Oral Antibiotic Bioavailability
Antibiotics with Excellent Bioavailability (≥90%)
The following oral antibiotics achieve serum and tissue concentrations comparable to intravenous formulations and are preferred for IV-to-oral switch therapy:
Fluoroquinolones: Ciprofloxacin has approximately 70% absolute bioavailability, with serum concentrations increasing proportionately with doses up to 1000 mg 1. Levofloxacin, gatifloxacin, and moxifloxacin achieve excellent bioavailability and high tissue concentrations in diabetic foot infections 2.
Linezolid: Demonstrates excellent oral bioavailability, making it suitable for early switch from parenteral therapy 2, 3.
Metronidazole: Achieves excellent bioavailability and is ideal for IV-to-oral switch programs 2, 3.
Clindamycin: Has excellent gastrointestinal absorption and is recommended for both diabetic foot infections and vertebral osteomyelitis 2, 3.
Trimethoprim-sulfamethoxazole (TMP-SMX): Demonstrates excellent bioavailability and is associated with significantly better clinical outcomes in gram-negative bloodstream infections compared to less bioavailable agents 2, 4.
Rifampicin: Achieves excellent oral absorption 2.
Doxycycline: Has excellent bioavailability and is appropriate for serious systemic infections 2, 3.
Antibiotics with Good to Moderate Bioavailability (40-90%)
Azithromycin: Has 38% absolute bioavailability for the 250 mg capsule formulation, with food increasing Cmax by 56% for suspension but not affecting AUC 5.
Amoxicillin: Demonstrates excellent bioavailability with serum levels increasing linearly with dose, making gastrointestinal absorption not a limiting factor even at high doses (4 g/day for adults, 90 mg/kg/day for children) 2.
Antibiotics with Poor Bioavailability (<40%)
Oral β-lactams should not be prescribed for initial treatment of serious infections like vertebral osteomyelitis given their low bioavailability 2.
Cephalosporins: Generally have lower bioavailability than amoxicillin, with baseline MICs fourfold higher than amoxicillin against S. pneumoniae, and active absorption in the gastrointestinal tract limits achievable concentrations regardless of dose 2.
β-lactams (general): Are associated with significantly worse clinical outcomes compared to highly bioavailable agents in gram-negative bloodstream infections, with higher rates of recurrent BSI (9.4% vs 5.4%, p<0.001) 4.
Clinical Application Framework
For serious systemic infections requiring oral therapy, select antibiotics with ≥70% bioavailability to ensure adequate serum and tissue concentrations 6.
Initial IV therapy is appropriate for patients in shock or with impaired intestinal absorption, but after clinical defervescence, complete therapy with oral antibiotics with high bioavailability 6, 3.
Highly bioavailable oral antibiotics (fluoroquinolones and TMP-SMX) reduce 90-day composite outcomes (mortality, recurrent BSI, readmission) by 26% compared to less bioavailable agents (adjusted OR 0.74,95% CI 0.60-0.92) 4.
Peripheral vascular disease, but not diabetes itself, may limit antibiotic delivery to infected tissues, though antibiotics remain important even in ischemic limbs 2.
Critical Pitfalls to Avoid
Do not use oral β-lactams for severe infections or initial treatment of vertebral osteomyelitis due to inadequate bioavailability 2.
Do not assume all oral antibiotics achieve therapeutic levels—bioavailability varies significantly between drug classes and even within the same class 2, 6.
Avoid IV therapy continuation when oral highly bioavailable alternatives exist, as this increases costs, length of stay, and risk of IV line complications without improving outcomes 3.