Abstract
BackgroundBartonella henselae is a Gram-negative bacterium transmitted to humans by a scratch from cat in the presence of ectoparasites. Humans infected with B. henselae can result in various clinical diseases including local lymphadenopathy and more serious systemic disease such as persistent bacteremia and endocarditis. The current treatment of persistent B. henselae infections is not very effective and remains a challenge. To find more effective treatments for persistent and biofilm Bartonella infections, in this study, we evaluated a panel of drugs and drug combinations based on the current treatment and also promising hits identified from a recent drug screen against stationary phase and biofilm recovered cells of B. henselae.ResultsWe evaluated 14 antibiotics and 25 antibiotic combinations for activity against stationary phase B. henselae (all antibiotics were at 5 μg/ml) and found that ciprofloxacin, gentamicin, and nitrofurantoin were the most active agents, while clofazimine and miconazole had poor activity. Drug combinations azithromycin/ciprofloxacin, azithromycin/methylene blue, rifampin/ciprofloxacin, and rifampin/methylene blue could rapidly kill stationary phase B. henselae with no detectable CFU after 1-day exposure. Methylene blue and rifampin were the most active agents against the biofilm B. henselae after 6 days of drug exposure. Antibiotic combinations (azithromycin/ciprofloxacin, azithromycin/methylene blue, rifampin/ciprofloxacin, rifampin/methylene blue) completely eradicated the biofilm B. henselae after treatment for 6 days.ConclusionsThese findings may facilitate development of more effective treatment of persistent Bartonella infections in the future.
Highlights
Bartonella henselae is a Gram-negative bacterium transmitted to humans by a scratch from cat in the presence of ectoparasites
minimum inhibitory concentration (MIC) of candidate drugs The candidate antibiotics evaluated were based on some antibiotics with good activity against stationary phase B. henselae [26] as well as antibiotics commonly used to treat B. henselae infections as controls
In this study, to develop more effective treatment for persistent Bartonella infections, we mainly focused on evaluating drugs and drug combinations for activity against stationary phase and biofilm B. henselae
Summary
Bartonella henselae is a Gram-negative bacterium transmitted to humans by a scratch from cat in the presence of ectoparasites. Humans infected with B. henselae can result in various clinical diseases including local lymphadenopathy and more serious systemic disease such as persistent bacteremia and endocarditis. Bartonella species are fastidious, Gram-negative intracellular bacteria [1] that are widely present in various mammals including cats, rodents, ruminants, and humans [2, 3]. They are transmitted mainly by direct contact such as animal scratches and bites, or by some arthropods. B. henselae biofilms have been involved in two distinct parts of the life cycle They colonize and persist in the arthropod vector which increases transmission from the flea to the vertebrate host [15]. Treatment of systemic B. henselae infections has been difficult with poor clinical outcomes despite antibiotic treatment for weeks and months [22]
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