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Cytotherapy Jun 2024The prevalence of chronic wounds continues to be a burden in human medicine. Methicillin-resistant Staphylococcus aureus (MRSA) is commonly isolated from infected...
The mesenchymal stromal cell secretome promotes tissue regeneration and increases macrophage infiltration in acute and methicillin-resistant Staphylococcus aureus-infected skin wounds in vivo.
BACKGROUND AIMS
The prevalence of chronic wounds continues to be a burden in human medicine. Methicillin-resistant Staphylococcus aureus (MRSA) is commonly isolated from infected wounds. MRSA infections primarily delay healing by impairing local immune cell functions. This study aimed to investigate the potential of mesenchymal stromal cell (MSC)-secreted bioactive factors, defined as the secretome, to improve innate immune responses in vivo. MSCs were isolated from the bone marrow of horses, which serve as valuable translational models for wound healing. The MSC secretome, collected as conditioned medium (CM), was evaluated in vivo using mouse models of acute and MRSA-infected skin wounds.
METHODS
Punch biopsies were used to create two full-thickness skin wounds on the back of each mouse. Acute wounds were treated daily with control medium or bone marrow-derived MSC (BM-MSC) CM. The antibiotic mupirocin was administered as a positive control for the MRSA-infected wound experiments. Wounds were photographed daily, and wound images were measured to determine the rate of closure. Trichrome staining was carried out to examine wound tissue histologically, and immunofluorescence antibody binding was used to assess immune cell infiltration. Wounds in the MRSA-infected model were swabbed for quantification of bacterial load.
RESULTS
Acute wounds treated with BM-MSC CM showed accelerated wound closure compared with controls, as illustrated by enhanced granulation tissue formation and resolution, increased vasculature and regeneration of hair follicles. This treatment also led to increased neutrophil and macrophage infiltration. Chronic MRSA-infected wounds treated with BM-MSC CM showed reduced bacterial load accompanied by better resolution of granulation tissue formation and increased infiltration of pro-healing M2 macrophages compared with control-treated infected wounds.
CONCLUSIONS
Collectively, our findings indicate that BM-MSC CM exerts pro-healing, immunomodulatory and anti-bacterial effects on wound healing in vivo, validating further exploration of the MSC secretome as a novel treatment option to improve healing of both acute and chronic wounds, especially those infected with antibiotic-resistant bacteria.
PubMed: 38944795
DOI: 10.1016/j.jcyt.2024.06.007 -
The Journal of Dermatological Treatment Dec 2024Cutaneous infection in epidermolysis bullosa (EB) can cause significant morbidity, mortality, and dangerous sequelae. This review article aims to delve into the known... (Review)
Review
Cutaneous infection in epidermolysis bullosa (EB) can cause significant morbidity, mortality, and dangerous sequelae. This review article aims to delve into the known epidemiology of EB, highlight the disease's primary causative agents and their antimicrobial resistance spectrum. A thorough literature search was conducted using Medline, EMBASE, JBI and PubMed to gather data on the microbial landscape of EB wounds. The focus was on identifying the most common bacteria associated with EB infections and assessing their antimicrobial resistance profiles. The analysis revealed that is the most frequently identified bacterium in EB wounds, with a notable prevalence of methicillin-resistant strains (MRSA). Specific studies on mupirocin resistance further indicated rising rates of mupirocin-resistant , with one study reporting rates as high as 16.07%. Additionally, high resistance to other antibiotics, such as levofloxacin and trimethoprim/sulfamethoxazole, was observed in MRSA isolates. The findings highlight the critical need for regular resistance surveillance and the prudent use of mupirocin to manage infections effectively in EB. The multi-drug resistant nature of pathogens in EB presents a significant challenge in treatment, highlighting the importance of antimicrobial stewardship. Ultimately, given the sparse literature and the rarity of large-scale studies, further longitudinal research on the antimicrobial resistance profile of bacteria isolated from EB wounds is essential.
Topics: Humans; Epidermolysis Bullosa; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Wound Infection; Mupirocin; Drug Resistance, Bacterial
PubMed: 38936964
DOI: 10.1080/09546634.2024.2370424 -
Pharmaceutics May 2024The treatment of skin and soft tissue infections (SSTIs) can be challenging due to bacterial resistance, particularly from strains like MRSA and biofilm formation....
