Utilizing Combination Drug Therapy to Inhibit /Haemophilus ducreyi/ Growth and Reduce Antibiotic Resistance

Abstract:

Antibiotic resistance has become a mounting issue in modern medicine that is in desperate need of a solution. One cause of antibiotic resistance is that specific types of bacteria are only susceptible to certain classes of antibiotics, two of which are beta-lactam antibiotics (BLAs) and macrolides. One pathogen of concern that has demonstrated antibiotic resistance to former front line macrolides and BLAs is Haemophilus ducreyi, which causes the sexually transmitted disease chancroid that is prevalent in regions of Africa and Southeast Asia. Empirical antibiotic usage is typically indicated for treatment which raises the risk of regional strains of H. ducreyi developing resistance to the antibiotics used. One potential avenue of treatment for chancroid is combination therapy, which allows for lower dosages of multiple antibiotics to be utilized concurrently thus lowering the concentration of antimicrobials needed and reducing the risk that the bacteria develop resistance to them. In this study, vancomycin (a BLA) and ampicillin (a macrolide), and their combination were used to reduce the minimum inhibitory concentration (MIC) of the antibiotics used and reduce the risk of resistance of H. ducreyi. A checkerboard assay with double serial dilutions in a 96 well plate was utilized to observe 77 differing concentrations of these antibiotics in combination in addition to varying concentrations of each antibiotic individually. The results of the assay were consistent with the prediction that the combination of ampicillin and vancomycin resulted in a lower MIC of antibiotic needed to clear an infection and less bacterial growth in the wells. The most common MICs were found to be the combination of 5.00 μg/mL of vancomycin with concentration below 1.25 μg/mL of ampicillin, with these pairings also being found to be the minimum lethal concentration (MLC). Alone, the MIC of ampicillin was 10 μg/mL while vancomycin was 5.00 μg/mL. Thus, combination therapy of ampicillin and vancomycin inhibited and killed /H. ducreyi/ at lower doses than the antibiotics alone. This study opens the door for more research to be completed in the realm of combination therapy as a safe, effective treatment for bacteria such as /H. ducreyi/.