• 1.

    Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, Levett PN, Gilman RH, Willig MR, Gotuzzo E, Vinetz JM, 2003. Leptospirosis: a zoonotic disease of global. Lancet Infect Dis 3: 757771.

    • Search Google Scholar
    • Export Citation
  • 2.

    Meites E, Jay MT, Deresinski S, Shieh WJ, Zaki SR, Tompkins L, Smith DS, 2004. Reemerging leptospirosis, California. Emerg Infect Dis 10: 406412.

  • 3.

    Tangkanakul W, Tharmaphornpil P, Plikaytis BD, Bragg S, Poonsuksombat D, Choomkasien P, Kingnate D, Ashford DA, 2000. Risk factors associated with leptospirosis in northeastern Thailand. Am J Trop Med Hyg 63: 204208.

    • Search Google Scholar
    • Export Citation
  • 4.

    Vijayachari P, Sugunan AP, Shriram AN, 2008. Leptospirosis: an emerging global public health problem. J Biosci 33: 557569.

  • 5.

    Griffith ME, Hospenthal DR, Murray CK, 2006. Antimicrobial therapy of leptospirosis. Curr Opin Infect Dis 19: 533537.

  • 6.

    World Health Organization, 2003. Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control. Geneva, Switzerland: World Health Organization.

    • Search Google Scholar
    • Export Citation
  • 7.

    Panaphut T, Domrongkitchaiporn S, Vibhagool A, Thinkamrop B, Susaengrat W, 2003. Ceftriaxone compared with sodium penicillin G for treatment of severe leptospirosis. Clin Infect Dis 36: 15071513.

    • Search Google Scholar
    • Export Citation
  • 8.

    Phimda K, Hoontrakul S, Suttinont C, Chareonwat S, Losuwanaluk K, Chueasuwanchai S, Chierakul W, Suwancharoen D, Silpasakorn S, Saisongkorh W, Peacock SJ, Day NP, Suputtamongkol Y, 2007. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother 51: 32593263.

    • Search Google Scholar
    • Export Citation
  • 9.

    Suputtamongkol Y, Niwattayakul K, Suttinont C, Losuwanaluk K, Limpaiboon R, Chierakul W, Wuthiekanun V, Triengrim S, Chenchittikul M, White NJ, 2004. An open, randomized controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin Infect Dis 39: 14171424.

    • Search Google Scholar
    • Export Citation
  • 10.

    Yoshimori RN, Goldberg HS, Blenden DC, 1965. Cephalothin in the treatment of experimental leptospirosis in hamsters. Antimicrob Agents Chemother 5: 450452.

    • Search Google Scholar
    • Export Citation
  • 11.

    Alexander AD, Rule PL, 1986. Penicillins, cephalosporins, and tetracyclines in treatment of hamsters with fatal leptospirosis. Antimicrob Agents Chemother 30: 835839.

    • Search Google Scholar
    • Export Citation
  • 12.

    Murray CK, Hospenthal DR, 2004. Broth microdilution susceptibility testing for Leptospira spp. Antimicrob Agents Chemother 48: 15481552.

  • 13.

    Murray CK, Hospenthal DR, 2004. Determination of susceptibilities of 26 Leptospira sp. serovars to 24 antimicrobial agents by broth microdilution technique. Antimicrob Agents Chemother 48: 40024005.

    • Search Google Scholar
    • Export Citation
  • 14.

    Ressner RA, Griffith ME, Beckius ML, Pimentel G, Miller RS, Mende K, Fraser SL, Galloway RL, Hospenthal DR, Murray CK, 2008. Antimicrobial susceptibilities of geographically diverse clinical human isolates of Leptospira. Antimicrob Agents Chemother 52: 27502754.

    • Search Google Scholar
    • Export Citation
  • 15.

    Griffith ME, Moon JE, Johnson EN, Clark KP, Hawley JS, Hospenthal DR, Murray CK, 2007. Efficacy of fluoroquinolones against Leptospira interrogans in a hamster model. Antimicrob Agents Chemother 51: 26152617.

    • Search Google Scholar
    • Export Citation
  • 16.

    Moon JE, Ellis MW, Griffith ME, Hawley JS, Rivard RG, McCall S, Hospenthal DR, Murray CK, 2006. Efficacy of macrolides and telithromycin against leptospirosis in a hamster model. Antimicrob Agents Chemother 50: 19891992.

