Emergence and spread of a mupirocin-resistant variant of the European epidemic fusidic acid-resistant impetigo clone of Staphylococcus aureus, Belgium, 2013 to 2023.

BackgroundAntimicrobial resistance to mupirocin and fusidic acid, which are used for treatment of skin infections caused by Staphylococcus aureus, is of concern.AimTo investigate resistance to fusidic acid and mupirocin in meticillin-susceptible S. aureus (MSSA) from community-acquired skin and soft tissue infections (SSTIs) in Belgium.MethodsWe collected 2013-2023 data on fusidic acid and mupirocin resistance in SSTI-associated MSSA from two large Belgian laboratories. Resistant MSSA isolates sent to the Belgian Staphylococci Reference Centre were spa-typed and analysed for the presence of the eta and etb virulence genes and the mupA resistance gene. In addition, we whole genome sequenced MSSA isolates collected between October 2021 and September 2023.ResultsMupirocin resistance increased between 2013 and 2023 from 0.5-1.5% to 1.7-5.6%. Between 2018 and 2023, 91.4% (64/70) of mupirocin-resistant isolates were co-resistant to fusidic acid. By September 2023, between 8.9% (15/168) and 10.1% (11/109) of children isolates from the two laboratories were co-resistant. Of the 33 sequenced isolates, 29 were sequence type 121, clonal and more distantly related to the European epidemic fusidic acid-resistant impetigo clone (EEFIC) observed in Belgium in 2020. These isolates carried the mupA and fusB genes conferring resistance to mupirocin and fusidic acid, respectively, and the eta and etb virulence genes.ConclusionWe highlight the spread of a mupirocin-resistant EEFIC in children, with a seasonal trend for the third quarter of the year. This is of concern because this variant is resistant to the two main topical antibiotics used to treat impetigo in Belgium.

Synthesis and characterization of mupirocin-LDH/PVA nanofibrous composite as a dual-carrier drug release system.

Nowadays, nanofibrous structures based on organic and inorganic materials are considered a drug delivery system for the controlled release of antibiotics and other antibacterial agents. The main goal of this research is a combination of the special properties of nanofibrous structure and Mupirocin-loaded Layered double hydroxide (LDH) to obtain a dual-carrier drug release system to provide long term antibacterial properties in wound healing process. Regards, unloaded layered double hydroxide (LDH) and Mupirocin-loaded LDH, which were synthesized by co-precipitation method, were added to Polyvinyl alcohol (PVA) solution in different mass ratio and electrospun using different processing conditions. The physico-chemical characterizations were performed using SEM, FTIR and tensile strength tests. The biological properties of the fabricated nanocomposites were evaluated using antibacterial test and in vitro cell culturing followed by MTT assay. The SEM results showed a bead-less and uniform morphology of nanofibrous composite containing Mupirocin(2.3 wt%)-LDH(15 wt%)/PVA with an average fiber diameter of about 270 ± 58 nm. According to the release study, the maximum release of the mupirocin drug was about 54 % in the first 6 h. The antibiogram analysis exhibited good antibacterial activity of mupirocin-loaded nanocomposite against both bacteria, especially gram-positive one. Finally, MTT assay approved the biocompatibility of the mupirocin-loaded nanocomposite. Overall, the produced nanofibrous composites would be a promising dual-carrier system for controlled release of antibiotic.

Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression.

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.

Topical antibiotics in the prevention of port-site infection after elective day care laparoscopic cholecystectomy.

BACKGROUND: Wound-related infections and complications are rare after day care laparoscopic cholecystectomy (LC). They can have a significant adverse impact on the postoperative course after an uneventful elective LC. The use of topical antibiotics over the port site may prevent such complications. MATERIALS AND METHODS: This trial was conducted from January 2018 to June 2019. Two hundred and fifty patients who met the inclusion and exclusion criteria were included in the study. They were randomized into the topical antibiotic group (Group A, n = 125) and control group (Group B, n = 125). All patients underwent four-port LC. Mupirocin 2% topical antibiotic ointment was applied to all four-port sites in Group A, whereas no topical antibiotic was used in Group B. One dose of prophylactic systemic antibiotics was given to all patients in both groups. RESULTS: The mean age was 43.22 ± 12.7 years in Group A and 43.44 ± 12.5 years in Group B. The comorbidities and the other variables were comparable between the two groups. The port-site infection (PSI) was observed in one patient in Group A and three patients in Group B, which was statistically nonsignificant (P = 0.622). The mean time of detection of infection was 4.75 ± 1.7 days. All the infections were superficial surgical site infections. Microbiological swabs culture of the infected wounds yielded no growth of bacteria. CONCLUSION: The PSI after LC is very less. The use of topical antibiotics to prevent PSIs after LC could not be established.

