Synergism of trimethoprim and ciprofloxacin in vitro against clinical bacterial isolates

  • P. Huovinen
  • J. S. Wolfson
  • D. C. Hooper


For the first time, the effects of combinations of trimethoprim and a fluoroquinolone (ciprofloxacin) against gram-positive and gram-negative bacterial isolates were evaluated in vitro. Synergism was found in 31 % (fractional inhibitory concentration, FIC) and 33 % (fractional bactericidal concentration, FBC) of 121 clinical isolates of various bacterial strains, most often inEscherichia coli, staphylococci, and enterococci. Antagonism occurred in 1 % (FIC) and 3 % (FBC). The combination of trimethoprim and ciprofloxacin merits further evaluation for potential usefulness as a clinical regimen.


Internal Medicine Bacterial Strain Inhibitory Concentration Clinical Isolate Fluoroquinolone 


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  1. 1.
    Huovinen P: Minireview. Trimethoprim resistance. Antimicrobial Agents and Chemotherapy 1987, 31: 1451–1456.PubMedGoogle Scholar
  2. 2.
    Wolfson JS, Hooper DC: Fluoroquinolone antimicrobial agents. Clinical Microbiology Reviews 1989, 2: 378–424.PubMedGoogle Scholar
  3. 3.
    Heikkilä E, Renkonen O-V, Sunila R, Uurasmaa P, Huovinen P: The emergence and mechanisms of trimethoprim resistance inEscherichia coli isolated in outpatients in Finland. Journal of Antimicrobial Chemotherapy 1990, 25: 275–283.PubMedGoogle Scholar
  4. 4.
    Hooper DC, Wolfson JS, Souza KS, Ng EY, McHugh GL, Swartz MN: Mechanisms of quinolone resistance inEscherichia coli: characterization ofnfxB andcfxB, two mutant resistant loci decreasing norfloxacin accumulation. Antimicrobial Agents and Chemotherapy 1989, 33: 283–290.PubMedGoogle Scholar
  5. 5.
    Kotilainen P, Nikoskelainen J, Huovinen P: Emergence of ciprofloxacin-resistant coagulase-negative staphylococcal skin flora in immunocompromised patients receiving ciprofloxacin. Journal of Infectious Diseases 1990, 161: 41–44.PubMedGoogle Scholar
  6. 6.
    Schaefler S: Methicillin-resistant strains ofStaphylococcus aureus resistant to quinolones. Antimicrobial Agents and Chemotherapy 1989, 27: 335–336.Google Scholar
  7. 7.
    Shalit I, Berger SA, Gorea A, Frimerman H: Wide-spread quinolone resistance among methicillin-resistantStaphylococcus aureus isolates in a general hospital. Antimicrobial Agents and Chemotherapy 1989, 33: 593–594.PubMedGoogle Scholar
  8. 8.
    Hallander HO, Dornbusch K, Gezelius L, Jacobson K, Karlsson I: Synergism between aminoglycosides and cephalosporins with antipseudomonal activity. Antimicrobial Agents and Chemotherapy 1982, 22: 743–752.PubMedGoogle Scholar
  9. 9.
    Wolfson JS, Hooper DC, Ng EY, Souza KS, McHugh GL, Swartz MN: Antagonism of wild-type and resistantEscherichia coli and its DNA gyrase by the tricyclic 4-quinolone analogs ofloxacin and S-25930 stereoisomers. Antimicrobial Agents and Chemotherapy 1987, 31: 1861–1863.PubMedGoogle Scholar
  10. 10.
    Gellert M, Mizuuchi K, O'Dea MH, Itoh T, Tomizawa JI: Nalidixic acid resistance. A second genetic character involved in DNA gyrase activity. Proceedings of the National Academy of Sciences of the USA 1977, 74: 4772–4776.PubMedGoogle Scholar
  11. 11.
    Eliopoulos GM, Eliopoulos CT: Ciprofloxacin in combination with other antimicrobials. American Journal of Medicine 1989, 87, Supplement 5A: 17–22.CrossRefGoogle Scholar
  12. 12.
    Bertolini A, Castelli M, Genedani S, Garuti M: Trimethoprim enhances the antibacterial activity of nalidixic acid and oxolinic acid and delays the emergence of resistance. Experientia 1980, 36: 243–244.CrossRefPubMedGoogle Scholar
  13. 13.
    Genedani S, Castelli M, Foresta P, Bertolini A: Oxolinic acid — trimethoprim combination: effects on DNA synthesis and on viability ofEscherichia coli. Chemotherapy 1983, 29: 24–27.PubMedGoogle Scholar

Copyright information

© Friedr. Vieweg & Sohn Venlagsgesellschaft mbH 1992

Authors and Affiliations

  • P. Huovinen
    • 1
    • 2
  • J. S. Wolfson
    • 1
    • 2
    • 3
  • D. C. Hooper
    • 3
  1. 1.Department of Medical MicrobiologyTurku UniversityTurkuFinland
  2. 2.Antimicrobial Research UnitNational Public Health InstituteTurkuFinland
  3. 3.Infectious Disease Unit, Medical ServicesMassachusetts General HospitalBostonUSA

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