Randomized controlled trial of chlorhexidine gluconate, intranasal mupirocin, rifampin, and doxycycline versus chlorhexidine gluconate and intranasal mupirocin alone for the eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonization

Background: Several decolonization regimens have been studied to prevent recurrent methicillin-resistant Staphylococcus aureus (MRSA) infections. Clinical equipoise remains with regard to the role of MRSA decolonization. We compared initial MRSA clearance and subsequent MRSA recolonization rates over a 12-month period after standard decolonization (using topical chlorhexidine gluconate, and intranasal mupirocin) or systemic decolonization (using topical chlorhexidine gluconate, intranasal mupirocin, oral rifampin, and oral doxycycline). Methods: MRSA-colonized patients were randomized to receive either standard or systemic decolonization. Follow-up with MRSA screening was obtained at approximately 3, 6, and 12 months after completion of therapy. Kaplan–Meier survival curves were calculated and assessed for significant differences using log-rank tests. Results: Of 98 enrolled patients (25 standard decolonization, 73 systemic decolonization), 24 patients (7 standard decolonization, 17 systemic decolonization) did not complete the study. Univariate analysis showed a marginally significant difference in the probability of remaining MRSA-negative post-treatment ( p = 0.043); patients who received standard decolonization had a 31.9% chance of remaining MRSA-negative compared with a 49.9% chance among those who received systemic decolonization. With multivariate analysis, there was no difference in the probability of remaining MRSA-negative between systemic and standard decolonization ( p = 0.165). Initial MRSA clearance was more readily achieved with systemic decolonization (79.1%; 95% CI 32.4% to 71.6%) than with standard decolonization (52.0%; 95% CI 69.4% to 88.8%; p = 0.0102). Conclusions: Initial MRSA clearance is more readily achieved with systemic decolonization than with standard decolonization. There is no significant difference in the probability of sustained MRSA clearance.

Decrease in MRSA Bacteremia After Implementation of Intranasal Mupirocin Decolonization Protocol

Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains a key pathogen in burn patients and is associated with increased morbidity and mortality. Disruption of skin barrier exposes these individuals to a myriad of infections. Various decolonization approaches, including chlorhexidine baths and intranasal mupirocin, have shown favorable outcomes in preventing MRSA infections in this cohort. Methods: In August 2020, a mupirocin decolonization protocol was implemented in Michigan’s largest trauma-level 1 burn intensive care unit. All patients admitted to the burn unit received daily intranasal mupirocin for the initial 5 days of hospitalization. We compared MRSA bacteremia rates per 1,000 patient days from January–July 2020 to those after August 2020. A hospital-acquired MRSA bacteremia infection was defined as a positive blood culture after hospital day 3. Patient characteristics and hospital course were collected through medical chart review. A 2-tailed t test was used for analysis. Results: We identified 5 cases of hospital-onset MRSA bacteremia and no cases of community-onset MRSA bacteremia. On average, there were 2.6 cases per 1,000 patient days before mupirocin implementation and 1.0 cases per 1,000 patient days after mupirocin implementation (P = .26) (Figure 1). In this patient cohort, the average total body surface area burned was 45.6% (range, 18%–90%), and 60% (n = 3) of patients had sputum culture positive for MRSA prior to developing bacteremia (Table 1). Also, 2 patients (40%) with MRSA bacteremia died. Notably, the patient in the postintervention cohort was admitted in July, prior to implementation. Conclusions: Implementation of a decolonization protocol with intranasal mupirocin in burn-surgery patients markedly decreased the incidence of MRSA bacteremia in this cohort. This is the first study to evaluate the use of mupirocin as a decolonizing agent in burn victims. Continued long-term surveillance is recommended, and this strategy has potential for application to other high-risk cohorts.Funding: NoDisclosures: None

Effect of mupirocin for Staphylococcus aureus decolonization on the microbiome of the nose and throat in community and nursing home dwelling adults

