Ecological disturbances and emergence of resistance in the oral and gastrointestinal microflora after drug exposure

Sammanfattning: Ecological disturbances and emergence of resistance in the oral and gastrointestinal microflora after drug exposure Christina Stark, Division of Oral Microbiology, Department of Immunology, Microbiology, Pathology and Infectious Diseases, Huddinge University Hospital, Karolinska Institute, Stockholm, SwedenThe exposure of antimicrobial agents and antacids may disturb the ecological balance ofthe normal microflora. This influence often leads to decreased colonization resistance dueto repression of sensitive bacteria and selection of resistant bacteria which have acquiredresistance during therapy. The predominant resistant mechanism to B-lactam agents inanaerobic bacteria is production of 13-lactamase, which can be either inducible orconstitutive. The purpose of this investigation was to study ecological disturbances andemergence of resistance in the oral and gastrointestinal normal microflora after exposureof different drugs and its relationship with B-lactamase production.The resistance pattern in the oral and intestinal anaerobic microflora was investigated inoutpatients and hospitalized patients with and without antimicrobial treatment. The oralmicroflora was not resistant to any of the antimicrobial agents tested. The intestinalmicroflora contained a large number of resistant bacteria that mainly belong to theBacteroides fragilis group in both outpatients and hospitalized patients regardless ofprevious treatment with antimicrobial agents. Hospitalization or intake of antimicrobialagents promoted an increase in the relative number of resistant anaerobic microorganismsin the intestinal tract.The relation between B-lactamase activity, drug concentration and ecological disturbanceswas recorded in volunteers perorally treated with amoxicillin and cephalosporins.Administration of amoxicillin resulted in an overgrowth with new amoxicillin-resistantenterobacteria. Administration of cefpodoxime proxetil, ceftibuten, and cefuroxime axetilresulted in moderate ecological disturbances of the intestinal microflora and lead tosignificant increases in 13-lactamase activity and to degradation of the cephalosporins.High B-lactamase activity corresponded to low cephalosporin levels in faeces and tominimal disturbance of the ecology whereas the converse was true for low orundetectable enzyme activities.The ecological effects on the normal oral, gastric and intestinal microflora weredetermined after oral administration of omeprazole in combination with amoxicillin orplacebo in patients with Helicobacter pylori infection. Treatment with omeprazole andamoxicillin caused ecological disturbances in the oral, gastric and intestinal microfloraselected for antibiotic resistant enterococci and enterobacteria and caused an increase in13-lactamase production in the intestinal microflora. Treatment with omeprazole causedecological disturbances in the gastric and intestinal microflora. All isolated H. pyloristrains were susceptible to amoxicillin.The induction ability in anaerobic bacteria was investigated. Anaerobic bacteria were ableto increase the production of B-lactamases after induction with cefoxitin, although to alesser extent than aerobic bacteria. The combination of inducer, inducible strains andfaecal suspension resulted in no or strongly repressed B-lactamase activities.The potential of an antimicrobial agent to have an impact on the normal microflora isrelated to the agent's antibacterial spectrum, route of administration, pharmacokineticproperties and the degree of inactivation in vivo. This should be considered whenantimicrobial agents are used for treatment and prophylaxis of infections.Key words: ecology / antimicrobial resistance / oral / gastrointestinal / microflora /B-lactamase / enzyme induction.ISBN 91-628-1916-X