The large multistate study was led by the University of California, Irvine, and included researchers from the CDC in Atlanta, the Harvard Pilgrim Health Care Institute in Boston, and HCA Healthcare in Nashville, Tennessee. The study determined that a nasal antibiotic ointment, mupirocin, which is currently used daily for ICU patients in only one-third of U.S. hospitals, is highly effective at preventing S aureus infections in critically ill patients. In fact, the study team advised, it outperformed an antiseptic solution.
In the Journal of the American Medical Association study, researchers examined the question of whether nasal iodophor antiseptic works as well as nasal mupirocin antibiotic for preventing S aureus clinical cultures in ICU patients receiving daily chlorhexidine bathing.
The noninferiority, cluster-randomized trial of 801,668 admissions at 137 hospitals reported that exposure to nasal mupirocin significantly reduced S aureus clinical cultures by 18.4% compared with iodophor in adult ICUs in the context of daily chlorhexidine bathing.
“Nasal iodophor antiseptic did not meet criteria to be considered non-inferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG [chlorhexidine gluconate] bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin,” the researchers wrote.
The article noted that universal nasal mupirocin plus CHG bathing in ICUs prevents methicillin-resistant S aureus (MRSA) infections and all-cause bloodstream infections.
Questions have been raised, however, about whether antibiotic resistance is likely to and about whether an antiseptic could be advantageous for ICU decolonization. The researchers sought to compare the effectiveness of iodophor versus mupirocin for universal ICU nasal decolonization in combination with CHG bathing.
To do so, they conducted a two-group noninferiority, pragmatic, cluster-randomized trial in U.S. community hospitals—all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Included were adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019).
The authors noted that universal decolonization involved switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline).
Among the patients in 233 ICUs, the mean age was 63.4 years and included 46.3% women; the mean (SD) ICU length of stay was 4.8 (4.7) days.
The researchers reported that hazard ratios (HRs) for S aureus clinical isolates in the intervention versus baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs. 4.3/1,000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs. 4.0/1,000 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. 2.1/1,000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs. 2.0/1,000 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. 2.7/1,000) for iodophor-CHG and 1.01 (2.6 vs. 2.6/1,000) 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%]),” the researchers advised.
S aureus is a common pathogen in ICUs, with estimates in North American hospitals that S aureus has caused 23% of ICU infections, according to background information in the article. “Both methicillin-susceptible S aureus and methicillin-resistant S aureus (MRSA) have produced a wide spectrum of ICU-associated infections, including ventilator-associated pneumonia, bloodstream infections, and surgical site infections,” the authors pointed out.
The authors added, “While universal CHG antiseptic bathing has been broadly adopted in ICUs, adoption of mupirocin as a universal topical antibiotic has been slowed by concerns for engendering mupirocin resistance. A 2021 survey of 5,000 U.S. hospitals found that 63% of U.S. hospitals have adopted universal ICU CHG bathing, but only 59% of those hospitals (37% overall) have adopted universal ICU nasal decolonization. This cluster-randomized, pragmatic, comparative effectiveness trial in adult ICUs was conducted to assess whether universal nasal antiseptic povidone-iodine (iodophor), to which minimal S aureus resistance is expected was an acceptable alternative to universal nasal mupirocin for reducing S aureus and MRSA clinical cultures as well as all-cause bloodstream infection in the setting of daily CHG bathing.”
“This study further supports CDC guidance on using a strategy that combines nasal decolonization plus CHG bathing in ICU patients. Furthermore, the data show that using mupirocin for nasal decolonization may be preferred over iodophor because it is more effective at preventing S aureus infections or colonization. S aureus infections account for nearly a quarter of the infections in ICUs in the United States,” stated John Jernigan, MD, branch chief, CDC’s Epidemiology, Research, and Innovations Branch.
Lead investigator Susan S. Huang, MD, MPH, professor in the Division of Infectious Diseases at the University of California, Irvine School of Medicine, suggested the results resolved the question about whether nasal treatment is necessary in addition to chlorhexidine bathing to prevent these ICU infections. “This large study confirms that clearing the nose of bacteria prevents infection and that the choice of product matters,” she explained. “Mupirocin antibiotic ointment remains the best treatment and serious ICU infections can be avoided by simply giving patients mupirocin for the first five days of an ICU stay along with daily chlorhexidine bathing. Povidone-iodine does not work as well.”
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