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Attributable mortality of bacteremia associated with the Bacteroides fragilis group.

Uncontrolled studies have suggested that Bacteroides fragilis group bacteremia has an attributable mortality rate between 13% and 33%. To determine the true attributable mortality rate and the mortality risk ratio associated with bacteremia due to the B. fragilis group, we conducted a matched-pair study in which cases were matched to controls for age, gender, year of admission, principal discharge diagnosis, and types of major surgery by an investigator blinded to survival status. Cases and controls were comparable in demographic and clinical characteristics. Cases had a significantly higher mortality rate (28% vs. 8.7%, P = .002, McNemar's test), with an attributable mortality rate of 19.3% (95% CI, 8%-30%; P = .003) and a mortality risk ratio of 3.2. In a multivariate analysis, three clinical factors were independently correlated with mortality: the presence of B. fragilis group bacteremia (RR: 4.9; 95% CI: 3.7-6.0; P = .009), congestive heart failure (RR: 8.0; 95% CI: 6.6-9.3; P = .003) or chronic liver disease (RR: 6.3; 95% CI: 4.8-7.7; P = .01). Cases also had a 16-day-longer stay in the hospital (P = .0007, Wilcoxon's signed rank test) compared with controls. Thus, B. fragilis group bacteremia contributes significantly to morbidity and mortality.

Bacteremia↗

Enterotoxigenic Bacteroides fragilis.

Enterotoxigenic Bacteroides fragilis (ETBF) has been recently associated with watery diarrheal disease in livestock and young children. These strains of B. fragilis secrete an extracellular heat-labile protein toxin with a mess of approximately 20 kD. This toxin has been shown to have two major biological activities: stimulation of secretion in ligated intestinal segments in lambs and calves and alteration of the morphology of intestinal epithelial cell lines in vitro. In vivo the pathology of animal intestine exposed to an ETBF strain is disruption of the colonic epithelium with rounded, swollen surface epithelial cells. Similarly, in vitro intestinal epithelial cells derived from human colonic carcinomas become rounded and detach from neighboring cells after treatment with the ETBF toxin. These results suggest that the ETBF toxin is a secretory cytoskeleton-altering toxin. However, the contribution of the ETBF toxin to the pathogenesis of ETBF-associated diarrheal disease remains to be determined.

Animals↗

Detection of toxin production by Bacteroides fragilis: assay development and screening of extraintestinal clinical isolates.

Strains of Bacteroides fragilis that produce an extracellular 20-kD heat-labile toxin have been epidemiologically associated with diarrheal disease. To standardize detection of the B. fragilis toxin (BFT), a detailed description of the methods for identifying BFT production by B. fragilis strains is reported. To further study the role of toxigenic strains of B. fragilis in clinical disease, extraintestinal clinical isolates that were recovered at an urban east-cost hospital were evaluated. Four (6.2%) of 65 isolates produced BFT. Three cases in which BFT-producing B. fragilis were isolated from extraintestinal sites are reported. In contrast to studies from Japan that have reported BFT production by 23.4% of extraintestinal B. fragilis isolates, we conclude that BFT-producing strains of B. fragilis are infrequently associated with extraintestinal B. fragilis disease at our institution. Additional study will be necessary to better define the importance of BFT production in human disease due to B. fragilis.

Adult↗

Analysis of trends in antimicrobial resistance patterns among clinical isolates of Bacteroides fragilis group species from 1990 to 1994.

Antimicrobial resistance, including plasmid-mediated resistance, among Bacteroides fragilis group species is well documented. A 5-year (1990-1994) prospective, eight-center survey of 3,177 clinical isolates of Bacteroides species was undertaken to review trends in resistance, using the breakpoints for full and intermediate susceptibility established by the National Committee for Clinical Laboratory Standards. No documented resistance to either metronidazole or chloramphenicol was found in this survey. Among B. fragilis isolates virtually no resistance was seen to imipenem, meropenem, ampicillin/sulbactam, piperacillin/tazobactam, or ticarcillin/clavulanate. Significant increases in resistance among B. fragilis isolates to cefotetan, ceftizoxime, and clindamycin (p < .01) were noted. Resistance to cefoxitin remained unchanged. Among the non-fragilis species of the B. fragilis group, there was virtually no resistance to imipenem, meropenem, chloramphenicol, or metronidazole. The three beta-lactamase inhibitors had increasing levels of resistance, although 95%-98% of strains were susceptible (p < .05). There was a significant decline in cefoxitin, cefmetazole, and clindamycin activity over time against these strains (p <.01). There was a significant (P < .001) increase in geometric mean minimum inhibitory concentration for most drugs and species tested from 1990 to 1994. Clusters in the eight institutions could not account for this rise in resistance. This survey demonstrates that rates of resistance of B. fragilis and non-fragilis species of B. fragilis group are increasing.

