4. 137 Hospital Cluster-Randomized Trial of Mupirocin-Chlorhexidine vs Iodophor-Chlorhexidine for Universal Decolonization in Intensive Care Units (ICUs) (Mupirocin Iodophor Swap Out Trial)

Abstract Background ICU universal decolonization with daily chlorhexidine (CHG) baths plus mupirocin nasal decolonization reduces all-cause bloodstream infections (BSI) and MRSA clinical cultures. We assessed nasal iodophor, an antiseptic less susceptible to resistance, in place of mupirocin. Methods We conducted a cluster randomized non-inferiority trial in ICUs, comparing universal decolonization with: 1) Mupirocin-CHG: daily CHG baths and 5 days of twice daily nasal mupirocin, to 2) Iodophor-CHG: same regimen, substituting twice daily 10% povidone-iodine for mupirocin. All adult ICUs in a hospital were assigned to the same strategy. We compared each hospital’s outcomes during the 18-month intervention (Nov 2017-Apr 2019) to its own baseline (May 2015-Apr 2017), during which all hospitals used mupirocin-CHG. The primary outcome was ICU-attributable S. aureus clinical isolates. Secondary outcomes included ICU-attributable MRSA clinical isolates and all-cause BSI. As randomized and as treated analyses used unadjusted proportional hazards models assessing differences in outcomes between baseline and intervention periods across the two groups, accounting for clustering by hospital and patient. Results We randomized 137 hospitals with 233 ICUs in 18 states. There were 442,544 admissions in the baseline period and 349,262 in the intervention period. Median ICU length of stay was 4 days. ICU types included mixed medical surgical (56%), medical (9%), surgical (11%), cardiac (15%), and neurologic (9%). CHG adherence was similar in both arms (85%), but adherence was greater for mupirocin (90%) than iodophor (82%). Primary as-randomized results (Table, Figure) exceeded the non-inferiority margin in favor of mupirocin, for S. aureus clinical cultures (21% superiority, P< 0.001) and for MRSA clinical cultures (20% superiority, P< 0.001). The regimens had similar BSI hazards. Analyses of fully adherent patients are in progress. Figure - Primary and Secondary Outcomes of Mupirocin Iodophor Swap Out Trial Conclusion Universal iodophor-CHG was equivalent to mupirocin-CHG for ICU BSI prevention. Mupirocin-CHG was superior to iodophor-CHG for S. aureus and MRSA clinical isolates, potentially due to greater adherence to mupirocin. Disclosures Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Lauren Heim, MPH, Medline (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Taliser R. Avery, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Syma Rashid, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Katherine Haffenreffer, BS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Lauren Shimelman, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Caren Spencer-Smith, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Selsebil Sljivo, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Ed Rosen, BS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Russell Poland, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Micaela H. Coady, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Eunice J. Blanchard, MSN RN, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Kimberly Reddish, DNP, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Brandon Carver, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Kimberly N. Smith, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jason Hickok, MBA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Karen Lolans, BS, Medline (Research Grant or Support) Nadia Khan, BS, Medline (Research Grant or Support) John A. Jernigan, MD, MS, Nothing to disclose Kenneth Sands, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Jonathan B. Perlin, MD, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Richard Platt, MD, MSc, Medline (Research Grant or Support, Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)


Figure -Primary and Secondary Outcomes of Mupirocin Iodophor Swap Out Trial
Conclusion. Universal iodophor-CHG was equivalent to mupirocin-CHG for ICU BSI prevention. Mupirocin-CHG was superior to iodophor-CHG for S. aureus and MRSA clinical isolates, potentially due to greater adherence to mupirocin.
Disclosures. Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Edward Septimus, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Lauren Heim, MPH, Medline (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Julia Moody, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Taliser R. Avery, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Syma Rashid, MD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Stryker (Sage) (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product)Xttrium (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic product) Katherine Haffenreffer, BS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Lauren Shimelman, BA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received con- Background. Nursing home (NH) residents are at high infection and hospital readmission risk. Colonization with multidrug-resistant organisms (MDROs) is common. In ICU and post-hospital discharge settings, decolonization has reduced infection rates. However, the effectiveness of this strategy in NHs is unclear.

Methods.
We performed a cluster randomized trial of 1:1 universal decolonization (decol) vs standard of care bathing (control) in 28 California NHs. After an 18 month baseline evaluation of hospitalization rates due to infection and MDRO prevalence, NHs were randomized to decol or control. Decol consisted of 1) chlorhexidine bathing; 2) nasal povidone iodine bid on admission x 5d and then M-F biweekly x 18 mo. Primary outcome was the probability that a transfer to a hospital was due to infection. Secondary outcome was the probability that a NH discharge was to a hospital.
Results. Four of 28 NHs dropped from the trial (3 decol, 1 control). Mean facility baseline of hospital transfers due to infection was 58% and 57% in the control and decol groups. In the intervention period, proportions were 57% and 48% in the control and decol groups. When accounting for clustering within NHs, hospital transfers due to infection had an OR of 0.91 (95% CI: 0.82-1.02) in the control group and an OR of 0.73 (95% CI: 0.56-0.95) in the decol group when comparing intervention to baseline period. For the primary outcome, decol had a 18% greater impact v. control (P=0.005, Fig. A). Baseline proportion of NH discharges due to hospitalization was 37% and 39% in the control and decol groups. In the intervention period, proportions were 36% and 33%. When accounting for clustering within NHs, the proportion of discharges due to hospitalization had an OR of 1.14 (95% CI: 1.06-1.22) in the control group and 0.91 (CI: 0.77-1.07) in the decol group when comparing the intervention period to the baseline period. For the secondary outcome, decol had a 23% greater impact v. control (P< 0.0001, Fig. B).
In this figure, each nursing home is represented by a circle. The size of the circle represents the amount of contributed patient days to the trial. The groups represent "as randomized" categories. Panel A) compares the probability that a transfer to a hospital was due to infection; panel B) compares the probability that a nursing home discharge was to a hospital. The y-axis represents the odds ratio of these probabilities comparing the baseline to the intervention period. The p values represent the significance of the difference between groups (the trial effect).
Conclusion. Universal NH decolonization with chlorhexidine and nasal iodophor significantly reduced the proportion of transfers to hospitals due to infection and discharges due to hospitalization. Our findings suggest that NH decolonization reduces serious infections and can decrease morbidity in this vulnerable population.
Disclosures. Loren G. Miller, MD, MPH, Medline (Grant/Research Support, Other Financial or Material Support, Contributed product) Stryker (Other Financial or Material Support, Contributed product) Xttrium (Other Financial or Material Support, Contributed product) James A. McKinnell, MD, Medline (Grant/Research Support) Raveena Singh, MA, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Gabrielle Gussin, MS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Ken Kleinman, PhD, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic products) Raheeb Saavedra, AS, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic products) Lauren Heim, MPH, Medline (Other Financial or Material Support, Conducted clinical trials and studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals received contributed antiseptic product) Stryker (Sage) (Other Financial or