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Pathogenicity of the Bacteroides Fragilis Group*

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Pathogenicity of the Bacteroides Fragilis Group* ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 19, No. 5 Copyright © 1989, Institute for Clinical Science, Inc. Pathogenicity of the Bacteroides fragilis Group* ITZHAK BROOK, M.D., M.Sc. Departments of Pediatrics and Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-5145 ABSTRACT The Bacteroides fragilis group is one of the most important pathogens in polymicrobial infections. The distribution of the different members of the B. fragilis group in clinical infections varies. Bacteroides fragilis accounts for 63 percent of all the group isolates, Bacteroides thetaiotaomi- cron for 14 percent, Bacteroides vulgatus and Bacteroides ovatus for seven percent each, Bacteroides distasonis for six percent and Bacteroides uniformis for two percent. All members of the group induced bacteremia that was associated with an average mortality of 27 percent. The B. fragilis group resist beta lactam antibiotics by producing the enzyme beta-lacta- mase. This enzyme can be detected in abscess fluid, and can interfere with the eradication of other bacteria that are susceptible to penicillins and cephalosporins. All members of the B. fragilis group can become encapsulated during an inflammatory process as was demonstrated in a subcutaneous abscess model in mice. Non-encapsulated strains can become encapsulated with the assistance of their aerobic counterparts. These encapsulated strains are more virulant to the host than non-encap- sulated strains. This increased virulence can be demonstrated by a higher rate of induction of bacteremia, and a greater enhancement of growth of other bacteria in mixed infection. Antimicrobial therapy directed only at the eradication of the aerobic bacteria did not prevent encapsulation, or reduce the number of Bacteroides species. The virulence of all members of the B. fragilis group highlights the need to direct antimicrobial therapy against all members of this group. Introduction is apparent in the majority of patients, The polymicrobial nature of abdomi­ where the number of isolates in an infec­ nal, pelvic and skin and soft tissue (prox­ tious site varies between 2 and 6 . 14,35 imal to the oral or rectal areas) infections The average number of isolates is 3.6 in skin and soft tissue infections (2 . 6 anaer­ obes and 1 .0 aerobes) per specimen,23,47 * Please send reprint request to Itzhak Brook, M.D., M.Sc., Armed Forces Radiobiology Research five in intraabdominal infection (3.0 Institute, Bethesda, MD 20814-5145. anaerobes and 2 . 0 aerobes) per speci­ 3 60 0091-7370/89/0900-0360 $02.00 © Institute for Clinical Science, Inc. PATHOGENICITY OF THE BACTEROIDES FRAGILIS GROUP 361 m en , 9 and four in pelvic infections (2 .8 TABLE I anaerobes and 1 . 2 aerobes) per speci­ Predominate Isolates at Various Body Sites m en . 66 In some types of infection, poly­ Facultative and microbic infections are known to be Miscellaneous more pathogenic for experimental ani­ Infection Site Anaerobic Bacteria Bacteria mals than those involving single organ­ Skin and B. fragilis group S. aureus isms. 2 subcutaneous (rectal) S. pyogenes wounds and B. melaninogenicus E. coli (rectal) The organisms recovered in polymi­ abscesses group (oral) Enterobacteriaceae crobial infections vary and depend on Abdomen B. fragilis group E. coli the location site and the circumstances peptostreptococcus Other Clostridia Enterobacteriaceae leading to the infection. Most polymicro­ Pelvis B. bivius N. gonorrhoeae bial aerobic-anaerobic infections origi­ B. disiens Streptococci B. fragilis group Chlamydia nate from the mucus flora adjacent to trachomatis the infected site. The recovery of anaer­ Enterobacteriaceae obes in these infections is not surprising since they outnumber aerobic and facul­ tative bacteria in ratios of 1 0 : 1 to reduction potential drop, and the pres­ 1 0 ,0 0 0 :1 in these normal flora sites. 14’35 ence of hemoglobin or blood in an The Bacteroides species predominate in infected site. most polymicrobial infection sites. The This review of our work describes evi­ Bacteroides fragilis group are generally dence supportive of the importance of all isolated in abdominal infections. The members of the Bacteroides fragilis Bacteroides melaninogenicus group and group in mixed infections. It is based on Bacteroides oralis are mainly found in clinical as well as animal studies, show­ oral infections and B. bivius and B. di- ing synergy between the aerobic and siens are most often recovered in pelvic anaerobic bacteria, and the importance infections. 14,35 Enterobacteriaceae are of encapsulation of anaerobic bacteria. predominant in abdominal and rectal infections; staphylococci and streptococci Recovery Rate of B. fragilis G roup in are important in wound and skin and Clinical Specimens subcutaneous tissue abscesses, and Neis­ seria gonorrhoeae and chlamydia are The recovery rate of members of the found in pelvic infections (table I). B. fragilis group varies in different sites. Bacteroides fragilis is one of the most These organisms predominate in abdom­ important pathogens in polymicrobial inal infections and their sequela and in infections. It possesses several virulence skin and soft tissue infections that origi­ factors which facilitate its pathogenicity nate from the gut flora. 