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ORIGINAL ARTICLE
Year : 2014  |  Volume : 27  |  Issue : 1  |  Page : 55-59

Study of fungal infections in pediatric intensive care unit in Menoufiya University Hospital


1 Department of Pediatric, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
2 Department of Microbiology, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt

Date of Submission03-Apr-2013
Date of Acceptance15-Jul-2013
Date of Web Publication20-May-2014

Correspondence Address:
Nagwan Y. Saleh
Department of Pediatric, Faculty of Medicine, Menoufiya University, Menoufiya
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.132742

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  Abstract 

Objective
The aim of the study was to determine the incidence and risk factors of fungal infections in patients admitted to pediatric intensive care unit (PICU) in Menoufiya University Hospital.
Background
Critically ill patients are immunosuppressed, invasively monitored, and exposed to aggressive interventions that put them at increased risk for infectious complications while residing in PICU. Fungal pathogens are an increasing important cause of infection among patients in PICU.
Patients and methods
This study was conducted on 492 critically ill pediatric patients admitted to PICU from July 2010 to July 2011; each patient was examined and sampled on the day of admission and after 5 and 7 days of admission. Samples were taken from oropharyngeal, axillary, and rectal areas in addition to blood sample. All specimens were cultured on Sabouraud dextrose agar. The analysis of samples included a direct examination, culture, and susceptibility of isolates to antifungal drugs.
Results
Candida albicans was the most common colonizing organisms, as about 156 (31.7%) patients were colonized by it on the day of admission. The most commonly acquired fungi were: C. glabrata in 71 (25.7%) patients, C. tropicalis in 61 (22.1%) patients, C. albicans in 46 (16.7%) patients, C. krusei in 33 (11.9%) patients, Aspergillus flavus in 20 (7.3%) patients, and mixed infection in 45 (16.3%) patients. Patients on previous antibiotic therapy, parenteral nutrition, and central venous line had an increased risk of acquiring fungal organisms.
Conclusion
Monitoring for colonization with Candida spp. in children admitted to PICU and children undergoing treatment for severe sepsis or septic shock in PICU for more than 5 days may offer an opportunity for early intervention for prevention of candidemia.

Keywords: Fungal infections, PICU infections, pediatric sepsis, pediatric septic shock


How to cite this article:
ElGendy FM, Hassan FM, Khatab AA, El-Hendawy GR, Saleh NY. Study of fungal infections in pediatric intensive care unit in Menoufiya University Hospital. Menoufia Med J 2014;27:55-9

How to cite this URL:
ElGendy FM, Hassan FM, Khatab AA, El-Hendawy GR, Saleh NY. Study of fungal infections in pediatric intensive care unit in Menoufiya University Hospital. Menoufia Med J [serial online] 2014 [cited 2024 Mar 28];27:55-9. Available from: http://www.mmj.eg.net/text.asp?2014/27/1/55/132742


  Introduction Top


The incidence of candidemia in the overall population ranges from 1.7 to 10 episodes per 100 000 inhabitants, and Candida is one of the 10 leading causes of blood stream infections in developed countries. An estimated 33-55% of all episodes of candidemia occurs in ICUs and is associated with mortality rates ranging from 5 to 71%. Candida fungemia may have an endogenous or exogenous origin, and in recent years a growing proportion of episodes of candidemia have been caused by Candida spp. other than C. albicans [1]. Candidemia and disseminated candidiasis are the major causes of morbidity and mortality in hospitalized patients, especially in the ICU. The incidence of invasive candidiasis is on a steady rise because of increasing use of multiple antibiotics and invasive procedures carried out in the ICUs. Worldwide, there is a shifting trend from C. albicans toward non-albicans species, with an associated increase in mortality and antifungal resistance [2]. In the ICU, a predisposed host is the one who is on broad-spectrum antibiotics, parenteral nutrition, and central venous catheters. There are no pathognomonic signs or symptoms. The clinical clues are unexplained fever or signs of severe sepsis or septic shock while on antibiotics and multiple, nontender, nodular erythematous cutaneous lesions. The spectrum of infection with Candida spp. ranges from superficial candidiasis of the skin and mucosa to more serious life-threatening infections [3]. Risk factors for invasive candidiasis and candidemia include prior antimicrobial therapy, venous and urinary catheters, ICU admission, parenteral nutrition, and immunosuppressive therapies [4]. Amphotericin B remains the initial drug of first choice in hemodynamically unstable critically ill children in the wake of increasing resistance to azoles. Evaluation of newer antifungal agents and precise role of prophylactic therapy in ICU patients is needed [5].


