Antibiotic Pharmacokinetics and Pharmacodynamics

An understanding of antibiotic pharmacokinetics and pharmacodynamics is critical, but these processes are complicated and may vary among classes of antibiotics and individual agents within the class. Pharmacokinetics refer to the serum and tissue levels of antibiotics, whereas pharmacodynamics refer to the antibiotics' abilities to inhibit and or kill bacterial pathogens (17,18). Pharmacodynamic properties of specific antibiotics should be considered in selecting an optimal dosing regimen. For example, while some antibiotics penetrate well and achieve high local concentrations at specific sites, others do not. Many antibiotics do not achieve therapeutic levels in specific tissues, like the prostate (ampicillin and cephalosporins), the lung (daptomycin), or the central nervous system (first- and second-generation cephalosporins), despite being reported as "sensitive" by in vitro laboratory testing. Also, most beta-lactam antibiotics achieve less than 50% of their serum concentration in the lung, but fluoroquinolones, macrolides, and oxazolazidones, such as linezolid, equal or exceed their serum concentration in bronchial secretions. Penicillins, sulfonamides, and most cephalosporins achieve high concentrations in the urine while other antibiotics, such as ceftriaxone, or the macrolides and linezolid, which are detoxified in the liver, may be excreted into the bile and gastrointestinal tract.

Antimicrobials may be bactericidal (kill bacteria) or bacteriostatic (inhibit growth, but do not kill) microorganisms (17,18). These differences may be important for treating selected infections, such as endocarditis, which requires bactericidal antibiotics, but are less important for urinary or respiratory tract infections for which host defenses play a greater role. Even among bactericidal agents, several mechanisms of killing can be present. For example, agents such as the aminoglyco-sides and quinolones are bactericidal in a concentration-dependent fashion, defined as killing more rapidly at higher concentrations. By comparison, vanco-mycin and the beta-lactams kill in a time-dependent fashion, defined as the time above the organism's minimal inhibitory concentration (MIC). Other antibiotics also have a postantibiotic effect (PAE), in which they are able to suppress bacterial growth even after the antibiotic level falls below the MIC of the organism. With Gram-negative bacilli, a prolonged PAE occurs with the use of aminoglycosides and quinolones, and a limited effect is seen with beta-lactam antibiotics, excluding the carbapenems (imipenem or meropenem). Therefore, beta-lactam antibiotics (penicillins, cephalosporins) are most effective when levels remain above the MIC of the infecting organism for as long as possible, while quinolones and aminogly-cosides can be dosed less frequently due to a prolonged PAE (17,18).

0 0

Post a comment