The treatment of skin and soft tissue infections (SSTIs) can be challenging due to bacterial resistance, particularly from strains like MRSA and biofilm formation. However, combining conventional antibiotics with natural products shows promise in treating SSTIs. The objective of this study is to develop a nanoemulsion-based hydrogel containing extract and mupirocin and evaluate its potential for the treatment of SSTIs. The nanoemulsion was obtained by phase inversion and subsequently characterized. The antibacterial activity was evaluated in vitro against MRSA, including the synergism of the combination, changes in membrane permeability using flow cytometry, and the anti-biofilm effect. In addition, the irritative potential was evaluated by the HET-CAM assay. The combination exhibited synergistic antibacterial activity against and MRSA due to the extract enhancing membrane permeability. The hydrogel demonstrated suitable physicochemical properties, inhibited biofilm formation, and exhibited low irritation. The formulation was nanometric (176.0 ± 1.656 nm) and monodisperse (polydispersity index 0.286 ± 0.011). It exhibited a controlled release profile at 48 h and high encapsulation efficacy (94.29 ± 4.54% for quercitrin and 94.20 ± 5.44% for mupirocin). Therefore, these findings suggest that the hydrogel developed could be a safe and effective option for treating SSTIs.
PubMed: 38931824
DOI: 10.3390/pharmaceutics16060700 -
BioMed Research International 2024In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with...
MATERIALS AND METHODS
In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with MRSA. Various treatments were applied to the burn wounds daily, including Myrtus ointment, silver nanoparticles, silver nanoparticles-Myrtus ointment, silver sulfadiazine-Myrtus ointment, silver sulfadiazine 1%, mupirocin ointment, and a positive control. The study measured the antimicrobial effects, wound area, percentage of wound healing, antioxidant capacities, malondialdehyde, and nitric oxide concentrations in the serum of the rats. Data analysis was performed using GraphPad software, with one-way ANOVA and Tukey's tests used to determine the statistical significance of the results.
RESULTS
Rats treated with Myrtus ointment, silver nanoparticles-Myrtus ointment, and mupirocin had reduced bacterial growth compared to the positive control group, nanoparticle ointment, and silver sulfadiazine ( < 0.05). The wound area of the Myrtus ointment group decreased significantly on the seventh and fourteenth days, as well as the level of MDA and nitric oxide, compared to the other groups. In Myrtus and silver sulfadiazine-Myrtus ointment increased the thickness of the epidermis and dermis compared to the other groups.
CONCLUSION
Based on the anti-inflammatory, antimicrobial, and wound healing properties of Myrtus, with further studies, an ointment of this plant may be used as a main or complementary treatment for burn wound infections caused by MRSA.
Topics: Animals; Wound Healing; Methicillin-Resistant Staphylococcus aureus; Burns; Plant Extracts; Male; Ointments; Rats; Rats, Wistar; Anti-Inflammatory Agents; Plant Leaves; Myrtus; Anti-Infective Agents; Wound Infection; Staphylococcal Infections; Metal Nanoparticles; Silver Sulfadiazine
PubMed: 38899039
DOI: 10.1155/2024/6758817 -
FP Essentials Jun 2024Bacterial skin infections represent a significant health care burden. Cellulitis and erysipelas are rapidly spreading, painful, superficial skin infections, usually... (Review)
Review
Bacterial skin infections represent a significant health care burden. Cellulitis and erysipelas are rapidly spreading, painful, superficial skin infections, usually caused by streptococci or . Folliculitis is an infection of hair follicles mostly caused by . Simple folliculitis typically is self-limited. Topical benzoyl peroxide is a first-line nonantibiotic treatment. Mupirocin and clindamycin are topical antibiotic options. For treatment-resistant cases, oral cephalexin or dicloxacillin is an appropriate option. Impetigo is a common, self-limited infection in children. Bullous impetigo is caused by , and nonbullous impetigo is caused by beta-hemolytic streptococci, , or both. In most cases, topical mupirocin or retapamulin (Altabax) is effective. Oral antibiotics should be considered for household outbreaks or patients with multiple lesions. Abscesses are red, painful collections of purulence in the dermis and deeper tissues caused by or polymicrobial infections. Furuncles are abscesses of a hair follicle, whereas carbuncles involve several hair follicles. In recurrent cases of these lesions, culture of the exudate is recommended. Abscess, furuncle, and carbuncle management consists of incision and drainage. Oral antibiotics are not necessary in most cases but should be prescribed for patients with severe immunocompromise or systemic signs of infection. In bacterial skin infections, methicillin-resistant coverage should be considered for patients with infections that have not improved with treatment.
Topics: Humans; Child; Anti-Bacterial Agents; Adolescent; Impetigo; Skin Diseases, Bacterial; Cellulitis; Folliculitis; Erysipelas; Abscess; Furunculosis; Carbuncle
PubMed: 38896826
DOI: No ID Found -
Cureus May 2024Infected wounds pose a special challenge for management, with an increased risk of wound chronicity, systemic infection, and the emergence of antibiotic resistance....
