In nature, some microbes produce substances that inhibit or kill other microbes that might otherwise compete for the same resources. Humans have successfully exploited these abilities, using microbes to mass-produce substances that can be used as antimicrobial drugs. Since their discovery, antimicrobial drugs have saved countless lives, and they remain an essential tool for treating and controlling infectious disease. But their widespread and often unnecessary use has had an unintended side effect: the rise of multidrug-resistant microbial strains. In this chapter, we will discuss how antimicrobial drugs work, why microbes develop resistance, and what health professionals can do to encourage responsible use of antimicrobials.
- 14.1: Discovering Antimicrobial Drugs
- Antimicrobial drugs produced by purposeful fermentation and/or contained in plants have been used as traditional medicines in many cultures for millennia. The purposeful and systematic search for a chemical “magic bullet” that specifically target infectious microbes was initiated by Paul Ehrlich in the early 20th century. The discovery of the natural antibiotic, penicillin, by Alexander Fleming in 1928 started the modern age of antimicrobial discovery and research.
- 14.2: Antibacterial Drugs
- Antimicrobial drugs can be bacteriostatic or bactericidal, and these characteristics are important considerations when selecting the most appropriate drug. The use of narrow-spectrum antimicrobial drugs is preferred in many cases to avoid superinfection and the development of antimicrobial resistance. Broad-spectrum antimicrobial use is warranted for serious systemic infections when there is no time to determine the causative agent or when narrow-spectrum antimicrobials fail.
- 14.3: Drugs Targeting Other Microorganisms
- Antibacterial compounds exhibit selective toxicity, largely due to differences between prokaryotic and eukaryotic cell structure. Cell wall synthesis inhibitors, including the β-lactams, the glycopeptides, and bacitracin, interfere with peptidoglycan synthesis, making bacterial cells more prone to osmotic lysis. There are a variety of broad-spectrum, bacterial protein synthesis inhibitors that selectively target the prokaryotic 70S ribosome, including those that bind to the 30S and 50S subunits.
- 14.4: Clinical Considerations
- Because fungi, protozoans, and helminths are eukaryotic organisms like human cells, it is more challenging to develop antimicrobial drugs that specifically target them. Similarly, it is hard to target viruses because human viruses replicate inside of human cells.
- 14.5: Testing the Effectiveness of Antimicrobials
- Antimicrobial resistance is on the rise and is the result of selection of drug-resistant strains in clinical environments, the overuse and misuse of antibacterials, the use of subtherapeutic doses of antibacterial drugs, and poor patient compliance with antibacterial drug therapies. Drug resistance genes are often carried on plasmids or in transposons that can undergo vertical transfer easily and between microbes through horizontal gene transfer.
- 14.6: The Emergence of Drug Resistance
- The Kirby-Bauer disk diffusion test helps determine the susceptibility of a microorganism to various antimicrobial drugs. However, the zones of inhibition measured must be correlated to known standards to determine susceptibility and resistance, and do not provide information on bactericidal versus bacteriostatic activity, or allow for direct comparison of drug potencies. Antibiograms are useful for monitoring local trends in antimicrobial resistance/susceptibility.
- 14.7: Current Strategies for Antimicrobial Discovery
- With the continued evolution and spread of antimicrobial resistance, and now the identification of pan-resistant bacterial pathogens, the search for new antimicrobials is essential for preventing the postantibiotic era.
- 1 “Treatment of War Wounds: A Historical Review.” Clinical Orthopaedics and Related Research 467 no. 8 (2009):2168–2191.
Thumbnail: Staphylococcus aureus - Antibiotics Test plate. (Public Domain; CDC / Provider: Don Stalons).