What is the recommended dosage and frequency of Ceftri-Sulbactam (ceftriaxone and sulbactam)?

Ceftriaxone-Sulbactam Dosing Recommendations

For adults with normal renal function, administer ceftriaxone-sulbactam as 1.5-3g IV every 6-8 hours (1g ceftriaxone + 0.5g sulbactam per dose), or for serious infections use 2g ceftriaxone once daily with appropriate sulbactam adjustment. 1

Adult Dosing by Indication

Standard Infections (Community-Acquired Pneumonia, Skin/Soft Tissue)

• Ampicillin-sulbactam 1.5-3g IV every 6 hours is the recommended regimen for moderate severity infections 2
• For serious infections requiring higher ceftriaxone doses, 2g ceftriaxone IV once daily can be used with sulbactam adjustment 1
• The once-daily ceftriaxone dosing maintains adequate plasma concentrations above MIC for 24 hours in most patients 3

HACEK Endocarditis

• Ampicillin-sulbactam 12g per 24 hours IV in 4 equally divided doses (3g every 6 hours) for 4 weeks for native valve endocarditis 2
• Extend treatment to 6 weeks for prosthetic valve endocarditis 1
• Alternative: Ceftriaxone 2g IV once daily for 4 weeks (6 weeks for prosthetic valve) 2

Severe Infections/ICU Patients

• Ampicillin-sulbactam 1.5-3g IV every 6 hours for ICU-level pneumonia 2
• Consider twice-daily dosing in critically ill patients with augmented renal clearance, as once-daily ceftriaxone may result in suboptimal concentrations 4

Pediatric Dosing

Standard Pediatric Dosing

• Ceftriaxone 50-75 mg/kg/day IV divided every 12-24 hours (maximum 2g/day) for most infections 1
• Ampicillin-sulbactam 300 mg/kg per 24 hours IV divided into 4 or 6 equally divided doses for HACEK endocarditis 2

Severe Infections (Meningitis, Endocarditis, Severe Sepsis)

• Ceftriaxone 100 mg/kg/day IV once daily or divided every 12 hours (maximum 4g/day) 1, 5
• For severe sepsis specifically, 80-100 mg/kg/day is appropriate 5
• Do not use the lower end of dosing range (50 mg/kg/day) for severe sepsis 5

Age-Specific Considerations

• Neonates ≤7 days: 50 mg/kg/day ceftriaxone every 24 hours 5
• Neonates >7 days and >2000g: 50-75 mg/kg/day ceftriaxone every 24 hours 5
• Avoid ceftriaxone in hyperbilirubinemic neonates 5

Renal Impairment Adjustments

Moderate Renal Impairment (CrCl 15-30 mL/min)

• Reduce sulbactam component by 50% while maintaining the same dosing interval 1
• Ceftriaxone component typically requires no adjustment up to 2g/day 6

Severe Renal Impairment (CrCl <15 mL/min)

• Reduce sulbactam component by 75% while maintaining the same dosing interval 1
• Monitor plasma ceftriaxone concentrations in dialysis patients, as elimination may be significantly reduced 6
• Ceftriaxone is not significantly removed by hemodialysis 6

Critical Dosing Considerations

Pharmacokinetic Rationale

• Ceftriaxone has an elimination half-life of 5.8-8.7 hours in normal adults 6 and 5.2 hours when combined with sulbactam 3
• Sulbactam has a much shorter half-life of 0.94 hours, necessitating more frequent dosing when used alone 3
• In critically ill patients with normal renal function, ceftriaxone clearance is increased 100% and volume of distribution increased 90%, potentially requiring twice-daily dosing 4

Common Pitfalls to Avoid

• Do not assume once-daily dosing is adequate in critically ill patients with augmented renal clearance—three of nine patients in one study had suboptimal concentrations with standard dosing 4
• Do not use ceftriaxone monotherapy for Pseudomonas aeruginosa infections—it has insufficient activity 7
• IM injection of ceftriaxone is painful—counsel patients accordingly 2
• Monitor renal function during treatment, especially in patients with pre-existing impairment 1

When to Consider Twice-Daily Dosing

• Critically ill patients with estimated GFR >80 mL/min/1.73 m² 8
• Areas with high prevalence of less-susceptible pathogens (MIC ≥0.5 mg/L) 8
• Pediatric patients requiring 50 mg/kg twice daily achieves 99.9% target attainment versus 96.8% with once-daily dosing 8