Effect of Topical Silver Nanoparticle Formulation on Wound Bacteria Clearance and Healing in Patients With Infected Wounds Compared to Standard Topical Antibiotic Application: A Randomized Open-Label Parallel Clinical Trial.
BACKGROUND
Infected wounds pose a special challenge for management, with an increased risk of wound chronicity, systemic infection, and the emergence of antibiotic resistance. Silver nanoparticles have multimodal effects on bacteria clearance and wound healing. This study aimed to document the efficacy of a topical silver nanoparticle-based cream on bacteria clearance and wound healing in infected wounds compared to Mupirocin.
METHODS
This open-label parallel randomized clinical trial allocated 86 participants with infected wounds (culture-positive) into Kadermin, silver nanoparticle-based cream arm (n=43) and Mupirocin arm (n=43) and documented the swab culture on day 5 and wound healing at day 28, along with periodic wound status using the Bates-Jensen Wound Assessment Tool. Patients received oral/systemic antibiotics and other medications for underlying diseases. The intention-to-treat principle was adopted for data analysis using the chi-square and Student t tests to document the differences between groups according to variable characteristics.
RESULTS
All participants completed the follow-up. On day 5, wound bacteria clearance was observed in 86% and 65.1% of the participants in the Kadermin and Mupirocin arms, respectively (p=0.023). At day 28, complete wound healing was observed in 81.4% and 37.2% of the participants in the Kadermin and Mupirocin arms, respectively (p≤0.001). No local or systemic adverse event or local reaction was observed in any of the participants.
CONCLUSION
Kadermin, the silver nanoparticle-based cream, has better efficacy in achieving faster wound bacteria clearance and healing in infected wounds compared to Mupirocin. This may have relevance for its use as an antibiotic-sparing agent in wound management.
PubMed: 38894757
DOI: 10.7759/cureus.60569 -
Biochemical Society Transactions Jun 2024Mupirocin is a broad-spectrum antibiotic that acts predominantly against Gram-positive bacteria. It is produced by Pseudomonas fluorescens NCIMB 10586 and has been... (Review)
Review
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.
Topics: Mupirocin; Isoleucine-tRNA Ligase; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus
PubMed: 38884776
DOI: 10.1042/BST20230581 -
IMeta Apr 2024The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing...
The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing factors remain largely unknown. We characterized resistome in 4132 metagenomes from 963 infants in six countries and 4285 resistance genes were observed. The inherent resistome pattern of healthy infants ( = 272) could be distinguished by two stages: a multicompound resistance phase (Months 0-7) and a tetracycline-mupirocin-β-lactam-dominant phase (Months 8-14). Microbial taxonomy explained 40.7% of the gut resistome of healthy infants, with (25.5%) harboring the most resistance genes. In a further analysis with all available infants ( = 963), we found age was the strongest influencer on the resistome and was negatively correlated with the overall resistance during the first 3 years ( < 0.001). Using a random-forest approach, a set of 34 resistance genes could be used to predict age ( = 68.0%). Leveraging microbial host inference analyses, we inferred the age-dependent assembly of infant resistome was a result of shifts in the gut microbiome, primarily driven by changes in taxa that disproportionately harbor resistance genes across taxa (e.g., more frequently harbored resistance genes than other taxa). We performed metagenomic functional profiling and metagenomic assembled genome analyses whose results indicate that the development of gut resistome was driven by changes in microbial carbohydrate metabolism, with an increasing need for carbohydrate-active enzymes from and a decreasing need for during infancy. Importantly, we observed increased acquired resistance genes over time, which was related to increased horizontal gene transfer in the developing infant gut microbiome. In summary, infant age was negatively correlated with antimicrobial resistance gene levels, reflecting a composition shift in the gut microbiome, likely driven by the changing need for microbial carbohydrate metabolism during early life.
PubMed: 38882494
DOI: 10.1002/imt2.169 -
JAC-antimicrobial Resistance Jun 2024We performed a multicentre study (2020-2022) to compare the activity of ozenoxacin and comparator agents against and clinical isolates from skin and soft-tissue...
OBJECTIVES
We performed a multicentre study (2020-2022) to compare the activity of ozenoxacin and comparator agents against and clinical isolates from skin and soft-tissue infections (SSTI).
METHODS
A total of 1725 isolates (1454 and 271 ) were collected in 10 centres from eight countries between January 2020 and December 2022. Antimicrobial susceptibility testing was determined (microdilution-SENSITITRE). Results were interpreted following European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 (clinical breakpoints, ECOFF) and CLSI criteria.
