- MRSA Is Putting Resistance in the News
- Humans Live with Many Pathogens
- Antibiotics Block Growth and Kill Pathogens
- Broad-Spectrum Antibiotics Also Perturb Our Microbiomes
- Antibiotic Resistance Protects Pathogens
- Antibiotic Resistance Is Widespread
- Antibiotic Resistance Is Divided into Three Types
- The Development of New Antibiotics Is Slowing
- Vaccines Block Disease
Antibiotic Resistance Protects Pathogens
Antibiotic resistance is the capability of a particular pathogen population to grow in the presence of a given antibiotic when the antibiotic is used according to a specific regimen. Such a long, detailed definition is important for several reasons. First, pathogens differ in their susceptibility to antibiotics; thus, pathogen species are considered individually. Second, resistance to one antibiotic may not affect susceptibility to another. This means that the antibiotics must also be considered separately. Third, dose is determined as a compromise between effectiveness and toxicity; dose can be changed to be more or less effective and more or less dangerous. Consequently, the definition of resistance must consider the treatment regimen.
Control of infection caused by a resistant pathogen requires higher doses or a different antibiotic. If neither requirement can be met, we have only our immune system for protection from lingering disease or even death. Indeed, infectious diseases were the leading cause of death in developed countries before the discovery of antibiotics. (They still account for one-third of all deaths worldwide.)
Antibiotic resistance is a natural consequence of evolution. Microbes, as is true for all living organisms, use DNA molecules to store genetic information. (Some viruses use RNA rather than DNA; both acronyms are defined in Appendix A, "Molecules of Life.") Evolution occurs through changes in the information stored in DNA. Those changes are called mutations, and an altered organism is called a mutant. Therefore, an antibiotic-resistant mutant is a cell or virus that has acquired a change in its genetic material that causes loss of susceptibility to a given antibiotic or class of antibiotics.
Antibiotic-resistant pathogens need not arise only from spontaneous mutations—bacteria contain mechanisms for moving large pieces of DNA from one cell to another, even from one species to another. This process, called horizontal gene transfer (see Chapter 6, "Movement of Resistance Genes Among Pathogens"), enables resistance to emerge in our normal bacterial flora and move to pathogens. It is part of the reason that excessive antibiotic use and environmental contamination are so dangerous.
A pathogen is considered to be clinically resistant when an approved antibiotic regimen is unlikely to cure disease. We quantify the level of pathogen susceptibility through a laboratory measure called minimal inhibitory concentration (MIC), which is the drug concentration that blocks growth of a pathogen recovered from a patient. (Pathogen samples taken from patients are called isolates.) A pathogen is deemed resistant if the MIC for the drug exceeds a particular value set by a committee of experts. Clinicians call that MIC value an interpretive breakpoint. Infections caused by pathogen isolates having an MIC below the breakpoint for a particular antibiotic are considered treatable; those with an MIC above the breakpoint are much less likely to respond to therapy. The MIC for a given patient isolate, reported by a clinical microbiology laboratory, helps the physician make decisions about which antibiotic to use. For example, if the isolate is resistant to penicillin but susceptible to fluoroquinolones, the physician may choose to prescribe a member of the latter class.
Resistant microbes can spread from one person to another. Consequently, an antibiotic-resistant infection differs qualitatively from a heart attack or stroke that fails to be cured by medicine: Antibiotic resistance moves beyond the affected patient and gradually renders the drug useless, whereas disseminated resistance does not occur with other drugs. Even resistance to anticancer drugs stays with the patient that developed the resistance because cancer does not spread from one person to another. This distinctive feature of antibiotics means that dosing, suitable effectiveness, and acceptable side effects must be decided by different rules than apply for treatment of noncommunicable diseases. The key concept is that using doses that are just good enough to eliminate symptoms may be fine for diseases such as arthritis, but it is an inadequate strategy for infectious diseases. Nevertheless, that strategy has been the norm ever since antibiotics were discovered.