Carriage of methicillin-resistant Staphylococcus aureus in children <6 years old: a retrospective follow-up study of the natural course and effectiveness of decolonization treatment.

BACKGROUND: Decolonization treatment of MRSA carriers is recommended in Denmark, except in households with MRSA-positive children <2 years old (wait-and-see approach). OBJECTIVES: To investigate a wait-and-see approach in children 2-5 years old, and the effect of decolonization treatment of MRSA carriage in all children <6 years old. PATIENTS AND METHODS: In this retrospective follow-up study, we included MRSA carriers <6 years old in the Capital Region of Denmark from 2007 to 2021. Data were collected from laboratory information systems and electronic patient records. We divided children into age groups of <2 years or 2-5 years and decolonization treatment versus no treatment. Treatment was chlorhexidine body washes and nasal mupirocin, sometimes supplemented with systemic antibiotics. Children were followed until becoming MRSA free, or censoring. The probability of becoming MRSA free was investigated with Cox regression (higher HRs indicate faster decolonization). RESULTS: Of 348 included children, 226 were <2 years old [56/226 (25%) received treatment] and 122 were 2-5 years old [90/122 (74%) received treatment]. Multivariable analyses did not show a larger effect of decolonization treatment versus no treatment in <2-year-olds (HR 0.92, 95% CI 0.52-1.65) or 2-5-year-olds (HR 0.54, 95% CI 0.26-1.12). Without treatment, 2-5-year-olds tended to clear MRSA faster than <2-year-olds (HR 1.81, 95% CI 0.98-3.37). CONCLUSIONS: We did not find a larger effect of decolonization treatment versus no treatment in children <6 years old, and 2-5-year-olds tended to become MRSA free faster than <2-year-olds. These results support a wait-and-see approach for all children <6 years old, but further studies are needed.

Effect of Different Local Antibiotic Regimens on Prevention of Postoperative Infection in Clean Surgical Wounds: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the efficacy of several local antibiotic regimens in preventing surgical site infection (SSI) in clean surgical wounds. DATA SOURCES: The authors searched CNKI (China National Knowledge Infrastructure), the VIP (VIP information resource integration service platform), Wanfang Data knowledge service platform (WANFANG), SinoMed, Cochrane Library, EMBASE, and PubMed. STUDY SELECTION: A total of 20 randomized controlled trials published between January 1, 2000 and April 1, 2021 were included in this meta-analysis. DATA EXTRACTION: Authors extracted the name of the first author, publication date, country, type of surgery, follow-up time, mean age of participants, sample size of each group, interventions, outcome indicators, and study type from each article. DATA SYNTHESIS: The overall effectiveness of eight local managements in reducing the incidence of the SSI effect were compared through the SUCRA (surface under the cumulative ranking curve) probabilities. The results of a network meta-analysis demonstrated that gentamicin ointment (odds ratio [OR], 0.16; 95% CI, 0.04-0.60), mupirocin ointment (OR, 0.44; 95% CI, 0.21-0.94), and gentamicin soaking of the graft (OR, 0.63; 95% CI, 0.44-0.91) significantly reduced the incidence of SSI compared with control. Further, vancomycin soaking of the graft (86.7%) ranked first, followed by gentamicin ointment (81.1%), gentamicin irrigation (79.9%), mupirocin ointment (56.8%), triple antibiotic ointment (47.8%), gentamicin soaking of the graft (42.3%), and vancomycin powder (22.1%); ampicillin powder (17.8%) was the least effective drug. CONCLUSIONS: The findings indicate that local antibiotics combined with conventional antibiotics in the wound before wound closure are effective in reducing the incidence of SSI in clean surgical wounds. Vancomycin inoculation of the graft exhibited the best effect.

