CEFOTAXIME
Clinical safety rating: safe
Human studies have proved safety
Cefotaxime inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidation, and activating autolytic enzymes.
| Metabolism | Cefotaxime is partially deacetylated in the liver to desacetylcefotaxime (active metabolite); both are further metabolized via hepatic pathways. |
| Excretion | Approximately 80-90% of the dose is excreted unchanged in the urine via glomerular filtration and tubular secretion. About 5-10% is excreted in bile and feces as desacetylcefotaxime, the active metabolite. |
| Half-life | Terminal elimination half-life: 1-1.5 hours in adults with normal renal function. In neonates, it is prolonged to 2-4 hours. In severe renal impairment (CrCl <20 mL/min), half-life extends up to 10-15 hours, requiring dose adjustment. |
| Protein binding | Approximately 30-50% bound to serum proteins, primarily albumin. Binding is saturable and concentration-dependent. |
| Volume of Distribution | 0.2-0.4 L/kg. This low Vd indicates limited extravascular distribution; however, it penetrates well into CSF (10-50% of serum levels) when meninges are inflamed. |
| Bioavailability | Intramuscular: 90-95% bioavailability. Oral: not administered orally due to poor absorption and degradation in GI tract. |
| Onset of Action | Intravenous: immediate; Intramuscular: 30 minutes to 1 hour (peak serum concentrations at 0.5-1 hour). |
| Duration of Action | Bactericidal levels persist for 6-8 hours after IV/IM administration, supporting an every 8-hour dosing interval. For serious infections, more frequent dosing may be needed. |
1-2 g IV every 6-8 hours; maximum 12 g/day. For uncomplicated infections: 1 g IV every 8-12 hours.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 30-50 mL/min: 1-2 g every 8-12 hours; CrCl 10-29 mL/min: 1-2 g every 12-24 hours; CrCl <10 mL/min: 1-2 g every 24 hours. |
| Liver impairment | No specific dose adjustment required based on Child-Pugh class. Caution in severe hepatic impairment. |
| Pediatric use | Neonates (0-1 week): 50 mg/kg IV every 12 hours; Neonates (1-4 weeks): 50 mg/kg IV every 8 hours; Infants and children (1 month-12 years): 50-180 mg/kg/day IV divided every 6-8 hours; maximum 6 g/day. |
| Geriatric use | Dose based on renal function; consider age-related GFR decline and ensure CrCl calculation. Use lowest effective dose. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Probenecid may decrease cephalosporin excretion May cause diarrhea including Clostridium difficile-associated diarrhea.
| Breastfeeding | Excreted into human milk in low concentrations; M/P ratio approximately 0.05-0.08. Considered compatible with breastfeeding by AAP. Monitor infant for potential gastrointestinal disturbances or allergic reactions. |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; inadequate human studies. Crosses placenta. Risks in first trimester not definitively established; use only if clearly needed. Second and third trimesters: no known fetal harm, but caution due to potential alteration of gut flora and risk of neonatal infections. |
■ FDA Black Box Warning
No FDA boxed warning.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to cefotaxime, other cephalosporins, or any component of the formulation; history of severe anaphylactic reaction to penicillins or other beta-lactams.
| Precautions | Hypersensitivity reactions (including anaphylaxis), Clostridium difficile-associated diarrhea, seizures (in renal impairment or high doses), bleeding risk (prolonged prothrombin time), superinfection, potential for nephrotoxicity when coadministered with aminoglycosides or loop diuretics. |
| Food/Dietary | Avoid alcohol and any products containing alcohol (e.g., some mouthwashes, cough syrups) during treatment and for 48 hours after last dose due to risk of disulfiram-like reaction (flushing, headache, nausea, vomiting). No specific food restrictions. |
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| Fetal Monitoring | Monitor maternal renal function and hepatic enzymes periodically. Assess for signs of superinfection (e.g., oral thrush, diarrhea). Fetal monitoring as per standard obstetric care; no specific fetal monitoring required. |
| Fertility Effects | No evidence of impaired fertility in animal studies. No human data on fertility effects. Not expected to significantly impact reproductive function. |
| Clinical Pearls | Cefotaxime is a third-generation cephalosporin with broad gram-negative coverage, including ESBL-producing Enterobacteriaceae. It has good CNS penetration and is used for meningitis due to susceptible organisms. It is not active against Pseudomonas aeruginosa; consider piperacillin-tazobactam or ceftazidime if Pseudomonas is suspected. Administer IV or IM; avoid mixing with aminoglycosides in same IV line due to inactivation. Monitor renal function as dose adjustment needed for CrCl <20 mL/min. Can cause a disulfiram-like reaction with alcohol. Prolonged use may increase risk of C. difficile infection. |
| Patient Advice | Take this medication exactly as prescribed; complete the full course even if you feel better. · Report any signs of allergic reaction: rash, itching, swelling, or difficulty breathing. · Avoid alcohol during treatment and for at least 48 hours after stopping to prevent severe nausea and vomiting. · Notify your doctor if you develop severe diarrhea, especially if bloody or watery, as this could be a sign of C. difficile infection. · This medication may cause false-positive urine glucose tests; inform your doctor if you have diabetes. · If you experience pain, redness, or swelling at injection site, report to your healthcare provider. |