Drug Resistance Mutation Frequency of Single-Genome Amplification-Derived HIV-1 Polymerase Genomes in the Cerebrospinal Fluid and Plasma of HIV-1-Infected Individuals under Nonsuppressive Therapy.

Overview

abstract

BACKGROUND: The recurrence of skin and soft tissue infections (SSTIs) caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-associated methicillin-sensitive Staphylococcus aureus (CA-MSSA) (range, 16%-43%) presents significant challenges to clinicians, patients, and families. OBJECTIVES: This hybrid type I pragmatic randomized controlled trial (RCT) evaluated whether an evidence-based intervention composed of CDC guideline education, decolonization, and decontamination procedures that were effective in hospital intensive care unit settings could be implemented in the community to reduce SSTI recurrence, improve patient-reported outcomes, and mitigate household contamination and transmission. METHODS: Participants (N = 186) with confirmed MRSA+ or MSSA+ SSTIs and their household members recruited from NYC federally qualified health centers (FQHCs, N = 3) and community hospital emergency departments (EDs, N = 3) were individually randomly assigned (1:1) to receive either a home-based intervention (experimental [EXP]) or usual care [UC]). All participants received medical treatment at their clinician's discretion (observation, incision and drainage [I&D], and/or antibiotics) and the same educational pamphlet. Promotoras (ie, trained community health workers [CHWs] who are trusted within Latino communities; N = 8) delivered the EXP intervention. Only EXP participants received instructions and a 5-day supply of topical mupirocin for nasal application, chlorhexidine for body cleansing, and Clorox disinfecting wipes with instructions for household cleaning. The stakeholder team (clinicians, academic stakeholders, research staff, and patient advisors) designed the protocol and met monthly to identify areas for improvement; develop strategies to enhance participant recruitment, engagement, and retention; and review the results. Study home visits (baseline and 3 months) and telephone assessments (baseline, 1 month, and 6 months) were used to collect self-reported data from both groups. All households provided surveillance culture swabs (from the nares, axilla, and groin) from index patients, participating household members, and 13 high-touch environmental surfaces at baseline and 3 months. The primary outcome was 6-month SSTI recurrence recorded by clinicians in electronic health records (EHRs). Secondary outcomes included quality of life ([QOL] pain interference, depression, and overall QOL scores) and patient satisfaction with care. We also examined patient-level self-reported factors (ie, CA-MRSA infection prevention knowledge, self-efficacy, decision-making autonomy, and prevention behaviors/adherence) and environment-level factors (ie, household surface contamination, household member colonization, and transmission to household members). Social network analyses reviewed the engagement of stakeholders to examine the effects of network density on recruitment and retention. RESULTS: Among those screened for eligibility (N = 421), wound cultures collected at the baseline FQHC or ED visit tested positive for MRSA in 19% of wounds and MSSA in 21% of wounds. The intention-to-treat (ITT) analysis (n = 186), with complete follow-up for EHR-documented SSTI recurrence, demonstrated no significant differences between the EXP and UC groups (odds ratio [OR], 1.4; 95% CI, 0.51-3.5). Among the enrolled cohort, all of whom had confirmed MRSA or MSSA wound cultures and who completed home visits at baseline and EHR follow-up at 6 months (n = 119), 19.5% of nasal surveillance cultures collected at the baseline FQHC or ED visit were positive for MRSA, and 40.2% were positive for MSSA. Home visits demonstrated that 60% of households had at ≥1 MRSA/MSSA-contaminated surfaces (20% MRSA+, 81% MSSA+); 33% of household members had ≥1 positive surveillance cultures (8% MRSA+, 92% MSSA+). As measured by EHR review (11.1% EXP, 10.7 UC [OR, 1.14; 95% CI, 0.35-3.6]) or self-report (22.2% EXP, 7.5% UC [OR, 3.5; 95% CI, 0.89-13.8]), there were no significant intervention effects for SSTI recurrence rates at the 6-month follow-up. However, both groups showed a lower than expected SSTI recurrence rate over the 6-month follow-up time period. Secondary outcome analyses revealed no significant improvements from baseline to 6 months for both the EXP and UC groups for patient-reported outcomes. No treatment heterogeneity, as defined by nonsignificant interaction terms between the treatment assignment variable and select covariates was observed, including interactions with MRSA (OR, 1.14; 95% CI, 0.36-3.65) vs MSSA (OR, 1.14; 95% CI, 0.36-3.65) wound culture; US-born (OR, 1.12; 95% CI, 0.23-5.46) vs non-US born (2.36; 95% CI, 0.36-3.65) participants; high number of contaminated household surfaces (OR, 1.39; 95% CI, 0.21-9.01) vs low number (OR, 1.04; 95% CI, 0.23-5.46); absence of household member MRSA/MSSA colonization status (OR, 0.83; 95% CI, 0.24-2.95); and I&D performed (OR, 0.80; 95% CI, 0.17-3.90) vs not performed (OR, 1.58; 95% CI, 0.25-9.80). The decolonization intervention reduced colonization rates at 3 months by about 50% for nares (OR, 0.41; 95% CI, 0.16-1.04), axilla (OR, 0.77; 95% CI, 0.31-1.91), and groin (OR, 0.53; 95% CI, 0.24-1.20), which were clinically but not statistically significant reductions. No differential reductions in the proportions of contaminated surfaces (β = −.381; 95% CI, −1.6 to 0.83; P = .54) or transmission to household members (P = .70) were observed. Mupirocin resistance did not increase between baseline (3%) and 3 months (0%). Social network analyses revealed an increase in network density over the course of the study, indicating that the network grew in complexity and added a measurable depth to the interactions between stakeholders. CONCLUSIONS: The Community-Associated MRSA Project 2 (CAMP2) intervention did not reduce the clinician-reported recurrence rates of Staphylococcus aureus-related SSTIs for the EXP vs UC groups. Both groups showed similar nonsignificant changes in patient-reported outcomes of infection hygiene, decision-making autonomy, emotional distress, and satisfaction with social roles; no interactions were observed for patient-reported outcomes. While there was some sign of the effectiveness of decolonization for index patients, no statistically significant differences were observed for decolonization of household members or decontamination of household surfaces. LIMITATIONS AND SUBPOPULATION CONSIDERATIONS: This trial was conducted largely among adults (n = 103) but with a lower age limit of 9 years, and we experienced significant challenges associated with both recruiting participants and implementing home visits due to participants either being unreachable or unwilling or unable to participate due to subsequent household nonconsent. The use of a “warm handoff” recruitment strategy, whereby the site clinician directly introduced the patient to the study recruiter and promoters and invited their participation in the study, facilitated a modest improvement in home visit completion rates. A lower than predicted 6-month recurrence rate (11%) may have hindered our ability to accomplish and detect predicted main effects similar in magnitude to those reported in the REDUCE MRSA (inpatient) and Project CLEAR (outpatient) trials,^, both of which used similar interventions, although delivered at a higher intensity than in CAMP2.