Development of resistance to beta-lactam antibiotics with special reference to third-generation cephalosporins

Insights

Mechanisms of bacterial resistance to cephalosporins involve outer membrane changes, beta-lactamase production, and altered penicillin-binding proteins. Resistance rates in Parisian hospitals were low for Enterobacteriaceae but higher for Pseudomonas species.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Beta-lactam antibiotics, including third-generation cephalosporins, are crucial for treating bacterial infections.
  • Bacterial resistance to antibiotics poses a significant public health threat.
  • Understanding resistance mechanisms is vital for effective antimicrobial therapy.

Purpose of the Study:

  • To review the mechanisms of bacterial resistance to third-generation cephalosporins.
  • To outline the prevalence of specific resistance mechanisms in Gram-negative and Gram-positive bacteria.
  • To report the frequency of resistance in clinical settings.

Main Methods:

  • Literature review of resistance mechanisms: outer membrane permeability, beta-lactamase production, and penicillin-binding protein (PBP) alterations.
  • Analysis of resistance prevalence related to specific bacterial types (Gram-negative vs. Gram-positive).
  • Data compilation on resistance frequency in two Parisian hospitals in 1983.

Main Results:

  • Resistance mechanisms include changes in outer membrane permeability, beta-lactamase production, and PBP modification.
  • Gram-negative bacteria often exhibit resistance via membrane permeability and chromosome-mediated beta-lactamases.
  • Gram-positive bacteria commonly show PBP-related resistance.
  • In 1983 Parisian hospitals, overall resistance to third-generation cephalosporins was under 2% in Enterobacteriaceae but approached 15% in Pseudomonas species.

Conclusions:

  • Outer membrane permeability, beta-lactamase activity, and PBP alterations are key cephalosporin resistance mechanisms.
  • Prevalence of these mechanisms differs between Gram-negative and Gram-positive bacteria.
  • Clinical resistance rates, exemplified by Pseudomonas, highlight the need for ongoing surveillance.

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