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.

Chromosomal and plasmid localization of ileS2 in high-level mupirocin-resistant Staphylococcus pseudintermedius and Staphylococcus aureus isolated from canine and feline origins.

OBJECTIVES: To characterize the mobile genetic elements and genetic localization of ileS2 in high-level mupirocin-resistant (Hi-MupR) methicillin-resistant Staphylococcus pseudintermedius (MRSP) and MRSA isolates recovered from canine and feline clinical samples. METHODS: The identification of bacterial species and presence of mecA and ileS2 genes in MRSP and MRSA isolates were performed using MALDI-TOF MS and PCR, respectively. Antimicrobial resistance (AMR) phenotypes were determined by broth microdilution assays. The genome characteristics, ileS2-containing elements and staphylococcal cassette chromosome mec (SCCmec) were illustrated using complete circular genomes obtained from hybrid assembly of Illumina short-reads and Oxford Nanopore Technologies long-reads. These were analysed through phylogenetic and bioinformatics approaches. RESULTS: A total of 18 MRSP clinical isolates and four MRSA clinical isolates exhibited the Hi-MupR phenotype and carried multiple AMR genes, including mecA and ileS2 genes. MRSP ST182-SCCmec V (n = 6) and ST282-ΨSCCmec57395-t10 (n = 4) contained the ileS2 transposable unit associated with IS257 on the chromosome. Three MRSA ST398-SCCmec V-t034/t4652 isolates carried ∼42 kb pSK41-like ileS2 plasmids, whereas similar ileS2 plasmids lacking tra genes were found in MRSP ST282-ΨSCCmec57395-t72/t21 isolates. Furthermore, a new group of ileS2 plasmids, carried by MRSP ST45-ΨSCCmec57395, ST433-ΨSCCmecKW21-t05 and ST2165-SCCmec IV-t06, and by one MRSA ST398-SCCmec V-t034 strain, shared the plasmid backbone with the cfr/fexA-carrying plasmid pM084526_1 in MRSA ST398. CONCLUSIONS: This study provides the first evidence of ileS2 integration into the S. pseudintermedius chromosome, which is a rare occurrence in staphylococcal species, and plasmids played a pivotal role in dissemination of ileS2 in both staphylococcal species.

Exploring mechanisms of mupirocin resistance and hyper-resistance.

Mupirocin is a broad-spectrum antibiotic that acts predominantly against Gram-positive bacteria. It is produced by Pseudomonas fluorescens NCIMB 10586 and has been clinically used to treat primary and secondary skin infections and to eradicate nasal colonisation of methicillin-resistant Staphylococcus aureus strains. Mupirocin inhibits protein synthesis by blocking the active site of isoleucyl-tRNA synthetase (IleRS), which prevents the enzyme from binding isoleucine and ATP for Ile-tRNAIle synthesis. Two types of IleRS are found in bacteria - while IleRS1 is susceptible to mupirocin inhibition, IleRS2 provides resistance to cells. These two types belong to distinct evolutionary clades which likely emerged from an early gene duplication in bacteria. Resistance in IleRS2 is based on the loss of interactions that govern mupirocin binding to IleRS1, such as hydrogen bonding to the carboxylate moiety of mupirocin. IleRS2 enzymes with Ki in the millimolar range have recently been discovered. These hyper-resistant IleRS2 variants surprisingly have a non-canonical version of the catalytic motif, which serves as a signature motif of class I aminoacyl-tRNA synthetases to which IleRS belongs. The non-canonical motif, in which the 1st and 3rd positions are swapped, is key for hyper-resistance and can be accommodated without abolishing enzyme activity in IleRS2 but not in IleRS1. Clinical use of mupirocin led to the emergence of resistance in S. aureus. Low-level resistance arises by mutations of the housekeeping IleRS1, while high-level resistance develops by the acquisition of the resistant IleRS2 on a plasmid. There is no evidence that hyper-resistant variants have been found in clinical isolates.

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.

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.

Fabrication of Mupirocin-Loaded PEGylated Chitosan Nanoparticulate Films for Enhanced Wound Healing.

Chitosan-based biomaterials are being investigated for their unique properties that support skin regeneration and wound healing. This study focused on the preparation and characterization of a mupirocin (Mup)-loaded PEGylated chitosan (CS-PEG) nanoparticulate film (NF) [CBNF]. The CBNF was characterized using FTIR spectroscopy and SEM analysis. The results demonstrated that CBNF was successfully incorporated into the composites, as shown by functional group modification through FTIR analysis. Additionally, the SEM micrograph revealed the deposition of nanoparticles (<200 nm) on the surface of transparent CBNF. The film has higher water absorption (≥1700%) and moderate water retention ability within 6 h. Furthermore, histological findings showed significant development, with re-epithelialization and granulation of tissues after 19 days, indicating the healing efficiency of CNBF. These results suggest that drug-loaded films could be an effective carrier and delivery agent for Mup-like anti-inflammatory drugs.

