Fusobacterial infections in children

Fusobacterial infections in children

7ournal of Infection (1994) 28, 155-165 Fusobacterial infections in children Itzhak B r o o k Department of Pediatrics, Georgetown University School...

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.7ournal of Infection (1994) 28, 155-165

Fusobacterial infections in children Itzhak B r o o k Department of Pediatrics, Georgetown University School of Medicine, Washington DC, U.S.A. Accepted for publication I I November 1993

Summary A total of 243 strains of Fusobacteria species was recovered from 226 of I399 (I6%) specimens obtained from 213 children. The strains included 65 (27%) Fusobacterium sp., 144 (59%) Fusobacterium nucleatum, 25 (lO%) Fusobacterium necrophorum, five (2 %) Fusobacterium varium, three (I %) Fusobacterium mortiferum, and one (o'4%) Fusobacterium gonidiaformans. Most Fusobacteria species were recovered from patients with abscesses (IOO), aspiration pneumonia (24), paronychia (I5), bites (I4) , chronic sinusitis (ten), chronic otitis media (nine), and osteomyelitis (eight). Predisposing conditions were noted in 32 (15 %) of the cases. These included immunodeficiency in nine (4 %), steroid therapy in eight (4 %), previous surgery in six (3 %), diabetes in six (3 %) and malignant neoplasms in five (2 %). Fusobacteria sp. was the only isolate in 16 (8 %) instances while mixed infections were encountered in 197 (92 %) patients. The organisms most commonly isolated with Fusobacteria sp. were anaerobic cocci (I55), pigmented Prevotella sp. and Porphyromonas sp. (95), Bacteroides fragilis group (8o), Escherichia coli (43) and Bacteroides sp. (39). Most strains of B. fragilis group and E. coli were recovered from intra-abdominal infections and skin and soft tissue infections proximal to the rectal area. Most pigmented Prevotella sp. and Porphyromonas sp. were recovered from oropharyngeal and pulmonary sites and from sites around the head and neck. Antimicrobial therapy was administered to all patients; surgical drainage was performed in 85 (40%). All patients, except two who died, recovered. These findings illustrate the prevalence of Fusobacteria sp. associated with infections in children.

Introduction Great interest has been generated in recent years as regards the role of anaerobic bacteria in infections of children, 1 mainly on the roles of Bacteroides sp. and Clostridium sp. A n o t h e r group of organisms implicated in infections arising within the respiratory, genital and gastrointestinal tracts consists of the Fusobacteria species? T h e incidence and significance o f these infections, however, remain poorly defined because o f variations in nomenclature and the techniques o f anaerobic culture. T h e role of Fusobacteria sp. in infections of children have b e c o m e m o r e important in recent years because o f the emergence of penicillin resistance b y m e m b e r s of the species t h r o u g h the p r o d u c t i o n of beta-lactamase that was first noticed in 1983 .3 T h i s article summarises m y experience in the past 15 years in the recovery T h e opinions and assertions contained herein are the private ones of the writer and are not to be construed as official or reflecting the views of the U.S.A. Navy Department, or the U.S.A. naval service at large. Request for off-prints: Dr Itzhak Brook, P.O. Box 7o412, Chevy Chase, NLD 2o813-0412, U.S.A.

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of Fusobacteria sp. from infections in children. Some of the findings have been published before in separate articles describing the role of anaerobic bacteria in infections of c h i l d r e n ) -19 Even so, the role of Fusobacteria sp. was not highlighted in any of these studies since they were recovered from a small proportion, generally less than IOn/o, of the patients. F u r t h e r m o r e , this overview includes cases, not previously reported, that were seen after the earlier studies were completed. P a t i e n t s and m e t h o d s

T h e children included in this article were studied between June I973 and June 1988. T h e y were seen in the following hospitals: University of California Medical Center, Los Angeles County Medical Center, Sara Memorial Hospital in Los Angeles and Fairview State Hospital, Costa Mesa, California as well as in the Children's Hospital National Medical Center and South-East C o m m u n i t y Medical Center in Washington, D C , and the Naval Medical Center in Bethesda, Maryland. T h e clinical microbiology laboratory records were reviewed so as to identify patients infected with Fusobacteria sp. T h e available case histories of all patients from w h o m Fusobacteria sp. had been isolated were reviewed in order to ascertain the presence and site of infection, the associated micro-organisms, disease processes and possible predisposing or associated conditions. Only specimens that were properly collected and submitted in transport media appropriate for anaerobic bacteria were accepted in the microbiology laboratory. Most specimens, except blood, were submitted by means of Porta-Cul transport swabs or liquid systems (BBL, Cockeysville, M D , U.S.A.) but exact records of the transport media used were not available. Blood was collected aseptically from patients suspected of having bacteraemia and was inoculated (IO %, vol/vol) into one bottle each of two commercially obtained broth media, both with added CO~. Specimens were cultured anaerobically on prereduced vitamin Kl-enriched Brucella blood agar, blood agar containing kanamycin and vancomycin, blood agar containing colistin sulfate and nalidixic acid, and in enriched thioglycolate broth containing haemin, sodium carbonate and vitamin K1. 2°'~ All agar cultures were incubated in GasPak jars (BBL) and examined at 48 and 96 h. Cultures that showed growth were held until the organisms were identified. All cultures without apparent growth were held for at least 5 days. Organisms were identified by use of the A P I anaerobic system (Analytab Products, Plainview, NY, U.S.A.) or by the Minitek system (BBL). In addition to these tests, when complete identification was not possible by means of them, other carbohydrate tests (Scott Laboratories, Fiskeville, RI, U.S.A.) and gas-liquid chromatography ~ were performed as needed in order to identify the organisms. T h e criteria for their identification were according to previously published guidelines. 2°, 21 Results

