Table of Contents

Ceftriaxone (Injectable) — Comprehensive Medical Guide

Introduction

Ceftriaxone is a third-generation cephalosporin antibiotic widely used in clinical practice for the treatment of serious bacterial infections. It is available as an injectable formulation—intravenous (IV) or intramuscular (IM)—allowing rapid systemic delivery and broad-spectrum antibacterial activity. Ceftriaxone is highly effective against many Gram-positive and Gram-negative pathogens, including resistant strains, making it a vital drug in hospitals and outpatient settings.

This article provides an in-depth review of ceftriaxone, covering its uses, pharmacology, dosing, side effects, warnings, drug interactions, and clinical considerations.

Uses & Indications

Ceftriaxone is indicated for treatment of a broad range of infections, including:

Lower respiratory tract infections: Pneumonia, including community-acquired and hospital-acquired types.
Urinary tract infections: Complicated and uncomplicated pyelonephritis and cystitis.
Intra-abdominal infections: Peritonitis, appendicitis, and biliary tract infections (often combined with metronidazole).
Skin and soft tissue infections: Cellulitis, wound infections.
Bone and joint infections: Osteomyelitis, septic arthritis.
Central nervous system infections: Meningitis caused by susceptible organisms.
Sexually transmitted infections: Gonorrhea (uncomplicated), often in single-dose regimens.
Sepsis and bacteremia: Empiric and targeted treatment.
Surgical prophylaxis: Prevention of postoperative infections in certain procedures.

Ceftriaxone is valued for its efficacy, long half-life, and ease of once- or twice-daily dosing.

Mechanism of Action

Ceftriaxone exerts bactericidal activity by interfering with bacterial cell wall synthesis. It binds to and inhibits penicillin-binding proteins (PBPs), enzymes essential for cross-linking peptidoglycan strands that provide structural integrity to the bacterial cell wall.

Inhibition of PBPs leads to defective cell wall synthesis, weakening the wall and causing bacterial lysis and death.
Its affinity for PBPs in many Gram-positive and Gram-negative bacteria underlies its broad spectrum.
Ceftriaxone is resistant to many beta-lactamases, enzymes produced by bacteria that inactivate some other beta-lactam antibiotics.

Pharmacokinetics

Absorption: Administered parenterally (IV or IM); complete bioavailability.
Distribution: Widely distributed into body fluids and tissues including cerebrospinal fluid, bone, bile, and lungs.
Protein Binding: Approximately 85–95% bound to plasma proteins.
Metabolism: Minimally metabolized by the liver.
Elimination: Primarily excreted unchanged via the kidneys and bile; dual elimination routes.
Half-life: Long elimination half-life of approximately 6–9 hours, enabling once or twice daily dosing.
Penetration: Good CNS penetration, especially with inflamed meninges.

Dosage and Administration

General Adult Dosage:

Usual doses range from 1 to 2 grams once or twice daily depending on infection severity.
Maximum daily dose generally does not exceed 4 grams.
Administered via IV injection or slow infusion (over 30 minutes) or deep IM injection.
For IM, reconstitution with appropriate diluent is necessary.

Special Populations:

Pediatrics: Dosage based on weight (50–75 mg/kg/day), divided into one or two doses.
Renal impairment: Dose adjustments typically not needed due to biliary excretion, but caution advised in severe dysfunction.
Hepatic impairment: Use with caution; monitor closely.

Typical Treatment Durations:

Vary from 7 to 14 days or longer depending on infection site and response.
Meningitis treatment often requires 10–14 days or more.

Side Effects

Common Side Effects:

Injection site reactions: pain, swelling, erythema (more common with IM).
Diarrhea, nausea, vomiting.
Rash or pruritus.
Elevated liver enzymes.

Serious Adverse Effects:

Hypersensitivity reactions: Anaphylaxis, Stevens-Johnson syndrome (rare).
Clostridioides difficile colitis: Antibiotic-associated diarrhea.
Biliary sludge and pseudolithiasis: Ceftriaxone may precipitate in bile, causing reversible gallbladder issues, especially with prolonged high-dose therapy.
Hemolytic anemia: Rare autoimmune reaction.
Nephrolithiasis: Crystalluria can lead to kidney stones.
Coagulopathy: Prolonged prothrombin time in some cases.

Contraindications

Known hypersensitivity to ceftriaxone, cephalosporins, or beta-lactam antibiotics.
Neonates (≤28 days) receiving calcium-containing IV solutions simultaneously due to risk of fatal precipitates.
History of severe allergic reaction to penicillins may increase risk of cross-reactivity.

Warnings and Precautions

Allergic reactions: Always assess history of beta-lactam allergy.
Calcium interaction: Avoid simultaneous IV administration with calcium-containing fluids in neonates; delay administration by at least 48 hours.
Renal and hepatic function: Monitor periodically during prolonged therapy.
Superinfection: Monitor for signs of fungal or bacterial superinfection.
Biliary complications: Monitor abdominal symptoms in long-term high-dose treatment.
Hematologic effects: Monitor blood counts if therapy prolonged.

Drug Interactions

Calcium-containing solutions: Risk of precipitation in neonates; avoid co-administration.
Aminoglycosides: May have additive nephrotoxicity; monitor renal function.
Oral anticoagulants: Ceftriaxone may potentiate effects; monitor INR/PT.
Loop diuretics and nephrotoxic drugs: Use caution; increased risk of kidney injury.

Clinical Considerations

Empiric therapy: Often used as initial broad-spectrum antibiotic in serious infections before culture results.
De-escalation: Therapy should be adjusted based on culture and sensitivity to avoid resistance development.
Outpatient parenteral antibiotic therapy (OPAT): Ceftriaxone’s long half-life and once-daily dosing make it convenient for outpatient IV therapy.
Pregnancy category B: Use when benefits outweigh risks; crosses placenta.
Monitoring: Renal, hepatic function, blood counts, signs of hypersensitivity.

Patient Counseling

Inform about possible injection site pain and common mild side effects.
Advise to report signs of allergic reactions immediately.
Emphasize adherence to full course even if symptoms improve.
Warn about diarrhea or unusual bowel symptoms and to seek care if severe.
Notify healthcare provider of all medications to avoid interactions.

FAQs

Q1: Can ceftriaxone be given orally?
A: No, ceftriaxone is only available for injectable use due to poor oral absorption.

Q2: Is ceftriaxone safe in pregnancy?
A: Classified as pregnancy category B; benefits must outweigh risks.

Q3: How quickly does ceftriaxone work?
A: Clinical improvement often seen within 48–72 hours.

Q4: Can ceftriaxone cause allergic reactions if I’m allergic to penicillin?
A: Cross-reactivity risk is low but possible; inform your doctor.

Q5: Why avoid calcium solutions with ceftriaxone in neonates?
A: They can form precipitates causing potentially fatal complications.

Summary

Ceftriaxone is a versatile, effective antibiotic crucial for treating a wide array of bacterial infections. Its broad-spectrum activity, convenient dosing, and favorable pharmacokinetics make it a mainstay in many clinical settings. Awareness of precautions, interactions, and patient education is essential to optimize safety and therapeutic outcomes.

References

U.S. National Library of Medicine. Ceftriaxone Injection. https://medlineplus.gov/druginfo/meds/a685032.html
Mandell GL, et al. Principles and Practice of Infectious Diseases, 9th Edition. Elsevier, 2010.
FDA Ceftriaxone Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050585s031lbl.pdf
Sanford Guide to Antimicrobial Therapy, 2023.
Lexicomp Online. Ceftriaxone Drug Information.