Bacterial resistance

Abstract

The development of drug resistance is apparently only one aspect of the continuing process of microbial evolution. Prevalence of antibiotics has resulted in the selection of new types of organisms by the principle of survival of the fittest. The changes leading to antibiotic resistance are not for the most part drug-induced but probably result from spontaneously occurring mutations leading to modified biochemical processes in the bacterial cell (resistant strains). Some microorganisms (resistant species and “naturally” resistant strains) may originally possess cytochemical systems that are not vulnerable to specific antibiotics. Categories of resistance and sensitivity are relative. Analyses of resistance patterns show two important types, the penicillin or obligatory multistep pattern and the streptomycin or facultative one-step pattern. The type of pattern is significant in predicting the probability that resistance will develop rapidly. Aside from the indirect evidence resulting from demonstrations of resistant clones in bacterial cultures prior to drug contact, a genetic basis for antibiotic resistance is suggested by experiments on bacterial transformation and by recombination following matings of unlike strains. Mutations to antibiotic resistance usually include a wide variety of types, separable into different classes if sufficient criteria of examination are employed. Some disparity of results with strains of separate origin is therefore inevitable, and isolated experiments may have little statistical validity. Gain or loss of resistance in bacterial populations, once mutations to resistance have occurred, depends primarily on selection. Here the presence or absence of antibiotics plays the major but not exclusive role. Multiple chemotherapy is at present the most efficient method for preventing the establishment of resistant strains but it has certain potential limitations, many of which also apply to the use of drugs singly. These limitations result from the growth of resistant clones before the onset of antibiotic therapy, the possible occurrence of induced multiple mutations, the multigenic basis of some types of resistance which leads to increased probability of mutation, the increased significance of cross resistance as new antibiotics are discovered and the possibility that non-specific resistance will protect bacteria to a slight degree against several types of anti-bacterial agents used simultaneously allowing multiplication, mutation and selection of more highly resistant forms. Through no intrinsic fault, multiple chemotherapy must often cope with bacterial populations that have previously been allowed to develop consecutive resistances by the unsuccessful application of several anti-biotics in sequence or in ineffective combination.