Staphylococcus aureus is a major cause of infectious diseases ranging from soft-tissue infections to bacteraemia, which causes substantial morbidity or mortality in hospital settings and communities (1, 2). Methicillin-resistant S. aureus (MRSA) is usually considered a hospital pathogen, and its infection has traditionally been confined to individuals with health care–associated factors, including recent hospitalization, residence in long-term care units, indwelling catheters, or haemodialysis (3). In the past decades, the prevalence of infections caused by MRSA has increased among healthy people, particularly among children without established risk factors for MRSA acquisition (4), namely, community-associated MRSA (CA-MRSA).

In Taiwan, CA-MRSA infections have been increasingly reported in children since 2002, and the proportion of MRSA infections to the community-associated S. aureus infections in children without risk factors increased from 9.8% during 1997–2000 to 56% in 2004–2005 (5). Chen et al. (4) showed that MRSA has accounted for 50% of childhood community-associated S. aureus infections in Taiwan since 2005. In addition, the burden of S. aureus infection in infants is high. In the United States, hospitalized infants under 1 yr of age had the highest risk of Staphylococcus infection, highest annual incidence, and highest mortality among children under 17 yr of age (6). Although a high incidence of childhood CA-MRSA infection has occurred in the past decade, the cause of this increase is not well understood.

Colonization by S. aureus may play an important role in the development of Staphylococcus infection (7). Previous studies have shown that MRSA colonization poses a significantly greater risk to the development of subsequent infection than methicillin-sensitive S. aureus (MSSA) colonization (8). To understand the increasing rate of CA-MRSA infections in children, an investigation on the timing and source of MRSA acquisition in infants is required. Maternal MRSA carriage may also play a role in neonatal or infantile colonization (9); however, the phenotypic and molecular features of S. aureus and MRSA isolates between mothers and infants have rarely been assessed.

A birth cohort study was conducted, and infants were prospectively examined for colonized S. aureus at the planned time points. The dynamics of S. aureus carriage during early childhood, the possible factors involved in MRSA colonization, and the molecular relationships between maternal and childhood S. aureus carriage were investigated.

Our cohort showed that 10.2–48.7% and 6.6–30.5% of infants had S. aureus and MRSA carriage between and 2013–2019, respectively. The percentage was lower than that reported in other populations of Taiwanese children (S. aureus in 90%; MRSA in 40% of children aged <2 years) from 2005 to 2010 (14). The difference in the colonization rate may be attributed to the different study locations or periods. In the United States, a decline in the proportion of MRSA among S. aureus isolates (60.4% decrease) or a trend of MRSA infection (52% decrease) has been observed in the pediatric population since 2010 (17, 18).

Among the S. aureus carriage trends during the first five yr of life, the highest prevalence of S. aureus and MRSA carriage was observed at the age of one month, and the trend declined gradually in the first yr of life; however, the rising trend occurred between two and five yr of age. By contrast, an increasing trend of Streptococcus pneumoniae colonization was found during the first three yr of life in our previous report (19). This finding is consistent with those of other longitudinal studies conducted in Taiwan (20). The inverse relationship between S. aureus and S. pneumoniae might be explained by the pneumococcal inhibiting effect on S. aureus, which is mediated by the production of hydrogen peroxide by S. pneumoniae (21).

Results from our study showed that only 3.7% of infants had S. aureus colonization at delivery, and the colonization rate peaked (48.7%) in the first month of life. This finding supports our understanding that the fetus is sterile until shortly before birth and that the neonate becomes colonized with bacteria after birth (22). This suggests that infants acquire S. aureus mainly through horizontal transmission from surrounding carriers, possibly from family members. To clarify the association between maternal and infantile colonized isolates, the genetic relatedness of concurrent S. aureus and MRSA-colonized dyads was investigated. The results showed that 56.8% and 69.6% of concurrent S. aureus and MRSA-colonized dyads had identical genotypes, respectively. In the United States, Jimenez-Truque et al. (1) reported that 43% of S. aureus–colonized maternal–infant dyads had indistinguishable isolates, and Huang et al. (23) also found that half of the paired S. aureus isolates were genetically identical in their cohort. These results demonstrate the important role of maternal–infant horizontal transmission in Staphylococcus or MRSA carriage in early infancy.

