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Otsuka, Taketo MD, PhDon behalf of the SADO-study Working group

The Pediatric Infectious Disease Journal: February 2014 - Volume 33 - Issue 2 - p 228–229
doi: 10.1097/INF.0000000000000107
Letters to the Editor

Supplemental Digital Content is available in the text.

Department of Pediatrics, Sado General Hospital, Chigusa, Sado, Niigata, Japan

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

The author has no funding or conflicts of interest to disclose.

We thank Drs. Gounder and Hennessy for their insightful comments and the opportunity to clarify a number of points from our work. Drs. Gounder and Hennessy question the relationship we described between antimicrobial usage and increased colonization1 because we did not consider confounding factors including the child’s age and receipt of the 7-valent pneumococcal conjugate vaccine.2 In response, we show data by age and 7-valent pneumococcal conjugate vaccine (see Table, Supplemental Digital Content 1, The overall colonization rates in subjects with antimicrobial prescription are higher than those without antimicrobial prescription at all ages except 36 months, at which point attending daycare center is likely the largest determinant for colonization. Furthermore, we found that 7-valent pneumococcal conjugate vaccine did not impact colonization rates in our study, which is likely related to its low rates of use.

Drs. Gounder and Hennessy also point out that, in our multivariable analysis, we did not find an association between colonization and the number of antimicrobial prescriptions that children received (Table 2 of our original article).1 However, in this analysis, we did not consider the period from antimicrobial prescription to sampling day as noted in our article.1 For example, in this analysis, Subject A who had bacterial colonization only once at 36 months of age and took antimicrobials only once at 1 month of age and Subject B who had bacterial colonization only once at 4 months of age and took antimicrobials only once at 36 months of age would be considered at the same risk. Therefore, the analyses presented in Table, Supplemental Digital Content 7,, in our original article1 and in the Table accompanying this response are more appropriate to discern the relationship between antimicrobial use and colonization, indicating that our original conclusions are correct.

Drs. Gounder and Hennessy have also expressed concern about our findings that antimicrobial use does not increase resistance rates. In fact, when they recalculate the risk using the total number of children exposed to antimicrobials instead of the total number of children with bacterial carriage as a denominator, antimicrobial use appears to be associated with increased colonization with resistant bacteria. The method would be appropriate if the overall rate of colonization was the same between the 2 groups with and without antimicrobial usage. However, because the overall rates of colonization are significantly different, the use of the number of children with bacterial carriage as a denominator is more appropriate. Furthermore, their assertion that “antimicrobials reduce overall colonization by eradicating susceptible bacteria” is not supported by our data, as 28% (96/342) of children who had received antimicrobials were colonized by susceptible bacteria compared with 18% (239/1312) of children who did not receive antimicrobials. Therefore, our results indicate that recent exposure to antimicrobials is significantly associated with increased risk of colonization, but not with resistance rates.

It is generally accepted that recent exposure to antimicrobials is one of the independent determinants for nasopharyngeal colonization.3,4 We do agree with Drs. Gounder and Hennessy that recent exposure to antimicrobials does increase the absolute number of resistant isolates. Therefore, introduction of appropriate usage of antimicrobials in areas of overuse could contribute to lower colonization of Streptococcus pneumoniae/Haemophilus influenzae, resulting in a decrease in the absolute number of resistant isolates.

Taketo Otsuka, MD, PhD

on behalf of the SADO-study

Working group

Department of Pediatrics

Sado General Hospital

Chigusa, Sado

Niigata, Japan

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1. Otsuka T, Chang B, Shirai T, et al.SADO-study Working Group. Individual risk factors associated with nasopharyngeal colonization with Streptococcus pneumoniae and Haemophilus influenzae: a Japanese birth cohort study. Pediatr Infect Dis J. 2013;32:709–714
2. Ghaffar F, Friedland IR, McCracken GH Jr. Dynamics of nasopharyngeal colonization by Streptococcus pneumoniae. Pediatr Infect Dis J. 1999;18:638–646
3. Bogaert D, De Groot R, Hermans PW. Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis. 2004;4:144–154
4. van der Poll T, Opal SM. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet. 2009;374:1543–1556
© 2014 by Lippincott Williams & Wilkins, Inc.