Antimicrobial Drugs : Chronicle of a Twentieth Century Medical Triumph

Between 1935 and 1944 the field of microbiology, and by implication medicine as a whole, underwent dramatic advancement. The discovery of the extraordinary antibacterial properties of sulphonamides, penicillin, and streptomycin triggered a frantic hunt for more antimicrobial drugs that was to yield an abundant harvest in a very short space of time. By the early 1960s more than 50 antibacterial agents were available to the prescribing physician and, largely by a process of chemical modification of existing compounds, that number has more than tripled today. We have become so used to the ready availability of these relatively safe and highly effective 'miracle drugs' that it is now hard to grasp how they transformed the treatment of infection. This book documents the progress made from the first tentative search for an elusive 'chemotherapy' of infection in the early days of the twentieth century, to the development of effective antiviral agents for the management of HIV as the millennium drew to a close. It also offers a celebration of the individuals and groups that made this miracle happen, as well as examining the inexorable rise of the global pharmaceutical industry, and, most intriguingly, the essential input of luck. Infection still maintains a high profile in both medicine and the media, with the current threats of 'superbugs' such as MRSA acquired in hospital, and a potential resistance to antibiotics. This book tracks the history of antimicrobial drugs, a remarkable medical triumph that has provided doctors with an amazing armoury of safe and effective drugs that ensure that reversion to the helpless state of the fight against infection witnessed in the early 1900s is extremely unlikely. This timely compendium acknowledges the agents that have surely led to the relief of more human and animal suffering than any other class of drugs in the history of medical endeavour. "Antimicrobial drugs developed in the twentieth century revolutionized the ability of doctors to manage life-threatening infectious diseases. Although a few useful drugs, notably quinine for malaria, were already known, it was Paul Ehrlich's quest for derivatives of dyes and arsenical chemicals, culminating in the antisyphilitic compound Salvarsan in 1910, that kick-started modern antimicrobial chemotherapy. In the 1930s a major breakthrough came with the first sulphonamides. Soon afterwards, Howard Florey and his team at Oxford turned Alexander Fleming's fortuitous discovery of penicillin into the first 'miracle drug', starting a frantic and outstandingly successful hunt for naturally occurring antibiotics and synthetic chemicals with antimicrobial properties. The rich harvest that ensued transformed the prospects for the cure of infections of all kinds, whether caused by bacteria, viruses, fungi, protozoa, or helminthic worms. Antimicrobial drugs have surely relieved more human and animal suffering than any other class of drugs in the history of medical endeavour." "The story of this extraordinary medical triumph encompasses tales of individual brilliance, remarkable team efforts, perseverance in the face of much frustration, international rivalry, and the rise of the global pharmaceutical industry. Though scientists and commerce produced the miracle and reaped the rewards, Lady Luck was never far from the scene, and her frequent interventions add extra spice to this truly fascinating story."--Jacket Contents 12 Acknowledgements 14 Personalia 16 1 Agents of infection 32 Evolving insights 32 Bacteria 35 Viruses 40 Fungi 44 Protozoa 45 Worms 47 References 52 2 Out of darkness 54 Combating infection before the twentieth century 54 Remedies against intestinal worms 60 Quinine 62 Emetine 71 References 75 3 From quinine to sulphonamides (by way of Serendip) 78 Cinchona bark and willow bark 78 From quinine to aniline dyes 80 Ehrlich and the foundation of chemotherapy 83 From dyes to sulphonamides 96 References 110 4 Wonder drugs 116 Penicillin 116 Cephalosporins 144 β-Lactam abundance 150 References 167 5 The taming of tuberculosis and leprosy 172 Fighting tuberculosis without drugs 173 Antituberculosis agents 176 Antileprosy agents 219 References 233 6 The golden years of pills and profits 240 The post-war bonanza 240 Antibiotics 243 Synthetic antibacterial agents 279 The party’s over? 293 References 294 7 Progress against parasites 300 Antiprotozoal agents 302 Anthelminthic agents 349 Shortcomings and challenges 367 References 368 8 The poor relations: fungi and viruses 376 Antifungal agents 377 Antiviral agents 393 References 417 9 The spectre at the feast 424 The problem of resistance 425 Understanding the problem 432 Tackling the problem 438 Envoi 441 References 442 Drug register 446 Subject index 454 A 454 B 455 C 455 D 456 E 456 F 456 G 456 H 456 I 456 J 457 K 457 L 457 M 457 N 457 O 458 P 458 Q 458 R 458 S 459 T 460 U 460 V 460 W 460 X 460 Y 460 Z 460