Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs

Abstract

ImportanceUniversal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.ObjectiveTo compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.Design, Setting, and ParticipantsTwo-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included.InterventionUniversal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline).Main Outcomes and MeasuresICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%.ResultsAmong the 801 668 admissions in 233 ICUs, the participants’ mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, −0.9% [95% CI, −9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]).Conclusions and RelevanceNasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin.Trial RegistrationClinicalTrials.gov Identifier: NCT03140423

At the Intersection of Critical Care and Infectious Diseases: The Year in Review

“…Adoption of mupirocin, though, lags behind reliance on CHG bathing. A recent survey reveals that less than 40% of US hospitals routinely utilize mupirocin in the regular nursing care of ICU patients [ 20 ]. One specific concern related to broad utilization of mupirocin relates to the potential for emergence of resistance.…”

“…Given its nature as an antiseptic, the emergence of resistance is much less of a worry. Iodophor also has general in vitro activity against S. aureus and has been evaluated as a preventive option in earlier studies [ 20 ]. Its efficacy in large, non-selected populations, though, has not been systematically determined.…”

Reducing Hospitalizations and Multidrug-Resistant Organisms via Regional Decolonization in Hospitals and Nursing Homes

“…While many MDRO prevention strategies exist, body-surface decolonization using topical antiseptic soap and nasal products has been broadly adopted in high-risk patient populations due to large randomized clinical trials demonstrating reductions in bloodstream infections and MDRO carriage . Decolonization not only affects MDROs but also provides broad protection against a range of potential pathogens.…”

Decolonization Strategies to Prevent Staphylococcal Infections

“…Now there is a new large-scale, pragmatic study, the Mupirocin-Iodophor ICU Decolonization Swap Out Trial, to help assess and clarify decolonization practice issues for ICU patients. Huang et al used their successful REDUCE MRSA trial partnership with HCA Healthcare to conduct a study that has wide-reaching implications on infection prevention practices across adult ICUs in the US. In this study, the authors presented an exceptionally well-designed, implemented, and analyzed pragmatic cluster-randomized clinical trial to understand which nasal decolonization agent when combined with routine CHG bathing is preferred to reduce ICU-attributable staphylococcal (MRSA and methicillin-sensitive S aureus ) infections.…”

“…Huang et al used their successful REDUCE MRSA trial partnership with HCA Healthcare to conduct a study that has wide-reaching implications on infection prevention practices across adult ICUs in the US. In this study, the authors presented an exceptionally well-designed, implemented, and analyzed pragmatic cluster-randomized clinical trial to understand which nasal decolonization agent when combined with routine CHG bathing is preferred to reduce ICU-attributable staphylococcal (MRSA and methicillin-sensitive S aureus ) infections. Performed among 137 hospitals across the US and including 233 ICUs and more than 3.3 million patient-days, their noninferiority study revealed a surprising finding: in the setting of a well-established mupirocin-CHG ICU decolonization program, a switch to an iodophor nasal agent resulted in a significant 18% higher hazard ratio for ICU-attributable staphylococcal clinical cultures.…”