Impact of active surveillance and decolonization strategies for methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.

OBJECTIVE: To assess the impact of active surveillance and decolonization strategies on methicillin-resistant Staphylococcus aureus (MRSA) infection rates in a NICU. STUDY DESIGN: MRSA infection rates were compared before (2014-2016) and during (2017-2022) an active surveillance program. Eligible infants were decolonized with chlorohexidine gluconate (CHG) bathing and/or topical mupirocin. Successful decolonization and rates of recolonization were assessed. RESULTS: Fifty-two (0.57%) of 9 100 hospitalized infants had invasive MRSA infections from 2014 to 2022; infection rates declined non-significantly. During the 6-year surveillance program, the risk of infection was 16.9-times [CI95 8.4, 34.1] higher in colonized infants than uncolonized infants. Those colonized with mupirocin-susceptible MRSA were more likely successfully decolonized (aOR 9.7 [CI95 4.2, 22.5]). Of 57 infants successfully decolonized who remained hospitalized, 34 (60%) became recolonized. CONCLUSIONS: MRSA infection rates did not significantly decline in association with an active surveillance and decolonization program. Alternatives to mupirocin and CHG are needed to facilitate decolonization.

The Hybrid Antibiotic Thiomarinol A Overcomes Intrinsic Resistance in Escherichia coli Using a Privileged Dithiolopyrrolone Moiety.

An impermeable outer membrane and multidrug efflux pumps work in concert to provide Gram-negative bacteria with intrinsic resistance against many antibiotics. These resistance mechanisms reduce the intracellular concentrations of antibiotics and render them ineffective. The natural product thiomarinol A combines holothin, a dithiolopyrrolone antibiotic, with marinolic acid A, a close analogue of mupirocin. The hybridity of thiomarinol A converts the mupirocin scaffold from inhibiting Gram-positive bacteria to inhibiting both Gram-positive and -negative bacteria. We found that thiomarinol A accumulates significantly more than mupirocin within the Gram-negative bacterium Escherichia coli, likely contributing to its broad-spectrum activity. Antibiotic susceptibility testing of E. coli mutants reveals that thiomarinol A overcomes the intrinsic resistance mechanisms that render mupirocin inactive. Structure-activity relationship studies suggest that the dithiolopyrrolone is a privileged moiety for improving the accumulation and antibiotic activity of the mupirocin scaffold without compromising binding to isoleucyl-tRNA synthetase. These studies also highlight that accumulation is required but not sufficient for antibiotic activity. Our work reveals a role of the dithiolopyrrolone moiety in overcoming intrinsic mupirocin resistance in E. coli and provides a starting point for designing dual-acting and high-accumulating hybrid antibiotics.

Antimicrobial susceptibilities and genomic characteristics of methicillin-resistant Staphylococcus aureus resistant to mupirocin in Stockholm, Sweden.

The aim of this study was to investigate antimicrobial susceptibilities and genomic characteristics of mupirocin-resistant MRSA isolates in Stockholm, Sweden. In total, 44 non-duplicate mupirocin-resistant MRSA isolates detected in Stockholm during 2010-2022 were investigated. Antimicrobial susceptibility testing was performed using broth microdilution method and further tested for high-level mupirocin-resistance (MuH) and rifampicin by Etest®. All isolates were subjected to whole genome sequencing. 41 isolates presented MuH with MICs ≥1024 mg/L whilst three isolates displayed low-level mupirocin resistance (MuL). mupA-gene was detected in all MuH isolates. Point mutations in ileS gene leading to N213D and V588F were identified in the three MuL isolates. Mutation in rpoB (H481N) was detected in a rifampicin-resistant isolate. Among the isolates, 15 multi-locus sequence types (MLST) were identified, with the four most common sequence types (ST22, ST72, ST8, and ST125) accounting for 66% of the isolates. Mupirocin-resistant MRSA in Stockholm was uncommon, with a percentage of <0.5% among MRSA cases during 2010-2022. In the present study, most mupirocin-resistant isolates were MuH and mupA-positive, predominantly linked to ST22 or ST72 isolates. MuL-resistance was associated with a point mutation in the IleS protein. A multidrug-resistant ST1-MRSA-IV strain was resistant to both mupirocin and rifampicin.

