title: Beta-lactamase production, beta-lactam sensitivity and resistance to synergy with clavulanate of 737 Bacteroides fragilis group organisms from thirty-three US centres.
abstract: Beta-Lactamase production and agar dilution sensitivities to amoxycillin, amoxycillin/clavulanate, ticarcillin, ticarcillin/clavulanate, cefoxitin, imipenem and metronidazole were determined for 737 Bacteroides fragilis group strains isolated between 1986 and 1988 from 33 US centres. The strains comprised 441 B. fragilis, 114 B. thetaiotaomicron, 35 B. ovatus, 58 B. distasonis, 58 B. vulgatus, 26 B. uniformis and five B. caccae. Overall, addition of clavulanate lowered the geometric mean MICs of of amoxycillin from 46.7 to 0.6 mg/l, and of ticarcillin from 37.2 to 1.3 mg/l. Addition of clavulanate increased the number of strains sensitive to amoxycillin from 9.5% to 90.0%, and to ticarcillin from 68.0% to 98.6%. However, synergy was not observed following addition of clavulanate to amoxycillin and ticarcillin for 48 strains (6.5%). These comprised 15 B. fragilis, two B. ovatus, 21 B. distasonis, six B. vulgatus and four B. uniformis strains. Ten of the 15 non-synergic B. fragilis isolates had the features of B. fragilis homology group II and were susceptible to amoxycillin alone; the other five strains were resistant to amoxycillin and ticarcillin. Geometric mean MICs (% susceptibility) of the non-synergic strains were as follows: amoxycillin, 6.2 mg/l (68.8); amoxycillin/clavulanate, 4.8 mg/l (72.9); ticarcillin, 11.8 mg/l (75.0); ticarcillin/clavulanate, 9.4 mg/l (77.1). Twenty-six strains (3.5% were resistant (greater than 32 mg/l) to cefoxitin, and two strains (0.3%) were resistant (4 mg/l) to imipenem. All were susceptible to metronidazole. Thus, on the basis of in-vitro activity, metronidazole, imipenem, ticarcillin/clavulanate, cefoxitin and amoxycillin/clavulanate are indicated for treatment of infections with B. fragilis strains. The clinical significance of the lack of synergy with clavulanate in the B. fragilis group is unclear; relatively low beta-lactam MICs for most of these strains suggests that they may be amenable to therapy with high doses of beta-lactams. Results of this study indicate that it cannot be assumed that clavulanate will uniformly inhibit beta-lactamases in the B. fragilis group (especially B. distasonis) and indicate the need for identification and susceptibility testing, especially in cases of serious infections with these strains.
authors.affiliation: Department of Pathology (Clinical Microbiology), Case Western Reserve University, Cleveland, OH.
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobs
authors.forename: S K
authors.initials: SK
authors.lastname: Spangler
authors.forename: P C
authors.initials: PC
authors.lastname: Appelbaum
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology*; D019980:Amoxicillin-Potassium Clavulanate Combination; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001441:Bacteroides fragilis / Q000187:drug effects* / Q000201:enzymology; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013045:Species Specificity; D014481:United States; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D019818:Clavulanic Acid; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin; D001618:beta-Lactamases