Drugs

, Volume 35, Supplement 2, pp 35–40 | Cite as

Evaluation of Bactericidal Activity of Cefotaxime and Other β-Lactams by a Novel Method

  • Giuseppe Satta
  • Giuseppe Cornaglia
  • Pietro Canpari
  • Raffaello Pompei
Section 1: The Current Situation on Bacterial Resistance to Third Generation Cephalosporins

Summary

In previous studies on Streptococcus faecium we proposed that the minimum β-lactam concentration killing 99.9% of a bacterial population within 3 hours be defined as the minimum directly bactericidal concentration (MDBC) of that drug. In the present study we first evaluated the kinetics of cellular killing by various β-lactams as related to penicillin-binding-protein (PBP) binding in Escherichia coli DC2, a hyperpermeable mutant. We concluded that in E. coli the MDBC for β-lactams coincides with the minimum concentration capable of saturating PBPs 1b, 2 and 3. Of the antibacterial drugs we studied, cefsulodin, meciliinam and aztreonam had a much greater affinity for one essential PBP (PBP 1b, 2 and 3, respectively) than for all others, whereas cefotaxime had close affinities for all the above PBPs. MDBC values of >500, 500, >50, Wand 1.5 mg/L were obtained for cefsulodin, meciliinam, aztreonam, ampicillin and cefotaxime, respectively. On the basis of the pharmacokinetic properties of these drugs, our results indicate that meciliinam, ampicillin and cefsulodin may be bactericidal in urine but not at other body sites; aztreonam is probably bactericidal in urine and blood, but not elsewhere; and cefotaxime is bactericidal in all the biological fluids we studied.

Keywords

Bactericidal Activity Cefotaxime Minimum Concentration Body Site Aztreonam 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Clark D. Permeability and susceptibility of Escherichia coli to beta-lactam compounds. Antimicrobial Agents and Chemotherapy 19: 369–370, 1981PubMedCrossRefGoogle Scholar
  2. Grasso S, Meinardi G, De Carneri I, Tamassia V. New in vitro model to study the effect of antibiotic and rate of elimination on antibacterial activity. Antimicrobial Agents and Chemotherapy 13: 570–576, 1978PubMedCrossRefGoogle Scholar
  3. Hayes MV, Ward GB. The role of penicillin-binding proteins in the antibacterial activity of beta-lactam antibiotics. In Lorian (Ed.) Antibiotics in laboratory medicine, pp. 722–756, Williams & Wilkins, Baltimore, 1986Google Scholar
  4. Jones RN, Barry AL, Gavan TL, Washington II GA. Susceptibility tests: microdilution and macrodilution broth procedures. In Lennette et al. (Eds) Manual of clinical microbiology, pp. 972–977, American Society for Microbiology, Washington DC. 1985Google Scholar
  5. Lleo’ MM, Canepari P, Cornaglia G, Fontana R, Satta G. Evidence that bacteriostatic and bactericidal activities of beta-lactams against Streptococcus (Enterococcus) faecium are associated with saturation of different penicillin-binding proteins. Antimicrobial Agents and Chemotherapy 31: 1625–1633, 1987Google Scholar
  6. Schoenknecht FD, Sabath LD & Thornsberry C. Susceptibility tests: special tests. In Lennette et al. (Eds) Manual of clinical microbiology, pp. 1000–1008, American Society for Microbiology, Washington DC, 1985Google Scholar
  7. Thrupp LD. Susceptibility testing of antibiotics in liquid media. In Lorian (Ed.) Antibiotics in Laboratory Medicine, pp. 93–150, Williams & Wilkins, Baltimore, 1986Google Scholar

Copyright information

© ADIS Press Limited 1988

Authors and Affiliations

  • Giuseppe Satta
    • 1
  • Giuseppe Cornaglia
    • 2
  • Pietro Canpari
    • 2
  • Raffaello Pompei
    • 3
  1. 1.Istituto di Microbiologia dell’ Università di SienaSienaItaly
  2. 2.Istituto di Microbiologia dell’Università di VeronaVeronaItaly
  3. 3.Istituto di Microbiologia dell’Università di CagliariCagliariItaly

Personalised recommendations