Objective To characterize the microbial communities of the anterior nares (nose) and posterior pharynx (throat) of adults dwelling in the community and in nursing homes before and after treatment with intranasal mupirocin. Methods Staphylococcus aureus-colonized adults were recruited from the community (n = 25) and from nursing homes (n = 7). S. aureus colonization was confirmed using cultures. Participants had specimens taken from nose and throat for S. aureus quantitation using quantitative PCR for the nuc gene and bacterial profiling using 16S rRNA gene sequencing over 12 weeks. After two baseline study visits 4 weeks apart, participants received intranasal mupirocin for 5 days with 3 further visits over a 8 week follow-up period. Results We found a decrease in the absolute abundance of S. aureus in the nose for 8 weeks after mupirocin (1693 vs 141 fg/ul, p = 0.047). Mupirocin caused a statistically significant disruption in bacterial communities of the nose and throat after 1 week, which was no longer detected after 8 weeks. Bacterial community profiling demonstrated that there was a decrease in the relative abundance of S. aureus (8% vs 0.3%, p<0.01) 8 weeks after mupirocin and a transient decrease in the relative abundance of Staphylococcus epidermidis in the nose (21% vs 5%, p<0.01) 1 week after mupirocin. Conclusions Decolonization with mupirocin leads to a sustained effect on absolute and relative abundance of S. aureus but not for other bacteria in the nose. This demonstrates that a short course of mupirocin selectively decreases S. aureus in the nose for up to 8 weeks.

854. Infection Prevention vs. Antimicrobial Stewardship: Does Nasal Povidone-Iodine Interfere with Methicillin Resistant Staphylococcus aureus (MRSA) Screening?

Background As part of universal decolonization, intensive care unit (ICU) patients may receive intranasal mupirocin to reduce MRSA infections. However, due to concerns about widespread use of mupirocin promoting resistance, some have proposed a bactericidal antiseptic, povidone-iodine (P-I), as an alternative. There are few data as to whether either agent reduces the sensitivity of MRSA nares screening. This study aimed to discern whether intranasal P-I interferes with MRSA screening via polymerase chain reaction (PCR) and/or culture. Methods We performed a prospective proof-of-concept cohort study at our &gt;1200-bed, community-based academic health care system, enrolling 20 patients who screened MRSA-positive by PCR on admission to a medical ICU, medical-surgical ICU, or medical stepdown unit. All patients received twice-daily intranasal P-I (7.5%) for 5 days or until unit discharge. We obtained follow-up nasal MRSA PCR tests after 4-6 days, and confirmed all PCR results with MRSA cultures using CHROMagar™. We calculated sensitivity of MRSA PCR at follow-up using culture as the gold standard. Results Twenty patients were enrolled, with a median age of 72 years (range, 53-91). Most (75%) were admitted with active infection, and 40% had known MRSA history. All baseline PCRs were confirmed by positive culture. Patients underwent a mean of 8.1 (range, 4-13) nasal P-I applications prior to follow-up testing. At follow up, 16/20 (80%) remained MRSA-positive via both PCR and culture. Of the 4 patients with negative follow-up results, 1 was both PCR-/culture-, 2 were PCR+/culture- and 1 was PCR-/culture+. All 4 had received ≥1 doses of vancomycin, and one person had received ≥1 doses of linezolid. The sensitivity of MRSA PCR at follow-up was 94%. Conclusion MRSA PCR remains highly sensitive even after multiple applications of P-I, and may be more sensitive than culture. If clinicians wish to screen for MRSA for stewardship or other purposes, receipt of nasal P-I should not be a deterrent. However, the fact that most patients remained culture-positive after 4-13 applications raises concerns that P-I is less effective than mupirocin for clearing nasal colonization. We recommend using quantitative cultures to further investigate the effectiveness of nasal P-I. Disclosures All Authors: No reported disclosures

Evaluation of the reliability of MRSA screens in patients undergoing universal decolonization

Purpose Colonization of methicillin-resistant Staphylococcus aureus (MRSA) can be detected via nasal screens. Evidence indicates that negative MRSA nasal screens may be used to de-escalate anti-MRSA antibiotics in pulmonary infections. In the ICU, universal decolonization with intranasal mupirocin is implemented to reduce MRSA infection risk. This study aimed to determine whether mupirocin administration affects the reliability of MRSA PCR nasal screens. Methods This retrospective study divided subjects based on timing of intranasal mupirocin administration—before and after MRSA screen. Subjects with confirmed pulmonary infection that received vancomycin, blood/respiratory cultures, and had MRSA PCR screen collected were included. Subjects with concurrent infection requiring vancomycin or MRSA infection in prior 30 days were excluded. Primary outcome of this non-inferiority study was the negative predictive value (NPV) of the screen. Secondary outcomes included the positive predictive value (PPV), sensitivity, and specificity of the screen and duration of vancomycin. Results Ultimately, 125 subjects were included in each group. The NPV in the group receiving mupirocin before screen was 95.2%, whereas the NPV in the group receiving mupirocin after screen was 99%. The difference between groups was -3.8% (90% CI -7.8%-0.2%; p=0.31), which failed to meet non-inferiority criteria. The secondary outcomes of PPV, sensitivity and specificity of the screen were similar in both groups. The duration of vancomycin was significantly longer in subjects receiving mupirocin before screen (3 days vs. 2 days; p&lt;0.05). Conclusion Intranasal mupirocin prior to the screen may reduce NPV in pulmonary infections. Approach de-escalation of vancomycin based on screen results with caution.

