Combination of Drugs: An Effective Approach for Enhancing the Efficacy of Antibiotics to Combat Drug Resistance
Currently available antibiotics have been effective in treating infectious diseases; however, the development of resistance to these drugs has led to the emergence of new and the re-emergence of old, infectious diseases. Therefore, newer antibiotic approaches with mechanistic differences are needed to combat antimicrobial resistance. Combining antibiotics is an encouraging strategy for increasing treatment efficacy and for controlling resistance evolution. This approach may include the combination of one antibiotic with another antibiotic and the development of adjuvants that either directly target resistance mechanisms, like inhibition of β-lactamase enzymes, or indirectly target resistance by interrupting the bacterial signaling pathways, such as two-component systems. Other natural products, like essential oils, plant extracts, and nanoparticles, can also be combined synergistically with antibiotics. The aim of this chapter is to highlight the strategy of treating infections with arrays of drugs rather than discrete drugs. We have addressed here three categories of approaches being used in combination therapy: the inhibition of targets in different pathways, the inhibition of distinct nodes in the same pathway, and the inhibition of the same target in different ways. Here, we have described the most recent developments toward combination therapies for the treatment of infectious diseases caused by multidrug-resistant bacteria.
KeywordsAntibiotic Combination therapy Drug resistance Synergy
We acknowledge the Department of Scientific Research, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia, for financial support in completing this work.
- Adikwu, M., Jackson, C., & Esimone, C. (2010). Evaluation of in vitro antimicrobial effect of combinations of erythromycin and Euphorbia hirta leaf extract against Staphylococcus aureus. Research in Pharmaceutical Biotechnology, 2, 22–24.Google Scholar
- Ahmed, Z., Khan, S. S., Khan, M., et al. (2009). Synergistic effect of Salvadora persica extracts, tetracycline and penicillin against Staphylococcus aureus. African Journal of Basic and Applied Sciences, 2, 25–29.Google Scholar
- Ghannad, M. S., & Mohammadi, A. (2012). Bacteriophage: Time to re-evaluate the potential of phage therapy as a promising agent to control multidrug-resistant bacteria. Iranian Journal of Basic Medical Sciences, 15, 693–701.Google Scholar
- Khan, M. S. A., & Ahmad, I. (2013). In vitro antifungal activity of oil of Cymbopogon citratus and citral alone and in combination with fluconazole against azole-resistant strains of Aspergillus fumigatus and Trichophyton rubrum. Pharmacognosy Communications, 3, 29–34.Google Scholar
- Lennox, J. L., DeJesus, E., Lazzarin, A., et al. (2009). Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: A multicentre, double-blind randomised controlled trial. Lancet, 374, 796–806.PubMedCrossRefPubMedCentralGoogle Scholar
- Markoishvili, K., Tsitlanadze, G., Katsarava, R., et al. (2002). A novel sustained-release matrix based on biodegradable poly(ester amide)s and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds. International Journal of Dermatology, 41, 453–458.PubMedCrossRefPubMedCentralGoogle Scholar
- Thati, V., Roy, A. S., Prasad, A. M. V. N., Shivannavar, C. T., et al. (2010). Nanostructured zinc oxide enhances the activity of antibiotics against Staphylococcus aureus. Journal of Bioscience and Technology, 1, 64–69.Google Scholar
- Wu, P., & Grainger, D. W. (2006). Drug/device combinations for local drug therapies and infection prophylaxis. Biomaterials, 27, 24500–22467.Google Scholar