  Patients and methods Top


This study was conducted on patients admitted to pediatric intensive care unit (PICU) of Menoufiya University Hospital from July 2010 to July 2011. A total of 492 patients were enrolled in the study; each patient was examined and sampled on the first day of admission and after 5 and 7 days of admission. All patients were subjected to the following: clinical findings of the patients, scoring system for assessment of mortality risk according to pediatric risk of mortality (PRISM III), laboratory parameters, and microbiological assessment for samples of patients.

(1) Collection of samples: Swabs were collected from each patient upon his admission to PICU, after 5 days and 7 days. Samples from oropharyngeal area, axillary folds, rectal area, and blood sample were also collected.

(2) Sample processing: All specimens were cultured as duplicates on Sabouraud dextrose agar plates aiming to isolate different Candida spp. Identification of different Candida spp. was carried out according to colony morphology, germ tube, fermentation tests, and KB006 Hicandida identification kit [6].

(3) Detection of susceptibility of isolates to antifungal drugs was carried out.

(4) Analysis of data was performed using statistical program for social science (SPSS, version 12; SPSS Inc., Chicago, Illinois, USA).


  Results Top


The present study included all patients admitted to PICU from July 2010 to July 2011; there were 492 patients with mean age of 3.4 ± 1.5 years, ranging from 1 month to 16 years. Most of the studied patients (46.4%) were below 1 year of age, and 60.6% of them were male patients and only 39.4% were female patients [Table 1].
Table 1: Distribution of studied patients with respect to age and sex

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Sepsis was the most common cause predisposed to mortality, 42.7% (90 patients) of the whole mortality was due to sepsis, whereas 21.3% (45 patients) of mortality was in part due to chest diseases, 16.6% (35 patients) of mortality was in part due to central nervous system diseases, 14.2% (30 patients) was due to CVS diseases, and 3.3% (seven patients) was due to abdominal diseases [Table 2]. With respect to the pattern of fungal colonization among studied patients on the day of admission, C. albicans was the most common colonizing organisms as about 156 (31.7%) patients, C. glabrata was isolated from 53 (10.8%) patients, Aspergillus flavus was isolated from 36 (7.3%) patients, and other fungi isolated by culture included C. krusei, C. parapsilosis, and C. tropicalis. The most commonly acquired fungi were C. glabrata, which was detected in 71 (25.7%) patients, C. tropicalis in 61 (22.1%) patients, C. albicans in 46 (16.7%) patients, C. krusei in 33 (11.9%) patients, A. flavus in 20 (7.3%) patients, and mixed infections in 45 (16.3%) patients [Table 3].
Table 2: Mortality rate in relationship with cause of admission to pediatric intensive care unit

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Table 3: Results of fungal blood culture of studied patients with fungal infection on day 5 of pediatric intensive care unit admissio

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The infection rate was significantly higher in patients on previous antibiotic therapy, parenteral nutrition, and central venous line. While using immunosuppressive therapy, urinary catheter and mechanical ventilator did not increase the risk for fungal infection [Table 4].
Table 4: Relationship between patients with negative versus positive fungal infection on day 5 in pediatric intensive care unit and different risk factors

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The infection rate was significantly higher in patients with high CRP titer, anemia, thrombocytopenia, and leukocytosis [Table 5].
Table 5: Comparison between patients with negative and positive fungal infection in pediatric intensive care unit with respect to laboratory data

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In the antifungal culture sensitivity results of pattern of fungal strains, it was found that all C. albicans isolates were sensitive to all antifungal drugs and all C. glabrata isolates were sensitive to amphotericin B [Table 6].
Table 6: The antifungal culture sensitivity results of pattern of fungal strains

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  Discussion Top


In our study, most of the studied patients (46.4%) were below 1 year of age, 60.6% of the total number of patients were male and only 39.4% were female patients; this may be explained by the vulnerability of this age group to life-threatening diseases. The same finding was noted by Lopes et al. [7] who studied the surveillance of nosocomial infection in a Portuguese pediatric hospital from January 1998 to March 2000. They reported that 56.7% of the total number of patients enrolled in their study in ICU were male and 43.3% were female. Most of the patients were below 6 months of age [7].