Polyaminosteroid Analogues as Potent Antibacterial Agents Against Mupirocin- Resistant Staphylococcus aureus Strains

Background: Nasal carriage of Staphylococcus aureus (S. aureus) constitutes an important risk factor for subsequent infections in some types of patient populations. Decolonization of carriers using intranasal mupirocin is widely used as a preventive measure. However, resistance to this agent has been rising and causing failure in the decolonization, highlighting the need for new alternatives. Objective: The objective of our study was to evaluate the antibacterial activity of polyaminosteroid analogues (squalamine and BSQ-1) against S. aureus strains with different levels of mupirocin-resistance. Methods: Using the broth microdilution method, we evaluated the minimum inhibitory concentration (MIC) of these molecules against S. aureus clinical strains including mupirocin-resistant strains. The emergence of resistance was evaluated by long-term and repeated exposure of a susceptible S. aureus strain to subinhibitory concentrations of squalamine, BSQ-1 or mupirocin. Results: We found that squalamine and BSQ-1 are active against mupirocin-susceptible and -resistant clinical isolates with MIC values of 3.125 μg/mL. Additionally, repeated exposure of a S. aureus strain to squalamine and BSQ-1 did not lead to the emergence of resistant bacteria, contrarily to mupirocin. Conclusion: Our study suggests that these molecules constitute promising new alternatives to mupirocin for nasal decolonization and prevention of endogenous infections.

Povidone Iodine: Properties, Mechanisms of Action, and Role in Infection Control and Staphylococcus aureus Decolonization

ABSTRACT Nasal decolonization is an integral part of the strategies used to control and prevent the spread of methicillin-resistant Staphylococcus aureus (MRSA) infections. The two most commonly used agents for decolonization are intranasal mupirocin 2% ointment and chlorhexidine wash, but the increasing emergence of resistance and treatment failure has underscored the need for alternative therapies. This article discusses povidone iodine (PVP-I) as an alternative decolonization agent and is based on literature reviewed during an expert’s workshop on resistance and MRSA decolonization. Compared to chlorhexidine and mupirocin, respectively, PVP-I 10 and 7.5% solutions demonstrated rapid and superior bactericidal activity against MRSA in in vitro and ex vivo studies. Notably, PVP-I 10 and 5% solutions were also active against both chlorhexidine-resistant and mupirocin-resistant strains, respectively. Unlike chlorhexidine and mupirocin, available reports have not observed a link between PVP-I and the induction of bacterial resistance or cross-resistance to antiseptics and antibiotics. These preclinical findings also translate into clinical decolonization, where intranasal PVP-I significantly improved the efficacy of chlorhexidine wash and was as effective as mupirocin in reducing surgical site infection in orthopedic surgery. Overall, these qualities of PVP-I make it a useful alternative decolonizing agent for the prevention of S. aureus infections, but additional experimental and clinical data are required to further evaluate the use of PVP-I in this setting.

HOME2 Study: Household Versus Personalized Decolonization in Households of Children With Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infection—A Randomized Clinical Trial

Background A household approach to decolonization decreases skin and soft tissue infection (SSTI) incidence, though this is burdensome and costly. As prior SSTI increases risk for SSTI, we hypothesized that the effectiveness of decolonization measures to prevent SSTI when targeted to household members with prior year SSTI would be noninferior to decolonizing all household members. Methods Upon completion of our 12-month observational Household Observation of Methicillin-resistant Staphylococcus aureus in the Environment (HOME) study, 102 households were enrolled in HOME2, a 12-month, randomized noninferiority trial. Pediatric index patients with community-associated methicillin-resistant Staphylococcus aureus (MRSA) SSTI, their household contacts, and pets were enrolled. Households were randomized 1:1 to the personalized (decolonization performed only by household members who experienced SSTI during the HOME study) or household (decolonization performed by all household members) approaches. The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily bleach-water baths. At 5 follow-up visits in participants’ homes, swabs to detect S. aureus were collected from participants, environmental surfaces, and pets; incident SSTIs were ascertained. Results Noninferiority of the personalized approach was established for the primary outcome 3-month cumulative SSTI: 23 of 212 (10.8%) participants reported SSTI in household approach households, while 23 of 236 (9.7%) participants reported SSTI in personalized approach households (difference in proportions, −1.1% [95% confidence interval, −6.7% to 4.5%]). In multivariable analyses, prior year SSTI and baseline MRSA colonization were associated with cumulative SSTI. Conclusions The personalized approach was noninferior to the household approach in preventing SSTI. Future studies should interrogate longer durations of decolonization and/or decontamination of the household environment to reduce household MRSA burden. Clinical Trials Registration NCT01814371.

