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[Bone and suppurative lesion distribution of antimicrobial agents (ampicillin and ofloxacin) in experimental infected
Abstract:
Using Streptococcus milleri and Bacteroides fragilis in the mandibula of the domestic rabbit, a jaw-bone infected model was prepared; ampicillin (ABPC) a penicillin derivative and ofloxacin (OFLX) a pyridonecarboxylic acid derivative, were administered orally, injected intramuscularly, or infused intravenously; their concentration in the pus, mandibula, supramaxilla, humerus, femur, sternum, ilium and serum were measured. Pharmacokinetic studies compared the penetration. (1) By oral administration, the maximum ABPC concentration in the pus and bone tissues was 5.9 to 34.3% of the serum, by intramuscular injection 10.4 to 27.5% and by i.v. infusion 12.1 to 42.4%. (2) The maximum concentration of orally administered OFLX in the pus and bone tissues was 52.5 to 111.7% of the serum, by intramuscular injection 56.4 to 100.3% and by i.v. infusion 61.2 to 121.8%. (3) When administered orally, injected intramuscularly, or infused intravenously ABPC showed good penetration into the pus, mandibula and ilium, and OFLX into the pus, sternum and ilium. When infused intravenously, OFLX in the pus and bone tissues was higher than the MIC of both strains. (4) When ABPC was administered as under 3 routes, T1/2 was longer in the pus and most bone tissues than in the serum. T1/2 of OFLX was shorter in most bone tissues by all administration routes than in serum, T1/2 was longer for OFLX than for ABPC, except when orally administered. (5) AUC of ABPC was in the order of intravenous infusion, intramuscular injection and oral administration. About the same AUC of OFLX was shown after i.v. infusion and i.m. injection, both values being about double after oral administration. In all administration routes, AUC of pus surpassed AUC of serum and AUC of OFLX greatly surpassed that of ABPC.
Insights
This study compared ampicillin (ABPC) and ofloxacin (OFLX) penetration into rabbit jawbone infections. Ofloxacin demonstrated superior penetration and higher concentrations in bone and pus compared to ampicillin across all administration routes.
Area of Science:
- Pharmacology
- Infectious Diseases
- Osteomyelitis Research
Context:
- Bacterial jawbone infections in rabbits caused by Streptococcus milleri and Bacteroides fragilis were modeled.
- Ampicillin (ABPC) and ofloxacin (OFLX) were administered via oral, intramuscular, and intravenous routes.
- Drug concentrations in pus, various bone tissues, and serum were quantified.
Purpose:
- To compare the pharmacokinetic profiles of ampicillin and ofloxacin in a rabbit jawbone infection model.
- To evaluate drug penetration into infected bone and pus following different administration routes.
- To assess the efficacy of these antibiotics against the target pathogens.
Summary:
- Ofloxacin showed significantly higher concentrations in pus and bone tissues than ampicillin, regardless of administration route (oral, intramuscular, intravenous).
- Ampicillin penetration into pus and specific bone sites was noted, while ofloxacin demonstrated broad penetration, exceeding minimum inhibitory concentrations (MICs) when infused intravenously.
- Pharmacokinetic parameters like half-life (T1/2) and area under the curve (AUC) indicated better and more sustained drug levels for ofloxacin in infected tissues compared to ampicillin.
Impact:
- Findings suggest ofloxacin may be a more effective therapeutic option for jawbone osteomyelitis due to superior tissue penetration.
- This research provides crucial pharmacokinetic data to guide antibiotic selection and treatment strategies for bone infections.
- The study highlights the importance of considering drug distribution in infected tissues for optimizing antimicrobial therapy.
