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Cefoxitin activity against multiply antibiotic-resistance Klebsiella pneumoniae in vitro
Abstract:
Due to the emergence of cephalothin- and gentamicin-resistant Klebsiella pneumoniae at this institution, we investigated the in vitro activity of two new cephalosporin compounds-cefoxitin and cefamandole. Whereas both drugs were active against cephalothin- and gentamicin-susceptible isolates of Klebsiella, only cefoxitin exhibited significant activity against cephalothin- and gentamicin-resistant isolates. Seventeen of 20 (85%) of the cephalothin- and gentamicin-resistant isolates were inhibited by =12.5 mug of cefoxitin per ml. The minimum bactericidal concentration in broth of representative isolates equaled the agar dilution minimum inhibitory concentration. Kirby-Bauer disk susceptibility testing correlated well with the agar dilution minimum inhibitory concentration. Cephalothin and cefamandole resistance of isolates could be correlated with antibiotic degradation by beta-lactamase. Cephalothin and cefamandole evoked only a transient decrease in viable bacterial cell count with rapid inactivation of antibiotics, and full regrowth of the organisms. Cefoxitin, on the other hand, was quite effective in vitro against multiply resistant Klebsiella. No beta-lactamase degradation of cefoxitin was detected. Growth curves with antibiotics indicated rapid killing of cephalothin- and gentamicin-resistant isolates by cefoxitin.
Insights
Cefoxitin shows significant in vitro activity against cephalothin- and gentamicin-resistant Klebsiella pneumoniae, unlike cefamandole. This new cephalosporin effectively inhibits and kills resistant bacterial isolates, offering a promising therapeutic option.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Emergence of antibiotic resistance in Klebsiella pneumoniae to cephalothin and gentamicin.
- Need for effective antimicrobial agents against multidrug-resistant bacterial strains.
Purpose of the Study:
- To investigate the in vitro activity of cefoxitin and cefamandole against resistant Klebsiella pneumoniae isolates.
- To compare the efficacy of cefoxitin and cefamandole in inhibiting and killing resistant strains.
Main Methods:
- In vitro susceptibility testing (agar dilution, minimum inhibitory concentration, minimum bactericidal concentration) of cefoxitin and cefamandole.
- Kirby-Bauer disk susceptibility testing.
- Analysis of antibiotic degradation by beta-lactamase.
- Growth curve analysis to assess bacterial killing kinetics.
Main Results:
- Cefoxitin demonstrated significant in vitro activity against 85% of cephalothin- and gentamicin-resistant Klebsiella pneumoniae isolates.
- Cefoxitin was not degraded by beta-lactamase, unlike cefamandole and cephalothin.
- Cefoxitin exhibited rapid killing of resistant isolates, confirmed by growth curves.
Conclusions:
- Cefoxitin is a promising therapeutic option against multidrug-resistant Klebsiella pneumoniae.
- The mechanism of resistance to cephalothin and cefamandole involves beta-lactamase degradation.
- Cefoxitin's stability against beta-lactamase contributes to its effectiveness against resistant strains.