Stephanie A. Fritz

Household Versus Individual Approaches to Eradication of Community-Associated Staphylococcus aureus in Children: A Randomized Trial

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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. CLINICAL TRIALS REGISTRATION NCT00731783.

Mupirocin and Chlorhexidine Resistance in Staphylococcus aureus in Patients with Community-Onset Skin and Soft Tissue Infections

ABSTRACT Decolonization measures, including mupirocin and chlorhexidine, are often prescribed to prevent Staphylococcus aureus skin and soft tissue infections (SSTI). The objective of this study was to determine the prevalence of high-level mupirocin and chlorhexidine resistance in S. aureus strains recovered from patients with SSTI before and after mupirocin and chlorhexidine administration and to determine whether carriage of a mupirocin- or chlorhexidine-resistant strain at baseline precluded S. aureus eradication. We recruited 1,089 patients with community-onset SSTI with or without S. aureus colonization. In addition to routine care, 483 patients were enrolled in a decolonization trial: 408 received intranasal mupirocin (with or without antimicrobial baths), and 258 performed chlorhexidine body washes. Patients were followed for up to 12 months with repeat colonization cultures. All S. aureus isolates were tested for high-level mupirocin and chlorhexidine resistance. At baseline, 23/1,089 (2.1%) patients carried a mupirocin-resistant S. aureus strain and 10/1,089 (0.9%) patients carried chlorhexidine-resistant S. aureus. Of 4 patients prescribed mupirocin, who carried a mupirocin-resistant S. aureus strain at baseline, 100% remained colonized at 1 month compared to 44% of the 324 patients without mupirocin resistance at baseline (P = 0.041). Of 2 patients prescribed chlorhexidine, who carried a chlorhexidine-resistant S. aureus strain at baseline, 50% remained colonized at 1 month compared to 48% of the 209 patients without chlorhexidine resistance at baseline (P = 1.0). The overall prevalence of mupirocin and chlorhexidine resistance is low in S. aureus isolates recovered from outpatients, but eradication efforts were less successful in patients carrying a mupirocin-resistant S. aureus strain at baseline.

Effectiveness of Measures to Eradicate Staphylococcus aureus Carriage in Patients with Community-Associated Skin and Soft Tissue Infections: A Randomized Trial

BACKGROUND Despite a paucity of evidence, decolonization measures are prescribed for outpatients with recurrent Staphylococcus aureus skin and soft-tissue infection (SSTI). OBJECTIVE Compare the effectiveness of 4 regimens for eradicating S. aureus carriage. DESIGN Open-label, randomized controlled trial. Colonization status and recurrent SSTI were ascertained at 1 and 4 months. SETTING Barnes-Jewish and St. Louis Childrens Hospitals, St. Louis, Missouri, 2007-2009. PARTICIPANTS Three hundred patients with community-onset SSTI and S. aureus colonization in the nares, axilla, or inguinal folds. INTERVENTIONS 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. RESULTS 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. CONCLUSIONS 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.

Virulence Gene Expression in Human Community-Acquired Staphylococcus aureus Infection

Isolates of methicillin-resistant Staphylococcus aureus (MRSA) were once linked uniformly with hospital-associated infections; however, community-acquired MRSA (CA-MRSA) now represents an emerging threat worldwide. To examine the association of differential virulence gene expression with outcomes of human infection, we measured transcript levels of target staphylococcal genes directly in clinical samples from children with active known or suspected CA-MRSA infections. Virulence genes encoding secreted toxins, including Panton-Valentine leukocidin, were highly expressed during superficial and invasive CA-MRSA infections. In contrast, increased expression of surface-associated protein A was linked only with invasive disease. Comparisons with laboratory-grown corresponding clinical isolates revealed that tissue-specific expression profiles reflect the activity of the staphylococcal accessory gene regulator during human infection. These results represent the first demonstration of staphylococcal gene expression and regulation directly in human tissue. Such analysis will help to unravel the complex interactions between CA-MRSA and its host environmental niches during disease development.

Prevalence of and Risk Factors for Community-Acquired Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Colonization in Children Seen in a Practice-Based Research Network

OBJECTIVE. We sought to define the prevalence of and risk factors for methicillin-resistant Staphylococcus aureus nasal colonization in the St Louis pediatric population. METHODS. Children from birth to 18 years of age presenting for sick and well visits were recruited from pediatric practices affiliated with a practice-based research network. Nasal swabs were obtained, and a questionnaire was administered. RESULTS. We enrolled 1300 participants from 11 practices. The prevalence of methicillin-resistant S aureus nasal colonization varied according to practice, from 0% to 9% (mean: 2.6%). The estimated population prevalence of methicillin-resistant S aureus nasal colonization for the 2 main counties of the St Louis metropolitan area was 2.4%. Of the 32 methicillin-resistant S aureus isolates, 9 (28%) were health care-associated types and 21 (66%) were community-acquired types. A significantly greater number of children with community-acquired methicillin-resistant S aureus were black and were enrolled in Medicaid, in comparison with children colonized with health care-associated methicillin-resistant S aureus. Children with both types of methicillin-resistant S aureus colonization had increased contact with health care, compared with children without colonization. Methicillin-sensitive S aureus nasal colonization ranged from 9% to 31% among practices (mean: 24%). The estimated population prevalence of methicillin-sensitive S aureus was 24.6%. Risk factors associated with methicillin-sensitive S aureus colonization included pet ownership, fingernail biting, and sports participation. CONCLUSIONS. Methicillin-resistant S aureus colonization is widespread among children in our community and includes strains associated with health care-associated and community-acquired infections.

A serologic correlate of protective immunity against community-onset Staphylococcus aureus infection

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 organisms 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 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. 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 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. 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.