Prevalence Of Staphylococcus Aureus Colonization In Patients For Total Joint Arthroplasty In South Africa

Background: Periprosthetic joint infections (PJIs) are a major source of morbidity and mortality for patients undergoing Total Joint Arthroplasty (TJA). Staphylococcus aureus (S aureus) colonization is an independent, modifiable risk factor for periprosthetic joint infections. Post-operative infections are reported to be ten times greater in S aureus carriers than in non-carriers in developed countries though recorded data is lacking for the developing world. This study aims to determine the prevalence of S aureus colonization in patients awaiting TJA in South Africa. Methods: We prospectively assessed 119 patients awaiting Total Knee Arthroplasty and Total Hip Arthroplasty between May and October 2016. We screened three separate anatomical sites on each patient for S aureus. Patients with positive cultures were treated with intranasal mupirocin ointment and chlorhexidine body wash. Univariate and comparative statistical analyses to determine risk factors for colonization was conducted using t-tests, Fisher’s exact tests, and chi square analyses. Results: The overall prevalence of Methicillin Sensitive S aureus colonization was 31.9% (n = 38). There were no patients colonized with Methicillin Resistant S aureus. Nasal swabs returned a yield of 81.6% (n=31), with groin swabs and axillary swabs at 39.5% (n=15) and 28.9% (n=11) respectively. Eradication was successful in 94.74% (n=36) after five days treatment. All patients (100%) were decolonized after counseling and repeat eradication treatment. The overall complication rate was 7.6% (n=9). The 30-day readmission rate in the S aureus -colonized group was 7.9% (n=3) as opposed to 7.4% (n=6) in the non-colonized cohort. There were no 60- and 90-day readmissions and no cases were revised at a mean follow-up of 2.26 years. Conclusions: The rate of S aureus colonization in patients undergoing elective TJA in a developing country was 31.9% and is equivalent to reported rates in developed countries. Eradication treatment with combined intranasal mupirocin ointment and chlorhexidine body wash is a successful treatment modality. A larger cohort of patients is recommended to determine risk factors and post-operative septic sequelae in this population group.

Prevalence Of Staphylococcus Aureus Colonization In Patients For Total Joint Arthroplasty In South Africa

Background: Periprosthetic joint infections are a major source of morbidity and mortality for patients undergoing Total Joint Arthroplasty. Staphylococcus aureus colonization is an independent, modifiable risk factor for periprosthetic joint infections. Post-operative infections are reported to be ten times greater in Staphylococcus aureus carriers than in non-carriers in developed countries though recorded data is lacking for the developing world. This study aims to determine the prevalence of Staphylococcus aureus colonization in patients awaiting Total Joint Arthroplasty in South Africa. Methods: We prospectively assessed 119 patients awaiting Total Knee Arthroplasty and Total Hip Arthroplasty between May and October 2016. We screened three separate anatomical sites on each patient for Staphylococcus aureus. Patients with positive cultures were treated with intranasal mupirocin ointment and chlorhexidine body wash. Univariate and comparative statistical analyses to determine risk factors for colonization was conducted using t-tests, Fisher’s exact tests, and chi square analyses. Results: The overall prevalence of Methicillin Sensitive Staphylococcus aureus colonization was 31.9% (n = 38). There were no patients colonized with Methicillin Resistant Staphylococcus aureus . Nasal swabs returned a yield of 81.6%(n=31), with groin swabs and axillary swabs at 39.5% (n=15) and 28.9% (n=11) respectively. Eradication was successful in 94.74% (n=36) after five days treatment. All patients (100%) were decolonized after counseling and repeat eradication treatment. The overall complication rate was 7.6% (n=9). The 30-day readmission rate in the Staphylococcus aureus -colonized group was 7.9% (n=3) as opposed to 7.4% (n=6) in the non-colonized cohort. There were no 60- and 90-day readmissions and no cases were revised at a mean follow-up of 2.26 years. Conclusions: The rate of Staphylococcus aureus colonization in patients undergoing elective Total Joint Arthroplasty in a developing country was 31.9% and is equivalent to reported rates in developed countries. Eradication treatment with combined intranasal mupirocin ointment and chlorhexidine body wash is a successful treatment modality. A larger cohort of patients is recommended to determine risk factors and post-operative septic sequelae in this population group.