Susceptibility Bacteroides fragilis to fusidic acid.
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The new fluorinated 4-quinolone temafloxacin was compared with cefoxitin, clindamycin, imipenem (with or without cilastatin) and ampicillin/sulbactam in a mouse subcutaneous abscess model of Bacteroides fragilis infection. Based upon in-vitro susceptibility data, temafloxacin may represent an effective oral and parenteral alternative to standard oral and parenteral anti-anaerobic agents currently in use. Temafloxacin therapy with dosage regimens of < 200 mg/kg/day typically yielded 2-3 x log10 reductions in cfu/abscess, similar to ampicillin/sulbactam, while cefoxitin and clindamycin were generally unable to produce similar reductions at doses up to 400 mg/kg/day. Imipenem (with or without cilastatin) was unable to produce a 1 x log10 reduction at doses of 400 mg/kg/day. This study suggests that temafloxacin has potential for the treatment of anaerobic or mixed aerobic-anaerobic infections in man.
Using a rat model of intraperitoneal abscess due to Bacteroides fragilis, we evaluated therapy with the combination of ceftriaxone plus the beta-lactamase inhibitor tazobactam in comparison with ceftriaxone or cefotaxime alone. When treatment was begun five hours after bacterial challenge, final bacterial counts within abscesses at 3.5 days of treatment were as follows (mean +/- S.D., log10 cfu/g): ceftriaxone plus tazobactam, 4.15 +/- 1.25; cefotaxime, 4.77 +/- 1.80; ceftriaxone alone, 5.68 +/- 1.04; untreated controls, 9.14 +/- 1.13. In spite of pharmacokinetic differences between the two drugs, coadministration of tazobactam significantly enhanced activity of ceftriaxone in this model.
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The epidemiology of antimicrobial resistance of clinical isolates and human intestinal strains of Bacteroides fragilis has assumed great importance in the last few years since this microorganism, like other members of the B. fragilis group, can be responsible for the spread of resistance determinants. It is possible that the presence of B. fragilis in polluted aquatic environments might contribute to the spread of resistance. The antimicrobial resistance profile of 44 clinical B. fragilis strains isolated from 1981-1988 and 1991-1998 from the University hospital of Rio de Janeiro, and of 17 faecal and 17 polluted aquatic environmental B. fragilis strains isolated between 1991 and 1998 was determined. The susceptibility tests against penicillin, cefoxitin, imipenem, meropenem, clindamycin, chloramphenicol and metronidazole were performed by Etest in Wilkins-Chalgren agar enriched with 5% sheep blood. Motivated by some high MIC values for cefoxitin and meropenem, the cfiA gene, which codes for a metallo-beta-lactamase, was investigated among all strains, using PCR amplification. The resistance to penicillin was high in the samples from 1981 to 1988 (92.9%) and also in those from 1991 to 1998 (100%), although the MIC90 decreased from 256 mg/L to 24 mg/L. An increase in the resistance level to clindamycin and cefoxitin was seen from one decade to the other, the MIC90 values changing from 4 mg/L to 12 mg/L and from 8 mg/L to 32 mg/L, respectively. The susceptibility profile for metronidazole, chloramphenicol, imipenem and meropenem remained stable, although two clinical strains showed MICs of 6 mg/L and 8 mg/L against meropenem. Almost all human intestinal strains were resistant to penicillin and all of them were susceptible to imipenem, meropenem, chloramphenicol and metronidazole. The MICs of meropenem against two strains isolated from a polluted aquatic environment were 6 mg/L and 32 mg/L. The cfiA gene was detected in five strains, two of which were isolated from clinical specimens against which the MIC values of cefoxitin were high and three from an aquatic environment, whose susceptibility to both cefoxitin and meropenem ranged from sensitive to resistant.
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OBJECTIVES: The aim of the present study was to determine correlation between bmeB efflux pump overexpression and resistance to fluoroquinolones and beta-lactams in Bacteroides fragilis clinical isolates (n = 51) and the effects of broad-spectrum efflux pump inhibitors (EPIs) on the MICs of the test antibiotics. METHODS: Susceptibility to garenoxacin, levofloxacin, moxifloxacin, cefoxitin and faropenem +/- EPIs (CCCP, MC-207,110, reserpine and verapamil) was determined. Expression of bmeB efflux pumps was measured, topoisomerase genes were sequenced and beta-lactamase production was determined. RESULTS: Isolates were grouped into categories based on susceptibility patterns, topoisomerase sequence and efflux pump expression. Panel I isolates (19/51, 37.3%) were highly resistant to fluoroquinolones and cefoxitin (resistance to all agents was significantly reduced by EPIs, P < 0.05), had a point mutation in gyrA (C-->T) causing a Ser-82-->Phe substitution, and overexpressed bmeB4 and bmeB15. Panel II isolates (7/51; 13.7%) had intermediate-level resistance to fluoroquinolones and cefoxitin and a GyrA substitution. Panel IIIA isolates (21/51; 41.2%) had intermediate-level fluoroquinolone resistance and high-level cefoxitin resistance [resistance to all agents was significantly reduced by EPIs (P < 0.05)] and overexpressed bmeB4 and bmeB15. Panel IIIB isolates (4/51; 7.8%) had low-level fluoroquinolone resistance and high-level resistance to cefoxitin [cefoxitin resistance was significantly reduced by EPIs (P < 0.05)] and overexpressed bmeB4, bmeB6, bmeB10 and bmeB14. All isolates were beta-lactamase-positive. CONCLUSIONS: These data suggest that bmeB efflux pump overexpression can (i) cause low- to intermediate-level clinically relevant fluoroquinolone resistance; (ii) be coupled with GyrA substitutions to cause high-level fluoroquinolone resistance; (iii) contribute to high-level clinically relevant resistance to beta-lactams.
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Eleven patients with serious infections involving anaerobic bacteria were treated with carbenicillin (four patients) or ticarcillin (seven patients). All patients were cured clinically and bacteriologically of their infections. An in vitro study testing 157 recently isolated anaerobic organisms against 11 antibiotics showed chloramphenicol, carbenicillin, and ticarcillin at blood level concentrations to be inhibitory to more anaerobic strains than the other eight antibiotics tested. Ticarcillin and carbenicillin appear to be safe and effective and deserve further consideration for use in the therapy of anaerobic infections.
A case of anaerobic hepatic abscess (Bacteroides fragilis), which initially was imaged as a cold defect on Ga-67 citrate scintigraphy and, following percutaneous drainage, became Ga avid, is presented. Proposed mechanisms for this occurrence are given.
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Indium-111 WBC imaging of a patient with occult septicemia revealed a large focal pattern of radiopharmaceutical distribution within the abdominal cavity at 24 hours post radiopharmaceutical administration. This finding was felt to represent a large intra-abdominal abscess. A five liter peritoneal abscess was found at surgery. This case illustrates an unusual presentation of an intra-abdominal abscess.
A young man with severe nephrotic syndrome and symptoms suggestive of peptic ulcer disease treated with steroids developed symptoms and signs of peritonitis and pneumoperitoneum. Laparotomy and ascitis fluid culture revealed B. fragilis peritonitis without any perforation, suggesting a diagnosis of spontaneous primary peritonitis.