Salicylate Potentiates Amikacin Therapy in Rodent Models of Klebsiella pneumoniae Infection

Abstract

In vitro effects of salicylate on Klebsiella pneumoniae include capsule repression and enhanced aminoglycoside activity. The effects of high-dose salicylate on amikacin therapy were assessed in animal models. In a mouse lethality model, amikacin protective doses were reduced up to 12-fold by salicylate doses of 277 mg/kg. Salicylate alone increased the LDso for K. pneumoniae in mice by nearly 1 log unit. In a lobar pneumonia model, rats received salicylate-amikacin intravenously 3 days after challenge, and bacteria were quantified from lung tissue on day 7. Rats receiving one-fourth the minimum effective amikacin dose had 1 × 10⁶ cfu/g of lung, while no bacteria were detected in those also receiving salicylate (173 mg/kg). At one-eighth the minimum effective dose of amikacin, salicylate prevented the development of pneumonia. Salicylate potentiation of antimicrobial therapy far surpassed that observed in vitro, yet the potentiation was abolished in neutropenic animals. Thus, salicylate may enhance phagocytosis rather than antibiotic action in therapy.