Patient compliance with the implementation of a decolonization strategy for Staphylococcus aureus in hip and knee replacements.

BACKGROUND: A preoperative, in-community antimicrobial decolonization protocol combining chlorohexidine gluconate (CHG) sponges and mupirocin ointment to reduce surgical site infections amongst hip and knee replacement patients has been adopted in Alberta, Canada. Patient compliance with the protocol is essential for effectiveness. It is, therefore, important to understand patterns, and reasons why, patients do, and do not, comply. METHODS: A descriptive survey of patients having elective total hip or knee replacement at seven clinics in Alberta was conducted to determine patient compliance and reasons for noncompliance. Descriptive statistics and multivariate logistic regression were computed. RESULTS: Patient compliance was assessed in 3,427 patients. There were no differences in compliance based on the baseline protocols and enhanced protocols, but there was a difference based on clinic location. The odds of compliance with three CHG sponges were 4.47 times higher in rural versus urban clinics (P < .001). The most common reason for noncompliance for patients instructed to use 3 CHG sponges was "patient forgot". CONCLUSIONS: Compliance did not change when enhanced protocols were introduced; however, compliance differed by clinic location. Reasons for noncompliance included "sponges not provided", "patient forgot", and "surgery date moved". Results may inform clinics on areas where improvements could be made to increase patient compliance.

Topical antibiotics prophylaxis for infections of indwelling pleural/peritoneal catheters (TAP-IPC): A pilot study.

BACKGROUND AND OBJECTIVE: Indwelling pleural catheter (IPC) and indwelling peritoneal catheter (IPeC) have established roles in the management of malignant pleural and peritoneal effusions but catheter-related infections remain a major concern. Topical mupirocin prophylaxis has been shown to reduce peritoneal dialysis catheter infections. This study aimed to assess the (i) compatibility of IPC with mupirocin and (ii) feasibility, tolerability and compliance of topical mupirocin prophylaxis in patients with an IPC or IPeC. METHODS: (i) Three preparations of mupirocin were applied onto segments of IPC thrice weekly and examined with scanning electron microscope (SEM) at different time intervals. (ii) Consecutive patients fitted with IPC or IPeC were given topical mupirocin prophylaxis to apply to the catheter exit-site following every drainage/dressing change (at least twice weekly) and followed up for 6 months. RESULTS: (i) No detectable structural catheter damage was found with mupirocin applied for up to 6 months. (ii) Fifty indwelling catheters were inserted in 48 patients for malignant pleural (n = 41) and peritoneal (n = 9) effusions. Median follow-up was 121 [median, IQR 19-181] days. All patients tolerated mupirocin well; one patient reported short-term local tenderness. Compliance was excellent with 95.8% of the 989 scheduled doses delivered. Six patients developed catheter-related pleural (n = 3), concurrent peritoneal/local (n = 1) and skin/tract (n = 2) infections from Streptococcus mitis (with Bacillus species or anaerobes), Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. CONCLUSION: This first study of long-term prevention of IPC- or IPeC-related infections found topical mupirocin prophylaxis feasible and well tolerated. Its efficacy warrants future randomized studies.

Chitosan and α-cellulose-based mupirocin topical film-forming spray: Optimization, in vitro characterization, antimicrobial studies and wound healing activity.