Bacteroides↗

Association of enterotoxigenic Bacteroides fragilis with bacteremia.

Polymerase chain reaction (PCR) assay was compared with cell culture assay performed with use of HT29/C1 (human colonic epithelial) cells for identifying strains of enterotoxin-producing Bacteroides fragilis (ETBF) isolated from extraintestinal specimens. A total of 188 unselected strains obtained over 2 years at a central clinical laboratory in Tokyo were tested. Overall, 35 strains (18.6%) were positive by cell culture and PCR assay, 152 strains were negative by both assays, and 1 strain was negative by cell culture assay but positive by the PCR assay; the same results were obtained in repeated assays. Among 64 strains from blood, 18 (28.1%) were ETBF, a rate that was significantly higher (P < .05) than the 17 ETBF (13.7%) among 124 strains from other sites. These results suggest that PCR assay is a simple and reliable tool for detecting ETBF and that enterotoxin may be a virulence factor in bacteremia caused by B. fragilis.

Bacteremia↗

Anaerobic bacteremia.

The results of early studies showed that anaerobes account for 20% of all bacteremias; more-recent data suggest that these organisms account for approximately 4% (0.5%-9%) of bacteremias ( or approximately one case per 1,000 admissions), with variation by geographic location, hospital patient demographics, and especially, patient age. Elderly persons seem to be at increased risk for developing anaerobic bacteremia while young children (2-5 years of age) are at the least risk. Bacteroides fragilis is the most common blood isolate recovered from patients with anaerobic bacteremia; this organism and species of the B. fragilis group account for approximately 55% of anaerobic bacteremias. B. fragilis bacteremia is associated with a mortality of 19%, with a mortality risk of 3.2; a 16-day increase in hospital stay; and often, intra-abdominal disease. Associated risks for mortality include chronic liver disease and congestive heart failure. There is value in performing separate anaerobic blood cultures; clinicians at each institution should determine the prevalence of anaerobic bacteremia and use this information to guide blood-culture practices.

Age Distribution↗

Detection of enterotoxigenic Bacteroides fragilis and its toxin in stool samples from adults and children in Italy.

Stool samples from children and adults with and without diarrhea were examined for the presence of enterotoxigenic Bacteroides fragilis (ETBF) and its enterotoxin. A cytotoxic assay with HT-29 cells followed by neutralization with a hyperimmune antiserum were used to detect B. fragilis enterotoxin. ETBF isolates were recovered from 12% of healthy children and 17% of children with diarrhea (P = .42) and from 15% of healthy adults and 9.4% of adults with diarrhea (P = .31). Fecal B. fragilis enterotoxin was detected in four children (two with diarrhea and two without diarrhea) and in four adults with diarrhea. This study shows that in Italy, the rate of ETBF carriage is high, regardless if diarrhea is present. In some instances, the presence of ETBF is associated with detectable levels of fecal enterotoxin, but the significance of this finding deserves further evaluation.

Adult↗

Antimicrobial resistance in anaerobes.

