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Pharmacokinetics of sparfloxacin and serum bactericidal activity against pneumococci
M Trautmann1, M Ruhnke, K Borner
1Department of Medical Microbiology and Hygiene, University of Ulm, Germany.
Abstract:
Sparfloxacin, a new fluorinated quinolone, exhibits higher in vitro activity against pneumococci than do ciprofloxacin and ofloxacin. Since up to 30% of cases of pneumococcal pneumonia are associated with bacteremia, and since an increasing percentage of pneumococci are resistant against penicillin, we studied the serum bactericidal activity of sparfloxacin against pneumococci in eight healthy, middle-aged volunteers. Pharmacokinetics in serum and urine after a 400-mg oral dose of sparfloxacin were comparable to those described by other authors. Inhibitory and bactericidal activities in serum were measured for four pneumococcal isolates representing penicillin-susceptible (one isolate), intermediately resistant (two isolates), and highly resistant (one isolate) strains. Geometric mean inhibitory titers ranged between 1:2.4 and 1:6.3 and bactericidal titers ranged between 1:1.3 and 1:3.6 during a time period of 1 to 6 h after drug intake. Although such titers were not sufficient to predict a clinical response based on previous pharmacodynamic studies using quinolone antibiotics, data obtained with volunteers may only partially reflect the clinical situation in which a rise of humoral antibodies directed against pneumococcal antigens may help to reinforce the bactericidal action of the antibiotic.
Insights
Sparfloxacin shows promising in vitro activity against pneumococci, including resistant strains. However, serum bactericidal activity in healthy volunteers was modest, suggesting a need for further clinical evaluation.
Area of Science:
- Pharmacology
- Microbiology
- Infectious Diseases
Background:
- Sparfloxacin, a novel fluorinated quinolone, demonstrates superior in vitro efficacy against pneumococci compared to ciprofloxacin and ofloxacin.
- Increasing penicillin resistance in Streptococcus pneumoniae necessitates alternative treatment options.
- Pneumococcal pneumonia frequently involves bacteremia, highlighting the importance of bactericidal agents.
Purpose of the Study:
- To evaluate the serum bactericidal activity of sparfloxacin against various pneumococcal isolates in healthy volunteers.
- To assess the pharmacokinetic profile of sparfloxacin following oral administration.
- To correlate in vitro activity with in vivo serum bactericidal effects.
Main Methods:
- Eight healthy volunteers received a single 400-mg oral dose of sparfloxacin.
- Serum and urine pharmacokinetics were analyzed.
- Serum inhibitory and bactericidal titers were determined against four pneumococcal isolates (penicillin-susceptible, intermediate, and highly resistant).
Main Results:
- Sparfloxacin pharmacokinetic parameters were consistent with existing literature.
- Geometric mean inhibitory titers ranged from 1:2.4 to 1:6.3, and bactericidal titers ranged from 1:1.3 to 1:3.6 within 1 to 6 hours post-dose.
- Observed serum titers were not definitively predictive of clinical efficacy based on prior quinolone studies.
Conclusions:
- Sparfloxacin exhibits measurable serum bactericidal activity against pneumococci in healthy volunteers.
- The observed bactericidal activity may be insufficient alone for clinical success in severe infections.
- Humoral immune responses could potentially enhance sparfloxacin's bactericidal effect in vivo.