Relationship Between Maternal and Neonatal Staphylococcus aureus Colonization

Relationship Between Maternal and Neonatal Staphylococcus aureus Colonization

WHAT’S KNOWN ON THIS SUBJECT: Staphylococcus aureus is a leading cause of infections in infants. Staphylococcal colonization is a known risk factor for infection, but whether maternal colonization plays a role in subsequent colonization in the infant is unclear.

WHAT THIS STUDY ADDS: This prospective study found that infants born to women colonized with S aureus either during their third trimester of pregnancy or at the time of delivery are more likely to harbor S aureus than are those born to noncolonized women.

abstract OBJECTIVE: The study aimed to assess whether maternal colonization with Staphylococcus aureus during pregnancy or at delivery was associated with infant staphylococcal colonization.

METHODS: For this prospective cohort study, women were enrolled at 34 to 37 weeks of gestation between 2007 and 2009. Nasal and vaginal swabs for culture were obtained at enrollment; nasal swabs were obtained from women and their infants at delivery and 2- and 4-month postbirth visits. Logistic regression was used to determine whether maternal colonization affected infant colonization.

RESULTS: Overall, 476 and 471 mother-infant dyads had complete data for analysis at enrollment and delivery, respectively. Maternal methicillin-resistant S aureus (MRSA) colonization occurred in 10% to 17% of mothers, with the highest prevalence at enrollment. Infant MRSA colonization peaked at 2 months of age, with 20.9% of infants colonized. Maternal staphylococcal colonization at enrollment increased the odds of infant staphylococcal colonization at birth (odds ratio; 95% confidence interval: 4.8; 2.4–9.5), hospital discharge (2.6; 1.3–5.0), at 2 months of life (2.7; 1.6–4.3), and at 4 months of life (2.0; 1.1–3.5). Similar results were observed for maternal staphylococcal colonization at delivery. Fifty maternal-infant dyads had concurrent MRSA colonization: 76% shared isolates of the same pulsed-field type, and 30% shared USA300 isolates. Only 2 infants developed staphylococcal disease.

CONCLUSIONS: S aureus colonization (including MRSA) was extremely common in this cohort of maternal-infant pairs. Infants born to mothers with staphylococcal colonization were more likely to be colonized, and early postnatal acquisition appeared to be the primary mechanism. Pediatrics 2012;129:e1252–e1259

AUTHORS: Natalia Jimenez-Truque, MQC, MSCI,a Sara Tedeschi, MD,b Elizabeth J. Saye, BS,a Brian D. McKenna, BS,a Weston Langdon, BS,a Jesse P. Wright, BS,a Andrew Alsentzer, BS,a Sandra Arnold, MD, MS,c Benjamin R. Saville, PhD,d Wenli Wang, MS,d Isaac Thomsen, MD,a and C. Buddy Creech, MD, MPHa

aDivision of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee; bDepartment of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; cDivision of Infectious Diseases, University of Tennessee Health Science Center, Memphis, Tennessee; and dDepartment of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee

KEY WORDS Staphylococcus aureus, child, colonization, epidemiology, pregnancy

ABBREVIATIONS CA-MRSA—community-associated methicillin-resistant Staphylo- coccus aureus GBS—group B Streptococcus GEE—generalized estimating equation MRSA—methicillin-resistant Staphylococcus aureus MSSA—methicillin-susceptible Staphylococcus aureus PCR—polymerase chain reaction PVL—Panton-Valentine leukocidin SSTIs—skin and soft-tissue infections VUMC—Vanderbilt University Medical Center

All authors have contributed appropriately to meet the criteria to warrant authorship.

www.pediatrics.org/cgi/doi/10.1542/peds.2011-2308

doi:10.1542/peds.2011-2308

Accepted for publication Dec 15, 2011

Address correspondence to Natalia Jimenez-Truque, MQC, MSCI, Epidemiology Graduate Student, Pediatric Infectious Diseases, Vanderbilt University Medical Center, 1161 21st Ave South, D-7215 MCN, Nashville, TN 37232. E-mail: natalia.jimenez@vanderbilt.edu

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: This work was supported by the Fogarty International Center at the National Institutes of Health (grant 1 R25 TW007697), the 2007 IDSA/SHEA Young Investigator Award in MRSA Research (Dr Creech), the Monroe Carell, Jr. Children’s Hospital Fund, and the National Center for Research Resources at the National Institutes of Health (grant 1 UL1 RR024975). Funded by the National Institutes of Health (NIH).

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Methicillin-resistant Staphylococcus au- reus (MRSA) causes ∼100 000 inva- sive infections and ∼20 000 deaths per year in the United States; of these, ∼1000 infections and ∼100 deaths oc- cur in children,1 year of age.1 Further, MRSA causes between 59% and 72% of all skin and soft-tissue infections (SSTIs),2,3 and up to 95% of all SSTIs in children are caused by community- associated MRSA (CA-MRSA).4 MRSA now affects previously healthy individ- uals without known risk factors,5,6 and CA-MRSA has become the most frequent clone of S aureus in many communities, causing disease in neonatal intensive care units (NICUs)7,8 and even among healthy full-term babies.9,10

Approximately one-third of the gen- eral population carries S aureus in their nares,11 and staphylococcal col- onization is a known risk factor for subsequent infection.11 Previous data suggest that the frequency of MRSA colonization ranges from 1% to 4% in infants and mothers,7–9,12–16 though some areas of the US experience higher rates of colonization.17–19 While known risk factors for infant S aureus colonization include breastfeeding, number of household members,20,21

low birth weight, early gestational age at birth, indwelling catheters, and du- ration of antibiotic or ventilator days,7

it is not clear whether maternal nasal and anogenital colonization plays a role in infant colonization. Colonized moth- ers can transmit MRSA to their infants,10,12,13 but it remains unclear whether there is real potential for sig- nificant vertical maternal-infant trans- mission of MRSA.