In the current study, sepsis was the commonest cause predisposed to mortality, as 42.7% (90 patients) of the whole mortality was in part due to sepsis, whereas 21.3% (45 patients) of mortality was due to chest diseases, 16.6% (35 patients) of mortality was due to central nervous system diseases, 14.2% (30 patients) was due to CVS diseases, 3.3% (seven patients) was due to abdominal diseases, and 1.9% (four patients) due to other diseases. Ben-Abraham et al. [8], who studied the predictors of adverse outcome from candidal infection in a tertiary care hospital, mentioned that the overall mortality was 42% in a tertiary care hospital. The direct reasons for death included candidemia or its complications (meningitis, endocarditis, and hepatitis) in 17.5%, septic shock in 65%, cardiogenic shock in 6.3%, complication of malignancy in 6.3%, and other reasons in 3.6% [8]. Lopes et al. [7] also found that death rate is more than 10% in children less than 6 months of age and the highest prevalence of septicemia was among those children.

In the current study, C. albicans was the most common colonizing organisms detected by conventional methods from all swabbed body sites, as about 156 (31.7%) patients were colonized by it on the day of admission to PICU. These results are in agreement with the study by Trick et al. [9], who conducted a similar study and swabbed patients on the day of admission to ICU and found that the overall colonization rate was 57.3% and Candida spp. were the most frequently isolated organisms from any body site, comprising 85% of the total number of isolates.

In our study, the most commonly acquired fungi were C. glabrata in 69 (14.3%) patients, C. tropicalis in 61 (12.5%) patients, C. albicans in 45 (8.9%) patients, C. krusei in 36 (7.1%) patients, and A. flavus in 26 (5.4%) patients. There was a different pattern of distribution of fungal infections in our ICU and a predominance of non-albicans Candida spp. These species are recently emerged as important nosocomial pathogen in centers wherein fluconazole is used for antifungal prophylaxis. Those species also are of special concern in critically ill patients in whom it is known to be associated with the use of central lines and parenteral nutrition.

Rezende et al. [10] studied the fungal pattern at ICU and they isolated C. albicans as the most common etiologic agent to be acquired from ICU, whereas non-albicans species were isolated in 31.9%; they attributed this pattern to the possibility of selection of less susceptible species by antifungal agents such as fluconazole in particular. Some Candida strains such as C. glabrata and C. krusei are less susceptible to fluconazole compared with C. albicans. However, Passos et al. [11] found that C. albicans was isolated in 69.1% of ICU patients, whereas other non-albicans species such as C. glabrata, C. parapsilosis, C. guilliermondii, C. krusei, and C. tropicalis were isolated in lower percentage.

In our study, 166 (60%) patients of younger age group below 1 year were infected by fungi at PICU - that is, more susceptible to infection compared with that in older age groups, with significant difference; this could be explained by the vulnerability of this group to critical illness that subject them to more invasive devices in ICU and to aggressive use of antibiotics, predisposing them to fungal infection. However, there was no statistically significant difference between the rates of fungal infection with respect to sex of patients. Ben-Abraham et al. [8] stated that mean age of the patients enrolled in their study was 48 years (range 5-91 years), with a male/female ratio of 3/2 with candidemia.

In our patients, the infection rate was determined to be significantly higher in patients on previous antibiotic therapy, parenteral nutrition, and central venous line using the Fisher exact test. While using immunosuppressive therapy, urinary catheter and mechanical ventilator did not increase the risk of acquiring fungal organisms. Lopes et al. [7] showed that the major risk factors associated with the development of fungal infection were anemia, antibiotic therapy, intravascular catheters, parenteral nutrition, hospital stay, and sex. The occurrence of fungal infections in children who had taken three or more antibiotics was 7.5 times higher as compared with that observed in children who received less than three antibiotics [7]. Caggiano et al. [12] showed that frequent predisposing factors for candidemia were the presence of central venous catheters (21.5%) and corticosteroid therapy (13.7%). Brissaud et al. [13] showed that the predisposing factors for candidemia were the presence of central venous catheters, total parenteral nutrition, immunocompromised status, and recent surgery.

