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

Abstract

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.

Rapid Isolation and Susceptibility Testing of Leptospira spp. Using a New Solid Medium, LVW Agar

“…Broth macroand microdilution methods have been developed and used to determine the MICs of small collections of Leptospira isolates (8,9,(11)(12)(13)(14)(15)(16) (13,14). In general, we did not observe regional differences in antimicrobial susceptibility in Thailand, Lao PDR, and Sri Lanka, and our findings support the continued use of penicillin, cephalosporin, and doxycycline for the treatment of leptospirosis in these areas.…”

“…Furthermore, antimicrobial therapy is invariably empirical because of a lack of simple antimicrobial susceptibility testing methods for Leptospira (7). Broth macro-and microdilution methods have been described (8)(9)(10)(11)(12)(13)(14)(15)(16), but these are too time-consuming for routine diagnostic microbiology laboratories. Simple diffusion-based methods such as disk diffusion and Etest methodology are not described for these species.…”

European consensus statement on leptospirosis in dogs and cats

“…First‐generation cephalosporins have been shown to be effective in a hamster model of leptospirosis (Harris et al . ). The iv use of the third generation cephalosporins ceftriaxone and cefotaxime has gained popularity for the treatment of severe forms of leptospirosis in humans, where these antimicrobials have mostly replaced penicillin (Panaphut et al .…”

“…, Harris et al . ). Such studies can unveil important information on the evolution of antimicrobial susceptibility under the pressure of commonly used antimicrobials.…”

Persistent Leptospiruria in Five Dogs Despite Antimicrobial Treatment (2000–2017)

“…6,7 In three of the dogs (cases 1-3 hamsters. 17,[21][22][23][24] In these studies, the mortality rate of untreated hamsters was 100%, whereas the survival rate was at or near 100% with many of the antimicrobials with which the hamsters were treated, including doxycycline, fluoroquinolones, and first-generation cephalosporins. Several studies have investigated the use of alternatives to penicillin G or doxycycline in the treatment of humans with leptospirosis and determined that azithromycin, cefotaxime, and ceftriaxone were as effective.…”