Usage
Ceftriaxone + Disodium edetate + Sulbactam is prescribed for the treatment of life-threatening infections caused by a broad spectrum of gram-negative bacteria, particularly Extended Spectrum Beta Lactamase (ESBL) and Metallo Beta Lactamase (MBL) producing strains. These infections can include respiratory tract infections, urinary tract infections, intra-abdominal infections, sepsis, meningitis, and infections of the skin, soft tissues, bones, and joints. It’s also used pre-operatively to prevent surgical site infections. This combination is particularly valuable in cases of multi-drug resistant (MDR) infections where other antibiotics might be ineffective.
Pharmacological Classification: Antibiotic combination. More specifically, it comprises a third-generation cephalosporin antibiotic (Ceftriaxone), a beta-lactamase inhibitor (Sulbactam), and an antibiotic resistance breaker, also known as a non-antibiotic adjuvant (Disodium edetate).
Mechanism of Action: Ceftriaxone inhibits bacterial cell wall synthesis, leading to bacterial cell death. Sulbactam inhibits beta-lactamase enzymes produced by some bacteria, which would otherwise inactivate Ceftriaxone. Disodium edetate enhances Ceftriaxone’s effectiveness by facilitating its entry into bacterial cells and also by inhibiting some forms of metallo-beta-lactamases.
Alternate Names
A common alternate name/brand name is Elores. CSE-1034 is another name encountered in research contexts.
How It Works
Pharmacodynamics: Ceftriaxone exerts its bactericidal effect by binding to penicillin-binding proteins (PBPs) in the bacterial cell wall, disrupting cell wall synthesis. Sulbactam irreversibly binds and inhibits various beta-lactamases, protecting Ceftriaxone from degradation. Disodium edetate acts synergistically by chelating metal ions, disrupting bacterial membrane stability and increasing Ceftriaxone and Sulbactam penetration into the bacterial cell. This is particularly crucial against bacteria harboring ESBLs and MBLs, where efflux pump mechanisms and beta-lactamase activity are often high.
Pharmacokinetics: Ceftriaxone is primarily excreted through the kidneys. Sulbactam is eliminated through both renal excretion and hepatic metabolism. Disodium edetate is excreted mainly through renal filtration. Dosage adjustments are needed for patients with renal impairment.
Mode of Action: The combination exerts its antimicrobial effect through a multifaceted approach. Ceftriaxone targets PBPs crucial for cell wall integrity, leading to cell lysis and death. Concurrently, Sulbactam tackles bacterial resistance by neutralizing beta-lactamases, thereby safeguarding Ceftriaxone. Disodium edetate further bolsters the antibiotic effect by destabilizing the bacterial membrane and thwarting antibiotic efflux mechanisms, thus increasing intracellular drug concentrations.
Elimination Pathways: Primarily renal excretion for Ceftriaxone and Disodium edetate. Sulbactam is eliminated via both renal and hepatic pathways.
Dosage
Standard Dosage
Adults:
The usual adult dose is 1.5 g (equivalent to 1 g of ceftriaxone) every 12 hours, administered intravenously (IV). For severe infections, this may be increased to 3g every 12 hours (equivalent to 2g of ceftriaxone). The maximum total daily dose of ceftriaxone component should not exceed 4g.
Children:
For children (15 days to 12 years old), the recommended dose is 50-75 mg/kg once daily, or in two equally divided doses, with a maximum of 1g per dose. Neonates (0-14 days): 20 to 50 mg/kg body weight once daily, not to exceed 50 mg/kg/day. Premature infants should follow neonatal dosage guidelines.
Special Cases:
- Elderly Patients: Dosage adjustments are usually unnecessary in elderly patients with normal renal and hepatic function, for doses up to 3g. Higher doses may require adjustment based on organ function.
- Patients with Renal Impairment: Dosage adjustment is crucial in patients with renal impairment. The dose needs to be reduced based on creatinine clearance levels.
- Patients with Hepatic Dysfunction: While dosage adjustments are usually not needed in mild to moderate liver impairment, patients with both hepatic and renal impairment should not receive more than 2 g per day of Ceftriaxone.
- Patients with Comorbid Conditions: Carefully consider the impact of comorbid conditions on drug metabolism and clearance, and adjust doses accordingly.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: The dosage follows the standard adult/pediatric guidelines, adjusted based on the severity of the infection and the patient’s renal and hepatic function.
- Emergency Situations: For severe infections or sepsis, the higher end of the recommended dose range should be considered.
