Risk factors associated with gut and nasopharyngeal colonization by common Gram-negative species and yeasts in neonatal intensive care units patients
Introduction
Colonization of mucosal surfaces with Gram negative microorganisms starts right after birth. We and others have previously shown that by the end of first week of life 52–83% neonates in the neonatal intensive care units (NICU) are colonized with Gram negative microorganisms half of which are ampicillin-resistant (AR) [1], [2]. On one hand mucosal colonization by Gram negative microorganisms is a normal process but on the other hand it could also serve as a source for invasive infection [1], [2], [3], [4], [5], [6], [7]. Therefore a better understanding of the factors associated with the colonization process should contribute to improved infection control-strategies and eventually improve outcomes for critically ill neonates [7], [8].
Numerous studies have looked at factors associated with early mucosal colonization; various factors like maternal microbiota [9], [10], intrapartum use of antibiotics [6], premature rupture of membranes (PROM) [6], route of delivery [5], [6], [9], [10], [11], gestational age (GA) [5], [9], [10], [12], surrounding environment [9], [10], feeding habits [9], [10], [11], and antibiotic use [5], [9], [10], [11], [12] have been identified. However, most of the studies have either included only a limited number of infants [13], [14], have focused on gut colonization alone [6], [11], [13], [14], [15], included healthy infants [5], [9], [10], [16] or looked at only a few microbial species or risk factors at a time [8], [15], [16], [17], [18], [19], [20] or concentrated on Gram-negative organisms rather than individual species [11], despite that the majority of factors are highly interrelated. The number of studies in critically ill neonates admitted to NICU and looking at multiple factors and species simultaneously is very limited.
We aimed to characterize the dynamics of mucosal colonization by common aerobic Gram negative microorganisms and Candida spp. in neonates admitted to NICU and to identify independent perinatal, neonatal, and environmental factors influencing the colonization process.
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Study design and data collection
This analysis was incorporated into a prospective, cluster-randomized, two-center study comparing the efficacy and safety of penicillin G to ampicillin (both combined with gentamicin) in neonates at risk of early onset sepsis (EOS) admitted into two Estonian third level NICUs from August 2, 2006 until November 30, 2007. Both units admit mostly patients requiring invasive ventilatory support and have facilities for high frequency ventilation and neonatal surgery. Neonates were included in the
Patients and study samples
A total of 283 neonates were included into the parent study; colonization data were available for 276 (97.5%). The study population with half of the neonates with BW < 1500 g, half born via cesarean section, three quarters mechanically ventilated and/or with indwelling catheters, and a quarter with culture proven neonatal sepsis is characteristic for a third level NICU (Table 1).
A total of 1242 rectal and 1145 NP swabs with a per patients median of 3 (rectal and NP interquartile ranges [IQR] 2–6
Discussion
In this prospectively conducted study in NICU we show that factors involved in mucosal colonization are species specific likely reflecting the origin of the particular organism. While colonization by E. coli, C. albicans and to a lesser extent K. oxytoca is mostly of maternal origin being associated with early perinatal factors like PROM, vaginal delivery and/or breast milk feeding, colonization by K. pneumoniae, E. cloacae including AR strains and by non-fermentative organisms Acinetobacter spp
Conclusions
Risk factors influencing NP and rectal colonization including AR strains are similar and species-specific and are closely inter-related making extrapolations from one site to the other feasible. Colonization by E. coli, K. oxytoca and C. albicans is mainly influenced by maternal and early perinatal factors, while K. pneumonia, E. cloaceae and non-albicans Candida spp. are predominantly affected by the hospital environment and prematurity. The impact of antibacterial therapy on colonization with
Conflict of interest
Financial disclosure and conflict of interest: all authors have no conflict.
Acknowledgements
The study was supported by Estonian Science Foundation Grant No. 6984; Estonian Target Financing No. 2726 and ESPID Small Grant Award. The authors are grateful to the colleagues from both participating NICUs for their support and help in documenting all clinical decisions, to the head nurse Tiina Kilg and all nurses for their help in collecting samples.
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