Molecular mechanisms of Bartonella henselae resistance to azithromycin, pradofloxacin and enrofloxacin

Extract

Sir,

Bartonella henselae are fastidious, facultative intracellular bacilli that can cause bacteraemia, endocarditis, cat-scratch disease in immunocompetent patients, and bacillary angiomatosis and peliosis hepatitis in immunocompromised patients.^1,2 There are a limited number of studies that have addressed the antibiotic treatment of cats infected with B. henselae.³ Azithromycin, a macrolide compound, has seemingly become the drug of choice to treat cats and dogs for B. henselae infection. However, relapses after antibiotic withdrawal have been reported.⁴ Azithromycin, which is derived from erythromycin, binds to the 50S subunit of the bacterial ribosome and, thus, inhibits the translation of mRNA. Fluoroquinolone antibiotics exert their antibacterial effects by inhibiting certain bacterial topoisomerase enzymes. Pradofloxacin, a third-generation fluoroquinolone, is being exclusively developed for use in veterinary medicine. Enrofloxacin is a broad-spectrum antimicrobial agent with bactericidal activity against Gram-negative and Gram-positive bacteria, mycobacteria and rickettsia. As for B. henselae, potential mechanisms of resistance to azithromycin, pradofloxacin and enrofloxacin are not known. Therefore, the objective of this study was to select in vitro azithromycin-resistant, pradofloxacin-resistant and enrofloxacin-resistant mutants to determine the molecular mechanism of resistance.