Evolution and Antibiotic Resistance

The leading causes of mortality and morbidity in the 1900's were infectious diseases. The most frequent causes of childhood deaths were tuberculosis and bacterial pneumonia. In 18h century France, half of the children died before age 2. In Bombay, the infant mortality rate was -50% between 1900 and 1920. In the second half of the 19th century, Western Europe and the United States, 1/3 of the children died before age 1. At Mount Sinai Hospital in New York, pediatric services examined 1000 children who were admitted with non-tuberculosis pneumonia between November 1926 and March 1933. The overall mortality rate was around 20% and higher rate was around 39% were among children under age 1.

In the 20th century, the discovery of penicillin marked a defining moment. Louis Pasteur left several plates on a bench in his lab, while preparing for vacation and studying the morphology of Staphylococcus aureus strains. When he returned, he threw away some of them because they had mold on them. As he was explaining his experiment to one of his colleges, he retrieved one of the plates he threw out. He noticed that the bacterial colonies on the plate had a different morphology and were undergoing lysis. This discovery led to the development of penicillin.

In 1943, B-lactam antibiotics were introduced. By using enzymes know as B-lactamases had acquired the ability to hydrolyze of the antibiotics. This threatened to compromise the effectiveness of the antibiotics. The percentages of S. aureus strains that are resistant to penicillin increased from 6% in 1946 to 50% by 1950 and to 80%-90% in recent years.

A semsynthetic penicillin derivative, in 1960 methicillin overcomes the problem of penicillin resistance. By a new mechanism the bacterial strains resistant to methicillin grew rapidly. They had acquired a new gene, encoding a protein with a lower ability to bind the antibiotic, but capable of containing bacterial cell wall synthesis even in the presence of the antibiotic. Less than a year after the antibiotic was introduce commercially, the first methicillin resistant strains were reported in 1961.

Enterococcus feecium, Staphlococcus aureu, Klebsiella pneumonil, Acinetabacter baumanni, Pscudomonas aeruginosa, and Enterobacter species are pathogens that Rice refers to as "ESKAPE". These pathogens have become a public health concern. These pathogens cause large numbers of nosocomial infections and they serves as models for understanding bacterial pathogenesis, transmission, and antimicrobial resistance in other pathogens.

A selective force that promotes the emergence of resistant microbial strains is the use of antimicrobial agents increasingly emerges. A bacterial strain that can become resistant to antimicrobials in 2 big ways. Introducing new mutations into existing genes, mutation, leads to the inability of the antibiotic to build its target. The bacteria may acquire new resistance genes from other bacteria