001;39:3254–9. 2. Wisplinghoff H, Seifert H, Tallent SM, Bischoff T, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in pediatric patients in United States hospitals: Epidemiology, clinical features and susceptibilities. Pediatr Infect Dis J. 2003;22:686–91. 3. Zaoutis TE, Prasad PA, Localio AR, Coffin SE, Bell LM, Walsh TJ, et al. Risk factors and predictors for candidemia in pediatric intensive care unit patients: Implications for prevention. Clin Infect Dis. 2010;51:e38–45. 4. Arslankoylu AE, Kuyucu N, Yilmaz BS, Erdogan S. Symptomatic and asymptomatic candidiasis in a pediatric intensive care unit. Ital J Pediatr. 2011;37:56. 5. Singhi S, Deep A. Invasive candidiasis in pediatric intensive care units. Indian J Pediatr. 2009;76:1033–44. 6. Filioti J, Spiroglou K, Panteliadis CP, Roilides E. Invasive candidiasis in pediatric intensive care patients: Epidemiology, risk factors, management, and outcome. Intensive Care Med. 2007;33:1272–83. 7. Zaoutis TE, Coffin SE, Chu JH, Heydon K, Zhao H, Greves HM, et al. Risk factors for mortality in children with candidemia. Pediatr Infect Dis J. 2005;24:736–9. 8. Zaoutis TE, Greves HM, Lautenbach E, Bilker WB, Coffin SE. Risk factors for disseminated candidiasis in children with candidemia. Pediatr Infect Dis J. 2004;23:635–41. 9. Zaoutis T. Candidemia in children. Curr Med Res Opin. 2010;26: 1761–8. 10. Smith MJ. Catheter-relatedbloodstreaminfections in children. Am J Infect Control. 2008;36(S173):e1–3. 11. Galal N, Badawy A, Khalaf-Allah O, Youssef A. Identification of Tlymphocyte function in healthy vs. septicpreterms and its relation to candidal infections in the hospital setting. Indian J Pediatr. 2012;79: 348–52. 12. Garcia-San Miguel L, Cobo J, Martos I, Otheo E, Muriel A, Pintado V, et al. Risk factors for candidemia in pediatric patients with congenital heart disease. Infect Control Hosp Epidemiol. 2006;27:576– 80. 13. Singhi S, Rao DS, Chakrabarti A. Candida colonization and candidemia in a pediatric intensive care unit. Pediatr Crit Care Med. 2008;9:91–5. 14. Belet N, Ciftçi E, Aysev D, Güriz H, Uysal Z, Taçyildiz N, et al. Invasive Candida infections in children: The clinical characteristics and species distribution and antifungal susceptibility of Candida spp. Turk J Pediatr. 2011;53:489–98. 15. Kuzucu C, Durmaz R, Otlu B, Aktas E, Gulcan H, Cizmeci Z. Species distribution, antifungal susceptibility and clonal relatedness of Candida isolates from patients in neonatal and pediatric intensive care units at a medical center in Turkey. New Microbiol. 2008;31:401–8. 16. Pemán J, Cantón E, Linares-Sicilia MJ, Roselló EM, Borrell N, RuizPérez-de-Pipaon MT, et al. Epidemiology and antifungal
1162
17.
18.
19.
20.
21.
22.
susceptibility of bloodstream fungal isolates in pediatric patients: A Spanish multicenter prospective survey. J Clin Microbiol. 2011;49: 4158–63. Singhi SC, Reddy TC, Chakrabarti A. Oral itraconazole in treatment of candidemia in a pediatric intensive care unit. Indian J Pediatr. 2004;71:973–7. Çelebi S, Hacımustafaoğlu M, Özdemir Ö, Özkaya G. Nosocomial candidaemia in children: Results of a 9-year study. Mycoses. 2007;51:248–57. Blyth CC, Chen SC, Slavin MA, Serena C, Nguyen Q, Marriott D, et al. Not just little adults: Candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients. Pediatrics. 2009;123:1360–8. Nucci M, Anaissie E. Should vascular catheters be removed from all patients with candidemia? An evidence-based review. Clin Infect Dis. 2002;34:591–9. Ayala-Gaytán JJ, Alemán-Bocanegra MC, Guajardo-Lara CE. Valdovinos-Chávez SB [Catheter-associated bloodstream infections. Review of five-year surveillance among hospitalized patients]. Rev Med Inst Mex Seguro Soc. 2010;48:145–50. Levin AS, Costa SF, Mussi NS, Basso M, Sinto SI, Machado C, et al. Candida parapsilosis fungemia associated with implantable and semi-implantable central venous catheters and
Indian J Pediatr (November 2014) 81(11):1158–1162
23.
24.
25.
26.
27. 28.
29.
the hands of healthcare workers. Diagn Microbiol Infect Dis. 1998;30:243–9. Dotis J, Prasad PA, Zaoutis T, Roilides E. Epidemiology, risk factors and outcome of candida parapsilosis bloodstream infection in children. Pediatr Infect Dis J. 2012;31:557–60. Bonassoli LA, Bertoli M, Svidzinski TI. High frequency of Candida parapsilosis on the hands of healthy hosts. J Hosp Infect. 2005;59: 159–62. Yapar N, Pullukcu H, Avkan-Oguz V, Sayin-Kutlu S, Ertugrul B, Sacar S, et al. Evaluation of species distribution and risk factors of candidemia: A multicenter case–control study. Med Mycol. 2011;49:26–31. Cano MV, Perz JF, Craig AS, Liu M, Lyon GM, Brandt ME, et al. Candidemia in pediatric outpatients receiving home total parenteral nutrition. Med Mycol. 2005;43:219–25. Vollaard EJ, Clasener HA. Colonization resistance. Antimicrob Agents Chemother. 1994;38:409–14. van der Waaij D. Colonization resistance of the digestive tract: clinical consequences and implications. J Antimicrob Chemother. 1982;10:263–70. Samonis G, Gikas A, Anaissie EJ, Vrenzos G, Maraki S, Tselentis Y, et al. Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans. Antimicrob Agents Chemother. 1993;37:51–3.
