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Antipneumococcal activity of MEN 10700, a new penem, compared with other compounds, by MIC and time-kill kinetics
G A Pankuch1, D B Hoellman, M R Jacobs
1Department of Pathology (Clinical Microbiology), Hershey Medical Center, PA 17033, USA.
Abstract:
The antipneumococcal activity of MEN 10700 was compared with those of nine other compounds by MIC and time-kill kinetics. MIC90s (mg/L) of 202 penicillin-susceptible, -intermediate and -resistant pneumococci were: 0.06, 1.0 and 2.0 (MEN 10700); 0.06, 0.5-1.0 and 2.0 (amoxycillin +/- clavulanate); 0.06, 0.5 and 4.0 (cefotaxime); 0.125, 0.5 and 2.0 (cefepime); 0.016, 0.125 and 0.25 (imipenem); 0.03, 0.5 and 1.0 (meropenem); 2.0 (ciprofloxacin); 0.125, >64.0 and >64.0 (clarithromycin); and 0.5 (vancomycin). Time-kill kinetics showed that MEN 10700, at 4 x MIC, was bactericidal for all 12 isolates tested at 4 x MIC. Kinetics of other beta-lactams were similar to those of MEN 10700, relative to MICs. Ciprofloxacin, at 4 x MIC, was uniformly bactericidal after 24 h. Clarithromycin exhibited slow kill kinetics, after 24 h. Vancomycin was bactericidal against 11/12 isolates at 2 x MIC after 24 h.
Insights
The novel compound MEN 10700 demonstrates potent antipneumococcal activity, comparable to other beta-lactams, and exhibits bactericidal effects against Streptococcus pneumoniae. This new antibiotic shows promise in combating pneumococcal infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Streptococcus pneumoniae is a leading cause of bacterial infections worldwide, necessitating the development of new antimicrobial agents.
- Antimicrobial resistance in S. pneumoniae poses a significant public health challenge, requiring continuous evaluation of existing and novel compounds.
Purpose of the Study:
- To evaluate the in vitro antipneumococcal activity of MEN 10700 against a panel of S. pneumoniae isolates.
- To compare the efficacy of MEN 10700 with established antibiotics using minimum inhibitory concentration (MIC) and time-kill kinetics.
Main Methods:
- Minimum inhibitory concentrations (MICs) were determined for 202 S. pneumoniae isolates against MEN 10700 and nine other antibiotics.
- Time-kill kinetic studies were performed to assess the bactericidal activity of MEN 10700 and comparator agents at various concentrations.
Main Results:
- MEN 10700 exhibited low MIC90 values (0.06-2.0 mg/L) across penicillin-susceptible, -intermediate, and -resistant pneumococcal strains.
- Time-kill kinetics demonstrated that MEN 10700 was bactericidal against all tested isolates at 4x MIC, with kinetics similar to other beta-lactams.
- Other tested antibiotics showed varying degrees of activity, with imipenem and meropenem displaying potent bactericidal effects, while clarithromycin showed slower kinetics.
Conclusions:
- MEN 10700 possesses significant in vitro antipneumococcal activity and bactericidal properties.
- Its efficacy is comparable to established beta-lactam antibiotics, suggesting potential as a therapeutic option for pneumococcal infections.
- Further clinical investigation is warranted to establish the therapeutic utility of MEN 10700.