Lethal Versus Inhibitory Effects

Antibiotics can be classified according to their effects on the biochemistry or molecular biology of pathogens. There are ribosomal inhibitors (macrolides), cell wall disrupters (p-lactams), DNA disturbers (fluoroquinolones), and metabolic poisons (trimethoprim-sulfamethoxazole). Antibiotics also can be classified according to whether they are static (inhibitory) or cidal (lethal). The classification of drugs as either static or cidal is based on laboratory assessment of the interaction of pathogen and antibiotic drug.

Cidal effects can be a result of the disruption of the cell wall or membrane. Cell lysis may occur when water diffuses into the high-osmolarity bacterial cytosol through the antibiotic-induced holes in the membrane, causing the bacteria to swell and burst. Cidal effects also can occur as a consequence of inhibition of bacterial DNA replication or transcription.

Static effects occur when the toxic effects of a chemotherapeutic drug are reversible. For example, inhi bition of folate synthesis interferes with methylation, an important biochemical synthetic process. Reversal of this static effect can occur when the antibiotic concentration falls or if a compensatory increase in the synthesis of the inhibited enzymes occurs. The static versus cidal designation is a false dichotomy, since there is a continuous spectrum of activity between the two categories. The place of a drug along this spectrum will depend on both the pharmacological properties of the drug and such clinical factors as immune system function, inoculum size, drug concentration in tissue, and duration of therapy. A cidal drug may prove to be merely static if an inappropriately low dose or short treatment course is prescribed. A static drug may be cidal if given in high doses for prolonged courses to exquisitely sensitive pathogens.

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