Cefotax

Approved Indications:

• Lower Respiratory Tract Infections: Including community-acquired and nosocomial pneumonia, caused by susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella spp., and Enterobacter spp.
• Urinary Tract Infections (UTIs): Including pyelonephritis and complicated or uncomplicated cystitis.
• Skin and Skin Structure Infections: Such as cellulitis, abscesses, and wound infections.
• Intra-abdominal Infections: Including peritonitis and infections associated with bowel perforation or abscess.
• Gynecological Infections: Including pelvic inflammatory disease, endometritis, and postpartum infections.
• Septicemia: Confirmed or suspected bloodstream infections caused by susceptible organisms.
• Central Nervous System Infections: Particularly bacterial meningitis caused by Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae.
• Gonorrhea: Uncomplicated cases due to Neisseria gonorrhoeae.
• Bone and Joint Infections: Including osteomyelitis and septic arthritis.
• Prophylaxis: For prevention of infections during surgical procedures involving the gastrointestinal or genitourinary tract.

Clinically Accepted Off-Label Uses:

• Typhoid Fever: Especially in multidrug-resistant cases.
• Empiric Therapy for Febrile Neutropenia: In combination with other agents.
• Bacterial Endocarditis: As part of combination regimens.
• Neonatal Sepsis: As first-line or empiric therapy in hospital settings.

Route of Administration: Intravenous (IV) infusion/bolus or Intramuscular (IM) injection

Adults:

• Mild to Moderate Infections: 1 g every 8–12 hours.
• Severe Infections: 1–2 g every 6–8 hours IV.
• Meningitis/Sepsis: Up to 2 g every 4–6 hours (maximum 12 g/day).
• Gonorrhea (Uncomplicated): Single 1 g IM or IV dose.

Pediatrics:

• Neonates (<1 week): 50 mg/kg every 12 hours IV.
• Neonates (1–4 weeks): 50 mg/kg every 8 hours IV.
• Infants and Children (1 month–12 years): 100–150 mg/kg/day IV or IM in 3–4 divided doses (max 12 g/day).
• Meningitis: 200 mg/kg/day in 4 divided IV doses (max 12 g/day).

Elderly:

• Same as adults. Adjust dose if renal impairment is present.

Renal Impairment:

• CrCl 10–30 mL/min: Administer every 12 hours.
• CrCl <10 mL/min: Reduce dose by 50%.
• Hemodialysis: Supplemental dose required after each session.

Hepatic Impairment:

• No adjustment usually needed unless renal dysfunction coexists.

Administration Notes:

• IV infusion over 20–60 minutes.
• IM injection deep into a large muscle mass.
• Lidocaine may be used as diluent for IM injection (not for IV).

Cefotaxime is a bactericidal third-generation cephalosporin that acts by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs), disrupting the transpeptidation process involved in the cross-linking of peptidoglycan chains. This leads to compromised cell wall structural integrity, resulting in osmotic lysis and bacterial cell death. It is particularly effective against Gram-negative organisms, with some retained activity against Gram-positive bacteria.

• Absorption: Not absorbed orally; must be administered parenterally.
• Distribution: Widely distributed in body fluids and tissues; excellent penetration into cerebrospinal fluid (especially with inflamed meninges).
• Plasma Protein Binding: 30–50%.
• Metabolism: Hepatically metabolized to active metabolite desacetylcefotaxime, which contributes to antibacterial effect.
• Half-life:
• Adults (normal renal function): 1 hour.
• Active metabolite: ~1.5 hours.
• Excretion: Primarily renal (via glomerular filtration); 60–70% excreted in urine as unchanged drug and active metabolite.
• Biliary Excretion: Minor; does not require hepatic dose adjustment unless combined impairment.

• FDA Pregnancy Category: Category B – Animal studies have shown no fetal harm, and human data is limited but reassuring.
• Lactation: Small amounts are excreted in breast milk. Generally considered safe during breastfeeding. Monitor infants for gastrointestinal disturbances such as diarrhea or oral thrush.

• Class: Third-Generation Cephalosporin Antibiotic
• Subclass: Broad-spectrum, beta-lactam antibiotic with enhanced Gram-negative coverage

• Known hypersensitivity to cefotaxime or any cephalosporin antibiotics
• Severe hypersensitivity reactions to penicillins or other β-lactams
• Intra-arterial administration (contraindicated due to risk of arterial damage)

• Allergic Reactions: Anaphylaxis and severe cutaneous adverse reactions can occur, especially in those with a history of penicillin allergy.
• Clostridioides difficile Infection: Persistent or severe diarrhea should prompt immediate evaluation.
• Superinfections: Prolonged therapy may promote fungal or resistant bacterial overgrowth.
• Seizure Risk: Especially in patients with renal impairment receiving high doses.
• Hematologic Effects: Regular monitoring of blood counts recommended during long-term therapy (risk of neutropenia, thrombocytopenia).
• Vitamin K Interference: May rarely prolong prothrombin time; monitor INR in anticoagulated patients.

Common Side Effects:

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal cramps
• Local: Pain or inflammation at injection site
• Skin: Rash, urticaria, pruritus

Hematologic:

• Eosinophilia
• Leukopenia
• Thrombocytopenia

Serious Adverse Effects:

• Anaphylaxis
• Stevens-Johnson Syndrome
• Pseudomembranous colitis
• Seizures (especially with high doses or renal dysfunction)
• Hemolytic anemia

Rare Side Effects:

• Elevated liver enzymes
• Interstitial nephritis
• Candidiasis (oral or vaginal)

• Aminoglycosides: Enhanced nephrotoxicity risk; use with caution and monitor renal function.
• Loop Diuretics: Increased risk of nephrotoxicity when used concurrently.
• Oral Anticoagulants (e.g., warfarin): May enhance anticoagulant effect by altering gut flora and vitamin K metabolism.
• Probenecid: Increases cefotaxime levels by inhibiting renal tubular secretion.

Enzyme System Involvement:

• Not significantly metabolized by CYP450 enzymes; low potential for CYP-mediated interactions.

• WHO Essential Medicines List: Cefotaxime remains listed as a key systemic antibacterial.
• Resistance Monitoring: Noted resistance in extended-spectrum beta-lactamase (ESBL)-producing strains; clinicians advised to use local antibiograms for guidance.
• Guideline Use in Meningitis and Neonatal Sepsis: Maintained as a first-line or empiric agent in many pediatric protocols.
• No recent changes in labeling, pregnancy classification, or black box warnings as of 2025.

• Unopened Vials (Powder Form):
• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Reconstituted Solutions:
• Stable for 24 hours at room temperature or up to 7 days if refrigerated (2°C to 8°C).
• Do not freeze reconstituted solutions.
• Use appropriate diluents as specified (e.g., sterile water, 0.9% saline, or 5% dextrose).
• Shake well before administration.