tially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of cefotaxime as well as other cephalosporins and penicillins against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cefotaxime's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Resistance to beta-lactam antibiotics can develop if there are changes in the PBPs, if cell wall permeability decreases, or if certain beta-lactamases are present. Cefotaxime retains activity against some beta-lactamase-producing isolates, including penicillinase and cephalosporinase; however, most extended spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to the drug.
PHARMACOKINETICS
Cefotaxime is administered intravenously and intramuscularly. It is not absorbed from the GI tract. Approximately 13—38% of the circulating drug is protein-bound. It is distributed into most body tissues and fluids including gallbladder; liver; kidney; bone; uterus; ovary; sputum; bile; and peritoneal, pleural, and synovial fluids. It penetrates inflamed meninges and reaches therapeutic levels within the CSF. It crosses the placenta.
Cefotaxime is metabolized primarily by the liver to desacetylcefotaxime, an active metabolite that displays 10% of the parent drug's antibacterial activity. Cefotaxime and its metabolites are excreted into the urine primarily via tubular secretion. A small percentage is excreted in breast milk. In patients with normal renal function, the elimination half-lives of cefotaxime and desacetylcefotaxime are 1—1.5 hours and 1.5—2 hours, respectively.
Intramuscular Route
Peak serum levels of cefotaxime occur within 30 minutes following an IM dose. |
