Effect of inhaled Nitric Oxide on bacterial burden and disease outcome in a murine model of Klebsiella pneumonia
Final Report Abstract
In vivo dose-response studies confirmed that efficacy of nitric oxide (NO) treatment against Klebsiella pneumoniae (Kp) is dose- and time dependent. Although lower NO concentrations (10-40ppm) were effective for the treatment of Pseudomonas aeruginosa, we did not observe any beneficial effect of low dose (80ppm) NO for Kp infections in mice. High-dose NO reduced not only the viable bacteria in lung and spleen in Kp pneumonia, but also reduced inflammation in lung, assessed by neutrophil infiltration and myeloperoxidase level. This study was the first study of murine Kp infection showing an improvement in survival after the treatment with NO. We could demonstrate that one possible mechanism how NO exerts its bactericidal effect involves degradation of bacterial cell wall. In addition, NO also has an inhibitory effect on multiple drug resistant Kp strains. The results of the study will help to promote the research of nitric oxide as a potential adjunctive therapy for lung infections. Unexpected, the use of nitric oxide as an antimicrobial therapy has become widely known, due to clinical trials worldwide, searching for effective treatments against Sars-CoV-2 and COVID-19. Many clinical trials investigate the effect of NO on COVID-19. They are still ongoing and recruiting COVID-19 patients ranging from mild, spontaneous breathing to severely ill, intubated patients. Some of the nitric oxide studies on COVID-19 have already received some media coverage and probably if the results of the larger clinical studies are promising, nitric oxide might be widely used for the treatment of COVID-19 in the near future.
Publications
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(2020). Antimicrobial effects of nitric oxide in murine models of Klebsiella pneumonia. Redox Biol. 39, 101826
Wiegand, S.B., Traeger, L., Nguyen, H.K., Rouillard, K.R., Fischbach, A., Zadek, F., Ichinose, F., Schoenfisch, M.H., Carroll, R.W., Bloch, D.B., et al.
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(2020). High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19). Obstet. Gynecol. 136, 1109–1113
Safaee Fakhr, B., Wiegand, S.B., Pinciroli, R., Gianni, S., Morais, C.C.A., Ikeda, T., Miyazaki, Y., Marutani, E., Di Fenza, R., Larson, G.M., et al.
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(2020). Intratracheal injection of nitric oxide, generated from air by pulsed electrical discharge, for the treatment of pulmonary hypertension in awake ambulatory lambs. Nitric Oxide Biol. Chem. 97, 11–15
Yu, B., Zadek, F., Fischbach, A., Wiegand, S.B., Berra, L., Bloch, D.B., and Zapol, W.M.
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(2020). Rescue Treatment With High-Dose Gaseous Nitric Oxide in Spontaneously Breathing Patients With Severe Coronavirus Disease 2019. Crit. Care Explor. 2, e0277
Wiegand, S.B., Safaee Fakhr, B., Carroll, R.W., Zapol, W.M., Kacmarek, R.M., and Berra, L.