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.

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.

Molecular basis for coordinating secondary metabolite production by bacterial and plant signaling molecules.

The production of secondary metabolites is a major mechanism used by beneficial rhizobacteria to antagonize plant pathogens. These bacteria have evolved to coordinate the production of different secondary metabolites due to the heavy metabolic burden imposed by secondary metabolism. However, for most secondary metabolites produced by bacteria, it is not known how their biosynthesis is coordinated. Here, we showed that PhlH from the rhizobacterium Pseudomonas fluorescens is a TetR-family regulator coordinating the expression of enzymes related to the biosynthesis of several secondary metabolites, including 2,4-diacetylphloroglucinol (2,4-DAPG), mupirocin, and pyoverdine. We present structures of PhlH in both its apo form and 2,4-DAPG-bound form and elucidate its ligand-recognizing and allosteric switching mechanisms. Moreover, we found that dissociation of 2,4-DAPG from the ligand-binding domain of PhlH was sufficient to allosterically trigger a pendulum-like movement of the DNA-binding domains within the PhlH dimer, leading to a closed-to-open conformational transition. Finally, molecular dynamics simulations confirmed that two distinct conformational states were stabilized by specific hydrogen bonding interactions and that disruption of these hydrogen bonds had profound effects on the conformational transition. Our findings not only reveal a well-conserved route of allosteric signal transduction in TetR-family regulators but also provide novel mechanistic insights into bacterial metabolic coregulation.

Chlorhexidine and Mupirocin for Clearance of Methicillin-Resistant Staphylococcus aureus Colonization After Hospital Discharge: A Secondary Analysis of the Changing Lives by Eradicating Antibiotic Resistance Trial.

BACKGROUND: The CLEAR Trial demonstrated that a multisite body decolonization regimen reduced post-discharge infection and hospitalization in methicillin-resistant Staphylococcus aureus (MRSA) carriers. Here, we describe decolonization efficacy. METHODS: We performed a large, multicenter, randomized clinical trial of MRSA decolonization among adult patients after hospital discharge with MRSA infection or colonization. Participants were randomized 1:1 to either MRSA prevention education or education plus decolonization with topical chlorhexidine, oral chlorhexidine, and nasal mupirocin. Participants were swabbed in the nares, throat, axilla/groin, and wound (if applicable) at baseline and 1, 3, 6, and 9 months after randomization. The primary outcomes of this study are follow-up colonization differences between groups. RESULTS: Among 2121 participants, 1058 were randomized to decolonization. By 1 month, MRSA colonization was lower in the decolonization group compared with the education-only group (odds ration [OR] = 0.44; 95% confidence interval [CI], .36-.54; P ≤ .001). A similar magnitude of reduction was seen in the nares (OR = 0.34; 95% CI, .27-.42; P < .001), throat (OR = 0.55; 95% CI, .42-.73; P < .001), and axilla/groin (OR = 0.57; 95% CI, .43-.75; P < .001). These differences persisted through month 9 except at the wound site, which had a relatively small sample size. Higher regimen adherence was associated with lower MRSA colonization (P ≤ .01). CONCLUSIONS: In a randomized, clinical trial, a repeated post-discharge decolonization regimen for MRSA carriers reduced MRSA colonization overall and at multiple body sites. Higher treatment adherence was associated with greater reductions in MRSA colonization.

Antimicrobial Photodynamic Therapy in the Nasal Decolonization of Maintenance Hemodialysis Patients: A Pilot Randomized Trial.

