Advertisement

Drugs

, Volume 29, Supplement 5, pp 49–56 | Cite as

Temocillin

In Vitro Antibacterial Activity
  • B. Slocombe
  • C. E. Cooper
  • K. E. Griffin
  • A. R. White
Section 1: The Microbiology of Temocillin

Summary

Temocillin, a 6-α-methoxy penicillin derivative, was tested in vitro against 516 recent clinical isolates of Enterobacteriaceae. The compound exhibited good antibacterial activity, with 95% of isolates inhibited by a range 2 to 16 mg/L. Further studies, against selected isolates resistant to ticarcillin, piperacillin and cefuroxime (Klebsiella oxytoca, 25; Enterobacter species, 34; and Citrobacter species, 5), showed about half of the isolates of K. oxytoca (11/25) to be resistant to aztreonam (MIC range 16-⩾128 mg/L), but susceptible to temocillin, cefotaxime and latamoxef In general, the resistant strains of Enterobacter species tested were not susceptible to cefotaxime (MIC range 16–128 mg/L), or aztreonam (MIC range 1.0–64 mg/L), and many exhibited reduced susceptibility to latamoxef (MIC range 2–128 mg/L). In contrast, all the strains were susceptible to temocillin (MIC range 4–16 mg/L).

The bactericidal activity of temocillin was confirmed against selected aztreonam-resistant strains of K. oxytoca and Enterobacter cloacae by conventional time-kill studies, and against a strain of E. cloacae in an in vitro model system designed to simulate the temocillin concentration profiles attained in extravascular fluid such as peripheral lymph. In the time-kill studies, temocillin concentrations of 16 and 32 mg/L were shown to effectively reduce the numbers of viable bacteria by 99 and 99.9%, respectively, within 12 hours. In the in vitro model system the numbers of bacteria were reduced 99.9% over the initial 4-hour period.

In combination with aminoglycoside antibiotics, temocillin exerted a synergistic or partially synergistic effect (∑FIC ⩽ 0.75) against the majority of strains of Pseudomonas aeruginosa tested. When combined with piperacillin, cefotaxime or latamoxef, temocillin, unlike cefoxitin, exhibited no antagonism against strains of Enterobacteriaceae producing inducible cephalosporinases.

Keywords

Cefotaxime Piperacillin Cefoxitin Minimum Inhibitory Concentration Aztreonam 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bergan, T.; Engeset, A. and Olszewski, W.: Temocillin in peripheral lymph. Journal of Antimicrobial Chemotherapy 12: 59–63 (1983).PubMedCrossRefGoogle Scholar
  2. Brown, R.M.; Wise, R. and Andrews, J.M.: Temocillin, in vitro activity and the pharmacokinetics and tissue penetration in healthy volunteers. Journal of Antimicrobial Chemotherapy 10: 295–302 (1982).PubMedCrossRefGoogle Scholar
  3. Edmondson, R.A. and Reading, C.: β-Lactamase stability of temocillin. Drugs 29(Suppl. 5): 64–66 (1985).PubMedCrossRefGoogle Scholar
  4. Goering, R.V.; Sanders, C.C. and Sanders, W.E. Jr: Antagonism of carbenicillin and cefamandole by cefoxitin in treatment of experimental infections in mice. Antimicrobial Agents and Chemotherapy 21: 963–967 (1982).PubMedCrossRefGoogle Scholar
  5. Grasso, S.; Meinardi, G.; de Carneri, I. and Tamassion, V.: New in vitro model to study the effect of antibiotic concentrations and rate of elimination on antibacterial activity. Antimicrobial Agents and Chemotherapy 13: 570–576 (1978).PubMedCrossRefGoogle Scholar
  6. Jules, K. and Neu, H.C.: Antibacterial activity and β-lactamase stability of temocillin. Antimicrobial Agents and Chemotherapy 22: 453–460 (1982).PubMedCrossRefGoogle Scholar
  7. Krogstad, D.J. and Moellering, R.C.: Combinations of antibiotics; Mechanisms of interaction against bacteria; in Lorian (Ed.) Antibiotics in Laboratory Medicine, pp.298–341 (Williams and Wilkins, Baltimore/London 1980).Google Scholar
  8. Kuck, N.A.; Testa, R.T. and Forbes, M.: In vitro and in vivo antibacterial effects of combinations of beta-lactam antibiotics. Antimicrobial Agents and Chemotherapy 19: 634–638 (1981).PubMedCrossRefGoogle Scholar
  9. Murray, P.R.; Granich, G.G.; Krogstad, D.J. and Niles, A.C.: In vivo selection of resistance to multiple cephalosporins by Enterobacter cloacae. Journal of Infectious Diseases 147: 490 (1983).Google Scholar
  10. Phillips, I.; King, A.; Shannon, K. and Warren, C.: Temocillin (BRL 17421): In vitro antibacterial activity and susceptibility to β-lactamases. Journal of Antimicrobial Chemotherapy 10: 271–278 (1982).PubMedCrossRefGoogle Scholar
  11. Sanders, C.C. and Sanders Jr, W.E.: Emergence of resistance during therapy with the newer β-lactam antibiotics: Role of inducible β-lactamases and implications for the future. Review of Infectious Diseases 5: 639–648 (1983).CrossRefGoogle Scholar
  12. Sanders, C.C.; Sanders Jr, W.E. and Goering, R.V.: In vitro antagonism of β-lactam antibiotics by cefoxitin. Antimicrobial Agents and Chemotherapy 21: 968–975 (1982).PubMedCrossRefGoogle Scholar
  13. Slocombe, B.; Basker, M.J.; Bentley, P.H.; Clayton, J.P.; Cole M.; Comber, K.R.; Dixon, R.A.; Edmondson, R.A.; Jackson, D.; Merrikin, D.J. and Sutherland, R.: BRL 17421, a novel β-lactam antibiotic, highly resistant to β-lactamases, giving high and prolonged serum levels in humans. Antimicrobial Agents and Chemotherapy 20: 38–46 (1981).PubMedCrossRefGoogle Scholar
  14. Sykes, R.B.; Bonner, D.P.; Bush, K. and Georgopapadakou, N.H.: Aztreonam (SQ 26776), a synthetic monobactam specifically active against aerobic Gram-negative bacteria. Antimicrobial Agents and Chemotherapy 21: 85–92 (1982).PubMedCrossRefGoogle Scholar

Copyright information

© ADIS Press Limited 1985

Authors and Affiliations

  • B. Slocombe
    • 1
  • C. E. Cooper
    • 1
  • K. E. Griffin
    • 1
  • A. R. White
    • 1
  1. 1.Beecham Pharmaceuticals Research DivisionBetchworthEngland

Personalised recommendations