Nixon

Approved Indications:
Ceftriaxone Sodium, a third-generation cephalosporin antibiotic, is approved for the treatment of infections caused by susceptible organisms, including:

• Lower Respiratory Tract Infections: Community-acquired pneumonia, hospital-acquired pneumonia.
• Acute Bacterial Otitis Media.
• Skin and Skin Structure Infections: Including cellulitis, abscesses, and wound infections.
• Urinary Tract Infections (UTIs): Complicated and uncomplicated.
• Pelvic Inflammatory Disease (PID): Usually with other antimicrobials for broad coverage.
• Bacterial Septicemia.
• Bone and Joint Infections: Osteomyelitis, septic arthritis.
• Intra-abdominal Infections: Peritonitis, infections following GI surgery (in combination with other antimicrobials).
• Bacterial Meningitis: Effective for many common community-acquired bacterial causes.
• Uncomplicated Gonorrhea: Cervical, urethral, rectal.
• Surgical Prophylaxis: To reduce the risk of postoperative infections in certain procedures.

Important Off-Label/Clinically Accepted Uses:

• Lyme Neuroborreliosis: Late-stage or disseminated Lyme disease involving CNS.
• Empiric Treatment of Severe Sepsis: In combination regimens for broad-spectrum Gram-negative coverage.
• Meningococcal Prophylaxis: Alternative to rifampin in certain situations.

Adults:

• General infections: 1–2 g IV or IM once daily, or divided in 12-hour intervals depending on severity.
• Serious infections (e.g., bacterial meningitis, severe sepsis): Up to 4 g/day IV, usually divided every 12–24 hours.
• Uncomplicated Gonorrhea: 250–500 mg IM single dose (CDC now recommends 500 mg IM single dose for adults).
• Surgical Prophylaxis: 1 g IV given 30–90 minutes prior to incision.

Pediatrics:

• General bacterial infections: 50–75 mg/kg/day IV or IM, once daily or divided twice daily (max 2 g/day).
• Meningitis: 80–100 mg/kg/day IV in 1 or 2 divided doses (max 4 g/day).
• Acute Otitis Media: Single IM dose of 50 mg/kg (max 1 g).

Elderly:

• No specific adjustment needed solely for age. Monitor renal function.

Renal Impairment:

• Usually no dose adjustment needed in mild/moderate renal impairment if liver function is normal.
• Severe renal impairment (CrCl <10 mL/min) or combined severe renal and hepatic impairment: Do not exceed 2 g/day.

Hepatic Impairment:

• No dose adjustment if only liver disease is present. Combined renal and hepatic impairment may require lower dosing.

Administration:

• Route: IV infusion or deep IM injection only.
• IV: Reconstitute and infuse over 30 minutes or inject slowly over 2–4 minutes.
• IM: Inject deep into a large muscle mass; reconstitute with lidocaine if desired (lidocaine-containing solution must not be given IV).

Duration:

• Depends on indication: typically 5–14 days; bacterial meningitis may require 7–21 days.

Ceftriaxone is a bactericidal, third-generation cephalosporin that inhibits bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) inside the bacterial cell wall, blocking the final transpeptidation step of peptidoglycan cross-linking. This weakens the cell wall, causing osmotic instability and bacterial cell death. Ceftriaxone is stable against many beta-lactamases, providing broad Gram-negative activity, moderate Gram-positive activity, and good penetration into cerebrospinal fluid when meninges are inflamed.

Absorption:

• Not absorbed orally. Administered parenterally by IV or IM routes only.

Distribution:

• Widely distributed; achieves therapeutic levels in many body fluids and tissues, including bone, pleural fluid, and CSF (especially during meningeal inflammation).
• Highly protein-bound (~85%–95%), with binding decreasing at higher concentrations.

Metabolism:

• Minimal hepatic metabolism; mostly excreted unchanged.

Excretion:

• About 33%–67% excreted unchanged in urine by glomerular filtration; remainder excreted via bile into feces.
• Half-life: Approximately 6–9 hours in healthy adults; prolonged in neonates and patients with significant renal/hepatic dysfunction.

Pregnancy:

• FDA Category B: Animal studies show no harm; no adequate well-controlled human studies, but used widely when indicated. Crosses placenta.

Lactation:

• Small amounts appear in human milk; generally considered compatible with breastfeeding. Observe infant for diarrhea or oral thrush if exposure is prolonged.

• Primary Class: Third-Generation Cephalosporin Antibiotic

• Known severe hypersensitivity to ceftriaxone, other cephalosporins, or beta-lactam antibiotics.
• History of severe anaphylactic reaction to penicillins (cross-reactivity possible).
• Neonates (≤28 days) with hyperbilirubinemia: Risk of kernicterus due to displacement of bilirubin.
• Neonates receiving IV calcium-containing solutions: Risk of fatal precipitates in lungs/kidneys.

• Hypersensitivity: Risk of severe allergic reactions, including anaphylaxis; cross-reactivity with other beta-lactams possible.
• Clostridioides difficile–associated diarrhea (CDAD): May occur; monitor for severe or persistent diarrhea.
• Superinfection: Long-term use may cause overgrowth of non-susceptible organisms (e.g., fungi).
• Biliary Sludge and Pseudolithiasis: Reported mainly in children; may cause biliary colic.
• Immune-mediated Hemolytic Anemia: Rare but potentially fatal.
• Calcium-containing IV solutions: Risk of precipitation in neonates — avoid mixing or simultaneous infusion.

Monitoring:

• Monitor renal function, CBC, LFTs if prolonged therapy is required.

Common:

• GI: Diarrhea, nausea, mild transient liver enzyme elevations.
• Injection site: Pain, induration, phlebitis (IV).
• Hematologic: Eosinophilia, thrombocytosis.

Serious/Rare:

• Severe allergic reactions, anaphylaxis.
• C. difficile–associated colitis.
• Biliary pseudolithiasis.
• Hemolytic anemia.
• Renal toxicity (rare).

Onset:

• Hypersensitivity can be immediate or delayed. GI and local site reactions may appear during early days of therapy.

• Calcium-containing IV solutions: Risk of precipitation — contraindicated in neonates; do not mix or infuse together.
• Aminoglycosides: Additive nephrotoxicity possible; monitor renal function if co-administered.
• Oral contraceptives: May reduce effectiveness; additional contraception advised.
• Vitamin K antagonists (e.g., warfarin): May increase prothrombin time; monitor INR.

Enzyme Systems:

• Not significantly metabolized by CYP450; interactions are mainly pharmacodynamic.

• CDC recommends ceftriaxone 500 mg IM single dose as first-line for uncomplicated gonorrhea in adults/adolescents.
• IDSA and WHO guidelines continue to include ceftriaxone as standard empiric treatment for severe community-acquired bacterial infections, bacterial meningitis, and serious Gram-negative infections.
• No major new contraindications or black box warnings.

• Dry powder: Store at 20–25 °C (68–77 °F); protect from light and moisture.
• Reconstituted solution:
• Stable for 24 hours at room temperature or 3 days if refrigerated (2–8 °C).
• Inspect for particulate matter; discard if discolored or precipitated.
• Handling: Avoid mixing with calcium-containing IV solutions in same line/syringe, especially for neonates.