As Ehrlich so clearly saw, a successful chemotherapeutic agent has selective toxicity: it kills or inhibits the microbial pathogen while damaging the host as little as possible.
The degree of selective toxicity may be expressed in terms of
(1) the therapeutic dose-the drug level required for clinical treatment of a particular infection, and
(2) the toxic dose-the drug level at which the agent becomes too toxic for the host.
The therapeutic index is the ratio of the toxic dose to the therapeutic dose. The larger the therapeutic index, the better the chemotherapeutic agent in general. A drug that disrupts a microbial structure or function not found in host cells often has greater selective toxicity and a higher therapeutic index. For example, penicillin inhibits bacterial cell wall peptidoglycan synthesis but has little effect on host cells because they lack cell walls; therefore penicillin’s therapeutic index is high. A drug may have a low therapeutic index because it inhibits the same process in host cells or damages the host in other ways. The undesirable effects on the host, or side effects, are of many kinds and may involve almost any organ system. Because side effects can be severe, chemotherapeutic agents must be administered with great care.
Some bacteria and fungi naturally produce many of the commonly employed antibiotics. In contrast, several important chemotherapeutic agents, such as sulfonamides, trimethoprim, ciprofloxacin, isoniazid, and dapsone, are synthetic manufactured by chemical procedures independent of microbial activity. Some antibiotics are semisynthetic-natural antibiotics that have been structurally modified by the addition of chemical groups to make them less susceptible to stomach acids and inactivation by pathogens (e.g., ampicillin and methicillin).
Drugs vary considerably in their range of effectiveness. Many are narrow-spectrum drugs; that is, they are effective only against a limited variety of pathogens. Others are broad-spectrum drugs that attack many different kinds of bacteria. In addition, many semisynthetic drugs have a broader spectrum of antibiotic activity than does their parent molecule. This is particularly true of the semisynthetic penicillins (e.g., ampicillin, amoxicillin) as compared to the naturally produced penicillin G and penicillin V.
Drugs may also be classified based on the general microbial group they act against: antibacterial, antifungal, antiprotozoan, and antiviral. A few agents can be used against more than one group; for example, sulfonamides are active against bacteria and some protozoa. Finally, chemotherapeutic agents can be either cidal or static. Static agents reversibly inhibit growth; if the agent is removed, the microorganisms will recover and grow again