Quantitative PCR assay to evaluate ampicillin, ofloxacin, and doxycycline for treatment of experimental leptospirosis.
The susceptibility of Leptospira interrogans serovar icterohaemorrhagiae strain Verdun to selected antibiotics used in medical practice (ampicillin, doxycycline, and ofloxacin) was evaluated in a Syrian hamster model, to determine the efficacy of these antibiotics during the course of the disease. A quantitative PCR assay was used to monitor the density of leptospires in blood and in target organs (liver, kidney, lung, heart, and spleen). Our results demonstrated the ability of ampicillin at a high dose (100 mg/kg of body weight) to clear leptospires from the host, except from kidneys and heart, where 10(2) leptospires/g remained at day 6. Ofloxacin (30 mg/kg) was unable to clear bacteria from blood or kidneys. With doxycycline (10 mg/kg), the clearance of leptospires occurred in 2 days in all the target organs studied, with the exception of liver, which required 3 days. Our data demonstrate the value of monitoring the kinetics of experimental leptospiral infection in order to accurately evaluate the efficacy of antibiotics. We have demonstrated the potential value of doxycycline for the treatment of leptospirosis cases, except in circumstances where it is contraindicated. This experimental model could be used to define better therapeutic strategies for human leptospirosis, by testing associations or new formulations of antibiotics.
Truccolo
Johann
J
Leptospira Laboratory, Institut Pasteur de Nouvelle-Calédonie, 98845 Nouméa Cedex, New Caledonia.
Charavay
Françoise
F
Merien
Fabrice
F
Perolat
Philippe
P
D000667:Ampicillin / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D006224:Cricetinae; D004318:Doxycycline / Q000627:therapeutic use*; D007919:Leptospira / Q000187:drug effects* / Q000235:genetics*; D007922:Leptospirosis / Q000188:drug therapy* / Q000382:microbiology*; D008647:Mesocricetus; D015242:Ofloxacin / Q000627:therapeutic use*; D010406:Penicillins / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010406:Penicillins; D000667:Ampicillin; D015242:Ofloxacin; D004318:Doxycycline