Abstract:
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.
journal_name
Open Forum Infect Disjournal_title
Open forum infectious diseasesauthors
DiNubile MJ,Levinson SL,Stossel TP,Lawrenz MB,Warawa JMdoi
10.1093/ofid/ofaa236subject
Has Abstractpub_date
2020-06-19 00:00:00pages
ofaa236issue
8issn
2328-8957pii
ofaa236journal_volume
7pub_type
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