Antibiotic-Resistant Streptococcus pneumoniae in the Heptavalent Pneumococcal Conjugate Vaccine Era: Predictors of Carriage in a Multicommunity Sample

Abstract

Objective. Despite immunization with heptavalent pneumococcal conjugate vaccine (PCV7), the rising prevalence of antibiotic resistance makes Streptococcus pneumoniae a continuing threat to child health. Data on carriage of resistant organisms by healthy children in communities in which immunization with PCV7 has been implemented will help to define and decrease these risks further. Methods. Children who were <7 years old, resided in a study community, and presented for routine well care or a “sick” visit between March 13 and May 11, 2001, at 31 primary care practices in 16 geographically distinct Massachusetts communities were studied. Consenting parents provided demographic information and data on potential risk factors for carriage of S pneumoniae and of penicillin-nonsusceptible S pneumoniae (PNSP). S pneumoniae isolates from nasopharyngeal specimens were tested for resistance to commonly used antibiotics including penicillin, ceftriaxone, erythromycin, and trimethoprim/sulfamethoxazole. Isolates were serotyped and grouped into PCV7-included serotypes, potentially cross-reactive serotypes (ie, an organism of a serogroup included in the vaccine), or non-PCV7 serotypes. Diagnosis on the day of collection, history of recent antibiotic use, and history of PCV7 immunization were obtained by chart review. Separate bivariate and multivariate analyses were performed to identify correlates of colonization with S pneumoniae and colonization with PNSP, accounting for clustering within communities. Results. S pneumoniae was isolated from the nasopharynx of 190 (26%) of the 742 children studied. Of the 166 tested, 33% were nonsusceptible to penicillin, with 14% showing intermediate susceptibility (minimum inhibitory concentration [MIC] 0.12–1.0) and 19% fully resistant (MIC ≥2). Nonsusceptibility to other antibiotics was common, including ceftriaxone (14%), erythromycin (22%), and trimethoprim/sulfa (31%); 20% of S pneumoniae isolates were not susceptible to ≥3 antibiotics. Thirty-six percent of isolates were of serotypes covered by PCV7; 30% were of PCV7 serogroups and potentially cross-reactive, but not 1 of the 7 included serotypes; and 34% were unrelated to PCV7 serogroups. Nonsusceptibility to penicillin was more common in PCV7-included strains (45%) and potentially cross-reactive strains (51%) than in non-PCV7 serotypes (8%). Risk factors for PNSP colonization included child care attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.3–6.5), current respiratory tract infection (OR: 4.7; 95% CI: 2.5–8.6), and recent antibiotic use (OR: 1.7; 95% CI: 1.0–2.8). PCV7 immunization was associated with decreased carriage of PCV7-included serotypes but not with an overall decrease in S pneumoniae colonization or with a decline in PNSP colonization. Conclusions. In this multicommunity sample, pneumococcal antibiotic resistance was common and was most frequently found in PCV7-included and PCV7 serogroup strains. The long-term impact of PCV7 immunization will be partially determined by the protection that it affords against invasive infection with potentially cross-reactive serotypes, as well as the virulence and future resistance patterns of unrelated serotypes.

Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage

“…We weighted the number of sensitive isolates to recover the correct overall prevalence of resistance. The Massachusetts data, collected as part of the SPARC (Streptococcus pneumoniae Antimicrobial Resistance in Children) project (25), were obtained from Croucher et al (15). To avoid confounding by vaccineassociated changes and changes in the rate of antibiotic consumption, only data from 2007 was included (the largest dataset of the available years).…”

Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success

“…First, our model considered a simplified scenario. Several factors not included in the model can be influential: population characteristics (e.g., age structure and clustering), vaccines (which may reduce, at least temporarily, the burden of resistance) (38)(39)(40)(41)(42), and the availability of drug sensitivity testing in some settings. Second, we did not consider antibiotics of other classes and crossresistance.…”

Impact of a 16-Community Trial to Promote Judicious Antibiotic Use in Massachusetts

“…Antibiotic resistance is a community-level public health concern, and randomization of individual patients or providers would be susceptible to unacceptable contamination between intervention and control states; therefore, we conducted a 16-community, cluster-randomized trial of the Reducing Antibiotics for Children in Massachusetts (REACH Mass) intervention. We previously reported measures of parental knowledge, 27 physician self-reported behavior, 28 and antibiotic resistance rates among colonizing isolates of S pneumoniae 29,30 ; however, our primary goal was to test whether a 3-year sustained intervention decreased the number of dispensings of antibiotics to children overall. A secondary analysis tested whether the intervention increased the fraction of appropriate, narrow-spectrum agents used, compared with patterns seen in control communities.…”