The study aimed to develop a biopolymer-based mupirocin film-forming spray (MUP-FFS) for wound healing using chitosan and α-cellulose. MUP-FFS formulation was optimized by box-Behnken design, wherein the amount of chitosan, glycerol, and microfluidizer cycles showed a significant effect on the drying time and sprayability, but drug release remained unaffected. The optimized MUP-FFS formulation prepared by 13 microfluidizer cycles containing chitosan (0.125 %), glycerol (2.76 %) was quickly sprayable with 235 s drying time. The viscosity, spray uniformity and occlusive potential were found optimum for MUP-FFS. MUP-FFS released 98.066 % of MUP, 2-fold and 4-fold greater than the marketed ointment and MUP-API. The transmission electron microscopy displayed a homogeneous fibrous network, and scanning electron microphotographs showed uniform drug distribution on the MUP-film surface. The antimicrobial study revealed the efficacy of MUP-FFS against S.aureus and E.coli, wherein the former was more susceptible to formulation than the later. MUP-FFS indicated better wound contraction and healing than other groups on 7th and 14th day in rats. On Day-21, MUP-FFS could regress TGF-ß1 to a normal level similar to the marketed formulation, which was also reflected in histopathological observations. Therefore, MUP-FFS can be a treatment option for chronic wounds, applied without touch and with minimal mechanical pressure.

Fabrication of geraniol nanophytosomes loaded into polyvinyl alcohol: A new product for the treatment of wounds infected with methicillin-resistant Staphylococcusaureus.

The current study was conducted to evaluate the effectiveness of geraniol nanophytosomes in accelerating the healing process of wounds infected with Methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model. The physicochemical properties confirmed physical properties and successful synthesis of the nanophytosomes. Wounds were induced and mice (n = 90) were treated with a base ointment (negative control group) and/or mupirocin (positive control) and also formulations prepared from geraniol (GNL), geraniol nanophytosomes (NPhs-GNL), and PVA/NPhs-GNL. Wound contraction, total bacterial count, pathological parameters and the expressions of bFGF, CD31 and COL1A were also assessed. The results showed that topical administration of mupirocin and PVA/NPhs/GNL increased wound contraction, fibroblast and epithelization and also the expressions of bFGF, CD31 and COL1A while decreased the expression of total bacterial count and edema compared with negative control mice (P = 0.001). The results also showed that PVA/NPhs-GNL and mupirocin could compete and PVA/NPhs-GNL formulation was safe. In conclusion, the prepared formulations accelerated the wound healing process by modulation in proliferative genes. Geraniol nanophytosomes loaded into PVA could improve the healing in infected full-thickness wounds healing process and can be used for the treatment of infected wounds after future clinical studies.

Tailoring polyethylene oxide-modified cross-linked chitosan/PVA nanofibrous membranes: Burn dressing scaffold developed for mupirocin release.

In emergency treatment research, the focus on chitosan-based products for wound healing has been consistent. This study specifically explores a dressing made by mixing chitosan (CS) and poly (vinyl alcohol) PVA. Using electrospinning technology, nanofiber membranes of CS and PVA are created with the assistance of non-toxic and hydrophilic polyethylene oxide (PEO). The outcome is a new nanofibrous membrane loaded with mupirocin, designed for healing burn wounds. The study delves into the influence of PVA, CS, and PEO concentrations on the structural and chemical characteristics of the mats. This comprehensive exploration involves techniques such as Scanning Electron Microscope (SEM), Atomic Force Microscopy (AFM) imaging, Fourier Transform Infrared Spectrometry (FTIR analysis), and Contact angle measurements. Additionally, the research evaluates the antibacterial performance and biomedical behavior of the developed scaffolds. PEO proves beneficial in the electrospinning process, contributing to smoother fibers. Meanwhile, the addition of CS and mupirocin leads to formation of the thinner nanofibers (251 ± 5 µm and 263 ± 4 µm, respectively) and scaffolds with higher swelling (up to ∼3.5 times at 90 min). Notably, the (MTT) assay confirms the non-cytotoxicity of the fabricated nanofibers, with proliferations exceeding ∼85% for all samples. The crosslinked samples released the drug more slowly than the non-crosslinked dressings, with 80% of the scaffolds releasing the drug within 24 h. The in-vivo investigations suggested that the drug-containing scaffolds performed reliably and showed promise as a medical dressing for treating burn wounds.

Exploring alternative strategies for Staphylococcus aureus nasal decolonization: insights from preclinical studies.

