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Recombinant Human Plasma Gelsolin Improves Survival and Attenuates Lung Injury in a Murine Model of Multidrug-Resistant Pseudomonas aeruginosa Pneumonia.
DiNubile, Mark J; Levinson, Susan L; Stossel, Thomas P; Lawrenz, Matthew B; Warawa, Jonathan M.
Afiliação
  • DiNubile MJ; BioAegis Therapeutics, North Brunswick, New Jersey, USA.
  • Levinson SL; BioAegis Therapeutics, North Brunswick, New Jersey, USA.
  • Stossel TP; BioAegis Therapeutics, North Brunswick, New Jersey, USA.
  • Lawrenz MB; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
  • Warawa JM; Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Open Forum Infect Dis ; 7(8): ofaa236, 2020 Aug.
Article em En | MEDLINE | ID: mdl-32766380
BACKGROUND: Plasma gelsolin (pGSN) is an abundant circulating protein quickly consumed by extensive tissue damage. Marked depletion is associated with later poor outcomes in diverse clinical circumstances. Repletion with recombinant human (rhu)-pGSN in animal models of inflammation lessens mortality and morbidity. METHODS: Neutropenic mice were treated with different meropenem doses ±12 mg of rhu-pGSN commencing 1 day before an intratracheal challenge with multidrug-resistant Pseudomonas aeruginosa. Survival, bacterial counts, and pulmonary pathology were compared between corresponding meropenem groups with and without rhu-pGSN. RESULTS: Overall survival was 35/64 (55%) and 46/64 (72%) in mice given meropenem without and with rhu-pGSN, respectively (Δ = 17%; 95% CI, 1-34). In control mice receiving meropenem 1250 mg/kg/d where the majority died, the addition of rhu-pGSN increased survival from 5/16 (31%) to 12/16 (75%) (Δ = 44%; 95% CI, 13-75). Survival with minor lung injury was found in 26/64 (41%) mice receiving only meropenem, vs 38/64 (59%) in mice given meropenem plus rhu-pGSN (Δ = 19%; 95% CI, 2-36). CONCLUSIONS: In a series of dose-ranging experiments, both mortality and lung injury were reduced by the addition of rhu-pGSN to meropenem against carbapenem-resistant P. aeruginosa. Rhu-pGSN offers a novel candidate therapy for antibiotic-resistant pneumonia.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article