Dosing regimens

Some antibiotics have excellent absorption by the oral route (e.g. amoxicillin); others are only partially absorbed (e.g. phenoxymethylpenicillin) and still others are not absorbed at all (e.g. gentamicin). In some cases, non-absorbable agents are used to act against enteric organisms (e.g. vancomycin for C. difficile). Metronidazole achieves good serum and tissue levels by the rectal route.

The antibacterial agent must achieve sufficient distribution to reach the site of infection. Factors such as lipid solubility, protein binding, intracellular penetration and the ability to cross the blood–brain barrier affect distribution. In order to eradicate bacteria, the antimicrobial serum level must be kept above the bacterial minimum inhibitory concentration (MIC; Fig. 3.41.2). However some antibiotics possess a postantibiotic effect (PAE), which delays bacterial regrowth even if the plasma antibiotic concentration falls below the MIC. These antibiotics (e.g. gentamicin) can be dosed once daily and are classified as concentration-dependent killing. In contrast, most β-lactam antibiotics do not exhibit any PAE and have to be given more than twice daily.

Fig. 3.41.2 Antibiotic serum concentration and minimum inhibitory concentration (MIC).