In the current study, cases of fungal infections were associated with high CRP titer, anemia, thrombocytopenia, and leukocytosis. Abnormal infection markers were a part of sepsis syndrome whether isolated or associated with other system diseases, which put the patient at higher morbidity and mortality and make him more immunocompromised, increasing the chance for opportunistic organisms. Ben-Abraham et al. [8] stated that the risk factors for systemic fungal infections were neutropenia, thrombocytopenia, renal failure, and broad-spectrum antibiotics. Badiee et al. [14] found that the risk factors for candidemia include fungal colonization from body sites, antimicrobial treatment, use of central venous catheters, underlying diseases status, and use of immunosuppressive drugs before admission to ICU.

In our study, the antifungal culture sensitivity results found that all C. albicans isolates were sensitive to all antifungal drugs, all C. glabrata isolates were sensitive to amphotericin B only, and all C. krusei isolates were resistant to all antifungal drugs.

Aliyu et al. [15] found that all isolates were sensitive to amphotericin B and 87% were sensitive to fluconazole. All C. albicans strains were sensitive to fluconazole compared with 78% of non-albicans Candida strains.

We conclude from this study that monitoring for colonization with Candida spp. in children undergoing treatment for severe sepsis or septic shock in PICU for more than 5 days may offer an opportunity for early intervention for prevention of candidemia.


  Acknowledgements Top


Conflicts of interest

None declared.

 
  References Top

1.Bougnoux ME, Kac G, Aegerter P, et al. Candidemia and candiduria in critically ill patients admitted to intensive care unit in France: incidence, molecular diversity, management and outcome. Intensive Care Med 2008; 34:292-299.  Back to cited text no. 1
    
2. Singhi S, Rao DS, Chakrabrati A. Candida colonization and candidemia in a pediatric intensive care unit. Pediatr Crit Care Med 2008; 9:91-95.  Back to cited text no. 2
    
3. Golan R. Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis. Ann Intern Med 2005; 143:857-869.  Back to cited text no. 3
    
4. Fleck R, Dietz A, Hof H. In vitro susceptibility of Candida species to five antifungal agents in a German university hospital assessed by the reference broth micro dilution method and Etest. J Antimicrob Chemother 2007; 59:767-767.  Back to cited text no. 4
    
5. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: persistent public health problem. Clin Microb Rev 2007; 20:133-163.  Back to cited text no. 5
    
6. NCCLS (1997). Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved standard. NCCLS document M27-A. Wayne, PA: NCCLS (ISBN 1-56238-328-0).  Back to cited text no. 6
    
7. Lopes MM, Barros R, Peres I, et al. Surveillance of nosocomial fungal infection in a Portuguese pediatric hospital: incidence and risk factors. J Mycol Med 2006; 16:212-219.  Back to cited text no. 7
    
8. Ben-Abraham R, Keller N, Teodorovitch U, et al. Predictors of adverse outcome from candidal infection in a tertiary care hospital. J Infect 2004; 49:317-323.  Back to cited text no. 8
    
9. Trick WK, Fridkin SK, Kdwards JR, et al. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999. Clin Infect Dis 2002; 35:627-630.  Back to cited text no. 9
    
10.1Rezende JCP, Rezende MA, Salib JL. Prevalence of Candida spp. in hospitalized patients and their risk factors. Mycoses 2002; 45:306-312.  Back to cited text no. 10
    
11.1Passos XS, Sales WS, PJ Maciel, et al. Candida colonization in intensive care unit patients′ urine. Mem Inst Oswaldo Cruz 2005; 100:925-928.  Back to cited text no. 11
    
12.1Caggiano G, Puntillo F, Coretti C, et al. Candida colonization index in patients admitted to an ICU. Int J Mol Sci 2011; 12:7038-7047.  Back to cited text no. 12
    
13.1Brissaud O, Guichoux J, Harambat J, et al. Invasive fungal disease in PICU: epidemiology and risk factors. Ann Intensive Care 2012; 2:6.  Back to cited text no. 13
    
14.1Badiee P, Alborzi A, Joukar M. Molecular assay to detect nosocomial fungal infections in intensive care units. Eur J Intern Med 2011; 22:611-615.  Back to cited text no. 14
    
15.1Aliyu SH, Enoch DA, Abubakar II, et al. Candidaemia in a large teaching hospital. Eur J Microb Infect Dis 2006; 23:745-750.  Back to cited text no. 15
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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