J. Med Microbiol. - Vol. 45 (1996), 21-26
`0 1996 The Pathological Society of Great Britain and Ireland
`
`CLINICAL M ICROB IOLOGY
`
`Isolation of non-sporing anaerobic rods from
`infections in children
`
`I. BROOK*
`
`Department of Pediatrics, Georgetown University School of Medicine, Washington DC, USA
`
`From 1974 to 1994, 2033 microbiological specimens from children were submitted for
`cultures for anaerobic bacteria. Fifty-seven
`isolates of Bifdobacterium spp. were
`obtained from 55 (3%) children, 67 isolates of Eubacterium spp. from 65 (3%) children
`and 41 isolates of Lactobacillus spp. from 40 (2%) children. Most Bifdobacterium
`isolates were from chronic otitis media, abscesses, peritonitis, aspiration pneumonia and
`paronychia. Most Eubacterium isolates were from abscesses, peritonitis, decubitus ulcers
`and bites. Lactobacillus spp. were mainly isolated from abscesses, aspiration pneumonia,
`bacteraemia and conjunctivitis. Most (> goo/,) infections from which these species were
`isolated were polymicrobial and yielded a mixture of aerobic and anaerobic bacteria.
`The organisms most commonly isolated with the non-sporing anaerobic gram-positive
`rods were Peptostreptococcus spp., Bacteroides spp., pigmented Prevotella and Porphyro-
`monas spp., Fusobacterium spp., Staphylococcus aureus and Escherichia coli. Most
`Bacteroides spp. and E. coli were isolated from intra-abdominal infection and skin and
`soft tissue infection around the rectal area, whereas most Prevotella, Porphyromonas and
`Fusobacterium isolates were from oropharyngeal, pulmonary and head and neck sites.
`The predisposing conditions associated with the isolation of non-sporing anaerobic gram-
`positive rods were previous surgery, malignancy, steroid therapy and immunodeficiency.
`Antimicrobial therapy was given to 149 (83%) of the 160 patients, in conjunction with
`surgical drainage or correction of pathology in 89 (56%).
`
`Introduction
`
`There has been increased interest in recent years about
`the role of anaerobic bacteria in paediatric infections
`[l]. The anaerobic species of most concern have been
`the genera Bacteroides, Clostridium,
`members of
`Fusobacterium
`and Peptostreptococcus
`[ 11. Non-
`sporing, anaerobic, gram-positive
`rods
`such as
`Bifidobacterium, Eubacterium and Lactobacillus spe-
`cies are usually considered to be of relatively low
`virulence. These organisms are taxonomically unrelated
`but are all non-motile and catalase-negative. These
`organisms have been
`isolated
`from adults with
`pulmonary infection (B. dentium)[2], from intra-uterine
`devices (E. nodatum) [3], and from peritonitis and the
`bloodstream (Lactobacillus spp.) [4,5]. However, their
`pathogenic role
`in
`these and other
`infections
`is
`uncertain. The organisms have been isolated in pure
`culture in only a few instances and are usually isolated
`in mixed culture from clinical specimens [ l , 61. The
`
`Received 14 Sept. 1995; revised version accepted 2 Dec.
`1995.
`*Correspondence should be sent to Professor I. Brook, PO
`Box 70412, Chevy Chase, MD 20813-0412, USA.
`
`infections where they have been found most often are
`chronic otitus media and sinusitis, aspiration pneumo-
`nia, and intra-abdominal, obstetric and gynaecological
`and skin and soft-tissue infections [l, 6,7].
`
`This retrospective review summarises my experience
`of the isolation of Bifidobacterium, Eubacterium and
`strictly anaerobic Lactobacillus spp. from infections in
`children over a 20-year period. Some of the data have
`been published previously in articles describing the
`role of anaerobic bacteria
`in various paediatric
`infections [l], but cases not previously presented are
`also
`included, and
`the clinical associations of
`Bifdobacterium, Eubacterium and strictly anaerobic
`Lactobacillus spp.
`in
`infections
`in children are
`emphasised.
