To the Editor: Xu and colleagues (1) examined the nasopharyngeal bacterial colonization rates in children with acute otitis media (AOM) and in healthy children. They found that Haemophilus influenzae colonization was competitively associated with Streptococcus pneumoniae and Morexella catarrhalis colonization in children with AOM but was not associated with S. pneumoniae and M. catarrhalis colonization in healthy children. We have a serious concern regarding their analysis.

The authors calculated odds ratios (ORs) by considering a bacterial colonization as an outcome variable and another bacterial colonization as an exposure variable. They considered an OR >1 as the presence of synergistic associations between bacteria (i.e., co-colonization is more likely to occur than it would by chance) and OR <1 as the presence of competitive associations (i.e., co-colonization is less likely to occur than it would by chance). This inference may be justified in a population-based cross-sectional study. If 2 bacterial colonizations occur independently in a stationary population, the prevalence of co-colonization will be the product (multiplication) of each prevalence, and the OR between 2 bacterial colonizations in the population (OR_pop) will be 1 (Technical Appendix).

However, the authors enrolled their case-patients according to clinical signs (i.e., AOM or healthy). Let us assume that case-patients are enrolled from a population of children during a time period of t. Let r_c be the risk for enrollment (that is, of developing the disease) among colonized children and r_n be the risk for enrollment among noncolonized children. The OR among the enrolled case-patients (OR_case-patient) becomes r_n/r_c, which is the reciprocal of the risk ratio (RR) of developing the disease (RR = r_c/r_n) (online Technical Appendix). Usually, RR is >1 for diseased children and <1 for healthy children. Therefore, even in this independent colonization scenario, OR_case-patient becomes <1 (“pseudo-competitive associations”) in diseased children, and OR_case-patient becomes >1 (“pseudo-synergistic associations”) in healthy children. This is probably what the authors have observed in the study.

We cannot infer an association of multiple bacterial colonizations in a population despite an observed association in the diseased (or healthy) children, and this association is widely misunderstood (2–4). The authors’ discussion regarding a potential emergence of H. influenzae, associated with AOM, after the introduction of pneumococcal conjugate vaccine is thus unjustifiable.

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