RATIONALE & OBJECTIVE: Infections are an important cause of mortality among patients receiving maintenance hemodialysis. Staphylococcus aureus is a frequent etiological agent, and previous nasal colonization is a risk factor for infection. Repeated antimicrobial decolonization reduces infection in this population but can induce antibiotic resistance. We compared photodynamic therapy, a promising bactericidal treatment that does not induce resistance, to mupirocin treatment among nasal carriers of S aureus. STUDY DESIGN: Randomized controlled pilot study. SETTING & PARTICIPANTS: 34 patients receiving maintenance hemodialysis who had nasal carriage of S aureus. INTERVENTIONS: Patients were randomly assigned to decolonization with a single application of photodynamic therapy (wavelength of 660nm, 400mW/cm2, 300 seconds, methylene blue 0.01%) or with a topical mupirocin regimen (twice a day for 5 days). OUTCOME: Nasal swabs were collected at time 0 (when the carrier state was identified), directly after treatment completion, 1 month after treatment, and 3 months after treatment. Bacterial isolates were subjected to proteomic analysis to identify the species present, and antimicrobial susceptibility was characterized. RESULTS: All 17 participants randomized to photodynamic therapy and 13 of 17 (77%) randomized to mupirocin were adherent to treatment. Directly after treatment was completed, 12 participants receiving photodynamic therapy (71%) and 13 participants treated with mupirocin (77%) had cultures that were negative for S aureus (risk ratio, 0.92 [95% CI, 0.61-1.38]; P=0.9). Of the patients who had negative cultures directly after completion of photodynamic therapy, 67% were recolonized within 3 months. There were no adverse events in the photodynamic therapy group. LIMITATIONS: Testing was restricted to assessing nasal colonization; infectious complications were not assessed. CONCLUSIONS: Photodynamic therapy is a feasible approach to treating nasal carriage of S aureus. Future larger studies should be conducted to determine whether photodynamic therapy is equivalent to the standard of care with mupirocin. FUNDING: Government grant (National Council for Scientific and Technological Development process 3146682020-9). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT04047914.

Novel recombinant endolysin ointment with broad antimicrobial activity against methicillin-resistant Staphylococcus aureus isolated from wounds and burns.

The major problem in the management of burn wounds is infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of infection in burn wounds. Antibiotic-resistant bacteria around the world have become a major therapeutic challenge. Bacteriophages and their lysin are suggested as an antimicrobial alternative agent. The approach of this study was to evaluate the potential of recombinant phage lysin ointment efficacy in MRSA burn wound infection in vitro. Whole genome sequencing was performed to the three isolated bacteriophages by ABM, USA using Illumina next-generation sequencing (NGS) technology. De novo assembly and genetic analysis carried out. Expression of lysin genes was performed by cloning using Escherichia coli JM109. Lysin protein extraction and purification was performed before and after cloning using precipitation by ammonium sulfate, dialysis, and gel filtration chromatography. Dose-dependent assay and time-kill curve experiment was performed for 2 lysins showed that recombinant lysin 2 functions more than its non-recombinant lysins 2 with the same concentration of 0.5 µg/mL. Both lysins' ointment was prepared and compared with commercial ointments. 62 (78.4%) out of 79 wounds a burns swabs were detected as S. aureus and S methicillin-resistant S. aureus (MRSA) rate was determined to be 29 (46.8%) in total, while 33 isolates (53.2%) determined as methicillin-sensitive S. aureus (MSSA). According to the antibiotic susceptibility test results, all S. aureus isolates were identified as sensitive against vancomycin, ceftaroline, and linezolid. Results shows one lysogenic bacteriophage and three distinct lytic specific S. aureus bacteriophage were isolated from sewage. For each of the three samples, a single contig was possible to be obtained. Sample BP-SA2 had the best coverage, and the contig was slightly longer than the other bacteriophages. In addition, BLAST search identified Staphylococcus bacteriophage vB-SscM-1 (accession KX171212.1) as the closest match to the public database. Finally, the gene annotation was checked, and two potential lysin genes were identified. Besides the two ends, there are only 4 SNPs between the three genomes. It should be noted that the two lysin genes from the genomes have no SNPs, and are identical across the three genomes. It can be seen that the three bacteriophages (BP-SA1), (BP-SA 2), and (BP-SA3) form their own tight cluster. It can be seen that (BP-SA 2) is more closely related to Staphylococcus bacteriophage vB-SscM-1 genome and most noticeable 5' region of S5 and vB-SscM-1 are now located at 3' end of vB-Sau-Clo6. The investigation of the two lysin genes in (BP-SA 2) by whole genome sequencing showed that there is some homology with vB-SscM-1; although the first gene is annotated as hypothetical protein, the second gene is annotated as amidase. The same two lysin genes are identified in all three bacteriophage genomes by the RAST. The putative protein sequences of the discovered phage lysin was analyzed using protein search with UniProt/Swiss-Prot database, and all matches suggest that the putative protein of the discovered phage lysin is a real endolysin. The three samples of bacteriophage were harboring both (Lysin 1 and lysin 2) genes were amplified. Afterward, 2-lysin genes were cloned successfully; for the dose-dependent assay, the same incubation time of recombinant lysins and its two non-recombinant lysins with the bacteria for 30 min. It is found that the bactericidal activity of these groups increased in correlation with their concentrations. For the time-kill curve experiment, it showed that Recombinant lysin 2 functions more than its non-recombinant lysins 2 with the same concentration of 0.5 µg/mL. Both lysins' ointments have potential activity against S. aureus isolates more than mupirocin and have a similar activity with Fusidic acid through applying 10 µL from lysin 1 ointment, lysin 2 ointment, mupirocin ointment 2%, and Fusidic acid cream 2%. In vitro lytic spectrum analysis revealed that 100% (29/29) tested S. aureus were sensitive. One dose of lysin ointment resulted in a reduction of 3.3 log units in the number of bacteria (from an initial count of 2 × 105 CFU/mg) at 18 hours compared with one dose of mupirocin, PBS, or Aquaphor. Specifically, this study provides evidence that the application of lysin ointment has significant potential as an alternative strategy for MRSA infections.

