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HR 756, a highly active cephalosporin: comparison with cefazolin and carbenicillin
Abstract:
HR 756, a new parenteral cephalosporin, was compared with cefazolin and carbenicillin for activity against a total of 264 strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus spp. (indole positive), Enterobacter spp., Salmonella typhi, Serratia marcescens, Providencia stuartii, and Staphylococcus aureus. In every comparison, except that with the last organism, HR 756 was clearly more active than cefazolin and carbenicillin. All three compounds had similar activity against penicillin-susceptible staphylococci; against penicillin-resistant strains, HR 756 and cefazolin were equally active and superior to carbenicillin. HR 756 was compared with penicillin for activity against strains of Streptococcus pyogenes, Lancefield group D streptococci, and Neisseria gonorrhoeae; with ampicillin against Haemophilus influenzae; and with cefoxitin against Bacteriodes fragilis. HR 756 was clearly more active than the respective reference compounds in all of these comparisons, except those involving the streptococci. HR 756 and penicillin were essentially equally active against S. pyogenes; against Lancefield group D, penicillin was 32 times as active as HR 756. HR 756 not only compared favorably with the reference compounds with respect to relative activity, but also effected growth inhibition of essentially all test organisms (P. aeruginosa and group D streptococci excepted) at remarkably low concentrations ranging from 0.015 to 2.0 mug/ml. A series of seven transfers of selected strains of E. coli, Klebsiella spp., S. aureus, and P. aeruginosa through medium containing HR 756 led to emergence of strains with significant levels of resistance to the agent. Resistance to HR 756 was retained for at least seven transfers through plain medium.
Insights
HR 756, a new cephalosporin antibiotic, demonstrated superior activity against many Gram-negative bacteria compared to cefazolin and carbenicillin. While effective against most tested pathogens, resistance developed with repeated exposure.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Parenteral cephalosporins are crucial in treating bacterial infections.
- Understanding the spectrum of activity and resistance potential of new antibiotics is vital.
Purpose of the Study:
- To evaluate the in vitro antimicrobial activity of HR 756 against a broad range of clinically relevant bacteria.
- To compare HR 756's efficacy against cefazolin, carbenicillin, penicillin, ampicillin, and cefoxitin.
Main Methods:
- In vitro susceptibility testing of 264 bacterial strains including Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., and Staphylococcus aureus.
- Comparative analysis of HR 756 against reference antibiotics across various bacterial species.
- Assessment of resistance development through serial passage experiments.
Main Results:
- HR 756 exhibited greater activity than cefazolin and carbenicillin against most Gram-negative organisms tested.
- HR 756 showed comparable or superior activity to reference drugs against Staphylococcus aureus, Neisseria gonorrhoeae, Haemophilus influenzae, and Bacteroides fragilis.
- Significant resistance to HR 756 emerged in E. coli, Klebsiella spp., S. aureus, and P. aeruginosa after serial passage, which persisted in plain medium.
Conclusions:
- HR 756 possesses a broad spectrum of activity, outperforming comparator agents against many common pathogens.
- The emergence and persistence of resistance highlight the need for careful monitoring and judicious use of HR 756.