`
`Patients and methods
`Patients
`The specimens included in this review were submitted
`for anaerobic investigation between June 1974 and June
`1994 in the following hospitals: University of Califor-
`nia Medical Center, County Medical Center and Serra
`
`Genome Ex. 1056
`Page 1 of 6
`
`

`

`22
`
`I. BROOK
`
`Memorial Hospital in Los Angeles, and Fairview State
`Hospital, Costa Mesa, CA; Children’s Hospital National
`Medical Center and South-East Community Medical
`Center in Washington DC; and the Naval Hospital in
`Bethesda, MD, USA. The clinical microbiology
`laboratory records were reviewed to identify patients
`from whom Bzfidobacterium, Eubacterium and anae-
`robic Lactobacillus spp. were isolated and reported as
`potentially significant pathogens. Where available, the
`case records of the patients were reviewed to ascertain
`the presence and site of infection, associated micro-
`organisms, underlying diseases and possible pre-
`disposing or associated conditions.
`
`Microbiological exam in at ion
`Only specimens that were collected properly without
`contamination by the normal skin or mucosal flora and
`submitted in transport media appropriate for anaerobic
`bacteria were accepted by the microbiology labora-
`tories. These were generally specimens obtained during
`surgery or by aseptic needle or biopsy aspiration of
`abscesses or fluid from body cavities. Lung aspirates
`were obtained by transtracheal aspiration or through a
`tracheostomy or endotracheal tube or by biopsy. When
`possible, pus and fluids were collected and transported
`in syringes. Tissues were transported in oxygen-free
`gassed-out tubes. Swab specimens were submitted in
`the Port-A-Cul transport swab system (BBL, Cockeys-
`ville, MD, USA). However, precise records of all of the
`transport media used were not available. Blood for
`culture was collected aseptically from patients sus-
`pected of having bacteraemia and was inoculated
`(10%) into the anaerobic bottle of one of
`two
`commercially produced blood culture broth media;
`both were under vacuum and with CO2 5% in the
`atmosphere.
`
`The specimens were inoculated on to pre-reduced
`vitamin K1 -enriched Brucella Blood Agar (BBL),
`blood agar with kanamycin and vancomycin, blood
`agar containing colistin sulphate and nalidixic acid,
`and an enriched thioglycolate broth containing haemin
`and vitamin K1 [8,9]. The cultures were incubated in
`GasPak jars (BBL) and examined after 48 and 9 6 h
`[9]. Plates that showed any growth were held until the
`micro-organisms had been identified. All cultures that
`showed no growth were incubated for at least 5 days
`before being discarded. Anaerobic
`isolates were
`identified by the API Anaerobic System (Analytab
`Products, Plainview, NY, USA) or by the Minitek
`system (BBL). When complete identification was not
`possible by these methods, other carbohydrate tests
`(Scott Laboratories, Fiskeville, RI, USA) and gas-
`liquid chromatography (GLC) [8,9] were performed as
`needed to identify the organisms. The criteria for
`identification were according to guidelines in pub-
`lished schemes [8-lo].
`
`In gram-stained
`
`films, Bzfzdobacterium spp. are
`
`generally branched or bifurcate, Eubacterium spp.
`are pleomorphic and Lactobacillus spp. are straight or
`from strictly anaerobic
`to
`curved. Species vary
`aerotolerant [8,9], Bzfidobacterium and Lactobacillus
`spp. are nitrate-positive and indole-negative. Lactoba-
`cillus spp. produce lactic acid as the sole end product
`whereas Bifidobacterium spp. produce acetic and
`lactic acids (with more of the former than the latter).
`The genus Eubacterium comprises gram-positive, non-
`sporing bacilli whose GLC pattern is not characteristic
`of other genera.
`
`Results
`
`the study period, 2033 specimens were
`During
`examined for anaerobic bacteria; 57
`isolates of
`Bzfzdobacterium spp., 67 of Eubacterium spp. and 41
`of strictly anaerobic Lactobacillus spp. were obtained
`from various sites that accounted for 1780 specimens.
`These species were not isolated from other sites, such
`as bile, joint, bone, sinuses, central nervous system and
`urinary tract, that accounted for 253 specimens.