Nasal decolonization of Staphylococcus aureus with the antibiotic mupirocin is a common clinical practice before complex surgical procedures, to prevent hospital acquired infections. However, widespread use of mupirocin has led to the development of resistant S. aureus strains and there is a limited scope for developing new antibiotics for S. aureus nasal decolonization. It is therefore necessary to develop alternative and nonantibiotic nasal decolonization methods. In this review, we broadly discussed the effectiveness of different nonantibiotic antimicrobial agents that are currently not in clinical practice, but are experimentally proved to be efficacious in promoting S. aureus nasal decolonization. These include lytic bacteriophages, bacteriolytic enzymes, tea tree oil, apple vinegar, and antimicrobial peptides. We have also discussed the possibility of using photodynamic therapy for S. aureus nasal decolonization. This article highlights the importance of further large scale clinical studies for selecting the most suitable and alternative nasal decolonizing agent.

Comparison of global decolonization efficacy with mupirocin nasal drop and chlorhexidine mouthwash in acute leukemia patients: randomized clinical trial.

PURPOSE: Neutropenic fever remains a major complication in acute leukemia. Decolonization is assumed as a promising intervention for eradicating causative agents of infection. METHODS: In this randomized clinical trial, 96 patients with acute leukemia were assigned randomly to mupirocin nasal drop 2% (n = 32), chlorhexidine mouthwash 0.2% (n = 33), and control group (n = 31). In control group, patients did not receive any medication for decolonization. All patients received treatment for 5 days (2 days prior to chemotherapy until 3 days after chemotherapy). Pharynx and nasal swabs were taken prior to the intervention and at the end of decolonization period in all groups. Antibiotic susceptibility testing was performed by the disc diffusion method in order to identify bacterial isolates. RESULTS: Bacterial recovery of both nasal and pharynx swabs was observed after global decolonization with mupirocin nasal drop. Decolonization with mupirocin significantly eradicated Coagulase-negative staphylococci (CONS) in both nasal and pharynx swabs (p-value = 0.000). Moreover, mupirocin decreased Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) species. Chlorhexidine mouthwash significantly eradicated CONS in pharynx swabs (p-value = 0.000). In addition, both decolonization strategies decreased both antibiotic use and frequency of fever in leukemic patients. CONCLUSION: Global decolonization with mupirocin nasal drop not only eradicates both nasal and pharynx microorganisms, but also reduces antibiotic requirement and frequency of fever in patients with acute leukemia. The protocol of the present study was approved on December 2016 (registry number: IRCT20160310026998N6).

Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs: A Randomized Clinical Trial.

Importance: Universal 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. Objective: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. Design, Setting, and Participants: Two-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. Intervention: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). Main Outcomes and Measures: ICU-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%. Results: Among 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 Relevance: Nasal 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 Registration: ClinicalTrials.gov Identifier: NCT03140423.

Nasal decolonization: What antimicrobials and antiseptics are most effective before surgery and in the ICU.

BACKGROUND: Staphylococcus aureus colonization is a key risk factor for S. aureus infections in surgical patients and in hospitalized patients. Many studies have assessed various decolonization agents, protocols, and settings. This review summarizes key findings about nasal decolonization for 2 different patient populations: patients undergoing surgery and patients hospitalized in intensive care units. METHODS: We reviewed major studies related to decolonization of patients colonized with S. aureus and who were either undergoing surgical procedures or were hospitalized in intensive care units. We focused on recent studies, particularly randomized controlled trials and robust quasi-experimental trials. We also reviewed select non-randomized trials when more rigorous trials were limited. DISCUSSION/CONCLUSIONS: Mupirocin is the best-studied agent for decolonization. Its use reduces the risk of surgical site infection following orthopedic surgery (strongest data) and cardiac surgery. Mupirocin decolonization also reduces the incidence of S. aureus clinical cultures in the intensive care unit. Povidone-iodine is less well-studied. Current data suggest that it decreases the risk of surgical site infections after orthopedic surgical procedures. In contrast, povidone-iodine is less effective than mupirocin for reducing the incidence of S aureus clinical cultures in the intensive care unit. Both mupirocin and povidone-iodine have important limitations, highlighting the need for future decolonization research.