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Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin
J Martínez-Beltrán1, R Cantón, J Liñares
1Servicio de Microbiología, Hospital Ramón y Cajal, Madrid, Spain.
Abstract:
The in vitro antibacterial activity of FK-037, a new parenteral cephalosporin structurally related to cefpirome and cefepime, was compared with that of cefotaxime, ceftazidime, aztreonam, cefpirome, cefepime, imipenem and meropenem against 1,837 clinical isolates obtained from three Spanish hospitals. FK-037 inhibited 90% of Enterobacteriaceae isolates at < or = 0.25 microgram/ml, with the exception of Enterobacter aerogenes (MIC90 1 microgram/ml), Enterobacter cloacae and Citrobacter freundii (MIC90 8 micrograms/ml). In cefotaxime- and ceftazidime-resistant Klebsiella pneumoniae strains producing SHV-2 and SHV-6 beta-lactamases, the activity of FK-037, cefpirome and cefepime was similar (MIC range 0.25-32 micrograms/ml). In Enterobacteriaceae strains hyper-producing chromosomally inducible beta-lactamases, FK-037 (MIC90 range, 0.25-8 micrograms/ml) was 8- to 16-fold more active than cefotaxime and ceftazidime but two- to eightfold less active than cefpirome and cefepime. FK-037 and cefpirome were twofold more active than ceftazidime and cefepime against Pseudomonas aeruginosa isolates, with MIC90 values of 16 micrograms/ml. The activity of FK-037, cefpirome and cefepime was two- to eightfold lower in ceftazidime-resistant derepressed Pseudomonas aeruginosa mutants. FK-037 (MIC range, 0.12-2 micrograms/ml) and the other beta-lactam agents tested were active against methicillin-susceptible staphylococci; however, only cefpirome and, particularly, FK-037 (MIC90 of 32 micrograms/ml) displayed some activity against methicillin-resistant strains. In penicillin-susceptible, -intermediate and -resistant Streptococcus pneumoniae isolates, the MIC90s of FK-037 were 0.03, 0.5 and 1 microgram/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
FK-037, a novel parenteral cephalosporin, demonstrates potent in vitro antibacterial activity against a broad spectrum of clinical isolates, including resistant strains. Its efficacy positions it as a promising new agent for treating bacterial infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Emerging antibiotic resistance necessitates the development of new antimicrobial agents.
- Parenteral cephalosporins are crucial in treating serious bacterial infections.
- Understanding the in vitro activity spectrum of novel antibiotics is essential for clinical application.
Purpose of the Study:
- To evaluate the in vitro antibacterial activity of FK-037 against a large collection of clinical bacterial isolates.
- To compare the efficacy of FK-037 with existing beta-lactam antibiotics, including cefotaxime, ceftazidime, cefpirome, and cefepime.
- To assess FK-037's activity against resistant bacterial strains, including those producing beta-lactamases and methicillin-resistant Staphylococcus aureus.
Main Methods:
- In vitro susceptibility testing using broth microdilution method.
- Testing against 1,837 clinical isolates from three Spanish hospitals.
- Determination of Minimum Inhibitory Concentrations (MICs) and MIC90 values for FK-037 and comparator agents.
Main Results:
- FK-037 exhibited potent activity against most Enterobacteriaceae (MIC90 ≤ 0.25 µg/ml), with exceptions for Enterobacter species and Citrobacter freundii.
- Against cefotaxime- and ceftazidime-resistant Klebsiella pneumoniae, FK-037 showed activity comparable to cefpirome and cefepime.
- FK-037 displayed notable activity against methicillin-susceptible staphylococci and some activity against methicillin-resistant strains, outperforming other cephalosporins in this regard.
Conclusions:
- FK-037 possesses broad-spectrum in vitro antibacterial activity, including against some resistant Gram-negative and Gram-positive pathogens.
- Its activity profile suggests potential utility in treating infections caused by susceptible and some resistant bacterial strains.
- Further clinical evaluation is warranted to establish the therapeutic role of FK-037.