In this study, we found a strong association between CoNS infections and lower gestational age and lower birth weight. This finding is consistent with previous studies.2,5
Preterm, low-birth-weight infants are more likely to require prolonged use of central catheters, prolonged use of parenteral nutrition, and mechanical ventilation—all risk factors for CoNS infection. We found that episodes of CoNS infection increased in the second postnatal week, and we found no difference in mortality between infants with definite, probable, or possible CoNS infection. Most surprisingly, we found lower mortality in infants diagnosed with CoNS compared to infants with negative cultures.
Consistent with our hypothesis, infants with the lowest gestational ages and birth weights had the highest incidence of CoNS infection. Interestingly, we observed a slightly higher incidence in CoNS infections in term infants (37–42 weeks’ gestation) compared to infants born near-term (34–36 weeks’ gestation). Most of the observed increase was due to the presence of possible CoNS infection. It is believed that this observation may be attributable to the underlying reason for the infant’s admission to the NICU. Infants in the NICU at 34 weeks’ gestational age are there primarily for feeding and growth, but, beyond this gestational age, the more likely it is that the infant has a serious underlying issue (e.g., a congenital anomaly, respiratory difficulties) that may increase his/her susceptibility to CoNS infection.
In our study, the highest incidence of CoNS infection was observed between postnatal day 7 and 14. This observation is consistent with findings from prior research4
and with the status of CoNS as one of the primary pathogens isolated in late-onset sepsis.1,2, 13
CoNS infection has been equated to a disease of medical advancement.14
The emergence of CoNS as a nosocomial infection has coincided with the use of life-extending measures such as intravascular catheters and mechanical ventilators, devices through which CoNS gains access to normally sterile body fluids.15
In our study, the vast majority of CoNS infections were isolated bloodstream infections, and only a small fraction of definite or probable CoNS infections were attributed to urine or CSF culture. One explanation for this observation is that diagnosis of CoNS infection was made primarily through blood cultures with lumbar punctures, and urine cultures are not always performed in infants with suspected infection in the NICU. 16
It is possible that we have underestimated the true incidence of urinary tract infections, as not all infants had urine obtained.
The similarity in mortality between infants with definite, probable, or possible CoNS sepsis in our study may be attributed to the low virulence of CoNS. Specifically, CoNS may be virulent enough to lead to increased morbidity,2, 4–9
but the organism is not sufficiently virulent to cause mortality unless the bacteremia (organism burden) is prolonged. Previous studies have documented an association between persistent recovery of pathogens from normally sterile body sites and adverse outcomes including death.17–19
Prolonged infections have been attributed to inappropriate antibiotic therapy or the delay in removal of contaminated in-dwelling catheters.20
Although the mortality attributed to CoNS infection compared to more virulent organisms historically has been significantly lower,1,2,21, 22
we observed a higher mortality for infants with persistently positive culture (>14 days); this is consistent with previous studies. Mortality is similar between CoNS and non-CoNS pathogens (e.g., Staphylococcus aureus, Escherichia coli, Pseudomonas s
spp. Enterobacter cloacae
) for prolonged infections.18
The finding that infants with CoNS infection had lower mortality than infants with negative cultures may be attributable to an overestimation of the number of CoNS infections in this cohort of infants. Although we used published criteria to define CoNS infection, we may have overestimated the incidence of CoNS infection, particularly in the probable and possible categories, as many neonatologists only obtain a single blood culture.23
Additionally, the small amount of blood (often <1 mL) obtained from infants for culture increases the risk for false-negative blood culture results for other infections.24
Missing true infections associated with increased mortality (Gram-negative rods and Candida
) may also account for the finding of increased mortality in infants with negative cultures compared to those with CoNS infection.
Although several researchers have proposed algorithms for distinguishing between true CoNS infections and contaminants,11, 25–28
no gold standard exists. Because presenting signs are usually nonspecific, definitive diagnosis of CoNS infection in infants is difficult.29
Further complicating the diagnosis is the fact that CoNS are a component of normal skin flora and thus can potentially contaminate blood cultures drawn peripherally or through venous catheters.30
The inability to distinguish between infection and contamination can lead to more laboratory tests, longer hospital stays, and unnecessary antibiotic exposures.26, 31
As proposed by Zaidi et al., a possible solution would be to obtain two peripheral blood cultures at the time of every sepsis evaluation.11
A strength of this study was the large sample size and diversity of NICUs included. We had access to contemporary culture data from blood, urine, and CSF, allowing us to evaluate the contributions of these cultures to the diagnosis of CoNS infection. This study was limited by precise documentation of the timing and dosage of antimicrobial therapy. We also lacked information about clinical signs of infection in the infant and the presence and removal of central venous catheters. Collection of urine via bag method may have also increased the risk of contamination relative to samples collected by in-and-out catheterization or suprapubic tap. We made no attempt to relate CSF cultures to CSF parameters (glucose, protein, white blood cell count) or urinalysis results and acknowledge that some positive cultures may have represented skin contamination. Finally, we lacked information on site-specific practices on skin disinfection (i.e., alcohol, chlorhexidine).
In summary, we found that CoNS infection was strongly related to lower gestational age and birth weight. We found no difference in mortality between infants diagnosed with definite, probable, and possible CoNS infection. We also found lower mortality in infants with clinical sepsis and CoNS positive cultures compared to infants with clinical sepsis and negative cultures. Future studies focusing on the differences in morbidities between infants with definite, probable, or possible CoNS infection are needed to further explore the long-term effect of CoNS infection in infants in the NICU.