The development of antibiotic resistance in anaerobic bacteria has a tremendous impact on the selection of antimicrobial agents for empirical therapy. Susceptibility studies have documented the emergence of antimicrobial resistance and indicate distinct differences in resistance patterns related to individual hospitals, geographic regions, and antibiotic-prescribing regimens. Resistance to beta-lactam drugs, clindamycin, tetracyclines, and 5-nitroimidazoles (metronidazole) has been observed. The prime mechanism for resistance to beta-lactam agents is the production of beta-lactamases. Resistance to clindamycin is mediated by modification of the ribosome. Tetracycline resistance is mediated by both tetracycline efflux and ribosomal protection. 5-Nitroimidazole resistance appears to be caused by a combination of decreased antibiotic uptake and decreased nitroreductase activity. The level of chloramphenicol susceptibility remains quite high, whereas uniform resistance to aminoglycosides and quinolones is observed. Understanding the mechanisms of resistance is critical for both informed selection of antimicrobial therapy and the design of new antimicrobial agents.

Bacteria, Anaerobic↗

Polymicrobial osteomyelitis: report of three cases and review of the literature.

Five percent of patients with acute osteomyelitis and 30%-60% of patients with chronic osteomyelitis have polymicrobial infections. Three illustrative cases and a review of the literature involving 104 patients are presented in this report. There were 2.4 isolates per child among the 31 pediatric cases ad 3.9 isolates per adult among the 71 adult cases reviewed. Staphylococcus aureus was the single most common isolate involved in polymicrobial disease in both adults and children. In adults, one-third of the aerobic isolates were gram-negative bacterial species; some enterococci were also involved. Of the isolates from adults, 46% were anaerobic. The number of isolates per case was similar for the acute (3.2) and chronic (3.1) forms of infection. Polymicrobial osteomyelitis resulted most frequently from spread of infection from a contiguous focus (59% of cases) or occurred in the patient with peripheral vascular insufficiency or neuropathy (17% of cases); however, the hematogenous route can produce polymicrobial disease (13% of cases). Bones mot often involved are those of the skull, face, and feet. Standard antibiotic therapy for monomicrobial osteomyelitis with semisynthetic penicillins or cephalosporins may lead to failures of treatment in polymicrobial disease.

Acute Disease↗

Anaerobic bacteria in bone and joint infections.

The etiologic importance of anaerobic microorganisms in bone and joint infections in certain settings has recently been emphasized. These settings include recovery of Actinomyces species, hematogenously acquired infection, the presence of anaerobes in pure culture, and prosthetic-joint infection. Frequently, mixed aerobic-anaerobic bone or joint infection develops as a consequence of infection in adjacent areas. The incidence with which anaerobes are present in these settings is undoubtedly underestimated and may often be unappreciated in regard to the selection of therapeutic agents. Therefore, a practical approach to the treatment of infections involving anaerobes that is based on our current knowledge is necessary. Animal models are now available for study of anaerobic osteomyelitis. In conjunction with prospective human studies utilizing careful microbiologic techniques, it should be possible to determine the significance of anaerobic bacteria when a polymicrobial flora is present in bone and joint infections.

Actinomycosis↗

Anaerobes in burn-wound infections.

Anaerobic bacteria are not routinely considered in discussions of the etiology of burn-wound infection. However, this review of the literature reveals that there are numerous case reports that document clinically significant anaerobic burn-wound infection and some prospective data that suggest a possible role of anaerobes in the clinical setting of burn-wound sepsis. Further studies are needed to answer the questions of how often anaerobes colonize burn wounds and how often anaerobes invade the wounds to cause clinically significant burn-wound sepsis.

Bacteria, Anaerobic↗

Intestinal perforation in typhoid fever: a historical and state-of-the-art review.

The appropriate therapy for intestinal perforation in typhoid fever has been controversial since the late 1880s. Around the turn of the century, surgery became the established mode of therapy, with a mortality of 69% based on 166 patients in the English-language medical literature, and continued to be the preferred treatment until the advent of chloramphenicol in 1948. At this time the surgical mortality was approximately 50%. Following the recovery of a few patients with perforation treated only with antimicrobial agents (six initially, then eventually 22), nonsurgical therapy became the accepted mode of treatment. This change was never justified and this review demonstrates this. Appropriate therapy is virtually always surgical, usually consisting of simple closure and irrigation. Chloramphenicol alone is inadequate antimicrobial therapy in a patient with perforation and must be supplemented by other antimicrobials directed against enteric aerobic gram-negative bacilli and enteric anaerobes.

Anesthesia↗