Although the colonized infants might have acquired MRSA from their mothers via horizontal transmission, we cannot completely confirm this assumption if maternal colonization status before delivery is not analyzed. Thus, the association between the vaginal Staphylococcus colonization of mothers during pregnancy and nasopharyngeal carriage of infants after birth was investigated. One-fourth of infants (6/23 [26.1%]) born to mothers with vaginal S. aureus colonization had concurrent nasopharyngeal colonization. Although the number of maternal–infant pairs was small in our series, most of the concordant colonized isolates (5/6 [83.3%]) were genetically indistinguishable genotypes. This finding implies that vertical transmission may still occur in a minority of cases even though horizontal spread within family members (particularly from mother to infants) remains the primary method of MRSA acquisition in early infancy. Jimenez-Truque et al. (1) reported that infants born to mothers with S. aureus vaginal colonization were five times more likely to be nasally colonized within two h of birth. However, only 8.2% of pregnant women may be vaginally colonized with S. aureus according to the previous report (24). Therefore, the occurrence of vertical transmission is relatively uncommon and does not lead to a significant risk of S. aureus acquisition in early infancy.

Given the importance of maternal carriage on infantile S. aureus colonization, the clinical characteristics of infants and mothers according to maternal carrier status were compared. We analyzed demographic, environmental, and health-related factors being suggested to influence the infantile S. aureus carriage including gender, breastfeeding, number of family members, history of labor and environmental conditions (i.e., passive smoking or burning incense) (25). The result showed that infants born to smoking carrier mothers were found to be at risk of S. aureus colonization. This finding was consistent with those of previous studies which showed that passive smoking was associated with increased S. aureus colonization (26). The cause of passive smoke exposure associated with the carriage of pathogenic bacteria is not fully understood. One possible explanation is mucociliary transport alteration. Several studies have shown that cigarette smoke may reduce the ciliary beat of respiratory epithelial cells or impair respiratory epithelial ciliogenesis (27). Tobacco smoke may inhibit interleukin-8 and human β-defensin in sinonasal epithelial cell cultures derived from patients with chronic rhinosinusitis, thus suggesting that passive smoke may have a suppressive function on sinonasal innate immunity (28). Therefore, passive smoke exposure may compromise the antibacterial function of leukocytes and increase the risk of colonization by pathogenic S. aureus on respiratory epithelial cells. The influence of lighted incense on infantile S. aureus carriage was also investigated, but the result was not inconsistent with that of passive smoking. The cause of this inconsistency may be due to different toxicants present in incense and tobacco smoke resulting in differential cytotoxic or mutagenic effects on the bacterial community (29). Vallès et al. (30) found that the effect of burning incense exposure on microbiota composition may differ from those of tobacco exposure, and exposure to lighted incense was associated with depletion of the Firmicutes class Bacilli (e.g., Staphylococcus), which was compatible with our study result.

In our study, the most common clone accounting for 54.3% (25/46) of the MRSA isolates among infant–mother pairs were identified as ST 59/PVL-negative/SCCmec IV, namely, “Asian-Pacific” clone. A previous molecular epidemiology study of CA-MRSA in Taiwan revealed that two genotypes accounted for the majority of CA-MRSA strains, including the “Taiwan” clone (ST 59/PVL-positive/SCCmec V_T) and an “Asian-Pacific” clone (ST 59/PVL-negative/SCCmec IV) (31). The isolates of both pulsotypes belonging to the ST 59 lineage had a similar genetic background; however, the Asian-Pacific clone was more prevalent in colonizing healthy individuals than the Taiwan clone (29). Among the MRSA carrier surveillance studies in 2001–2002 and 2005–2006, 62–78.3% of colonized isolates belonged to the Asian-Pacific clone, and these findings were similar to our study results (32, 33).

This study has some limitations. First, this is an ongoing project, but the period of this study was limited to 2013–2019; therefore, some enrolled cases could not complete the entire 60-month study course. Second, the number of pregnant women with vaginal Staphylococcus colonization was relatively small; therefore, the role of vertical transmission in infantile MRSA carriage should be interpreted with caution in our series.

In conclusion, most concordant MRSA-colonizing isolates were of indistinguishable genotypes, thus suggesting that maternal–infant horizontal transmission may be the primary source for MRSA acquisition in early infancy. Cigarette smoke may contribute to increased susceptibility to Staphylococcus colonization, and the avoidance of passive smoking could be recommended as an important strategy for the prevention of S. aureus carriage in infants.

The data analyzed in this study is subject to the following licenses/restrictions: Participant privacy prevents public sharing of individual-level data. Requests to access these datasets should be directed to H-JS, adashih4016@gmail.com.

The studies involving human participants were reviewed and approved by the Institutional Review Board of Keelung Chang Gung Memorial Hospital, Taiwan. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.

M-HT designed the study, collected and analyzed the data, and drafted and revised the manuscript. C-YC, K-WS, S-LL, M-CH, T-CY, S-HL, K-WY, and L-CC collected the data and reviewed the manuscript. H-JS did the experiment and collected the data. M-HT and J-LH reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version.

This study was supported by grants from Keelung Chang Gung Memorial Hospital, Taiwan (CMRPG2E0125 and CMRPG2K0311).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.