RESULTS
Ozenoxacin exhibited high activity against (MIC = 0.002/0.12 mg/L) and (MIC = 0.015/0.03 mg/L), inhibiting 99% of the isolates at MIC ≤ 0.5 mg/L and at MIC ≤ 0.06, respectively. The most active comparators against were retapamulin (MIC = 0.12 mg/L), fusidic acid (MIC = 0.25 mg/L) and mupirocin (MIC = 0.5 mg/L); and against were retapamulin (MIC = 0.03 mg/L), clindamycin (MIC = 0.12 mg/L) and mupirocin (MIC = 0.25 mg/L). Ciprofloxacin and methicillin resistant rates for were 31.3% (455/1454) and 41% (598/1454), respectively. Additionally, 62% (373/598) of the MRSA were also ciprofloxacin non-susceptible, whereas only 10% (23/271) of the MSSA were ciprofloxacin resistant. Ozenoxacin was more active against ciprofloxacin-susceptible than against ciprofloxacin-resistant isolates, and showed a slightly higher MIC in MRSA isolates than in MSSA. However, ozenoxacin activity was comparable in both ciprofloxacin-resistant MSSA and MRSA subsets. On the other hand, ozenoxacin had similar activity in ciprofloxacin-susceptible and resistant isolates.
CONCLUSIONS
Ozenoxacin is a potent antimicrobial agent of topic use against Gram-positive bacteria causing SSTI, including MRSA isolates non-susceptible to ciprofloxacin.
PubMed: 38872714
DOI: 10.1093/jacamr/dlae088 -
Heliyon Jun 2024The increasing emergence of as the primary causative agent of otitis externa has been noted; however, detailed information regarding the molecular characteristics of...
The increasing emergence of as the primary causative agent of otitis externa has been noted; however, detailed information regarding the molecular characteristics of these strains in Iran remains scarce. The current study aims to investigate both genotypic and phenotypic attributes of strains implicated in ear infections. In the present work, we analyzed 60 strains isolated from cases of otitis externa over a period of 45 months. The resistance patterns were determined using disk diffusion and microbroth dilution methods. All isolates were confirmed by the polymerase chain reaction assay, and their biofilm production was assessed by a microtiter plate assay. Molecular characterization of the isolates was performed using the staphylococcal cassette chromosome multilocus sequence typing, and staphylococcus protein A typing methods. Overall, the results indicated that 44 out of 60 isolates (73.3 %) were methicillin-resistant . Resistance to mupirocin and vancomycin was observed in 13.3 % and 1.7 % of the tested isolates, respectively. Furthermore, out of the 60 isolates, 56 strains (93.4 %) were classified as positive biofilm strains at different levels. Twelve distinct clonal lineages were identified. The vast majority of isolates belonged to CC30/ST30-MRSA IV/t019 (41.7 %). Among the 31 strong biofilm producers, the majority (64.5 %) belonged to CC30/ST30-MRSA IV/t019 clone. Biofilm negative isolates belonged to CC22/ST22 (2 isolates), CC8/ST585 (one isolate), and CC8/ST8 (one isolate). Our result revealed that about three-quarters of PVL-positive strains belonged to CC30/ST30. Our data confirmed the presence of MSSA strains among CC30/ST30 and CC22/ST22 isolates. The mupirocin resistant isolates (n = 8) belonged to CC8/ST585-MRSA III/t713 (37.5 %), CC8/ST239-MRSA III/t030 (25 %), CC8/ST8-MRSA IV/t008 (12.5 %), CC8/ST239-MRSA III/t037 (12.5 %), and CC22/ST22-MRSA IV/t790 (12.5 %) lineages. The VRSA strain belonged to the CC8/ST8-MRSA IV/t008 lineage, carrying the determinant. iMLS phenotypes (n = 14) were distributed across different lineages, including CC30/ST30-MRSA IV/t019 (21.5 %), CC30/ST30-MSSA/t021 (21.5 %), CC22/ST22-MSSA/t005 (14.3 %), CC8/ST239-MRSA III/t030 (14.3 %), CC22/ST22-MSSA/t1869 (7.1 %), CC22/ST22-MRSA IV/t790 (7.1 %), CC8/ST239-MRSA III/t037 (7.1 %), and CC1/ST772-MRSA IV/t10795 (7.1 %). These findings highlight significant genotypic diversity and high biofilm formation among our isolates. The frequent occurrence of the CC/ST30 clone in strains isolated from otitis externa reflects the emergence of these lineages as a predominant clone in Iran, posing a significant public health concern.
PubMed: 38868027
DOI: 10.1016/j.heliyon.2024.e32002