3 Resistance
3.1 Resistance Mechanisms
There are numerous mechanisms through which bacteria can develop resistance to
antimicrobial drugs. These all involve a change in proteins made by the cell and
include:
l Alteration in ribosomal binding sites)
l Gene up-regulation (e.g. synthesis of inactivating enzymes such asb-lactamases)
l Changes in target site binding (e.g. alteration in penicillin binding proteins)
l Changes in membrane permeability
- Porin closure
- Efflux pumps
These changes in protein synthesis are caused by changes to DNA which are
l Plasmid-mediated
l Mutational
l Conjugation
l Ingestion of DNA-materials
The mechanisms through which resistance occurs have generally been consid-
ered to be specific to the drug class and to the bacterial species against which the
drug acts. However, there are an increasing number of examples where resistance
mechanisms traverse drug classes, including classes such as phenicols, lincosa-
mides, oxazolidinones, pleuromutilins and streptogramin A (Long et al. 2006 ).
Table 2 provides a summary of the mechanisms of drug resistance that have
traditionally been associated with specific drug classes.
3.2 Defining the Term “Resistance”
Although some bacteria have exhibited natural resistance even prior to the use of
antibiotics (Davies 1994 ), the emergence of resistance in previously susceptible
bacterial populations has been attributed to the use of antimicrobial agents. Terms
such as intrinsic and acquired resistance and single, multiple and cross-resistance
have been introduced to describe the nature and clinical implications of these
changes in bacterial subpopulations (Prescott and Baggot 1993 ).
The global impact of a shrinking therapeutic arsenal has precipitated numerous
efforts to track the emergence and prevalence of drug resistance. Expert panels have
been convened to consider potential solutions to this problem. However, discus-
sions of this issue and interpretation of study data have been confounded by a lack
of uniformity in how the term “resistance” has been defined. To illustrate this point,
Davison et al. ( 2000 ) published definitions of antibiotic resistance, confirming the
Antimicrobial Drug Resistance 233