In 1942, the same year penicillin saved the life of an American woman, an English policeman developed a Staphylococcus aureus infection after cutting himself shaving. Alexander Fleming treated the patient with penicillin and initially he responded well. However, after two weeks the infection had not receded, but increased in size. Within the month the policeman died with a Staphylococcus aureus infection resistant to penicillin. As a consequence of this case Fleming forewarned society and the medical community, saying that the misuse of penicillin could lead to the selection and propagation of mutant forms of bacteria resistant to the drug.

Fleming’s prophecy has become reality. Today, only 5% of Staphylococcus aureus infections are susceptible to penicillin, whereas in 1942 almost all were vulnerable. This is particularly disconcerting because Staphylococcus aureus is the second leading cause of bacterial infection in hospitals worldwide and may lead to pneumonia or severe infections within the blood stream. Staphylococcus aureus resists penicillin by making ß-lactamase, an enzyme that resides between the outer membrane and periplasmic space. ß-lactam antibiotics, the most common class of antibiotics, cross the outer membrane of gram-negative bacteria by passive diffusion through porin channels. Once inside the bacteria, ß-lactamase hydrolyze the drug, resulting in antibiotic resistance. Increased use of penicillin, since 1942, has created over 200 types of ß-lactamases specific for a majority of antibiotics. The most recent and concerning bacteria encoding ß-lactamases has been Streptococcus pneumonia, the common cause of community-acquired pneumonia. Since the first case of penicillin resistant pneumonia in 1981, pneumonia has evolved resistance in approximately 12% of cases nationwide. Globally, the data are even more staggering; in South Africa over 50% of strains are resistant and in Hungary 58% are resistant. Fortunately, pneumonia susceptible to penicillin cause fatality in only 5% of cases, however in resistant strains fatality reaches 25%. The escalating cases of penicillin resistant bacteria were showing that without new and improved drug therapies people would once again be at the mercy of microbes.