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).

Peritoneal Dialysis Exit-Site Care Protocols in Portugal and Its Association with Catheter-Related Infections.

INTRODUCTION: Exit-site infection (ESi) prevention is a key factor in lowering the risk of peritonitis. This study aimed to evaluate the associations between exit-site (ES) care protocols and the annual incidence rates of ESi and peritonitis in Portugal. METHODS: We performed a national survey using two questionnaires: one about the incidence of catheter-related infections and the other characterizing patients' education and ES care protocols. RESULTS: In 2017 and 2018, 14 Portuguese units followed 764 and 689 patients. ESi incidence rate was 0.41 episodes/year, and the peritonitis incidence rate was 0.37. All units monitor catheter-related infections on a yearly basis, use antibiotic prophylaxis at the time of catheter placement, and treat nasal carriage of S. aureus, although with different approaches. Screening for nasal carriage of S. aureus is performed by 12 units, and daily topical antibiotic cream is recommended by 6 out of 14 of the units. We did not find statistical differences in ESi/peritonitis, comparing these practices. The rate of ESis was lower with nonocclusive dressing immediately after catheter insertion, bathing without ES dressing, with the use of colostomy bags in beach baths and was higher with the use of bath sponge. The peritonitis rate was lower with bathing without ES dressing and if shaving of the external cuff was performed in the presence of chronic ESi. CONCLUSIONS: We found potential proceedings associated with ESi and peritonitis. A regular national audit of peritoneal dialysis units is an important tool for clarifying the best procedures for reduction of catheter-related infections.

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.

Prevalence and Characterization of Staphylococcus aureus Isolated from Retail Raw Milk Samples in Chennai, India.

Milk is an important source of food, and it is also a nutrient-rich medium, which can harbor multiple microorganisms. Staphylococcus aureus is an important foodborne pathogen in food-producing animals, and there have been many reports on its infection and antimicrobial resistance (AMR), which has significant global public health concerns. This study was designed to isolate, characterize, and analyze the AMR pattern of S. aureus from milk samples collected in Chennai, India. A total of 259 raw milk samples from 3 groups: dairy farms, local vendors, and retail outlets were analyzed, and it was found that 34% (89/259) were positive for S. aureus. Positive isolates were further characterized by pulsed-field gel electrophoresis and isolates recovered from different sources, study areas, and locations showed high genetic diversity with no similarity. The presence of AMR has been further assessed by phenotypic methods as per CLSI-M100 performance standards, and all the isolates were susceptible to ampicillin/sulbactam, mupirocin, and tylosin. Additionally, all of the isolates were resistant to ampicillin. There were 28 isolates categorized as multidrug-resistant, which showed resistance to more than 2-3 classes of antimicrobials. This is the first report of inducible clindamycin resistance and mupirocin sensitivity pattern from S. aureus isolates recovered from milk. This study established the occurrence varied with genetic diversity in the isolates prevalent in the study area and divergence pattern of AMR S. aureus. The AMR in these isolates and with methicillin-resistant S. aureus could pose a serious threat to food safety and economic implications.

Topical delivery of mupirocin calcium nanostructured lipid carriers using a full-thickness excision wound healing model.

