Adverse Drug Effects: A Nursing Concern

Drug resistance 219in permeability of the outer membrane and hence resistance. Bacterialstrains that have become resistant through this mechanism mayexhibit cross-resistance to unrelated antibiotics which use the sameporins.Table 14.1 Mechanisms of action of antibiotics (Walters 1988, 1989, 1990, 1993)Mechanism of actionPrevent formation of cell wallAlter permeability of cell membraneInterfere with protein synthesisInterfere with nucleic acid synthesisInterfere with cell metabolismExamplesCarbapenems, cephalosporins, penicillins,vancomycinCyclic polypeptides, polyene antifungalsAminoglycosides, chloramphenicol,erythromycin, tetracyclinesRifampicins, quinolonesSulphonamides, trimethoprimAnother highly topical example is methicillin-resistant Staphylococcusaureus (MRSA). These bacteria use enzymes termed ‘penicillin bindingproteins’ (PBP), which are important in the final stages of cross-linkingthe building blocks of the bacterial cell wall. Antibiotics such as penicillinwork by blocking these enzymes. Resistant species such as MRSAsynthesise an additional penicillin binding protein that has a muchlower affinity for the antibiotics than the normal enzyme. Consequentlythe bacteria are able to continue cell wall synthesis even whenother penicillin binding proteins are inhibited (Mims et al., 1993).Selecting for resistanceOnce one bacterium has become resistant to an antibiotic, it willspread this resistance on to its offspring, as well as to other bacteriathrough plasmid transfer. However, the making of an abnormalprotein is often costly to a bacterium and so in straight competitionwith other bacteria without the abnormal protein it will often notsurvive. However, if antibiotic is added to the environment the resistantbacteria will have a selective advantage. This means that theantibiotic will kill the surrounding non-resistant bacteria, while theresistant bacteria will be free to multiply, without competition forfood and space. The resistant bacteria will then become common inthe environment. It can thus be seen that the use of antibiotics canactually encourage the development of resistant bacteria.