Efficacy of cefepime, ertapenem and norfloxacin against leptospirosis and for the clearance of pathogens in a hamster model

Animals and humans with severe leptospirosis may require empirical treatment. Although many antibiotics are active against multiple leptospira serovars in vitro, their efficacy in vivo is limited. We evaluated the efficacy of cefepime (daily dose: 2, 5, 10, and 20 mg/kg), ertapenem (daily dose: 2.5, 5, and 10 mg/kg) and norfloxacin (daily dose: 20, 40, and 80 mg/kg) for the treatment of leptospirosis and the ability to clear leptospira in target organs (liver, kidney, lung, heart, and spleen) in a lethal hamster model using Leptospira interrogans serovar Autumnalis. The histopathology of infected kidney, lung and liver was also evaluated using hematoxylin and eosin stain (H&E stain). All untreated animals, serving as a negative control, died with leptospira existing in the target organs between the 5th and 7th day after infection. All of the treated groups displayed improved survival compared to the untreated group and demonstrated a dose-dependent decrease in the presence of leptospira in the target organs. Cefepime showed survival benefit comparable to the standard treatment, doxycycline. We conclude that all of the antibiotics tested in vivo produce a statistically significant survival advantage, alleviate tissue injury and decrease the abundance of leptospira in target organs.