Our objective was to determine the clinical and molecular epidemiology of staphylococcal colonization in mothers and their infants from the third tri- mester of pregnancy to 4 months after birth. By obtaining nasal swabs at each time point, we estimated the frequency of staphylococcal colonization and

analyzed the molecular characteristics of these isolates. We also sought to examine whethermaternal MRSA nasal and/or vaginal colonization is associ- ated with subsequent colonization or infection in the infant.

METHODS

Study Population

We conducted a prospective study of MRSA colonization in a cohort of maternal-infant pairs between June 2007andMarch2009.We invitedwomen who were in their third trimester of pregnancy (34–36 weeks of gestation) and cared for at the Obstetrics Clinic of Vanderbilt University Medical Center (VUMC) in Nashville, Tennessee, or the UT Medical Group Obstetrics Clinic at the University of Tennessee Health Science Center in Memphis, Tennessee, to participate. Women had to be .18 years of age, willing to comply with study-related procedures (including na- sal swabs, enrollment of her child when born, andwillingness to attend follow-up visits), and capable of providing written informed consent. The local institutional review boards of VUMC and University of Tennessee Health Science Center ap- proved the study.

Study Procedures

An in-person interview questionnaire was administered to determine risk factors for staphylococcal exposure/ carriage, and a moistened nasal swab was collected from the mother at the time of enrollment and on the day of delivery. Additionally, the group B Streptococcus (GBS) culture collected from the mother during her routine prenatal care was sampled to detect S aureus.

After the infant was born, the nursing staff of the newborn nursery or NICU alerted study personnelwithin 2 hours of delivery. Cultures of nares and umbilicus were obtained with a moistened cotton

swab before triple dyewas applied to the umbilicus. For newborns, cultures were repeated immediately before discharge.

After discharge, infants and mothers enrolled at VUMC were asked to return to the Pediatric Clinical Research Cen- ter fornasal swabculturesamples tobe taken at 2 and 4 months of age, while samples from Memphis were collected only if participants voluntarily returned. Questionnaires were administered at each visit to assess risk factors for staphylococcal exposure and carriage, history of maternal/infant staphylococ- cal infection, history of hospitalization or other medical illnesses/procedures, and antibiotic use. Medical charts were reviewed for clinically relevant illnesses consistent with staphylococcal infec- tions.Motherswere instructed to alert study personnel if their infants devel- opedSSTIs or if they or their infantswere hospitalized for any reason. This allowed for additional cultures to be obtained, where appropriate.

Cultures and Molecular Laboratory Testing

All samples collected in this study were processedatVUMC.Nasal andumbilical swabs were placed in tryptic soy broth with 6.5% NaCl and incubated for 24 hours at 37°C as an enrichment step. Vaginal swabs were first processed at the VUMC Microbiology Laboratory and inoculated into Lim Broth (Becton, Dickinson, and Co, Franklin Lakes, NJ) for the detection of GBS. After broth enrichment of all samples, a 10-mL in- oculum was plated onto mannitol salt agar plates with and without 4 mg/mL oxacillin and incubated for 48 hours at 37°C. If yellow growth was observed, colonies were plated onto tryptic soy agar with 5% sheep blood and incu- bated for 24 hours at 37°C. Latex ag- glutination testing was performed for the detection of clumping factor (Staphaurex; Remel, Lenexa, KS), and the presence of the nuc gene (specific

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to S aureus) was confirmed by poly- merase chain reaction (PCR). Isolates confirmed to be MRSA by PCR detection of the mecA gene were further char- acterized by SCCmec typing, by using the multiplex strategy of Oliveira and de Lencastre.22 Nontypeable isolates by the multiplex strategy underwent ccr and mec class typing as previously described.23 Detection of the Panton- Valentine leukocidin (PVL) gene locus was performed, as described else- where.24 Genotyping of MRSA isolates was performed by repetitive element sequence–based PCR.25 Isolates with .95% similarity were defined as in- distinguishable.

Statistical Methods

Wilcoxon rank sum tests and Pearson x2 tests were used to compare patient characteristics between the 2 study centers and between those with and without infant colonization at birth. Correlations between patient charac- teristics were assessed by using Spearman’s correlation coefficient, and pairs of variables with a high correla- tion were noted before proceeding to modeling. Logistic regression models with generalized estimating equations (GEEs) were used to model child colo- nization as a function of maternal colo- nization at birth or enrollment and time since birth (birth, discharge, 2 months, 4 months), adjusting for the following potential confounders: number of pre- vious births, gestational age at enroll- ment, mode of delivery, race, and admission to the NICU. The model also included an interaction term between maternal colonization at birth or en- rollment and time. Due to potential col- linearity, separate logistic regression models were fitted with either maternal colonization at birth or maternal colo- nization at enrollment as predictors. A sensitivity analysis was conducted in which both GEE models were fitted by using data from patients enrolled at VUMC alone.