`
`Bijidobacterium spp.
`The 57 Bzfzdobacterium isolates were from 55 patients
`aged 2 weeks-16 years (mean 5 years and 8 months);
`37 were males (Table 1). The isolates comprised 19
`(33%) B. adolescentis, five (9%) B. dentium and 33
`(58%) other Bzfidobacterium spp. Infections were
`polymicrobial in 53 (96%) patients, but in two (4%)
`a Bzfidobacterium spp. was isolated in pure culture;
`these were an isolate of B. adolescentis from chronic
`otitis media and a Bzfidobacterium sp. from cervical
`adenitis.
`
`Most Bzfidobacterium isolates were from chronic otitis
`media (23; 40%), abscesses or peritonitis (7; 12%
`each), cholesteatoma, aspiration pneumonia and paro-
`nychia (3; 5% each). In the 53 specimens that yielded
`mixed growth including a Bzfzdobacterium sp., there
`were 148 other isolates; 89 (60%) of these were strict
`anaerobes and 59 (40%) were facultative or aerobic
`species. The number of isolates in mixed cultures
`varied from two to five (average 2.8 isolates/specimen;
`1.7 anaerobes and 1.1 facultative or aerobic species).
`
`The anaerobic organisms isolated most commonly
`with Bzfidobacterium spp. were Peptostreptococcus
`spp. (28 isolates), Fusobacterium spp. (1 7), pigmented
`Prevotella and Porphyromonas spp. ( 16) and Bacter-
`oides spp. (6). The most common aerobic and
`facultative organisms isolated with Bzfidobacterium
`spp. were a-haemolytic streptococci ( 15 isolates),
`Staphylococcus aureus
`(9), Escherichia
`coli
`(7),
`Pseudomonas aeruginosa (5) and Streptococcus pyo-
`genes (5). Most Bacteroides and E. coli isolates found
`in mixed culture with Bzfidobacterium spp. were from
`peritonitis, whereas most Prevotella, Porphyromonas
`
`Genome Ex. 1056
`Page 2 of 6
`
`

`

`Table 1. Significant isolates of Bij?dobacterium, Eubacterium and Lactobacillus from clinical specimens in children
`Number of isolates of
`
`Bifidohacterium
`
`Eubacterium
`
`Lactobacillus
`
`d
`%
`
`‘U s
`
`2
`
`Type of infection
`
`- m Y G
`
`428
`342
`53
`142
`24
`24
`
`cri
`
`5
`
`1
`
`1
`7
`
`1
`
`6
`
`1
`11
`
`2
`
`7
`
`2
`23
`
`3
`
`01
`E
`2
`rri
`
`1
`
`rri
`
`4
`
`1
`
`rri
`
`2
`
`rri
`
`1
`
`2
`
`d
`%
`
`-
`
`Y
`
`24
`
`28
`
`4
`
`4
`
`2
`
`2
`
`1
`
`4
`
`1
`
`4
`
`2
`
`4
`
`1
`
`1
`
`1
`
`d
`%
`
`8
`4
`1
`3
`
`6
`
`14
`4
`1
`4
`
`8
`
`Abscess
`Bacteraemia
`Cervical lymphadenitis
`Ears: chronic otitis media
`chronic mastoiditis
`cholesteatoma
`Pulmonary
`aspiration pneumonia
`lung abscess
`pneumonia in cystic
`fibrosis
`Tracheostomy site
`Paronychia
`Wounds
`Burns
`Bites
`Gastrostomy site
`Decubitus ulcers
`Peritonitis
`Conjunctivitis
`Total
`
`74
`10
`6
`
`25
`33
`75
`180
`39
`22
`58
`116
`129
`1780
`
`1
`1
`
`2
`
`1
`
`4
`
`5
`
`19
`
`2
`1
`
`1
`1
`
`2
`1
`
`3
`2
`33
`
`3
`2
`
`1
`3
`
`2
`2
`
`7
`2
`57
`
`1
`
`1
`2
`
`1
`6
`
`2
`1
`
`6
`
`1
`
`7
`1
`11
`
`1
`
`1
`
`1
`
`2
`1
`3
`
`1
`
`1
`10
`
`42
`
`2
`2
`3
`2
`3
`1
`4
`17
`2
`67
`
`1
`
`2
`
`3
`
`1
`
`1
`
`1
`
`2
`
`1
`3
`30
`
`1
`
`2
`
`2
`
`1
`4
`41
`
`1
`
`1
`5
`
`
`
`
`
`z
`0
`f:
`z
`m
`
`E
`0
`>
`2:
`%
`w
`E
`
`cl
`
`E
`2
`cl
`z r
`
`U
`
`N W
`
`Genome Ex. 1056
`Page 3 of 6
`
`

`

`24
`
`I. BROOK
`
`and Fusobacterium spp. were from ear, head and neck
`and pulmonary sites. Anaerobic cocci were isolated
`from all sites.
