Background
Healthcare-associated infections (HAI) are frequent complications occurring during hospitalization of neonates in intensive care units, resulting in increased morbidity and mortality, prolonged lengths of stay, and increased medical costs [
1,
2]. Low-birth weight and use of central venous catheterization and mechanical ventilation were identified as risk factors of HAIs in the neonatal intensive care unit (NICU) [
3‐
6]. Etiology of device-associated infections in NICUs shows that
Candida spp. are among the most frequent pathogens responsible for HAIs in NICUs, followed by gram positive or gram negative bacteria according to different clinical setting [
1‐
9]. Although
Candida albicans remains the most frequently isolated in many centers [
9,
10],
Candida parapsilosis has emerged as the most frequent non-albicans
Candida species and the predominant pathogen of invasive candidiasis in neonates [
8,
11‐
17]. In the tertiary care NICU of University Hospital in Naples, Italy,
C. parapsilosis was the most frequent pathogen responsible for device-associated bloodstream infections (BSI) during 2006–2010 [
6].
Aims of the present study were to: i) analyse phenotypic and genotypic features of C. parapsilosis clinical isolates from the NICU of University Hospital in Naples, Italy; ii) identify underlying clinical conditions associated with C. parapsilosis bloodstream infection in the NICU.
Discussion
C. parapsilosis is an increasing cause of healthcare-associated infections and in particular device-associated blood stream infections in the NICU [
6,
11‐
13,
31]. In the tertiary care level NICU of University Hospital in Naples, Italy,
C. parapsilosis was responsible for 50% and 35% of UC-associated and CVC-associated bloodstream infections during 2006–2010 [
6].
The data presented here demonstrate that a single clone of
C. parapsilosis was responsible for UC or CVC-associated bloodstream infections in 17 neonates from our NICU from April 2009 to April 2012.
C. parapsilosis strains assigned to
C. parapsilosis group I and showing identical PCR fingerprinting profiles were isolated from blood cultures of all 17 neonates and pharynx swab of 1 neonate, while
C. parapsilosis environmental isolate showed different PCR fingerprinting profiles. A previous study showed that that the increase of
C. parapsilosis bloodstream infections in a NICU in Helsinki, Finland was caused by the spread of a single clone with identical DNA fingerprinting profile [
14]. In accordance with previous findings [
13,
14], the majority (15 out of 17)
C. parapsilosis isolates were susceptible to echinocandins, azoles, 5-fluorocytosine and amphotericin B, but 2 were resistant to fluconazole and one resistant to fluconazole and intermediate resistant to itraconazole. The occurrence of resistance to fluconazole in
C. parapsilosis isolates from 2 out of 14 neonates ≤1500 g BW under fluconazole prophylaxis is in agreement with previous study showing that fluconazole prophylaxis increase the incidence of invasive infections involving fluconazole-resistant
C. parapsilosis [
31].
Molecular typing data presented herein exclude the environment as the source or reservoir of C. parapsilosis in the ward. Also, the absence of isolation of C. parapsilosis from the pharynx or rectal swabs in 16 neonates with C. parapsilosis bloodstream infection and the concomitant isolation of C. parapsilosis from pharynx swab and emocolture in only 1 neonate suggest that mucosal colonization by C. parapsilosis does not precede invasive infection as observed for C. albicans bloodstream infection. Although our data did not identify the route of transmission of C. parapsilosis among neonates in the NICU, the assignment of all C. parapsilosis clinical isolates to a single epidemic genotype suggests that infected neonates were the reservoir and source of C. parapsilosis epidemic in the NICU.
Several studies analyzed risk factors for neonatal candidiasis without distinguishing among isolated
Candida species [
7‐
11], while few studies analyzed risk factors for invasive
C. parapsilosis infections in neonates by univariate analysis [
13‐
15] or multivariate analysis [
15‐
17]. Neonatal risk factors for invasive
C. parapsilosis infections were birth weight <1500 g, prematurity, prior colonization, parenteral nutrition, intravascular catheters and use of antibiotics, steroids and H2 blockers (13–15). Similarly, we found that birth weight, gestational age, time to exposure to UC, CVC, and AV were risk factors for
C. parapsilosis infection in neonates in the NICU at univariate analysis. In a case-control population-based study on 78 episodes of
C. parapsilosis fungemia compared with 175
C. albicans controls, neonate patients, transplant patients, and patients who received antifungal therapy or parenteral nutrition were significantly associated with
C. parapsilosis bloodstream infection on multivariate analysis [
15]. When non-
albicans Candida species bloodstream infections including those caused by
C. parapsilosis were compared with
C. albicans bloodstream infections, multivariate logistic regression analysis identified neonatal age, fluconazole exposure and having received an hematological transplant as factors associated with a risk of candidemia caused by non-
albicans Candida species [
16]. Risk factors analysis of nosocomial candidemia in an adult intensive care unit (ICU) and a NICU in Brazil identified sex and parenteral nutrition as independent risk factors of
C. parapsilosis bloodstream infections, which were more frequent in NICU than in adult ICU [
17]. In agreement with these findings, we identified low birth weight and gestational age (explaining more than 55.0% of the variance) as risk factors for
C. parapsilosis bloodstream infection in neonates in the NICU. Moreover, we demonstrated that time to exposure to invasive devices (explaining ca 34.0% of the variance), with predominance of assisted ventilation, is independent risk for
C. parapsilosis bloodstream infection in neonates in the NICU at multivariate analysis. Based on our data, we speculate that prematurity and extremely low birth weight (<1000 g) and any manoeuvre associated with AV usage may have been involved in the transmission between patients and acquisition of
C. parapsilosis infections in our NICU.
We recognize that our study has limitations that affect the generalization of our results. The first limitation relies on the retrospective nature of the study, which did not allow to evaluate the efficacy of specific infection prevention measures against C. parapsilosis bloodstream infection in the NICU. For example, the appropriateness of antifungal prophylaxis was not assessed by our study despite the isolation of two C. parapsilosis isolates resistant to fluconazole. Additional limitation of the study was the lack of analysis of inborn and outborn status, mortality, total parenteral nutrition, probiotics administration, days and type of antenatal and postnatal antibiotic use and other concomitant drugs therapeutic variables of neonates included in the study. Future studies will be necessary to investigate the above issues.
Acknowledgements
The authors thank the staff in the NICU for their help and interest in the study. RZ thanks Valeria Crivaro for critical reading of the manuscript.