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MEN 10700, a new penem antibiotic: in-vitro activity and its correlation with beta-lactamase stability, PBP affinity
R Fontana1, M Altamura, F Arcamone
1Istituto di Microbiologia, Università di Verona, Italy.
Abstract:
The in-vitro activity of MEN 10700, a novel penem, was compared with that of imipenem, ritipenem, ampicillin/sulbactam, cefotaxime, ciprofloxacin and amikacin against 1088 strains taken from 21 genera, including Gram-negative, Gram-positive and anaerobic bacteria. MIC data showed that MEN 10700 was very active against staphylococci and streptococci (MIC90 < or = 0.5 mg/L) and against most members of the Enterobacteriaceae (MIC90 < or = 2 mg/L), with reduced activity only against Providencia stuartii (MIC90 = 8 mg/L). MEN 10700 was also active against anaerobic species such as Clostridium perfringens and Bacteroides fragilis as well as Moraxella catarrhalis. It was moderately active against Enterococcus faecalis and inactive against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Aeromonas spp. and Acinetobacter spp. Its antibacterial spectrum was thus slightly narrower than that of imipenem, but compared favourably with those of a third-generation cephalosporin and ritipenem. MEN 10700 was highly stable to a number of beta-lactamases and was a poor inducer of class I enzymes. It bound penicillin-binding protein 2 with the highest affinity and easily permeated the outer membrane of Escherichia coli.
Insights
MEN 10700, a novel penem antibiotic, demonstrates potent in-vitro activity against Gram-positive and Gram-negative bacteria, including anaerobes. Its broad spectrum and stability to beta-lactamases suggest potential clinical utility.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- The emergence of antibiotic resistance necessitates the development of novel antimicrobial agents.
- Penem antibiotics represent a class of beta-lactam antibiotics with broad-spectrum activity.
Purpose of the Study:
- To evaluate the in-vitro antibacterial activity of MEN 10700, a novel penem.
- To compare MEN 10700's activity against a wide range of bacterial pathogens with established antibiotics.
Main Methods:
- In-vitro susceptibility testing using broth microdilution to determine Minimum Inhibitory Concentrations (MICs).
- Testing against 1088 bacterial strains from 21 genera, encompassing Gram-negative, Gram-positive, and anaerobic bacteria.
- Assessment of stability against various beta-lactamases and induction potential of Class I enzymes.
Main Results:
- MEN 10700 exhibited high activity against staphylococci and streptococci (MIC90 ≤ 0.5 mg/L) and Enterobacteriaceae (MIC90 ≤ 2 mg/L).
- It showed activity against anaerobic species like Clostridium perfringens and Bacteroides fragilis, and Moraxella catarrhalis.
- Moderate activity was observed against Enterococcus faecalis, with inactivity against Pseudomonas aeruginosa and Acinetobacter spp. MEN 10700 demonstrated high stability to beta-lactamases.
Conclusions:
- MEN 10700 possesses a favorable in-vitro activity profile against a broad spectrum of clinically relevant bacteria.
- Its stability to beta-lactamases and potent activity suggest it as a promising candidate for further clinical investigation.
- The penem antibiotic MEN 10700 shows comparable or superior activity to some reference agents, highlighting its potential therapeutic value.