Penicillins clinical uses

Combination treatments often involve the use of broad-spectrum penicillin and P-lactamase-stable penicillin. Clinically useful combinations include ampidox (ampi-dllin and doxadllin) and magnapen (ampidUin and fludoxadllin). These combinations are usually indicated for infections caused by susceptible organisms where a mixed infection is present and includes penidllin-resistant staphylococd. 

Resistance to commonly prescribed antimicrobials such as the penicillins and macrolides/azalides increased dramatically in the late 1980s through the middle to late 1990s. Table 68-2 provides resistance information collected nationally from 1999 to 2004 using the Tracking Resistance in the US Today (TRUST) surveillance database.26 In 2004, the average national rate of resistance to penicillin and macrolides was approximately 18% and 25%, respectively. Susceptibility results alone do not account for clinical success or failures when treating pneumonia. 

It was quite clear that the scale of production in the William Dunn School could barely provide enough material for further clinical trials hence, Florey tried to elicit the help of drug companies. ICI, Burroughs Wellcome, Boots and a small London company, Kemball-Bishop, all showed interest but due to the exigencies of war-tom Britain, none had sufficient funds for speculative research. They were probably also worried that a chemical synthesis of penicillin would be devised once its structure had been elucidated thus, money spent on culture technology would be wasted. They were also probably worried about the patent situation. Florey had mentioned this issue to the Medical Research Council, which had provided a modest amount of research money. Apparently, the senior MRC officials were vehemently opposed to patenting on the grounds that it was unethical for medical researchers to benefit from their discoveries. The American pharmaceutical companies suffered no such qualms of conscience, and in due course the British companies had to pay royalties to their US counterparts before they could produce penicillins. 

Howard W. Florey, Ernst B. Chain, and their colleagues which led to the successful preparation of a stable form of penicillin and the demonstration of its remarkable antibacterial activity and lack of toxicity in mice. Production of penicillin by the strain of Penicillium notatum in use was so slow, however, that it took over a year to accumulate enough material for a clinical test on humans [3]. When the clinical tests were found to be successful, large-scale production became essential. Florey and his colleague Norman Heatley realized that conditions in wartime Britain were not conducive to the development of an industrial process for producing the antibiotic. They came to the US in the summer of 1941 to seek assistance and convinced the US Department of Agriculture in Peoria, Illinois, and several American pharmaceutical companies, to develop the production of penicillin. Heatley remained for a period at the USDA laboratories in Peoria to work with Moyer and Coghill. 

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