    • Search Google Scholar
    • Export Citation
  • 17.

    Moon JE, Rivard RG, Griffith ME, Ressner RA, McCall S, Reitstetter RE, Hospenthal DR, Murray CK, 2007. Effect of timing and duration of azithromycin therapy of leptospirosis in a hamster model. J Antimicrob Chemother 59: 148151.

    • Search Google Scholar
    • Export Citation
  • 18.

    Alt DP, Bolin CA, 1996. Preliminary evaluation of antimicrobial agents for treatment of Leptospira interrogans serovar pomona infection in hamsters and swine. Am J Vet Res 57: 5962.

    • Search Google Scholar
    • Export Citation
  • 19.

    Alt DP, Zuerner RL, Bolin CA, 2001. Evaluation of antibiotics for treatment of cattle infected with Leptospira borgpetersenii serovar hardjo. J Am Vet Med Assoc 219: 636639.

    • Search Google Scholar
    • Export Citation
  • 20.

    Kirby WMM, Regamey C, 1973. Pharmacokinetics of cefazolin compared with four other cephalosporins. J Infect Dis 128: S341S345.

  • 21.

    Clinical and Laboratory Standards Institute, 2008. Performance Standards for Antimicrobial Susceptibility Testing; Eighteenth Informational Supplement. CLSI Document M100-S18. Wayne, PA: Clinical and Laboratory Standards Institute.

    • Search Google Scholar
    • Export Citation
  • 22.

    Levison ME, Johnson WD, Thornhill TS, Kaye D, 1969. Clinical and in vitro evaluation of cephalexin. JAMA 209: 13311336.

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In Vitro and In Vivo Activity of First Generation Cephalosporins Against Leptospira

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  • Department of Medicine, Wilford Hall Medical Center, Lackland Air Force Base, Texas; Departments of Medicine and Clinical Investigation, Brooke Army Medical Center, Fort Sam Houston, Texas; Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Medicine, Elgin Hospital, Elgin Air Force Base, Florida
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Third generation cephalosporins are commonly used in the treatment of leptospirosis. The efficacy of first generation cephalosporins has been less well-studied. Susceptibility testing of 13 Leptospira strains (11 serovars) to cefazolin and cephalexin was conducted using broth microdilution. Median minimal inhibitory concentration (MIC) for cefazolin and cephalexin ranged from < 0.016 to 2 μg/mL (MIC90 = 0.5 μg/mL) and from 1 to 8 μg/mL (MIC90 = 8 μg/mL), respectively. Efficacy of cefazolin and cephalexin in an acute lethal hamster model of leptospirosis was studied. Survival rates for cefazolin were 80%, 100%, and 100%, and survival rates for cephalexin were 50%, 80%, and 100% (treated with 5, 25, and 50 mg/kg per day for 5 days, respectively). Each treatment group showed improved survival compared with no treatment (P < 0.01), and none of the therapies, regardless of dose, was statistically significantly different than doxycycline. These results support a potential role for first generation cephalosporins as alternative therapies for leptospirosis.

Author Notes

*Address correspondence to Duane R. Hospenthal, Infectious Disease Service (MCHE-MDI), Brooke Army Medical Center, 3551 Roger Brooke Drive, Fort Sam Houston, TX 78234. E-mail: duane.hospenthal@us.army.mil

Authors' addresses: Brande M. Harris, Department of Medicine, Wilford Hall Medical Center, Lackland Air Force Base, TX, E-mail: brande.harris.1@us.af.mil. Peter J. Blatz, Mary K. Hinkle, Matthew E. Griffith, Clinton K. Murray, and Duane R. Hospenthal, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX, E-mails: peter.blatz@us.af.mil, mary.hinkle@amedd.army.mil, matthew.griffith@amedd.army.mil, and clinton.murray@us.army.mil, and duane.hospenthal@us.army.mil. Suzanne McCall and Miriam L. Beckius, Department of Clinical Investigation, Brooke Army Medical Center, Fort Sam Houston, TX, E-mails: suzanne.mccall@amedd.army.mil and miriam.beckius@amedd.army.mil. Katrin Mende, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX and Infectious Disease Clinical Research Program, Uniformed Services, University of the Health Sciences, Bethesda, MD, E-mail: katrin.mende@amedd.army.mil. Janelle L. Robertson, Department of Medicine, Elgin Hospital, Elgin Air Force Base, FL, E-mail: janelle.robertson@us.af.mil.

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