Antibiotic Resistance

Antibiotic resistance is a form of drug resistance whereby some (or, less commonly, all) sub-populations of a microorganism, usually a bacterial species, are able to survive exposure to one or more antibiotics. Accordingly, pathogenic species which have become resistant cause infections which can not be treated with the usual, formerly efficacious antibiotic drugs and/or their usual, formerly efficacious, dosages and concentrations. Resistance may be instrinsic or acquired. Some clinically relevant pathogens have developed resistance to multiple antibiotics and are dubbed multidrug resistant (MDR pathogens). More recently, the colloquial term superbug has become widespread in both popular and technical accounts of the phenomenon with which it is synonymous.

Antibiotic resistance is a serious and growing phenomenon in contemporary medicine and has emerged as one of the eminent public health concerns of the 21st century, particularly as it pertains to pathogenic organisms (the term is not especially relevant to organisms which don't cause disease in humans). In the simplest cases, drug-resistant organisms may have acquired resistance to first-line antibiotics, thereby necessitating the use of second-line agents. Typically, the first-line agent is selected on the basis of several advantages including safety, availability and cost; comparatively, the second-line agent is usually broader in spectrum, possesses a less favourable risk-benefit profile and may be more expensive or, in more dire circumstances, locally unavailable. In the case of some MDR pathogens, resistance to second and even third-line antibiotics is sequentially acquired, a case quintessentially illustrated by Staphylococcus aureus in some nosocomial settings. Some pathogens, such as Pseudomonas aeruginosa, additionally possess a high level of intrinsic resistance.

It may take the form of a spontaneous or induced genetic mutation, or the acquisition of resistance genes from other bacterial species by horizontal gene transfer via conjugation, transduction, or transformation. Many antibiotic resistance genes reside on transmissible plasmids, facilitating their transfer. Exposure to an antibiotic naturally selects for the survival of the organisms with the genes for resistance. In this way, a gene for antibiotic resistance may readily spread through an ecosystem of bacteria. Antibiotic-resistance plasmids frequently contain genes conferring resistance to several different antibiotics.

Genes for resistance to antibiotics, like the antibiotics themselves, are ancient. However, the increasing prevalence of antibiotic-resistant bacterial infections seen in clinical practice stems from antibiotic use both within human medicine and veterinary medicine. Any use of antibiotics can increase selective pressure in a population of bacteria to allow the resistant bacteria to thrive and the susceptible bacteria to die off. As resistance towards antibiotics becomes more common, a greater need for alternative treatments arises. However, despite a push for new antibiotic therapies there has been a continued decline in the number of newly approved drugs. Antibiotic resistance therefore poses a significant problem.

The growing prevalence and incidence of infections due to MDR pathogens is epitomised by the increasing number of familiar acronyms used to describe the causative agent and sometimes the infection generally; of these, MRSA is probably the most well-known, but others including VISA (vancomycin-intermediate S. aureus), VRSA (vancomycin-resistant S. aureus), ESBL (Extended spectrum beta-lactamase), VRE (Vancomycin-resistant Enterococcus) and MRAB (Multidrug-resistant A. baumannii) are prominent examples. Nosocomial infections overwhelmingly dominate cases where MDR pathogens are implicated, but multidrug-resistant infections are also becoming increasingly prevalent in the community.