Therapeutic Limitations due to Antibiotic Drug Resistance: Road to Alternate Therapies

The antibiotics are destined for obsolescence as microbes would find a way to deal with them either by innate or by acquired genes. It is truly said that the power of bacteria should never be underestimated. There is a constant race between the humans for design and use of new drugs and the acquisition of genes by bacteria to render these novel drugs harmless. Situation has worsened with the indiscriminate use of antibiotics in human and animal health, agriculture, aquaculture and poultry. There have been reports of extremely drug resistant (XDR), totally drug resistant (TDR) bacteria and superbugs that have complicated the treatment of infectious diseases. Methicillin–resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) recognized as the bane of hospitals are some of the most dreaded bugs. This chapter discusses various mechanisms of multiple drug resistance (MDR) in bacteria and the limitations of antibacterial chemotherapy due to MDR. Various innate and acquired mechanisms of drug resistance like integrons, SXT elements, efflux pumps and quinolone resistance mechanisms are described in details. Some of the important databases related to these genetic factors have also been described here. The possibility of attacking the virulence of bacteria rather than the bug itself in order to circumvent the crisis of MDR has been discussed. It further highlights some of the novel strategies such as efflux pump inhibition and quorum sensing inhibition as anti-virulence strategies. It is advocated that this never-ending war with bacteria would probably require multifaceted approach combining antibacterial, antivirulent regimes in addition to the constant search for novel drug targets and newer drugs by the pharmaceutical companies. Success of these strategies would involve cumulative and strenuous efforts from public, policy makers, research community, clinicians and pharmaceutical companies.

Keywords: Databases, efflux pumps, government policies, inhibitors, integrons, multidrug resistance, phage therapy, plasmids, quinolone resistance, quorum sensing, SXT elements, virulence, vaccines.