Candida parapsilosis is a significant neonatal pathogen: a systematic review and meta-analysis

Abstract

Background: Candida is the third most common cause of late-onset neonatal sepsis in infants born at <1500 g. Candida parapsilosis infections are increasingly reported in preterm neonates in association with indwelling catheters.

Methods: We systematically reviewed neonatal literature and synthesized data pertaining to percentage of C. parapsilosis infections and mortality by meta-analyses. We also reviewed risk factors, virulence determinants, antimicrobial susceptibility patterns and outlined clinical management strategies.

Results: C. parapsilosis infections comprised 33.47% (95% confidence interval [CI]: 30.02, 37.31) of all neonatal Candida infections. C. parapsilosis rates were similar in studies performed before the year 2000, 33.53% (95% CI: 30.06, 37.40) (28 studies), to those after 2000, 27.00% (95% CI: 8.25, 88.37) (8 studies). The mortality due to neonatal C. parapsilosis infections was 10.02% (95% CI: 7.66, 13.12). Geographical variations in C. parapsilosis infections included a low incidence in Europe and higher incidence in North America and Australia. Biofilm formation was a significant virulence determinant and predominant risk factors for C. parapsilosis infections were prematurity, prior colonization and catheterization. Amphotericin B remains the antifungal drug of choice and combination therapy with caspofungin or other echinocandins may be considered in resistant cases.

Conclusion: C. parapsilosis is a significant neonatal pathogen, comprises a third of all Candida infections and is associated with 10% mortality. Availability of tools for genetic manipulation of this organism will identify virulence determinants and organism characteristics that may explain predilection for preterm neonates. Strategies to prevent horizontal transmission in the neonatal unit are paramount in decreasing infection rates.

Fig. 1. Forest plot depicting percentage of C. parapsilosis infections

Red squares and black horizontal lines through the squares represent proportion with 95% confidence intervals. First subgroup labeled 1.1.1 represents studies that were predominantly performed before the year 2000 and the second subgroup labeled 1.1.2 represents studies performed after the year 2000. Abbreviations: CP – Candida parapsilosis, SE- standard error, IV- inverse variance, Random-Random effects model for meta-analyses, CI- confidence intervals.

Fig. 2. Forest plot of percentage of C. parapsilosis infections by geographical regions

Red squares and black horizontal lines through the squares represent proportion with 95% confidence intervals. Studies were sub grouped into 5 different regions; North America (12 studies), South America (2 studies), Europe (12 studies), Asia (7 studies) and Australia (2 studies). Abbreviations: CP – Candida parapsilosis, SE- standard error, IV- inverse variance, Random-Random effects model for meta-analyses, CI- confidence intervals.

Fig. 3. Mortality of C. parapsilosis infections

Red squares and black horizontal lines through the squares represent proportion with 95% confidence intervals. The combined mortality of neonatal C. parapsilosis infection was 10.02 [95% CI 7.66, 13.12]. Abbreviations: CP – Candida parapsilosis, SE- standard error, IV- inverse variance, Random- Random effects model for meta-analyses, CI- confidence intervals.

Fig. 4. Electron microscopy of in vivo biofilms

Biofilm formation on central venous catheters inserted into rats and inoculated with C. parapsilosis (wild type strain CLIB214) and a bcr1 deletion (CDb71) strain. The catheters were removed after 24 hrs and visualized using scanning electron microscopy at two different magnifications. The wild type strain formed a thick biofilm, whereas the bcr1 deletion strain displayed impaired biofilm formation, indicating the essential role of the transcription factor BCR1 in biofilm formation. [Reproduced with permission from Ding C, Vidanes GM, Maguire SL, Guida A, Synnott JM, Andes DR and Geraldine Butler. Conserved and divergent roles of Bcr1 and CFEM proteins in Candida parapsilosis and Candida albicans. PLoS One. 2011;6(12):e28151].