SKIN INFECTION IN CHILDREN COLONIZED WITH COMMUNITY-ASSOCIATED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

OBJECTIVES 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Contribution of Genetically Restricted, Methicillin-Susceptible Strains to the Ongoing Epidemic of Community-Acquired Staphylococcus aureus Infections

BACKGROUND Within the current worldwide epidemic of community-acquired Staphylococcus aureus infections, attention has focused on the role of methicillin-resistant strains. We characterize methicillin-susceptible strains that also contribute to this epidemic. METHODS We tracked cultures from abscess specimens submitted to the microbiology laboratory at St. Louis Childrens Hospital and examined Panton-Valentine leukocidin (PVL) genes in methicillin-susceptible S. aureus (MSSA) isolates. We further characterized some isolates by multilocus sequence typing, pulsed-field gel electrophoresis, antibiotic susceptibility, accessory gene regulator (agr) allele, and presence of the arcA gene of the arginine catabolic mobile element. RESULTS From 1999 to 2007, we detected a 250-fold increase in cultures of abscesses yielding methicillin-resistant S. aureus (MRSA) and a 5-fold increase in abscess cultures yielding MSSA. MSSA isolates from abscesses and wounds were more likely to encode PVL than isolates from other sources. In contrast to PVL-negative isolates of MSSA, which were genetically diverse, PVL-positive isolates were predominantly multilocus sequence typing type 8 and agr type 1. More than half of PVL-positive MSSA isolates were resistant to erythromycin and susceptible to clindamycin with the absence of inducible resistance, a pattern uncommon in PVL-negative MSSA but frequent in the USA300 clone of MRSA. In addition, pulsed-field gel electrophoresis of PVL-positive MSSA strains revealed the USA300 pattern. CONCLUSIONS In addition to methicillin-resistant strains, the current epidemic of S. aureus infections includes infections caused by methicillin-susceptible strains that are closely related genetically and share phenotypic characteristics other than susceptibility to methicillin. These findings suggest that factors other than methicillin resistance are driving the epidemic.

Staphylococcus aureus Colonization in Children With Community-Associated Staphylococcus aureus Skin Infections and Their Household Contacts

OBJECTIVES To measure prevalence of Staphylococcus aureus colonization in household contacts of children with acute S aureus skin and soft tissue infections (SSTI), determine risk factors for S aureus colonization in household contacts, and assess anatomic sites of S aureus colonization in patients and household contacts. DESIGN Cross-sectional study. SETTING St Louis Childrens Hospital Emergency Department and ambulatory wound center and 9 community pediatric practices affiliated with a practice-based research network. PARTICIPANTS Patients with community-associated S aureus SSTI and S aureus colonization (in the nose, axilla, and/or inguinal folds) and their household contacts. OUTCOME MEASURES Colonization of household contacts of pediatric patients with S aureus colonization and SSTI. RESULTS Of 183 index patients, 112 (61%) were colonized with methicillin-resistant S aureus (MRSA); 54 (30%), with methicillin-sensitive S aureus (MSSA); and 17 (9%), with both MRSA and MSSA. Of 609 household contacts, 323 (53%) were colonized with S aureus: 115 (19%) with MRSA, 195 (32%) with MSSA, and 13 (2%) with both. Parents were more likely than other household contacts to be colonized with MRSA (odds ratio, 1.72; 95% CI, 1.12 to 2.63). Methicillin-resistant S aureus colonized the inguinal folds more frequently than MSSA (odds ratio, 1.67; 95% CI, 1.16 to 2.41), and MSSA colonized the nose more frequently than MRSA (odds ratio, 1.75; 95% CI, 1.19 to 2.56). CONCLUSIONS Household contacts of children with S aureus SSTI had a high rate of MRSA colonization compared with the general population. The inguinal fold is a prominent site of MRSA colonization, which may be an important consideration for active surveillance programs in hospitals.

A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses

BACKGROUND Uncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community‐associated methicillin‐resistant Staphylococcus aureus (MRSA) is unclear. METHODS We conducted a multicenter, prospective, double‐blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis. Participants with a skin abscess 5 cm or smaller in diameter were enrolled. After abscess incision and drainage, participants were randomly assigned to receive clindamycin, trimethoprim–sulfamethoxazole (TMP‐SMX), or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after the end of treatment. RESULTS We enrolled 786 participants: 505 (64.2%) were adults and 281 (35.8%) were children. A total of 448 (57.0%) of the participants were male. S. aureus was isolated from 527 participants (67.0%), and MRSA was isolated from 388 (49.4%). Ten days after therapy in the intention‐to‐treat population, the cure rate among participants in the clindamycin group was similar to that in the TMP‐SMX group (221 of 266 participants [83.1%] and 215 of 263 participants [81.7%], respectively; P=0.73), and the cure rate in each active‐treatment group was higher than that in the placebo group (177 of 257 participants [68.9%], P<0.001 for both comparisons). The results in the population of patients who could be evaluated were similar. This beneficial effect was restricted to participants with S. aureus infection. Among the participants who were initially cured, new infections at 1 month of follow‐up were less common in the clindamycin group (15 of 221, 6.8%) than in the TMP‐SMX group (29 of 215 [13.5%], P=0.03) or the placebo group (22 of 177 [12.4%], P=0.06). Adverse events were more frequent with clindamycin (58 of 265 [21.9%]) than with TMP‐SMX (29 of 261 [11.1%]) or placebo (32 of 255 [12.5%]); all adverse events resolved without sequelae. One participant who received TMP‐SMX had a hypersensitivity reaction. CONCLUSIONS As compared with incision and drainage alone, clindamycin or TMP‐SMX in conjunction with incision and drainage improves short‐term outcomes in patients who have a simple abscess. This benefit must be weighed against the known side‐effect profile of these antimicrobials. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00730028.)