OBJECTIVE: Treatment of contaminated wounds represents a significant challenge in healthcare and there is a need to develop approaches maximising skin retention to maintain therapeutic concentrations of anti-infectives at the wound site. The objective of the present study was to develop and evaluate mupirocin calcium nanolipid emulgels to enhance wound healing performance and patient acceptability. METHODS: Nanostructured lipid carriers (NLCs) of mupirocin calcium were prepared by the phase inversion temperature method using Precirol ATO 5 (Gattefosse, India) and oleic acid as lipids and Kolliphor RH 40 (BASF, India) as surfactant and further incorporated into a gel base for topical delivery. RESULTS: The particle size, polydispersity index and zeta potential of mupirocin NLCs were found to be 128.8±1.25nm, 0.283±0.003 and -24.2±0.56mV, respectively. In vitro release studies from developed emulgel showed sustained drug release over 24 hours. Ex vivo drug permeation studies through excised rat abdominal skin showed better skin permeation (1712.38±15. 57µg/cm2) from developed emulgel compared to marketed ointment (827.92±21.42µg/cm2) after 8 hours, which was in agreement with in vitro antibacterial activity. Studies on Wistar rats indicated the nonirritant potential of developed emulgels. Further, mupirocin emulgels showed improved efficacy in percent wound contraction of acute contaminated open wounds in Wistar rats using a full-thickness excision wound healing model. CONCLUSION: The emulgels of mupirocin calcium NLCs appear to be effective in the treatment of contaminated wounds due to increased skin deposition and sustained release, thereby enhancing the wound healing potential of existing molecules.

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.

Genomic and clinical case characterisation of Staphylococcus haemolyticus isolated from dogs and cats in the United States, including strains with high-level mupirocin tolerance.

BACKGROUND: Staphylococcus haemolyticus is a coagulase-negative commensal organism of both people and companion animals. It has pathogenic potential and when cultured is often meticillin- and multidrug-resistant. OBJECTIVES: To characterise the clinical features of dogs and cats with clinical skin disease that had positive S. haemolyticus skin cultures, and to employ whole-genome sequencing (WGS) to identify resistance genes and characterise the genetic relatedness of strains. MATERIALS AND METHODS: Isolates were identified by the institutional clinical microbiology laboratory by routine aerobic culture and susceptibility from seven veterinary hospitals across the United States. Then, WGS and analysis of each isolate were performed and clinical data collected via a retrospective clinician questionnaire. RESULTS: S. haemolyticus was identified from superficial (seven of 12) and deep (five of 12) cutaneous infections in our study. Most animals had received antimicrobials (10 of 12) and/or immunomodulatory drugs (nine of 12) within the six months before culture. WGS analysis revealed a variety of genetic lineages and a wide array of antimicrobial resistance genes. Meticillin resistance was identified in nine of 12 isolates and four of 12 isolates demonstrated mupirocin tolerance. CONCLUSIONS AND CLINICAL RELEVANCE: Staphylococcus haemolyticus may be an under-recognised pathogen in companion animals, and its demonstrated potential for multidrug-resistance, meticillin-resistance, and high-level mupirocin tolerance may create a therapeutic challenge. Further studies should evaluate the prior antimicrobial use and immunocompromised status as risk factors for infection with S. haemolyticus.

Staphylococcus Aureus Swabbing and Decolonization Before Neuromodulation Procedures: A Systematic Review and Meta-Analysis.

INTRODUCTION: Staphylococcus aureus (S aureus) is the foremost bacterial cause of surgical-site infection (SSI) and is a common source of neuromodulation SSI. Endogenous colonization is an independent risk factor for SSI; however, this risk has been shown to diminish with screening and decolonization. MATERIALS AND METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, Cochrane Library, and Embase data bases from inception to January 1, 2022, for the purposes of identifying all studies reporting on the use of S aureus swabbing and/or decolonization before neuromodulation procedures. A random-effects meta-analysis was performed using the metaphor package in R to calculate odds ratios (OR). RESULTS: Five observational cohort studies were included after applying the inclusion and exclusion criteria. The average study duration was 6.6 ± 3.8 years. Three studies included nasal screening as a prerequisite for subsequent decolonization. Type of neuromodulation included spinal cord stimulation in two studies, deep brain stimulation in two studies, intrathecal baclofen in one study, and sacral neuromodulation in one study. Overall, 860 and 1054 patients were included in a control or intervention (ie, screening and/or decolonization) group, respectively. A combination of nasal mupirocin ointment and a body wash, most commonly chlorhexidine gluconate soap, was used to decolonize throughout. Overall infection rates were observed at 59 of 860 (6.86%) and ten of 1054 (0.95%) in the control and intervention groups, respectively. Four studies reported a significant difference. The OR for intervention (screen and/or decolonization) vs no intervention was 0.19 (95% CI, 0.09-0.37; p < 0.001). Heterogeneity between studies was nonsignificant (I2 = 0.43%, τ2 = 0.00). CONCLUSIONS: Preoperative S aureus swabbing and decolonization resulted in significantly decreased odds of infection in neuromodulation procedures. This measure may represent a worthwhile tool to reduce neuromodulation SSI, warranting further investigation.