Background: Based on previous animal studies showing promising immunomodulatory efficacy esmolol, a selective β1-blocker, it was assumed that administration of esmolol in experimental pyelonephritis by multidrug-resistant Pseudomonas aeruginosa would prolong survival and modulate immune response.
Methods: Acute pyelonephritis was induced in 80 rabbits and assigned to eight groups receiving normal saline (controls), esmolol, amikacin, or both agents as pretreatment and as treatment. Blood was sampled for measurement of malondialdehyde and tumor necrosis factor alpha. Animals were followed up for survival, and after death quantitative tissue cultures were performed. The in vitro effect of esmolol on bacterial growth and on the oxidative burst of neutrophils of healthy controls and of sepsis patients was studied.
Results: Survival of pretreatment groups administered single esmolol or esmolol and amikacin was prolonged compared with that of controls (P = 0.018 and P = 0.014, respectively); likewise, survival of treatment groups administered single esmolol or both agents was prolonged compared with that of controls (P = 0.007 and P = 0.014, respectively). Circulating malondialdehyde was significantly lower in pretreated animals administered esmolol or esmolol and amikacin compared with that in controls and in treated animals administered both agents compared with in controls (P = 0.020). In these groups, the bacterial load of the lung was significantly lower compared with controls. Serum tumor necrosis factor alpha did not change. Amikacin was increased in serum of esmolol-treated animals at levels which inhibited the in vitro growth of the studied isolate. Esmolol did not modify the in vitro growth of P aeruginosa and the oxidative burst of neutrophils.
Conclusions: It is concluded that esmolol prolonged survival after experimental infection by multidrug-resistant P aeruginosa. Survival benefit may be related with pleiotropic actions connected with modulation of pharmacokinetics and attenuation of inflammation.
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