Methimazole in Treatment of Thyrotoxicosis
Authors: L. A. G. Davidson
Journal: BMJ (1953)

COMBINED ANTIBIOTIC TREATMENT longer show interaction; under the same conditions streptomycin and chloramphenicol not only lose their initial antagonism, but with some organisms become synergistic.Unlike some workers (Jawetz et al., 1952 ;Bliss et al., 1952), we have not found at 18-24 hours that a pair of antibiotics will be synergistic with one organism and antagonistic with another.In our experience any pair of antibiotics will react at this time in the same way, varying only in degree with different organisms.We therefore believe that a limited forecast can be made of the behaviour in vitro of a pair of antibiotics when tested against any organism.The value of such a forecast in controlling therapy cannot yet be assessed, since further knowledge of the correlation between laboratory and clinical findings is needed.Before any prediction can be made of the probable corre- lation between laboratory and clinical results several diffi- cult questions have to be considered.The first is the problem of the relative importance of bacteriostatic and bactericidal action of antibiotics in the body.The para- mount importance of the former mode of action in most forms of infection was not questioned until the combined action of antibiotics was investigated.It then became apparent that the results of testing bacteriostatic activity in vitro agreed less well with animal experiments than did the results of tests based on bactericidal action, and the idea has grown up that the lethal activity of antibiotics is the more impor- tant in vivo.Concentrations used in tests of combined lethal activity have, however, been closer to those attained in the body than the sub-inhibitory levels usually employed in tests based on combined bacteriostatic action, and this may ex- plain some of the divergent results.There can be no doubt that the pattern of interaction alters with time.Jawetz and his colleagues suggest that early readings are of clinical importance, although other workers came to the opposite conclusion (Ahem et al., 1952).Since antibiotic treatment is usually prolonged, we feel that results after 24 hours' contact with the drugs are more likely to be significant.It may even be that results observed after still longer periods are of greatest value.Finally the synergistic lethal action of two antibiotics by allowing fewer survivors may lessen the chance of the emergence of resistant variants.There can be no definite answer to these questions until more work is done to correlate in vitro and clinical findings.The method described here may help to serve this purpose. SummaryThere is both experimental and clinical evidence that two antibiotics used simultaneously may be more efficient (synergistic) or less efficient (antagonistic) in their action than either drug used alone.A simple method suitable for routine diagnostic work is described.It reveals interactions of the bactericidal effect of antibiotics in vitro.Sixty-five strains of com- mon pathogens were tested against three pairs of anti- biotics.Penicillin with either chloramphenicol or aureomycin generally showed antagonism.Streptomycin with chloramphenicol was synergistic.These results refer to interaction after 18 to 24 hours.The only ex- ceptions-to these findings were that no interaction occurred.We wish to express our thanks to