`
`Eleven (20%) of the patients had predisposing or
`underlying medical or surgical conditions. These were
`previous surgery (5), malignancy (2), steroid therapy
`(2) and
`tympanostomy
`tubes
`(2). Antimicrobial
`therapy was administered to all patients, in conjunc-
`tion with surgical drainage with or without correction
`of pathology in 21 (38%). The infections resolved in
`49 (89%) of the patients. Six (29%) of the 21 cases
`with chronic otitis media did not resolve. The
`systemic antimicrobial agents given were clindamycin
`(in 16 instances), a cephalosporin (14), oxacillin (8),
`co-amoxyclav (8), gentamicin (7), penicillin (4) and
`chloramphenicol (3). Local therapy with erythromycin
`ointment was used
`to
`treat
`the
`two cases of
`conjunctivitis.
`
`Eubacterium spp.
`The 67 isolates of Eubacterium spp. were from 65
`patients aged 7 days-16 years (mean 6 years and 2
`months); 39 patients were male (Table 1). The isolates
`comprised 11 (No/) E. lentum, six (1 1%) each of E.
`limosum and E. tenue, and one (2%) each of E.
`moniliforme and E. multiforme and 42 (74%) Eu-
`bacterium spp. Infections were polymicrobial in 6 1
`(94%) patients, but in four (6%) a Eubacterium sp. was
`the only isolate. The four isolates found in pure culture
`were one each of E. lentum and Eubacterium sp. in
`subcutaneous abscesses, and one isolate of a Eubacter-
`iurn sp. in each of a wound and a burn site.
`
`Most Eubacterium isolates were from abscesses (28;
`41%), peritonitis (17; 25%), decubitus ulcers (4; 6%)
`and bites (3; 4%). The 26 abscesses from which
`eubacteria were isolated were peritonsillar (8), retro-
`pharyngeal (4), perirectal (4), dental (3), abdominal
`(3), subcutaneous (2) and scalp (2). In
`the 61
`specimens that yielded a mixed growth including a
`Eubacterium sp., there were 152 other isolates; 94
`(62%) of these were strict anaerobes and 58 (38%)
`were facultative or aerobic bacteria. The number of
`isolates in mixed infection cultures varied from two to
`six (average 2.5 isolates/specimen; 1.5 anaerobes and
`1 .O facultative or aerobic). The anaerobic organisms
`isolated most commonly with eubacteria were Pepto-
`streptococcus spp. (40 isolates), Bacteroides spp. (1 6),
`Prevotella and Porphyromonas spp. (1 5) and Fuso-
`bacterium spp. (6). The most common aerobic and
`facultative organisms isolated with Eubacterium spp.
`were S. aureus (16 isolates), Esch. coli (13), a-
`haemolytic streptococci (12) and Str. pyogenes (5).
`Most Bacteroides spp. and E. coli found in mixed
`culture with Eubacterium spp. were from peritonitis
`and abscesses and wounds around the rectal area.
`Most Prevotella, Porphyromonas and Fusobacterium
`
`spp. were isolated from wounds and abscesses around
`or in the oropharynx.
`
`Twelve (18%) of the children had predisposing or
`underlying medical or surgical conditions. These were
`previous surgery (4), malignancy (3), steroid therapy
`(2), diabetes (2) and sickle cell disease (1). Systemic
`antimicrobial therapy was given to 59 (91%) patients,
`in conjunction with surgical drainage with or without
`correction of pathology in 47 (72%) instances. All the
`infections resolved. The antimicrobial agents given
`were clindamycin (in
`IS), a cephalosporin (16),
`gentamicin (12), oxacillin (9), co-amoxyclav (8),
`penicillin (6), chloramphenicol (4), erythromycin (3)
`and ticarcillin-clavulanate (2). Local therapy with an
`antibiotic or anti-infective ointment was given to two
`patients with wounds, two with burns and two with
`conjunctivitis.
`
`Lactobacillus spp.
`The 41 isolates of Lactobacillus spp. were from 40
`children aged 8 months-16 years (mean 7 years and 5
`months). The isolates were five (12%) L. acidophilus,
`three (7%) L. fermentum, two (5%) L. jensenii, one
`(2%) L. catenaforme and 30 (75%) Lactobacillus spp.
`Infections were polymicrobial in 36 (900/) patients.
`The four Lactobacillus isolates from blood cultures
`were in pure culture and were from four patients with
`intravenous catheter-related bacteraemia.
`
`Most Lactobacillus isolates were from abscesses ( 14;
`34%), aspiration pneumonia (8; 20%), ear infection,
`bacteraemia and conjunctivitis (4; 10% each). The 14
`abscesses from which Lactobacillus spp. were isolated
`were dental (4), subcutaneous (3), vulvovaginal (2),
`abdominal (2), subdiaphragmatic (l), lung (1) and
`tonsillar (1). In the 36 specimens that yielded mixed
`growth including a Lactobacillus sp., there were 76
`other isolates; 49 (64%) of these were strict anaerobes
`and 27 (36%) were facultative or aerobic bacteria. The
`number of isolates in mixed cultures varied from two
`to five (average 2.1 isolates/specimen, 1.4 anaerobes
`and 0.7 facultative of aerobic). The anaerobic organ-
`isms isolated most often with Lactobacillus spp. were
`Peptostreptococcus spp. (20 isolates), pigmented Pre-
`votella and Porphyromonas spp. (1 5) and Fusobacter-
`iurn
`spp.
`(8). The most common aerobic and
`facultative organisms isolated with Lactobacillus spp.
`were 5'. aureus (7 isolates), a-haemolytic streptococci
`(6), Haemophilus injhenzae (3) and E. coli (2). All
`Prevotella, Porphyromonas and Fusobacterium spp.
`were from abscesses and wounds around or in the
`oropharynx. Most S. aureus
`isolates were
`from
`subcutaneous abscesses and wounds, and the H.
`inguenzae isolates were from conjunctivitis and otitis.
`
`Eight of the patients had one or two predisposing or
`underlying medical or surgical conditions. These were
`intravenous catheter (4), immunodeficiency (3), ma-
`
`Genome Ex. 1056
`Page 4 of 6
`
`

`

`labsorption (2) and malignancy (1). Systemic anti-
`microbial therapy was given to 35 (87%) patients, in
`conjunction with drainage with or without correction
`of pathology in 21 (52%) instances. All the infections
`resolved. The antimicrobial agents used were clinda-
`mycin (1 2), gentamicin (1 0), amoxycillin (9), co-
`amoxyclav (7), a cephalosporin (7), ticarcillin-clavu-
`lanate (4) and methicillin (3). In addition to systemic
`antimicrobial
`therapy,
`two of
`the
`four catheters
`associated with bacteraemia were removed. The two
`other patients recovered without the removal of the
`catheters. Local therapy with ophthalmic ointment
`containing antimicrobial agents resulted in recovery in
`the four cases of conjunctivitis.
`
`Discussion
`
`of
`prevalence
`the
`demonstrates
`review
`This
`Bijidubacteriurn, Eubacterium and Lactobacillus spp.
`in various infections in children. The 57 Bzjidobacter-
`ium isolates were obtained from 55 (3%) of the 2033
`specimens submitted for anaerobic cultures, the 67
`isolates of Eubacterium spp. were from 65 (3%)
`patients and the 41 Lactobacillus isolates were from
`40 (2%) children. These micro-organisms were found
`most commonly in infections associated with predis-
`posing or underlying conditions such as previous
`surgery, malignancy, immunodeficiency and the pre-
`sence of a foreign body.
`
`All three genera of non-sporing gram-positive anaero-
`bic rods were found in abscesses. Bzfidobacterium spp.
`were found mostly in head and neck and pulmonary
`infections, and in a smaller number of cases of
`peritonitis. In contrast, Eubacterium spp. were not
`isolated from chronic otitis media but were more
`frequent in peritonitis and wounds. Lactobacillus spp.
`were most commonly found in aspiration pneumonia
`and bacteraemia associated with intravenous catheters.
`
`Species of the genus Bifidobacterium are part of the
`commensal flora of the mouth, gastrointestinal tract
`and female genital
`tract and constitute a high
`proportion of the normal intestinal flora in man,
`especially in breast-fed infants [ 1 11. Although some
`infections caused by
`these organisms have been
`reported [12-151,
`little is known about their patho-
`genic potential. Eubacterium spp. are part of the flora
`of
`the mouth and
`the bowel. They have been
`recognised as pathogens in chronic periodontal disease
`[ 161, and in infections associated with intra-uterine
`devices [3], and have been isolated from patients with
`bacteraemia associated with malignancy [ 171 and from
`female genital tract infection [ 181. Lactobacillus spp.
`are ubiquitous inhabitants of the human oral cavity,
`the vagina and the gastrointestinal tract [19]. They
`have been implicated in various serious deep-seated
`infections, amnionitis [ 191 and bacteraemia [20].
`
`NON-SPORING ANAEROBIC RODS IN CHILDREN
`
`25
`
`The isolation of non-sporing anaerobic gram-positive
`rods from sites of sometimes serious infections in
`children suggests that they should not be automatically
`dismissed as contaminants. It appears that they may
`have clinical significance in high-risk patients with
`illnesses. As
`serious underlying
`they can cause
`significant infections, especially in high-risk patients,
`efforts should be made to secure specimens free of
`contamination by the normal flora of the mucous
`membranes and the skin, and the clinical significance
`of each isolate must be carefully evaluated. Eradica-
`tion of these micro-organisms from deep-seated sites
`of
`infection may be difficult. All non-sporing
`anaerobic gram-positive
`rods are
`susceptible
`to
`penicillin G, carbenicillin and chloramphenicol [2 11.
`Clindamycin is effective against 94% of
`isolates,
`erythromycin against 88% and tetracycline against
`60% [22]. Metronidazole is effective against only 50%
`of isolates [21-231. The efficacy of cephalosporins
`varies between 89% and 95%.
`
`The assistance of the staff of the microbiology laboratories at the
`University of California Medical Center, County Medical Center and
`Serra Memorial Hospital in Los Angeles, Fairview State Hospital in
`Costa Mesa, and Children’s Hospital National Medical Center and
`South-East Medical Center in Washington, DC, and the Naval
`Hospital in Bethesda, MD, and the secretarial support of Sarah
`Blaisdell are gratefully acknowledged.
`
`References
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`10.
`
`11.
`
`12.
`
`13.
`
`14.
`
`Brook I. Pediatric anaerobic infection: diagnosis and manage-
`ment, 2nd edn. St Louis, Mosby. 1989.
`Georg LK, Roberstad GW, Brinkman SA, Hicklin MD. A new
`pathogenic anaerobic Actinomyces species. J Infect Dis 1965;
`115: 88-99.
`Hill GB, Ayers OM, Kohan AP Characteristics and sites and
`infection of Eubacterium nodatum, Eubacterium
`timidum,
`Eubacterium brachy, and other asaccharolytic eubacteria.
`J Clin Microbiol 1987; 25: 1540-1545.
`Bayer AS, Chow AW, Betts, D, Guze LB. Lactobacillemia -
`report of nine cases: important clinical and therapeutic
`considerations. Am J Med 1978; 64: 808-813.
`Bourne KA, Beebe JL, Lue YA, Ellner PD. Bacteremia due to
`Bifidobacterium, Eubacterium or Lactobacillus; twenty-one
`cases and review of the literature. Yale J Biol Med 1978; 51:
`505-512.
`Finegold SM. Anaerobic bacteria in human disease. New York,
`Academic Press. 1977.
`Brook I, Frazier EH. Significant recovery of nonsporulating
`anaerobic rods from clinical specimens. Clin Infect Dis 1993;
`16: 476-480.
`Holdeman LV, Cat0 EP, Moore WEC, eds. Anaerobe laboratory
`manual, 4th edn. Blacksburg, VA, Anaerobe Laboratory,
`Virginia Polytechnic Institute and State University. 1977.
`Summanen P, Baron EJ, Citron DM, Strong CA, Wexler HM,
`Finegold SM. Wadsworth anaerobic bacteriology manual, 5th
`edn. Belmont, CA, Star Publishing Company. 1993.
`Murray PR, Baron EJ, Pfalter MA, Tenover FC, Yolken RH.
`Manual of clinical microbiology, 6th edn. Washington DC,
`ASM Press. 1995.
`Sat0 J, Mochizuki K, Homma N. Affinity of the Bzjidobacter-
`ium to
`intestinal mucosal epithelial cells. Bipdobacteria
`Microflora 1982; 1: 51-54.
`Gorbach SL, Thadepalli H. Clindamycin in pure and mixed
`anaerobic infections. Arch Intern Med 1974; 134: 87-92.
`O’Connor J, MacCormick DE. Mixed organism peritonitis
`complicating continuous ambulatory peritoneal dialysis. NZ
`Med J 1982; 95: 811-812.
`Thomas AV, Sodeman TH, Bentz RR. Bifidobacterium
`(Actinomyces) eriksonii infection. Am Rev Respir Dis 1974;
`
`Genome Ex. 1056
`Page 5 of 6
`
`

`

`26
`
`I. BROOK
`
`110: 663-668.
`15. Hata D, Yoshida A, Ohkubo H et al. Meningitis caused by
`Bifidobacterium in an infant. Pediatr Infect Dis J 1988; 7:
`669-67 1.
`16. Vincent JW, Falkler WA, Suzuki JB. Systemic antibody
`response of clinically characterized patients with antigens of
`Eubacterium brachy initially and following periodontal therapy.
`J Periodontol 1986; 57: 625-63 1.
`17. Fainstein V, Elting LS, Bodey GF! Bacteremia caused by non-
`sporulating anaerobes in cancer patients. A 12-year experience.
`Medicine (Baltimore) 1989; 68: 151-162.
`18. Brook I. Anaerobic bacterial bacteremia: 12-year experience in
`two military hospitals. J Infect Dis 1989; 160: 1071-1075.
`19. Cox SM, Phillips LE, Mercer LJ, Stager CE, Waller S, Far0 S.
`Lactobacillemia of amniotic fluid origin. Obstet Gynecol 1986;
`
`68: 134-135.
`20. Sherman ME, Albrecht M, DeGirolami PC et al. Lactobacillus:
`an unusual case of splenic abscess and sepsis in an
`immunocompromised host. Am J Clin Path01 1987; 88: 659-
`662.
`21. Sutter VL, Finegold SM. Susceptibility of anaerobic bacteria to
`23 antimicrobial agents. Antimicrob Agents Chemother 1976;
`10: 736-752.
`22. Rolfe RD, Finegold SM. Comparative in vitro activity of
`ceftriaxone against anaerobic bacteria. Antimicrob Agents
`Chemother 1982; 22: 338-341.
`23. Wexler HM, Finegold SM. In vitro activity of cefotetan
`compared with that of other antimicrobial agents against
`anaerobic bacteria. Antimicrob Agents Chemother 1988; 32:
`60 1-604.
`
`Genome Ex. 1056
`Page 6 of 6
`
`