Chapter Summary


  • The importance of antibiotics in treating disease was recognized in the early 1940s.
  • Some antimicrobial agents are initially inactive until converted by the body to an active agent.
  • Florey and Chain purified penicillin and capitalized on Fleming’s discovery of penicillin.


  • Antimicrobial agents may be produced naturally or artificially.
  • Selective toxicity refers to the ability of an antibiotic to attack a unique component of microbial physiology that is missing or distinctly different from eukaryotic physiology.
  • Antibiotic side effects on mammalian physiology can limit the clinical usefulness of an antimicrobial agent.
  • Antibiotic spectrum of activity refers to the range of microbes that a given drug affects.
  • Bactericidal antibiotics kill microbes; bacteriostatic antibiotics inhibit microbial growth.


  • The spectrum of an antibiotic and the susceptibility of the infectious agent are critical points of information required before prescribing antibiotic therapy.
  • Minimal inhibitory concentration (MIC) of a drug, when correlated with average attainable tissue levels of the antibiotic, can predict the effectiveness of an antibiotic in treating disease.
  • MIC is measured using tube dilution techniques but can be approximated using the Kirby-Bauer disk diffusion technique.


  • Antibiotic specificity for bacteria can be achieved by targeting a process that occurs only in bacteria, not host cells; by targeting small structural differences between components of a process shared by bacteria and hosts; or by exploiting a physiological condition such as anaerobiosis present only in certain bacteria.
  • Antibiotic targets include cell wall synthesis, cell membrane integrity, DNA synthesis, RNA synthesis, protein synthesis, and metabolism.
  • Antibiotics targeting the cell wall bind to the transglycosylases, transpeptidases, and lipid carrier proteins involved with peptidoglycan synthesis and cross-linking.
  • Antibiotics interfering with DNA include the antimetabolite sulfa drugs that inhibit nucleotide synthesis, quinolones that inhibit DNA topoisomerases, and a drug, metronidazole, that, when activated, randomly nicks the phosphodiester backbone.
  • Inhibitors of RNA synthesis target RNA polymerase (rifampin and pyronins) or bind DNA and inhibit polymerase movement (actinomycin D).
  • Aminoglycosides and tetracyclines bind the 30S subunit of the prokaryotic ribosome.
  • A variety of antibiotics bind the 50S ribosomal subunit and inhibit translocation (macrolides, lincosamides), peptidyltransferase (chloramphenicol), formation of 70S complex (oxazolidinones), or peptide exit through the ribosome exit channel (streptogramins).


  • Antibiotics are synthesized as secondary metabolites.
  • Microbes may make antibiotics to eliminate competitors in the environment.
  • Antibiotic producers prevent self-destruction by means of various antibiotic resistance mechanisms.


  • Antibiotic resistance is a growing problem worldwide.
  • Mechanisms of antibiotic resistance include modifying the antibiotic, destroying the antibiotic, altering the target to reduce affinity, and pumping the antibiotic out of the cell.
  • Multidrug resistance efflux pumps use promiscuous binding sites to bind antibiotics of diverse structure.
  • Antibiotic resistance can arise spontaneously through mutation, can be inherited by gene exchange mechanisms, or can arise de novo through gene duplication and mutational reengineering.
  • Indiscriminate use of antibiotics has significantly contributed to the rise in antibiotic resistance.
  • Measures to counter antibiotic resistance include chemically altering the antibiotic, using combination antibiotic therapy, and adding a chemical decoy.


  • Potential targets for rational antimicrobial drug design include proteins expressed only in vivo or proteins expressed both in vivo and in vitro.
  • Candidate antimicrobial compounds can be designed to interact at the active site of a known enzyme and inhibit its activity.
  • Combinatorial chemistry is used to make random combinations of compounds that can be tested for enzyme inhibitory activity and antimicrobial activity.


  • Fewer antiviral agents than antibacterial agents are available because it is harder to identify viral targets that provide selective toxicity.
  • Preventing viral attachment to, or release from, host cells is a mechanism of action for antiviral agents, such as amantadine and zanamivir, used to treat influenza virus.
  • Inhibiting DNA synthesis is the mode of action for most antiviral agents, although they work only for DNA viruses and retroviruses.
  • HIV treatments include reverse transcriptase inhibitors that prevent synthesis of DNA and protease inhibitors that prevent maturation of viral polyproteins into active forms.


  • Fungal infections are difficult to treat because of similarities in human and fungal physiologies.
  • Imidazole-containing antifungal agents inhibit sterol synthesis.
  • Griseofulvin inhibits mitotic spindle formation.
  • Nystatin produces membrane pores.
  • Amphotericin B binds to membranes and destroys membrane integrity.