Penicillins, cephalosporins, and tetracyclines in treatment of hamsters with fatal leptospirosis

Alexander, A. D.; Rule, Patricia

doi:10.1128/aac.30.6.835

Cited by 49 publications

(23 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observed efficacy of doxycycline was consistent with that reported in previous leptospiral animal research (1,8). The efficacy of the two macrolide antimicrobial agents azithromycin and clarithromycin supports earlier research that demonstrated in vivo efficacy of erythromycin in treating various rodent models of leptospirosis (2, 5, 9).…”

Section: Discussionsupporting

confidence: 81%

“…Antimicrobial therapy in all experiments was begun on day 2 (infection was on day 0) and continued for 5 days. Six concentrations of azithromycin (6.25, 12.5, 25, 50, 100, and 200 mg/kg), eight concentrations of clarithromycin (1,5,10,15,20,40,60, and 100 mg/kg), and six concentrations of telithromycin (1,5,10,15,20, and 40 mg/kg) were tested. The efficacy of various doxycycline concentrations (1,5,10,15,50, and 100 mg/kg) was also examined in the model for further comparison.…”

Section: Methodsmentioning

confidence: 99%

“…Amoxicillin, ampicillin, and erythromycin have been suggested in less-severe disease, although no randomized, controlled human data are available to support this recommendation (23). Additional antimicrobials, primarily ␤-lactams and fluoroquinolones, have shown treatment efficacy in various animal models (1,4,5,6,9,19,24). However, to date, neither animal model nor human trial has addressed the efficacy of most other modern antimicrobials in leptospirosis.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of Macrolides and Telithromycin against Leptospirosis in a Hamster Model

Moon

Ellis

Griffith

et al. 2006

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Human studies support the use of ␤-lactams and tetracyclines in the treatment of leptospirosis. Additional agents from these and other classes of antimicrobials also have in vitro activity against Leptospira species, though corroborating in vivo data are limited or lacking. We evaluated the therapeutic efficacy of azithromycin, clarithromycin, and telithromycin in a lethal hamster model of leptospirosis using Leptospira interrogans serogroup Canicola serovar Portlandvere. A range of dosages for each antimicrobial was given to the infected animals on days 2 through 7 (5 days) of the 21-day survival model. All untreated control animals survived less than 10 days from infection. Leptospirosis is an acute febrile illness caused by spirochetes of the genus Leptospira whose clinical manifestations can range from asymptomatic infection to death. Current treatment of leptospirosis includes symptomatic support with or without directed antimicrobial administration, depending on the severity and duration of symptoms (12). Specific antimicrobial therapy for leptospirosis has been examined for over 60 years (13,17). Antimicrobials of choice include penicillin, doxycycline, cefotaxime, and ceftriaxone (7,13,16,20,22). This is based on randomized, controlled human studies that have demonstrated the efficacy of these drugs in reducing symptoms and leptospiruria but not necessarily in improving survival. Amoxicillin, ampicillin, and erythromycin have been suggested in less-severe disease, although no randomized, controlled human data are available to support this recommendation (23). Additional antimicrobials, primarily ␤-lactams and fluoroquinolones, have shown treatment efficacy in various animal models (1,4,5,6,9,19,24). However, to date, neither animal model nor human trial has addressed the efficacy of most other modern antimicrobials in leptospirosis. Such agents might provide equal or superior efficacy, with easier administration, fewer contraindications (e.g., doxycycline's contraindication in pregnancy or restriction of penicillin use due to allergy), and fewer adverse events (e.g., doxycycline's associated phototoxicity and gastrointestinal side effects) than the proven options. This report describes our experience in using macrolides and telithromycin in treating acute leptospirosis in a lethal hamster model. MATERIALS AND METHODSAnimal model. The animal model utilized was adapted from previously published work by Alexander and Rule (1). Female golden Syrian hamsters (Mesocricetus auratus) weighing 50 to 100 g (Harlan, Indianapolis, IN) were inoculated intraperitoneally with 0.5 ml of Ellinghausen-McCullough-Johnson-Harris (EMJH) medium (Becton Dickinson, Sparks, MD) containing 10 5 leptospires. Leptospira interrogans serogroup Canicola serovar Portlandvere (CA-12-029/ CDC Nic 1808) was used for all trials (obtained from David Haake, University of California Los Angeles). This strain was maintained by hamster passage and recovered between passages in semisolid EMJH medium. Inoculum was produced by subculture of these ...

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of Macrolides and Telithromycin against Leptospirosis in a Hamster Model

Moon

Ellis

Griffith

et al. 2006

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…In contrast to the previous studies with experimental animals (2,20), we tried to define experimental conditions as close as possible to those in a natural infection: (i) the infecting serovar…”

Section: Discussionmentioning

confidence: 99%

Quantitative PCR Assay To Evaluate Ampicillin, Ofloxacin, and Doxycycline for Treatment of Experimental Leptospirosis

Truccolo

Charavay

Mérien

et al. 2002

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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.

show abstract

“…10 However, when this work was repeated 20 years later by Alexander and Rule, 11 first generation cephalosporins (cefadroxil and cephalexin), even in high doses, were not shown to be effective against leptospirosis in their hamster model. Their work did show a survival benefit for second (cefamandole) and third (cefoperazone, cefotaxime, and moxalactam) generation cephalosporins.…”

Section: Introductionmentioning

confidence: 99%

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

Harris

Blatz²,

Hinkle³

et al. 2011

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

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.

show abstract

Penicillins, cephalosporins, and tetracyclines in treatment of hamsters with fatal leptospirosis

Cited by 49 publications

References 10 publications

Efficacy of Macrolides and Telithromycin against Leptospirosis in a Hamster Model

Efficacy of Macrolides and Telithromycin against Leptospirosis in a Hamster Model

Quantitative PCR Assay To Evaluate Ampicillin, Ofloxacin, and Doxycycline for Treatment of Experimental Leptospirosis

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

Contact Info

Product

Resources

About