Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low birth weight (<1000-g) infants. We quantified risk factors that predict infection in premature infants at high risk and compared clinical judgment with a prediction model of invasive candidiasis.
The study involved a prospective observational cohort of infants ≤1000 g birth weight at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures were obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: (1) potentially modifiable risk factors; and (2) a clinical model at time of blood culture to predict candidiasis.
Invasive candidiasis occurred in 137 of 1515 (9.0%) infants and was documented by positive culture from ≥1 of these sources: blood (n = 96); cerebrospinal fluid (n = 9); urine obtained by catheterization (n = 52); or other sterile body fluid (n = 10). Mortality rate was not different for infants who had positive blood culture compared with those with isolated positive urine culture. Incidence of candida varied from 2% to 28% at the 13 centers that enrolled ≥50 infants. Potentially modifiable risk factors included central catheter, broad-spectrum antibiotics (eg, third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model had an area under the receiver operating characteristic curve of 0.79 and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis.
Previous antibiotics, presence of a central catheter or endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment.
Dear Editor, We read with great interest the recent article by Benjamin et al (1), in which the authors tried to indentify risk factors for invasive candidiasis in ELBW infants to better develop future prevention initiatives and to test prediction models. They concluded that clinical prediction model, including some clinical properties in addition to lowest glucose in preceding 24 hours in increments of 50 mg/dl and platelet count in increments of 50000, was superior to clinical judgment. This study seems to have assessed the association of known risk factors for invasive candidiasis rather than laboratory tests as a predictive method because it included only glucose and thrombocyte levels. On the other hand, only two among 19 centers had a policy of antifungal prophylaxis in this trial, and incidence of candida showed high variation (2% to 28%) between the centers. Being largest referral Level III NICU with approximately 5000 newborn admissions per year we had to deal with Candida infection with high incidence in the past and this led us to develop some strategies for early prediction and prevention of the infection (2-4). First, we examined the predictive value of the combined evaluation of the CRP and IL-6 responses for differentiating fungal and bacterial aetiologies in patients with neonatal sepsis (NS). In this study, based on their blood culture results the neonates were divided into two groups: group of fungal sepsis (FS) and group of bacterial sepsis (BS). Significant differences were observed in the CRP (FS vs. BS: 28.10 +/- 11.03 vs. 11.39 +/- 2.94 mg/L, p=0.026) and IL-6 (FS vs. BS: 38.60 +/- 24.24 vs. 392.82 +/- 102.46 ng/L, p=0.000) levels between groups, and we defined that the combined evaluation of the CRP and IL-6 responses could predict the fungal infection (3). Secondly, we conducted the first prospective, randomised placebo-controlled trial of nystatin (1 ml suspension, 100 000 U/ml, every 8 h) compared with fluconazole (3 mg/kg, every third day) for the prevention of fungal infection in VLBW neonates. 278 infants (fluconazole group, n=93; nystatin group, n=94; control group, n=91) weighing <1500 g at birth were enrolled in this trial. Fungal colonisation occurred in 11.7% of the nystatin group and 10.8% of the fluconazole group, as compared with 42.9% of the control group. The incidence of invasive fungal infection was 4.3% in the nystatin group and 3.2% in the fluconazole group, as compared with 16.5% in the control group (4). Experience gained from these trials led us to apply nystatin prophylaxis in addition to combined evaluation of the CRP and IL-6 responses for differentiating fungal infection, and we suggest that these strategies reduce the incidence of fungal infection successfully.
References
1.Benjamin DK Jr, Stoll BJ, Gantz MG, Walsh MC, Sánchez PJ, Das A, Shankaran S, Higgins RD, Auten KJ, Miller NA, Walsh TJ, Laptook AR, Carlo WA, Kennedy KA, Finer NN, Duara S, Schibler K, Chapman RL, Van Meurs KP, Frantz ID 3rd, Phelps DL, Poindexter BB, Bell EF, O'Shea TM, Watterberg KL, Goldberg RN; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal candidiasis: epidemiology, risk factors, and clinical judgment. Pediatrics. 2010;126(4):e865-73.
2.Aydemir C, Erdeve O, Oguz SS, Altug N, Dilmen U. Successful treatment of Candida albicans endocarditis vegetations with recombinant tissue plasminogen activator in an extremely low birth weight preterm infant. Mycoses. doi:10.1111/j.1439-0507.2010.01893.x
3.Oguz SS, Sipahi E, Dilmen U. C-reactive protein and interleukin-6 responses for differentiating fungal and bacterial aetiology in late-onset neonatal sepsis. Mycoses. doi:10.1111/j.1439-0507.2009.01802.x
4.Aydemir C, Oguz SS, Dizdar EA, Akar M, Sarikabadayi YU, Saygan S, Erdeve O, Dilmen U. Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants. Arch Dis Child Fetal Neonatal Ed. doi:10.1136/adc.2009.178996
Conflict of Interest:
None declared