[Show abstract][Hide abstract] ABSTRACT: Background. Staphylococcus aureus is among the foremost causes of human infection. Widespread drug resistance, emergence of highly virulent strains, and the ability of S. aureus to colonize >30% of the human population contribute to this organism's pathogenic success. Human serologic responses to S. aureus and their relationship to protective immunity remain incompletely defined, challenging the strategic development of efficacious vaccines. Methods. We measured humoral responses to two staphylococcal exotoxins, α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL; LukF-PV/LukS-PV subunits), both premier targets of current vaccine and immunotherapy development. We correlated acute and convalescent serum antibody levels with incidence of recurrent infection over 12 months follow-up in 235 children with S. aureus colonization, primary or recurrent skin and soft tissue infection, or invasive disease. Results. Cutaneous infection elicited transient increases in anti-Hla and anti-PVL antibodies; however, subsequent infection risk was similar between primary and recurrent cutaneous infection cohorts. Patients with invasive infections had the lowest pre-existing titers against Hla and LukF but displayed the highest convalescent titers. Across cohorts, convalescent anti-Hla titers correlated with protection against subsequent S. aureus infection. Conclusions. Cutaneous S. aureus infection does not reliably provoke durable, protective immune responses. This study provides the first link between protection from disease recurrence and the humoral response to Hla, a virulence factor already implicated in disease pathogenesis. These observations can be utilized to refine ongoing vaccine and immunotherapy efforts and inform the design of clinical trials.
[Show abstract][Hide abstract] ABSTRACT: Community-associated Staphylococcus aureus infections often affect multiple members of a household. We compared 2 approaches to S. aureus eradication: decolonizing the entire household versus decolonizing the index case alone.
An open-label, randomized trial enrolled 183 pediatric patients (cases) with community-onset S. aureus skin abscesses and colonization of anterior nares, axillae, or inguinal folds from 2008 to 2009 at primary and tertiary centers. Participants were randomized to decolonization of the case alone (index group) or of all household members (household group). The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily chlorhexidine body washes. Colonization of cases and subsequent skin and soft tissue infection (SSTI) in cases and household contacts were ascertained at 1, 3, 6, and 12 months.
Among 147 cases with 1-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 50% of cases in the index group and 51% in the household group (P = 1.00). Among 126 cases completing 12-month follow-up, S. aureus was eradicated from 54% of the index group versus 66% of the household group (P = .28). Over 12 months, recurrent SSTI was reported in 72% of cases in the index group and 52% in the household group (P = .02). SSTI incidence in household contacts was significantly lower in the household versus index group during the first 6 months; this trend continued at 12 months.
Household decolonization was not more effective than individual decolonization in eradicating community-associated S. aureus carriage from cases. However, household decolonization reduced the incidence of subsequent SSTI in cases and their household contacts.
[Show abstract][Hide abstract] ABSTRACT: Despite a paucity of evidence, decolonization measures are prescribed for outpatients with recurrent Staphylococcus aureus skin and soft-tissue infection (SSTI).
Compare the effectiveness of 4 regimens for eradicating S. aureus carriage.
Open-label, randomized controlled trial. Colonization status and recurrent SSTI were ascertained at 1 and 4 months.
Barnes-Jewish and St. Louis Children's Hospitals, St. Louis, Missouri, 2007-2009.
Three hundred patients with community-onset SSTI and S. aureus colonization in the nares, axilla, or inguinal folds.
Participants were randomized to receive no therapeutic intervention (control subjects) or one of three 5-day regimens: 2% mupirocin ointment applied to the nares twice daily, intranasal mupirocin plus daily 4% chlorhexidine body washes, or intranasal mupirocin plus daily dilute bleach water baths.
Among 244 participants with 1-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 38% of participants in the education only (control) group, 56% of those in the mupirocin group (P = .03 vs controls), 55% of those in the mupirocin and chlorhexidine group (P = .05), and 63% off those in the mupirocin and bleach group (P = .006). Of 229 participants with 4-month colonization data, eradication rates were 48% in the control group, 56% in the mupirocin only group (P = .40 vs controls), 54% in the mupirocin and chlorhexidine group (P = .51), and 71% in the mupirocin and bleach group (P = .02). At 1 and 4 months, recurrent SSTIs were reported by 20% and 36% of participants, respectively.
An inexpensive regimen of dilute bleach baths, intranasal mupirocin, and hygiene education effectively eradicated S. aureus over a 4-month period. High rates of recurrent SSTI suggest that factors other than endogenous colonization are important determinants of infection. Trial registration. ClinicalTrials.gov identifier: NCT00513799.
Infection Control and Hospital Epidemiology 09/2011; 32(9):872-80. · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The natural history of contemporary Staphylococcus aureus nasal colonization was evaluated in community children during a 1-year period. Methicillin-susceptible S. aureus nasal carriage was more persistent than methicillin-resistant S. aureus nasal carriage, which was usually self-limited. Children with persistent staphylococcal colonization often carried identical strains. Identification of persistent methicillin-resistant S. aureus carriers might inform strategies for decolonization and reduction of staphylococcal transmission.
[Show abstract][Hide abstract] ABSTRACT: The relationship between community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) nasal colonization and subsequent infection in children is unknown. We sought to define risk factors for skin and soft tissue infection (SSTI) in community children.
A prior study measured S. aureus nasal colonization prevalence for 1300 community children. To detect subsequent SSTI in these children or a household member, surveys were administered 6 and 12 months following enrollment.
SSTIs were reported by 56/708 (8.1%) respondents during the initial 6-month interval. SSTI developed in 6/26 (23%) initially colonized with MRSA, 16/194 (8%) with methicillin-sensitive S. aureus colonization, and 34/474 (7%) not colonized with S. aureus (MRSA vs. not MRSA, univariate analysis, p = 0.014). In multivariable analysis, factors associated with SSTI included history of SSTI in the child during the year preceding enrollment (p < 0.01) and SSTI in household contacts during the follow-up interval (p<0.01); MRSA nasal colonization approached statistical significance (p = 0.08).
In the current era of community MRSA transmission, SSTI is a disease of households, with recurrences in index cases and occurrences among household contacts. Children with MRSA colonization may be at risk for subsequent SSTI. Further study of MRSA transmission dynamics in households and preventive strategies should receive high priority.
The Journal of infection 09/2009; 59(6):394-401. · 4.13 Impact Factor