SCHUBERT S, ULLMANN U, DALHOFF A; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. A-2078.
Dept. Med. Microbiol., Univ. Hosp. Kiel, Kiel, Germany
BACKGROUND: Measurement of the bacteriolytic action of beta-lactams can be antagonized by hyperosmolaric media or body-fluids, which allow spheroblasts regrowth upon elimination of the agents from the test media. Furthermore, protein binding may affect the apparent bactericidal activity of drugs. We compared the bactericidal and bacteriolytic action of faropenem (FAR; ~ 95% protein bound) and amoxicillin (AMX; ~ 38%) in the absence or presence of the bacteriolytic protectant sucrose. METHODS: Killing kinetics of S. pneumoniae (No. 4241) were monitored in brain heart infusion (BHI) broth +/- 50% human serum +/- 10% sucrose at 37C. The final inoculum was ~ 10[6] CFU/ml. Multiples of the individual MICs of the test organisms (ranging from 1 to 32 times the MIC) were added to the cultures. Samples were taken at 1, 2, 4, 6, 8 h and subcultured quantitatively. RESULTS: In the absence of serum, FAR exhibited a significantly greater bactericidal effect than AMX against S. pneumoniae throughout the whole range of drug concentrations studied. In the presence of serum the bactericidal action of both drugs was diminished, yet FAR was still bactericidal. However, the bactericidal activity of FAR in the presence of serum was not reduced proportionally to its protein binding. Sucrose supplementation of 50% serum containing BHI decreased the bactericidal action of AMX. In contrast, sucrose supplementation augmented the bactericidal action of FAR. BHI +/- serum were iso-osmol. CONCLUSIONS: 1) FAR demonstrated bactericidal activity against S. pneumoniae. 2) Although human serum reduced the bactericidal activity of both FAR and AMX, FAR retained bactericidal activity despite being protein bound. 3) The osmo-protectant sucrose increased the bacteriolytic activity of FAR, but reduced that of AMX. 4) Other yet unknown factors may antagonize the lysis of bacteria.
Publication Types:
Keywords:
- Amoxicillin
- Animals
- Antigens, Bacterial
- Humans
- Lactams
- Microbial Sensitivity Tests
- Serum
- Streptococcus pneumoniae
- Sucrose
- beta-Lactams
- fropenem
- immunology
Other ID:
UI: 102270196
From Meeting Abstracts