Dosage Adjustments
Dosage adjustments are necessary in patients with renal or hepatic impairment. The dose is generally reduced to prevent drug accumulation.
Side Effects
Common Side Effects:
Pain and swelling at the injection site, diarrhea, rashes, nausea, vomiting, abnormalities in white blood cell and platelet counts.
Rare but Serious Side Effects:
Anaphylaxis, severe skin reactions (e.g., Stevens-Johnson syndrome), pseudomembranous colitis, liver dysfunction, seizures.
Long-Term Effects:
With prolonged use, there is a potential for antibiotic-associated diarrhea and Clostridium difficile infection.
Adverse Drug Reactions (ADR):
Anaphylaxis, severe skin reactions are serious ADRs requiring immediate medical attention.
Contraindications
Hypersensitivity to ceftriaxone, sulbactam, other cephalosporins, or penicillins. Neonates with hyperbilirubinemia or those receiving calcium-containing solutions.
Drug Interactions
- Probenecid: May decrease renal excretion of Ceftriaxone.
- Anticoagulants: May enhance the anticoagulant effect.
- Alcohol: Concurrent use with alcohol should be avoided.
- Other antibiotics: Concomitant use with certain antibiotics may alter their effectiveness.
Pregnancy and Breastfeeding
Pregnancy Safety Category B. While animal studies haven’t shown harm, there are no well-controlled studies in pregnant women. Use only if clearly needed. Ceftriaxone and Sulbactam are excreted in breast milk. Caution is advised when administering to breastfeeding mothers. Breastfeeding should be held until the treatment of the mother is completed and the drug is eliminated from her body.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis, combined with beta-lactamase inhibition and enhancement of drug entry by Disodium edetate.
- Side Effects: Injection site reactions, diarrhea, rash, nausea, vomiting; rarely, anaphylaxis, severe skin reactions.
- Contraindications: Hypersensitivity to components, certain neonatal conditions.
- Drug Interactions: Probenecid, anticoagulants, alcohol.
- Pregnancy & Breastfeeding: Category B; caution advised.
- Dosage: Adults: 1.5 g IV every 12 hours, up to 3g every 12 hours for severe infections; children: dose adjusted by weight.
- Monitoring Parameters: Renal and hepatic function, complete blood count, signs of hypersensitivity.
Popular Combinations
Often used alone due to its broad spectrum of activity. In certain infections, may be combined with metronidazole (e.g. abdominal infections) or other antibiotics depending on the identified pathogens.
Precautions
- Pre-screening for allergies to beta-lactam antibiotics is essential.
- Monitor renal and hepatic function, especially in patients with pre-existing conditions.
- Assess for superinfections (e.g., C. difficile).
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ceftriaxone + Disodium edetate + Sulbactam?
A: Adults: 1.5g IV every 12 hours, up to 3g every 12 hours; Children: weight-based dosage. Neonates: 20-50 mg/kg/day, not to exceed 50 mg/kg.
Q2: What are the common side effects?
A: Pain and swelling at the injection site, diarrhea, skin rash, nausea, vomiting.
Q3: What are the contraindications?
A: Hypersensitivity to any component, use with calcium-containing IV solutions in neonates, certain other neonatal conditions.
Q4: How does Disodium edetate contribute to the effectiveness of this combination?
A: It destabilizes bacterial membranes, increases Ceftriaxone and Sulbactam penetration into the bacterial cell, and can inhibit certain metallo-beta-lactamases.
Q5: Is it safe to use in pregnancy?
A: Pregnancy Category B. Use only if clearly needed after careful risk-benefit assessment.
Q6: Are there any significant drug interactions?
A: Yes, with probenecid and anticoagulants. Alcohol should be avoided during treatment.
Q7: What infections is it typically used for?
A: Serious bacterial infections, particularly those caused by multi-drug resistant Gram-negative bacteria, including respiratory, urinary tract, intra-abdominal, and soft tissue infections, as well as sepsis and meningitis.
Q8: What is the mechanism of action?
A: Inhibition of bacterial cell wall synthesis by Ceftriaxone, coupled with beta-lactamase inhibition by Sulbactam and membrane destabilization and enhanced drug uptake facilitated by Disodium edetate.
Q9: How is it administered?
A: Intravenous infusion over 30 minutes to one hour.
Q10: Can it be used in patients with renal impairment?
A: Yes, but with careful dosage adjustments based on creatinine clearance.
