Objective

The introduction of heptavalent conjugate pneumococcal vaccine (PCV7) has raised concerns for replacement with nonvaccine serotypes in both invasive disease and asymptomatic carriage. Analysis of colonizing serotypes among healthy children in the community provides critical data on such changes.

Methods

Nasopharyngeal specimens were obtained from children who were younger than 7 years during well-child or sick visits in primary care practices in 16 Massachusetts communities during 2001 and 2004. Susceptibility testing and serotyping were performed on isolated Streptococcus pneumoniae strains. Vaccination history with PCV7 was abstracted from the medical record.

Results

Among colonizing pneumococcal isolates, PCV7 serotypes decreased from 36% to 14%, and non-PCV7 serotypes increased from 34% to 55%. Overall carriage did not change (26% to 23%); neither did carriage of potentially cross-reactive serotypes (30% to 31%). The most common non-PCV7 serotypes were serotypes 11, 15, and 29. There was a substantial increase in penicillin nonsusceptibility from 8% to 25% in non-PCV7 serotypes; 35% were highly resistant to penicillin. Penicillin nonsusceptibility increased from 45% to 56% among PCV7 serotypes while remaining stable among PCV7 potentially cross-reactive strains (51% vs 54%).

Conclusions

Pneumococcal colonization has changed after the introduction of PCV7, both in serotype distribution and in patterns of antibiotic resistance. The frequency of nonvaccine strains has increased, and the proportion of nonvaccine isolates that are not susceptible to penicillin has tripled. This shift toward increased carriage of nonvaccine serotypes warrants vigilance for changes in the epidemiology of invasive pneumococcal disease.

New prophylactic approaches are needed to control infection with the Gram-positive bacterium Staphylococcus aureus, which is a major cause of nosocomial and community-acquired infections. To develop these, greater understanding of protective immunity against S. aureus infection is needed. Human immunity to extracellular Gram-positive bacterial pathogens is primarily mediated by opsonic killing (OPK) via antibodies specific for surface polysaccharides. S. aureus expresses two such antigens, capsular polysaccharide (CP) and poly-N-acetyl glucosamine (PNAG). Here, we have shown that immunization-induced polyclonal animal antisera and monoclonal antibodies specific for either CP or PNAG antigens have excellent in vitro OPK activity in human blood but that when mixed together they show potent interference in OPK activity. In addition, reductions in antibody binding to the bacterial surface, complement deposition, and passive protection were seen in two mouse models of S. aureus infection. Electron microscopy, isothermal calorimetry, and surface plasmon resonance indicated that antibodies to CP and PNAG bound together via an apparent idiotype-anti-idiotype interaction. This interaction was also found in sera from humans with S. aureus bacteremia. These findings suggest that the lack of effective immunity to S. aureus infections in humans could be due, in part, to interference in OPK when antibodies to CP and PNAG antigens are both present. This information could be used to better design S. aureus vaccine components.

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 > or =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 > or =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.

Objectives

Reducing unnecessary antibiotic use, particularly among children, continues to be a public health priority. Previous intervention studies have been limited by size or design and have shown mixed results. The objective of this study was to determine the impact of a multifaceted, community-wide intervention on overall antibiotic use for young children and on use of broad-spectrum agents. In addition, we sought to compare the intervention's impact on commercially and Medicaid-insured children.

Methods

We conducted a controlled, community-level, cluster-randomized trial in 16 nonoverlapping Massachusetts communities, studied from 1998 to 2003. During 3 years, we implemented a physician behavior-change strategy that included guideline dissemination, small-group education, frequent updates and educational materials, and prescribing feedback. Parents received educational materials by mail and in primary care practices, pharmacies, and child care settings. Using health-plan data, we measured changes in antibiotics dispensed per person-year of observation among children who were aged 3 to <72 months, resided in study communities, and were insured by a participating commercial health plan or Medicaid.

Results

The data include 223,135 person-years of observation. Antibiotic-use rates at baseline were 2.8, 1.7, and 1.4 antibiotics per person-year among those aged 3 to <24, 24 to <48, and 48 to <72 months, respectively. We observed a substantial downward trend in antibiotic prescribing, even in the absence of intervention. The intervention had no additional effect among children aged 3 to <24 months but was responsible for a 4.2% decrease among those aged 24 to <48 months and a 6.7% decrease among those aged 48 to <72 months. The intervention effect was greater among Medicaid-insured children and for broad-spectrum agents.

Conclusions

A sustained, multifaceted, community-level intervention was only modestly successful at decreasing overall antibiotic use beyond substantial secular trends. The more robust impact among Medicaid-insured children and for specific medication classes provides an argument for specific targeting of resources for patient and physician behavior change.

Background

Hospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge.

Methods

We conducted a multicenter, randomized, controlled trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence).

Results

In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval [CI], 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary outcomes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants.

Conclusions

Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone. (Funded by the AHRQ Healthcare-Associated Infections Program and others; ClinicalTrials.gov number, NCT01209234 .).