Risk factors associated with gut and nasopharyngeal colonization by common Gram-negative species and yeasts in neonatal intensive care units patients

https://doi.org/10.1016/j.earlhumdev.2011.02.007Get rights and content

Abstract

Aim

To characterize dynamics of mucosal colonization of neonates by common aerobic Gram negative species and Candida spp. and to identify independent perinatal, neonatal, and environmental factors influencing the colonization process.

Study design

The nasopharyngeal (n = 1145) and rectal (n = 1242) swabs were collected on admission and thereafter twice a week in neonates with risk factors of early onset sepsis (n = 276) admitted within the first 72 h of life. The association between colonization by different microbes and a total of 22 predefined risk factors was assessed using univariate and multiple logistic regression analyses.

Results

Throughout the study about half of the patients had rectal (55.8%) or nasopharyngeal colonization (42.8%) with common Gram-negative microorganisms. Colonization dynamics and risk factors were in general similar for a given bacterial species in both mucosal sites; nonfermentative microbes more often found in nasopharyngeal swabs and Enterobacteriaceae in rectal swabs. All organisms except Escherichia coli were influenced by the duration of intensive care unit stay but other risk factors were species specific, perhaps reflecting their mode of acquisition. While colonization by E. coli and Candida albicans was associated with perinatal factors like term birth, vaginal delivery, and breast milk feeding; colonization by Klebsiella pneumoniae, Enteribacter cloacae, Acinetobacter spp. and non-albicans Candida spp. were mostly determined by hospital environment (treatment unit and period, artificial interventions and their duration) and gestation age ≤ 28 weeks.

Conclusions

The knowledge of risk factor profiles may permit the development of strategies to prevent heavy colonization and subsequent invasive disease in high risk infants.

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.

Section snippets

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.

References (43)

  • J.A. Garcia-Rodriguez et al.

    Dynamics of nasopharyngeal colonization by potential respiratory pathogens

    J Antimicrob Chemother

    (Dec 2002)
  • M. Duman et al.

    Beta-lactam antibiotic resistance in aerobic commensal fecal flora of newborns

    Pediatr Int

    (2005 Jun)
  • C.J. Donskey

    The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens

    Clin Infect Dis

    (Jul 15 2004)
  • O.C. Thompson-Chagoyan et al.

    Colonization and impact of disease and other factors on intestinal microbiota

    Dig Dis Sci

    (Sep 2007)
  • S. Fanaro et al.

    Intestinal microflora in early infancy: composition and development

    Acta Paediatr Suppl

    (Sep 2003)
  • A. Smith et al.

    Concordance of gastrointestinal tract colonization and subsequent bloodstream infections with gram-negative bacilli in very low birth weight infants in the neonatal intensive care unit

    Pediatr Infect Dis J

    (Sep 2010)
  • Mshvildadze M., Neu J. The infant intestinal microbiome: friend or foe? Early Hum Dev. 2010 Jul;86 Suppl...
  • T. Tapiainen et al.

    Dynamics of gut colonization and source of intestinal flora in healthy newborn infants

    APMIS

    (Nov 2006)
  • I.H. Gewolb et al.

    Stool microflora in extremely low birthweight infants

    Arch Dis Child Fetal Neonatal Ed

    (May 1999)
  • J. Penders et al.

    Factors influencing the composition of the intestinal microbiota in early infancy

    Pediatrics

    (Aug 2006)
  • A. Pierro et al.

    Clinical impact of abnormal gut flora in infants receiving parenteral nutrition

    Ann Surg

    (Apr 1998)
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