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Synergistic interaction between ofloxacin and cefotaxime against common clinical pathogens

Synergistische Interaktion zwischen Ofloxacin und Cefotaxim gegen häufige Erreger von Krankenhausinfektionen

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Summary

Antimicrobial synergy resulting from combined antibiotic therapy is often important in the treatment of serious bacterial infections. To investigate the interactions between cefotaxime (CTX), desacetylcefotaxime (DES), and ofloxacin (OFL), 247 recent clinical isolates were tested forin vitro susceptibility to each antibiotic alone by an agar dilution technique and retested with the various antibiotic combinations using a checkerboard protocol. Fractional inhibitory concentrations were calculated for all organisms with all drug combinations. Time kill kinetic studies were performed on selected isolates to examine the bactericidal activity of the various antimicrobial combinations. Of the 110 gramnegative organisms tested, synergy or partial synergy between CTX, DES and OFL was demonstrable for 89 (81%). Included in the study were 70 members of the Enterobacteriaceae family, 20 isolates ofPseudomonas aeruginosa, 10 strains ofAcinetobacter baumannii, and 10 isolates ofXanthomonas maltophilia. Additive activity was observed against an additional 13 (11%) isolates. Findings were similar for the 89 gram-positive isolates examined. Organisms tested included methicillin-resistantStaphylococcus aureus (20), methicillin-susceptibleStaphylococcus aureus (20), methicillin-resistantStaphylococcus epidermidis (9), methicillin-susceptibleS. epidermidis (10),Enterococcus faecalis (10), andStreptococcus pneumoniae (20). Synergy or partial synergy was observed against 81 (91%). Less synergistic activity was detected, however, with members of theBacteroides fragilis group. Of the 48 organisms tested, synergy or partial synergy was noted for only 27 (57%). Isolates representative of each major group of organisms included in the study were tested to determine whether synergistic bactericidal activity was also demonstrable with the three drugs. Time kill studies supported the checkerboard results. Enhanced bactericidal activity was evident with the combination of CTS, DES, and OFL against each isolate tested. Antagonism was not demonstrable with any organism examined. Results from this investigation indicate that cefotaxime and ofloxacin in combination are synergisticin vitro against most commonly encountered clinical pathogens. How thisin vitro interaction translates into clinical utility remains to be determined in additional clinical trials.

Zusammenfassung

In der Behandlung schwerer bakterieller Infektionen hat die synergistische Wirkung kombinierter Antibiotikatherapieschemata oft große Bedeutung. Um die Interaktion zwischen Cefotaxim, Desacetylcefotaxim und Ofloxacin zu beurteilen, wurden 247 frische klinische Isolate auf ihreIn-vitro Empfindlichkeit gegen jedes der Antibiotika allein im Agardilutionstest geprüft und anschließend die Testung mit dem Checkerboard-Protokoll für alle Antibiotikakombinationen vorgenommen. Die fraktionierte inhibitorische Konzentration wurde für alle Isolate mit allen Antibiotikakombinationen bestimmt. Die Abtötungsstudien wurden mit ausgewählten Isolaten vorgenommen, um die bakterizide Aktivität der verschiedenen Kombinationen zu prüfen. Ein Synergismus zwischen Cefotaxim, Desacetylcefotaxim und Ofloxacin fand sich bei 69 der 110 geprüften gramnegativen Isolate (81). In die Studie wurden 70Enterobacteriaceae, 20 Isolate vonPseudomonas aeruginosa, 10 Stämme vonAcinetobacter baumannii, und 10 Isolate vonXanthomonas maltophilia aufgenommen. Gegen weitere 13 Isolate (11%) fand sich eine additive Wirkung. Die Befunde für die 89 grampositiven Isolate waren ähnlich, die geprüften Erreger schlossen methicillinresistente (20) und methicillinempfindliche (20) Stämme vonStaphylococcus aureus, methicillinresistente (9) und methicillinempfindliche (10) Stämme vonStaphylococcus epidermidis ein,Enterococcus faecalis (10) undStreptococcus pneumoniae (20) Synergismus oder partieller Synergismus fand sich nur bei 27 (57%) dieser Isolate. Repräsentative Isolate aller größeren Erregergruppen, die in die Studie eingeschlossen wurden, wurden auf synergistische bakterizide Wirkung der drei Antibiotika getestet. Abtötungsstudien bestätigten die Checkerboard-Werte. Eine erhöhte baterizide Aktivität fand sich mit der Kombination von Cefotaxim, Desacetylcefotaxim und Ofloxacin gegen alle geprüften Isolate. Keiner der Erreger ließ einen Antagonismus erkennen. Die Ergebnisse dieser Untersuchung sprechen dafür, daß Cefotaxim und Ofloxacin in Kombinationin vitro synergistisch gegen die meisten häufigen klinischen Isolate wirken. Jedoch muß durch klinische Studien zusätzlich geprüft werden, ob dieseIn vitro-Interaktion von klinischem Nutzen ist.

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Authors and Affiliations

  1. University of Florida Health Science Center, 653 West Eighth Street, 32209-6597, Jacksonville, Florida, USA

    S. G. Jenkins Ph. D.

  2. University Medical Center, 655 West Eighth Street, 32209-6597, Jacksonville, Florida, USA

    Julia W. Lewis B. S.

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  1. S. G. Jenkins Ph. D.
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Jenkins, S.G., Lewis, J.W. Synergistic interaction between ofloxacin and cefotaxime against common clinical pathogens. Infection 23, 154–162 (1995). https://doi.org/10.1007/BF01793856

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