METHODS: MSCs and Oh-LAAO were isolated and characterized by standard methodologies. The effects of the experimental therapies were evaluated in C57/BL6 mice. The animal study groups consisted of full-thickness uninfected and MRSA-infected wound models which received Oh-LAAO, MSCs, or both. Oh-LAAO was administered directly on the wound while MSCs were delivered via intradermal injections. The animals were housed individually with wound measurements taken on days 0, 3, and 7. Histological analyses and bacterial enumeration were performed on wound biopsies to determine the efficacy of each treatment.
RESULTS: Immunophenotyping and differentiation assays conducted on isolated MSCs indicated expression of standard cell surface markers and plasticity which corresponds to published data. Characterization of Oh-LAAO by proteomics, enzymatic, and antibacterial assays confirmed the identity, purity, and functionality of the enzyme prior to use in our subsequent studies. Individual treatments with MSCs and Oh-LAAO in the infected model resulted in reduction of MRSA load by one order of magnitude to the approximate range of 6 log10 colony-forming units (CFU) compared to untreated controls (7.3 log10 CFU). Similar wound healing and improvements in histological parameters were observed between the two groups. Co-administration of MSCs and Oh-LAAO reduced bacterial burden by approximately two orders of magnitude to 5.1 log10 CFU. Wound closure measurements and histology analysis of biopsies obtained from the combinational therapy group indicated significant enhancement in the wound healing process compared to all other groups.
CONCLUSIONS: We demonstrated that co-administration of MSCs and Oh-LAAO into a mouse model of MRSA-infected wounds exhibited a synergistic antibacterial effect which significantly reduced the bacterial count and accelerated the wound healing process.
METHODS: This is a cross-sectional study performed at 28 hospitals under the Ministry of Health, Malaysia, involved in the National Surveillance of Multidrug-Resistant Organism, which surveys 6 MDROs (Acinetobacter baumanii, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae, carbapenem-resistant Entrobacterales (CRE), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE)).
RESULTS: In terms of mortality, 9.6% (n = 951) of the patients died overall, whereas 90.4% (n = 8931) of the patients survived. Healthcare-acquired infection (HCAI) poses a high risk of mortality, with an adjusted odds ratio (aOR) of 2.91 (95% CI: 2.15-3.94). The presence of sterile specimens was significantly associated with increased mortality risk (aOR: 2.33, 95% CI: 2.02-2.68). Gram-negative bacteria had a greater mortality risk (aOR 1.63 95% CI: 1.37-1.93), whereas Acinetobacter baumanii had the highest prevalence of 30.7% (3033) among the 6 MDRO organisms isolated. Patients in medical-based departments had a greater mortality risk (aOR: 1.47, 95% CI: 1.22-1.75).
CONCLUSION: HCAIs, Gram-negative bacteria, sterile specimens, medical-based departments and state hospitals have been shown to be associated with increased mortality risk in patients with MDRO infections. Improved surveillance and reporting mechanisms are necessary to better understand the burden of MDRO infections and guide research funding allocation.