Antibiotic Resistance

Introduction Antibiotic resistance became a major concern for the UK government in the 1960s and remains a growing problem with serious implications for morbidity and mortality in hospitalized patients. Although most antibiotics are prescribed in the community, antibiotic resistance is most frequently seen in hospitals and is most prevalent in areas where their use is high, notably ICUs and other acute care units. Infections arising from antibiotic resistant organisms are:  More difficult to treat  Last longer and are often more severe  Increase the period of infectiveness  Increase the length of hospitalization  Increase the likelihood of adverse side-effects due to the use of less desirable antibiotic agents. As antibiotic resistance evolves, the antibiotic agents currently available become less effective. (REMEMBER: The “environment selects for organisms found IN THAT ENVIRONMENT!” This is a great concern, as agents introduced in the last 20 years have mostly been modifications of existing compounds. Emergence of antibiotic resistance Antibiotic resistance has developed as a natural evolutionary response by organisms following their exposure to antimicrobial agents. Antibiotic resistance may be:  An intrinsic, naturally occurring trait of the organism, e.g. vancomycin resistance in Escherichia coli  Acquired by: o Spontaneous mutation of the target enzymes o Transfer of genetic resistance determinants from other organisms. Genetic resistance determinants are easily spread to other organisms, including commensals, particularly if they are plasmid-borne. Plasmids often contain many genes encoding resistance to multiple classes of antibiotics, conferring multi-drug resistance to the recipient organisms. T Mechanisms of antibiotic resistance There are several mechanisms that confer antibiotic resistance:  Enzymatic modification or destruction of the antibiotic o Evolution of enzyme (result of a series of mutations via the unfaithful DNA polymerase) o Acquisition of the gene encoding the enzyme  Conjugation – plasmid transfer  Transduction – bacteriophage-mediated gene transport  Transformation – bacteria picking up and taking in DNA from other bacteria o e.g. b-lactamase destruction of penicillin  Exclusion of the drug due to reduced permeability of the organism o Mutations occurring in the transmembrane protein genes that encode proteins that would ordinarily mediate the transport of the antibiotic into the cell (mechanism: unfaithful DNA polymerase enzyme)  Active efflux of the antibiotic (“drug pumps”) o Evolution of efflux transmembrane proteins (result of a series of mutations via the unfaithful DNA polymerase) o Acquisition of the gene encoding the drug pumps  Conjugation – plasmid transfer  Transduction – bacteriophage-mediated gene transport  Transformation – bacteria picking up and taking in DNA from other bacteria  Loss or modification of the drug target. o Modification of drug target (result of mutation via the unfaithful DNA polymerase)  e.g. metabolic antagonism o Acquisition of the gene encoding an alternative enzyme  Conjugation – plasmid transfer  Transduction – bacteriophage-mediated gene transport  Transformation – bacteria picking up and taking in DNA from other bacteria Factors that increase the risk of infection with resistant strains  Vulnerable patients.  Prior antibiotic therapy.  Antibiotic prophylaxis (e.g. before a dentist appoint to have a tooth extracted).  Prolonged hospitalization.  Severity of underlying disease.  Use of invasive devices. Principles of prevention The foundation for preventing antibiotic resistance is controlled use of antibiotic agents. The main considerations for overcoming antibiotic resistance include:  Development of antibiotic policies that incorporate “rational antibiotic prescribing” with reservation of certain antibiotics for difficult-to-treat infections  Efficient infection control to prevent the spread of infectious organisms. Management of infection If you suspect a pathogen with antibiotic resistance capabilities, consult your local microbiologist and local antibiotic policies. Local resistance patterns should be defined in order to customize treatment.