[Show abstract][Hide abstract] ABSTRACT: Background:
Staphylococcus aureus is among the leading 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.
We measured humoral responses to 2 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.
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 preexisting 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.
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.
Full-text · Article · Feb 2013 · Clinical Infectious Diseases
[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.
Full-text · Article · Dec 2011 · Clinical Infectious Diseases
[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.
Full-text · Article · Sep 2011 · Infection Control and Hospital Epidemiology
[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: Background:
Community-associated Staphylococcus aureus (CA-SA) causes recurrent skin and soft tissue infections (SSTI). Eradication of CA-SA colonization may prevent recurrent skin infections. However, decolonization regimens traditionally used in the healthcare setting have not been evaluated in the community.
To evaluate the efficacy of three different decolonization methods in the eradication of S. aureus carriage in patients presenting with community-acquired SSTI.
Patients with acute SSTI who were colonized with S. aureus were enrolled into a 4-arm (n=300; 75 in each arm) randomized controlled trial. All participants were educated on proper personal hygiene measures to prevent recurrences of SSTI as recommended in the literature. The control group only received the educational materials while the intervention groups received education materials and were treated with a decolonization strategy. The intervention arms were (i) application of 2% mupirocin ointment to both anterior nares twice daily for 5 days, (ii) 2% mupirocin ointment intranasally in addition to daily showers with 4% chlorhexidine solution for 5 days, and (iii) 2% mupirocin ointment intranasally in addition to daily 30-minute soaking in dilute bleach water daily for 5 days. Patients were screened for colonization by obtaining swab cultures from the nares, axillae, and both groins at 1 month and 4 months post intervention. Efficacy was analyzed by a modified intention-to-treat analysis. Only evaluable patients were included in the final analysis. Proportions of decolonized patients were compared using chi-square analysis. A P-value of ≤ 0.05 was considered significant.
300 patients were enrolled into the trial. 64% (193/300) were children and 54% (161/300) were female. Mean age was 17.8 ± 16.4 years (0.6-70 years). Majority were African-Americans (66%; 198/300). The sites of infection included: the extremities (40%; 120/300), the groin/perineum/buttocks (39.3%; 118/300), the trunk (19%; 57/300), and the head (9.3%; 29/300). Most common adverse reactions included: dry skin (7.7%; 23/300) and rash (2.7%; 8/300). 77% (174/225) found using the mupirocin easy, 75% reported daily chlorhexidine showers were easy to perform, and 68% (51/75) found the daily bleach baths easy to perform. 21% (47/225) reported having another infection within four months of enrollment into the trial.
In a randomized controlled trial, all three regimens were effective at eradicating S. aureus colonization at 1 month post-intervention. At four months post-intervention, the nasal application of 2% mupirocin and bleach baths was more effective than the other regimens at eradicating S. aureus colonization. All treatment arms were well-tolerated.
[Show abstract][Hide abstract] ABSTRACT: Background: Colonization with CA-MRSA is associated with development of skin and soft tissue infections. The objective of this study was to determine the prevalence of CA-MRSA colonization at three different body sites in patients presenting with skin and soft tissue infections.
Methods: Swabs of the anterior nares, axilla, and groin were collected from patients with community-acquired skin and soft tissue infections who presented to the emergency departments of both an adult and pediatric hospitals.
Results: To date, 923 adults and children were approached for participation and 85% consented. Data on 698 patients [278 adults (40%); 420 children (60%)] are available. 56% (390/ 698) were female. 70% (491/698) were African-American, 24% (170/698) Caucasian, 5.2% (37/698) of other races. 38% presented with an infection in the perineal/genital area, 28% lower extremity, 13% upper extremity, 11% trunk area, 10% (67/698) head or neck, and 8% (56/798) axillae. 590/698 (85%) had clinical wound cultures and 56% (393/698) grew MRSA, 12% (86/698) MSSA, 12% (84/698) other pathogens, and 3.8% (27/698) were no growth.16% (112/698) had clinical blood cultures done and 10% (11/112) were positive. Of the 11 positive blood cultures, 64% (7/11) had MRSA, 18% (2/11) MSSA, and 18% (2/11) grew skin commensals. 45% (317/698) of patients screened were colonized with MRSA and 24% (166/698) were colonized with MSSA. MRSA colonization at any site was associated with positive MRSA wound cultures [uOR 1.7 (1.3, 2.2); P < 0.001].Site of infection, gender, race, history of skin disorder, and previous antibiotic use was not associated with MRSA colonization. Susceptibility of 315 isolates included: erythromycin 6%, clindamycin 86% (7% D-test positive), ciprofloxacin 44%, linezolid 99.6% (1 intermediate), rifampin 99%, tetracycline 96%, TMP/SMX 99%, and vancomycin 100%.
Conclusions: MRSA accounted for 56% of all patients presenting with community-acquired skin and soft tissue infections. 81% of these patients were colonized with MRSA. Susceptibility rate to most antimicrobials remain high except for clindamycin.
[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.
Preview · Article · Sep 2009 · The Journal of infection