Effect of different drugs and drug combinations on killing stationary phase and biofilms recovered cells of Bartonella henselae in vitro

Abstract

Background: 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. 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. Results: We 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. Conclusions: These findings may facilitate development of more effective treatment of persistent Bartonella infections in the future.

Efficacy of Double-Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases and Retrospective Chart Review

“…Resistance to standard treatments has been reported for both Babesia and Bartonella spp. [ 69 , 70 ], and resistant biofilm and persister forms have also recently been reported for Bartonella [ 132 , 133 ]. Would addressing Babesia and/or Bartonella with newer medication regimens, including tafenoquine for Babesia [ 134 ] and/or novel combination therapies for Bartonella (i.e., macrodantin, rifampin, methylene blue, gentamycin with essential oils) [ 133 ], prior to DDD CT improve clinical outcomes in co-infected patients?…”

“…[ 69 , 70 ], and resistant biofilm and persister forms have also recently been reported for Bartonella [ 132 , 133 ]. Would addressing Babesia and/or Bartonella with newer medication regimens, including tafenoquine for Babesia [ 134 ] and/or novel combination therapies for Bartonella (i.e., macrodantin, rifampin, methylene blue, gentamycin with essential oils) [ 133 ], prior to DDD CT improve clinical outcomes in co-infected patients? Similarly, the three biofilm agents (Stevia, oregano oil, Biocidin) we used in our study were all found to have efficacy against biofilms and morphological forms of Borrelia [ 33 , 34 , 104 ], but would other biofilm agents or combinations against Borrelia and/or associated co-infections be more efficacious [ 33 , 135 ]?…”

What Is in a Cat Scratch? Growth of Bartonella henselae in a Biofilm

“…Treatment failure in patients diagnosed with B. henselae endocarditis has been largely attributed to the ability of B. henselae to form a biofilm and resist antibiotics. Recent in vitro data suggests drug combination treatments are more effective in eliminating B. henselae chronic infection, compared to current single drug treatments [ 22 ]. Despite the continued use of antibiotics, systemic cases of B. henselae infection remain difficult to treat and often require more invasive treatment courses [ 23 ].…”

Efficacy of Double Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases

“…Resistance of Babesia and Bartonella spp. to standard treatments have both been reported[69] [70] and resistant biofilm and persister forms have also recently been reported for Bartonella[132] [133]. Would addressing Babesia and/or Bartonella with newer medication regimens including tafenoquine for babesia[134] and/or novel combination therapies for Bartonella (i.e., macrodantin, rifampin, methylene blue, gentamycin with essential oils)[133] prior to DDD CT improve clinical outcomes in co-infected patients?…”

“…to standard treatments have both been reported[69] [70] and resistant biofilm and persister forms have also recently been reported for Bartonella[132] [133]. Would addressing Babesia and/or Bartonella with newer medication regimens including tafenoquine for babesia[134] and/or novel combination therapies for Bartonella (i.e., macrodantin, rifampin, methylene blue, gentamycin with essential oils)[133] prior to DDD CT improve clinical outcomes in co-infected patients? Similarly, the three biofilm agents (Stevia, oregano oil, Biocidin) we used in our study were all published to have efficacy against biofilms and morphological forms of Borrelia[34] [33][104], but would other biofilm agents or combinations against Borrelia and/or associated co-infections be more efficacious[33] [135]?…”