Viewpoints Fifty Years of Explosive Growth in Antibacterial Drugs But relatively little development in drugs to treat non-bacterial infections

In the last 50 years the growth of varieties of antibacterial agents has been prolific, especially in the ~­lactam group. There are now over 70 different ,B-Iactam derivatives in use throughout the world. Most are derived from 6-aminopenicillanic acid or 7 -aminocephalosporanic acid. Of the agents that overcome fJ­laclamase mediated resistance in coliform bacteria, celoxil in and cefuroxime are very stable but only moderately active while cefotaxime, cetlizoxime, ceffazidime, cellriaxone, cefmenoxime and latamoxet [moxalactam] combine stability to ,B·laetamase with activi ty against a wide range of bacteria. Although these compounds, particularly cefolaxime and ceflizoxime, are active against the common causes of meningitis, they have reduced antistaphylococcal activity and none is active against Streptococcus 'aeca/is. Each of Ihese compounds has gaps in its antibacterial spectrum of activity. Newly·developed Q-Iactam agents include those with a narrow spectrum, targeted approach to therapy (aztreonam, temocillin) and those with a very broad range spectrum of activity (imipenem, sulbactam/ampicillin).

Other recently developed antibacterials include the quinolones norfloxacin (of use in urinary tract infections since it is excreted in high concentrations in the urine) and ciprofloxacin (which has a spectrum of activity similar to that of some ,8·laclams). Gentamicin and tobramycin remain the most useful aminoglycosides although some derivatives have been developed (amikacin, netitmicin, sisomicin, dibekacin) and other antibacterial compounds may prove useful. For example, the glycoprotein teicoplanin is active against staphylococci and streptococci, mupirocin is also active against Gram-positive cocci, and bicozamycin is active against Gram·negative bacilli.

In contrast, there have been relatively few new developments in the field of non-bacterial infections. The antiherpes drug, acyclovir, has given rise to several potentially useful antiviral drugs. Antifungal agents include ketoconazole, useful in systemic mycoses, and itraconazole, which may be efficacious in aspergillosis. The spread of resislance to anliprotozoal agents, particularly chloroquine in Plasmodium falciparum, has affected lheir usefulness and may even spread to melloquine, a recenlly developed antimalarial. One antimalarial causing interest in the west is artemisinin [ginghaosu] which has been used for centuries in China. Drugs used to treat protozoal infections include metronidazole and its derivatives (for amoebiasis, giardiasis and trichomoniasis), antimonials (for leishmaniasis), arsenicals (for African trypanosomiasis) and nifurtimox and benznidazole (for South American trypanosomiasis). Thiabendazole, mebendazole and praziquantel are used for helminthic infections, as are drugs formerly used only for veterinary purposes: albendazole and ivermectin. GlHnWOOCf. D.: Jcvma/ cillle Royal CCIIege 01 PIlf5#dan$ cllondon 19: 23 1·234 (()(;I 1985)

2 INPHAAMA'" 21 Dec 1985 OI56_27fJ3/ 85/ IOO5-«J02{OSOUXJ/O Cl ADiS Preu