title: Combination therapy: the propitious rationale for drug development.
abstract: Therapeutic options for many infections are extremely limited and at crisis point. We run the risk of entering a second pre-antibiotic era. There had been no miracle drug for the patients infected by resistant microbial pathogens. Most of the very few new drugs under development have problems with their toxicity, or pharmacokinetics and pharmacodynamics. We are already decades behind in the discovery, characterization and development of new antimicrobials. In that scenario, we could not imagine surviving without newer and effective antimicrobial agents. Bacteria have been the champions of evolution and are still evolving continuously, where they pose serious challenges for humans. Along with the crisis of evolving resistance, the condition is made worst by the meager drug pipeline for new antimicrobials. Despite ongoing efforts only 2 new antibiotics (Telavancin in 2009 and Ceftaroline fosamil in 2010) have been approved since 2009 pipeline status report of Infectious Disease Society of America (IDSA). Recent approval of new combination based antiviral drugs such as Stribild (combination of four drugs for HIV treatment) and Menhibrix (combination vaccine to prevent meningococcal disease and Haemophilus influenzae type b in children) proves that combination therapy is still the most promising approach to combat the ever evolving pathogens. Combination therapy involves the drug repurposing and regrouping of the existing antimicrobial agents to provide a synergistic approach for management of infectious diseases. This review article is an effort to highlight the challenges in new drug development and potential of combination drug therapy to deal with them.
authors.forename: Neetu
authors.initials: N
authors.lastname: Phougat
authors.forename: Savita
authors.initials: S
authors.lastname: Khatri
authors.forename: Anu
authors.initials: A
authors.lastname: Singh
authors.forename: Mrridula
authors.initials: M
authors.lastname: Dangi
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.forename: Rajesh
authors.initials: R
authors.lastname: Dabur
authors.affiliation: Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana-124001, India. anil.chhillar@gmail.com.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Chhillar
mesh_terms: D000222:Adaptation, Physiological; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000191:economics / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D005075:Biological Evolution; D001692:Biological Transport; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D058492:Drug Repositioning; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000191:economics / Q000379:methods*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000502:physiology; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents