Antibiotics with Long Post-Antibiotic Effect for Once Daily Dosing
Aminoglycosides and ceftriaxone are the antibiotics with the longest post-antibiotic effects that allow for once-daily dosing, with aminoglycosides having the most pronounced post-antibiotic effect. 1
Aminoglycosides
Aminoglycosides demonstrate concentration-dependent killing and a prolonged post-antibiotic effect, which is defined as a prolonged effect on bacterial growth that continues after antibiotic therapy ceases. These pharmacodynamic properties make them ideal for once-daily dosing regimens 1.
Key benefits of once-daily aminoglycoside dosing:
- May offer therapeutic advantages over multiple daily doses
- May reduce the incidence of nephrotoxicity and ototoxicity
- Simplifies administration schedule
Important Considerations and Cautions
Once-daily aminoglycoside therapy should be used with caution in:
- Pregnant women
- Children
- Elderly persons
- Critically ill patients
- Patients with renal dysfunction
- Patients with neutropenia
- Patients with burns
- Patients with liver disease
- Patients with endocarditis
These populations have not been fully evaluated for once-daily dosing safety and efficacy 1.
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin with a sufficiently long half-life to provide serum concentrations above the MICs for most susceptible organisms for 12-24 hours, allowing for once-daily administration 1, 2.
Key features of ceftriaxone:
- Can be administered once daily (2g IV/IM) 2
- Has a long serum half-life of 5.8-8.7 hours (mean 6.5 hours) 3
- Distributes well throughout body spaces 3
- No dosage adjustment needed unless there is combined hepatic and renal dysfunction 3
Specific Dosing Recommendations
- Infective endocarditis: 2 grams IV every 12 hours or 4 grams once daily 2
- Bacterial meningitis: 100 mg/kg/day once daily or divided every 12 hours (maximum 4 grams/day) 2
- Uncomplicated UTI/pyelonephritis: 1-2 grams IV/IM daily 1
Comparison with Other β-lactams
Most β-lactam antibiotics have short half-lives and time-dependent killing with only brief post-antibiotic effects, requiring multiple daily doses 1. However:
- Ceftriaxone and ertapenem have sufficiently long half-lives for once-daily dosing
- Other β-lactams like ampicillin have short half-lives and may need to be administered as frequently as every 4 hours 1
Clinical Applications
The convenience of once-daily dosing with these antibiotics offers several advantages:
- Reduces disruption of daily activities
- Limits potential for complications
- Particularly valuable in outpatient parenteral antimicrobial therapy (OPAT) settings 1
- Can result in cost savings with proper use 3
Monitoring Requirements
For aminoglycosides:
- Regular monitoring of serum levels
- Assessment of renal function
- Monitoring for ototoxicity
For ceftriaxone:
- Generally well tolerated with fewer monitoring requirements
- Potential side effects include diarrhea (32%), thrombocytosis (77%), and neutropenia (9%) 4
When selecting an antibiotic with a long post-antibiotic effect for once-daily dosing, consider the specific infection, patient factors, local resistance patterns, and monitoring capabilities.