title: Low-dose norfloxacin and ciprofloxacin therapy worsen leptospirosis in hamster.
abstract: Antibiotics play an important role in the treatment of leptospirosis. Many antibiotics at appropriate concentrations improved the survival rate and alleviated tissue injury, while, when dosing strategies fall below subtherapeutic levels, worse therapeutic effects are seen. In the present study, we investigated the efficacy of low-dose norfloxacin (10, 20 and 30 mg/kg) and ciprofloxacin (1, 2 and 5 mg/kg) against leptospirosis in a hamster model using Leptospira interrogans serovar Icterohaemorrhagiae. The histopathology and bacterial loads of target organs (liver, kidney and lung) were also studied by treatment with norfloxacin at the dose of 10 mg/kg in this model. Using RT-PCR, the expression of inflammatory factor IL-1β and TNF-α was analyzed by comparing the norfloxacin and untreated group. All untreated animals, serving as a negative control, displayed 50% survival rate, while hamsters treated with norfloxacin at the dose of 10 and 20 mg/kg and ciprofloxacin at the dose of 1 and 2 mg/kg showed a lower survival rate than the untreated group. Furthermore, norfloxacin at the dose of 10 mg/kg increased bacterial loads and aggravated tissue injury of target organs. The delayed induction of IL-1β and TNF-α was found in tissues of norfloxacin group. Our study indicates an increased risk associated with low-dose norfloxacin and ciprofloxacin in leptospirosis.
authors.affiliation: College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, People's Republic of China; Department of Clinical Science, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Dianjun
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Clinical Science, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Science, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD 57007, United States.
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Clinical Science, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Clinical Science, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Clinical Science, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Clinical Science, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, People's Republic of China. Electronic address: ygcao82@jlu.edu.cn.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, People's Republic of China. Electronic address: fuhewu@126.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D058491:Bacterial Load; D001706:Biopsy; D002939:Ciprofloxacin / Q000008:administration & dosage*; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D007919:Leptospira / Q000187:drug effects* / Q000235:genetics; D007922:Leptospirosis / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D009643:Norfloxacin / Q000008:administration & dosage*; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D018836:Inflammation Mediators; D002939:Ciprofloxacin; D009643:Norfloxacin