14,35 They are less to humans. Included among the factors is frequently isolated in pelvic infections the production of a capsule. In addition and respiratory infections. 35,66 to a capsule, anaerobic bacteria possess The B. fragilis group is comprised of other important virulence factors. These several subspecies that were recently include the production of superoxide elevated to a species level.31 Data pre­ dismutase and catalase, immunoglobulin sented in this review will support the proteases, coagulation-promoting and statement that all of these can participate -spreading factors (such as hyaluroni- in polymicrobial infections and are also dase, collagenase, and fibrinolysin), and capable of causing infections by them­ adherence factors.35 Other factors that selves. enhance the virulence of anaerobes The recovery rate of the different include mucosal damage, oxidation- members of the B. fragilis group varies 362 BROOK in different infection sites. The relative distribution of the different Bacteroides distribution of the different members of species in clinical isolates18 (table III). the B. fragilis group has important clini­ Bacteroides fragilis accounted for 63 cal implications on the management of percent of all B. fragilis group isolates; infections involving anaerobic bacteria. B. thetaiotaomicron for 14 percent; Bac­ This is because of the different antimi­ teroides vulgatus and Bacteroides ovatus crobial susceptibility of the various Bac- for seven percent each; B. distasonis for te r o id e s species. Although most six percent; and Bacteroides uniformis members of B. fragilis groups produce for two percent. The highest frequency beta-lactamase and resist penicillins, of recovery of B. fragilis compared to their susceptibility to second and third other members of B. fragilis group was generation cephalosporins is variable 1 in blood cultures (78 percent of all B. but predictable . 65 W hile B. fragilis is fragilis group isolates), wounds (69 per­ generally the most susceptible, Bacte- cent), abscesses (65 percent), and roides thetaiotaomicron and Bacteroides abdominal infection (59 percent). Bac­ distasonis generally are more resistant. 1 teroides thetaiotaomicron was most fre­ The distribution of the different quently isolated in chest infections (35 members of the B. fragilis group was percent) (data not shown in table III), illustrated in three recent studies of cysts (22 percent), and tumors (19 per­ intraabdominal infections9,38,64 (table II). cent). Bacteroides vulgatus was mostly Among the B. fragilis group, B. fragilis recovered from pelvic infections (2 0 per­ accounted for 40 percent to 57 percent of cent), and B. ovatus from bile infections the Bacteroides isolates recovered from (19 percent), B. distasonis from pelvic intraabdominal infections. However, ( 1 0 percent) and abdominal infections another important pathogen that belongs (nine percent), and B. uniformis in to the B. fragilis group is B. thetaiotao­ wounds (three percent). micron, which accounts for 13 percent to The incidence of recovery of the dif­ 23 percent of the isolates; other ferent members of the B. fragilis group members of the B. fragilis group account in Walter Reed Army Hospital and Navy for a total of 23 percent to 37 percent. Hospital varied. Of the total of 800 iso­ A review of 12 years experience (1973 lates of B. fragilis, 183 (23 percent) were to 1985) of the Walter Reed Army Medi­ recovered in abscesses, 153 (19 percent) cal Center in Washington, DC and the in wounds, 139 (17 percent) in abdomen, Navy Hospital in Bethesda, MD 129 (16 percent) in blood, and 103 (13 revealed certain trends regarding the percent) in pelvic infections. Of 181 iso­ lates of B. thetaiotaomicron, 42 (23 per­ TABLE II cent) were isolates in abscesses, 34 (18 Percent Recovery of 8. Group percent) each in abdomen and wounds, from Various Infections 23 (13 percent) in blood, 13 (seven per­ S u t t e r e t a i * B r o o k f cent) in pelvic infections, and 1 2 (seven (185 Abdominal (97 Abdominal H e s e l t i n e i Isolates) Isolates) (270 Isolates) percent) in chest infections. Of 92 iso­ (percent) (percent) (percent) lates of B. vulgatus, 36 (39 percent) were recovered in pelvic infections, 18 ( 2 0 B. fragilis 40 56 57 S. thetaiotaomicron 23 13 20 percent) in abdomen, and 13 (14 per­ B. vulgatus 7 8 B. uniformis 10 2 cent) in abscesses. Of 8 6 B. ovatus, 26 B. distasonis -37 3 8 B. o v a t u s 10 5 (30 percent) were found in abscesses, 22 (26 percent) in abdomen and nine each * Wadsworth Bacteriology Manual, 4th ed. Star Publishing Company, Belmont, CA 1985, pp. 8-9. ( 1 0 percent) in pelvic infections and t Ann. Surg. 192:208-212, 1980. i Rev. Infect. Dis. 6:S254-S259, 1984. wounds. Of 81 B.
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