Staphylococcus aureus, a type of spherical gram-positive bacteria. French microbiologist René Dubos isolated tyrothricin, a mixture of gramicidin D and tyrocidine, from the soil bacteria Bacillus brevis, which effectively inhibited a whole class of bacteria. It is toxic to humans if ingested, so can only be used topically. In the 1940s, American microbiologist Selman Waksman conducted a systematic study of the antimicrobial behaviour of soil bacteria, especially Streptomyces spp. He created a framework to showcase bacterial species with antagonistic relationships and, using it, discovered 15 major antibiotics and antifungals, including actinomycin, neomycin and streptomycin, which was the first effective treatment for tuberculosis. resistance became endemic in the U.S., reaching 29% of hospitalized S. aureus-infected patients. Strains of S. pneumoniae also became resistant to penicillin in 1967. Between 1979 and 1999, the percentage of cases associated with antibiotic-resistant pneumococcus tripled.2 In 1976, penicillinase-producing gonococci were found in England and the U.S. During the 10-year period after the first introduction of penicillin to treat gonorrhea, the prevalence of penicillin-resistant strains reached its peak.3 In 1983, an outbreak of gonorrhea in North Carolina proved to be caused by a bacterial strain that didn’t respond to penicillin because of a mutation not related to penicillinase. These events led to the prohibition of penicillin as the first-line drug for gonococcus treatment. The patterns of other antibiotics were similar: drugs that were effective became less effective with use. Streptomycin was an effective treatment for tuberculosis for a few years, but then a combination of antibiotics was required. Researchers sought to understand how resistance developed and whether the antibiotics themselves played a role in their declining efficacy. Using methods like Waksman’s, several pharmaceutical firms began to use rational screens for the development of new molecules using knowledge of antibiotics’ mechanisms of action. Several new antibiotic groups were found: tetracyclines in 1948, macrolides in 1952, nitrofuran in 1953, quinolones in 1960, and oxazolidinones in 1987. More than 150 antibiotics and 20 classes have been discovered since penicillin, but no new classes have been found for nearly the last 40 years. Antimicrobial resistance The first signs of antimicrobial resistance to penicillin were documented before the antibiotic was widely released. In 1940, two scientists reported that an E. coli strain was able to deactivate penicillin by releasing an enzyme called penicillinase that breaks it down. By 1942, four Staphylococcus aureus strains were found to be resistant to penicillin in hospitalized patients. During the next few years, the proportion of infections caused by penicillin-resistant S. aureus rose, spreading from hospitals to communities. By the late 1960s, more than 80% of all strains of S. aureus were penicillin resistant. Thankfully, a semisynthetic antibiotic called methicillin, the first penicillinaseresistant penicillin, was released around that time. The respite was short lived; about 20 years later, methicillin 21 Issue 3 | 2025 | Issues and People
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