Of the total of 1399 specimens that were studied for anaerobic bacteria, 243 strains ofFusobacteria sp. were recovered from 226 (I6 %) specimens obtained

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from 2I 3 patients. Clinical records were not available for nine other cases. These were not included in the final analysis. T h e strains of Fusobacteria sp. isolated included 65 (27%) Fusobacterium sp., 144 (59%) Fusobacteriurn nucleatum, 25 (Io%) Fusobacterium necroforum, five (2%) Fusobacterium varium, three (i %) Fusobacterium mortiferum, and one (o'4 %) Fusobacterium gonidiaformans (Tables I and II). Most infections were polymicrobial (in z97 (9z %) patients) but in i6 (8 %) patients Fusobacteria sp. were recovered in pure culture (Table III). Most Fusobacteria sp. isolated were recovered from abscesses (IOO (4I %) of 243 strains), aspiration p n e u m o n i a (24 or zo %), paronychia (z5 or 6 0/0), bites (z4 or 60,/0), chronic sinusitis (zo or 4 % ) chronic otitis media (9 or 4 % ) , and osteomyelitis (8 or 3 %). T h e ages of patients ranged from 22 days to 18 years (mean 8 years and 4 months); I32 were males, 8z were females. Predisposing or underlying conditions were noted in 32 ( I 5 % ) cases. A single condition was noted in 24 instances and two such conditions were found in eight. T h e conditions noted were immunodeficiency (nine or 4 %), steroid therapy (eight or 4 % ) , previous surgery (six or 3 %), diabetes (six or 3 %), malignancy (five or 2 %), sickle cell anemia (two or I ~o), trauma (two or 1 0/0), and foreign body (two or z 0/0). T h e r e were 696 isolates recovered mixed with Fusobacteria sp. from r97 specimens from patients with mixed infections, (Table I and II). T h e isolates included 465 (67 %) anaerobic and 23I (33 %) facultative or aerobic bacteria. T h e n u m b e r of these other isolates varied between 2 to 8 (average 3" i) strains per specimen, z.I anaerobic and I.o aerobic or facultative. T h e anaerobic organisms most commonly recovered with Fusobacteria sp. were: Peptostreptococcus sp. (z55 isolates), Bacteroides fragilis group (8o isolates including 35 B. fragilis, I9 Bacteroides distasonis, and eight each of Bacteroides thetaiotaomicron and Bacteroides vulgatus and seven Bacteroides uniformis), pigmented Prevotella sp. and Porphyromonas sp. (95, previously called Bacteroides melaninogenicus group, including 55 Prevotella melaninogenica, 24 Prevotella intermedia, I6 Prevotella oralis, z4 Porphyromonas assacharolytica, and seven Prevotella oris/bucca); Bacteroides sp. (39), Clostridium sp. (I7) and Eubacreriurn sp. and Veillonella sp. (I6 each). T h e r e were also 27 strains of microaerophilic streptococci isolated. T h e most c o m m o n aerobic and facultative organisms recovered with Fusobacteria sp. were: alpha haemolytic streptococci (56), Escherichia coli (43), gamma haemolytic streptococci (5I), Staphylococcus a u r e u s (28), Klebsiella pneumoniae (z6), Haemophilus parainfluenzae (nine), Haemophilus influenzae (eight), Streptococcus pyogenes (seven), Pseudomonas aeruginosa (six), and Streptococcus pneurnoniae (five). Most isolates of the B. fragilis group and of E. coli were recovered with Fusobacteria sp. from intra-abdominal infections and from skin and soft tissue infections proximal to the rectal area. Most strains of pigmented Prevotella sp. and Porphyromonas sp. were recovered from oropharyngeal and p u l m o n a r y sites as well as from sites on the head and neck. A m o n g the 85 patients with abscesses containing a mixture of species (Table II), the most c o m m o n sites for the abscesses were peritonsillar (z3), retropharyngeal (I I), intracranial (I2, eight brain abscesses and four subdural

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empyemata) and finger (seven). T h e most common other anaerobic organisms recovered with Fusobacteria sp. from abscesses were Peptostreptococcus sp. (72 isolates), pigmented Prevotella sp. and Porphyromonas sp. (58 isolates), B. fragilis group (I8 isolates), Veillonella sp. (eight isolates), and Clostridium sp. (six isolates). T h e most common aerobic and facultative organisms isolated with Fusobacteria sp. were alpha haemolytic streptococci (27), gamma haemolytic streptococci (IS), Staphylococcus aureus (I4), E. coli (IO), and Haemophilus sp. (seven). T h e distribution of these organisms in abscesses was as described in the previous paragraph. Of the I4 strains of Fusobacteria sp. recovered from 13 bites, nine were from h u m a n bites and four were from animal bites. T h e y were recovered from bites at various body sites and were mixed mostly with Peptostreptococcus sp., and Streptococcus sp. Two isolates were from burns on the face. T h e I3 strains of Fusobacteria sp. isolated from I2 patients with chronic otitis media, cholesteatoma and chronic mastoiditis were recovered mixed with pigmented Prevotella sp., Porphyromonas sp., Peptostreptococcus sp. and

Pseudomonas aeuruginosa. T h e 23 strains of Fusobacteria sp. isolated with other flora from patients with aspiration pneumonia were from 2I of the 74 (28 %) specimens collected by means of transtracheal aspiration. T h e predominant other organisms isolated with Fusobacteria sp. were pigmented Prevotella sp. and Porphyromonas sp., Peptostreptococcus sp. and species of Enterobacteriaceae. In four cases, similar strains of Fusobacteria sp. were also recovered from associated empyemata. O f six strains isolated from empyemata four were recovered from cases of empyema associated with aspiration pneumonia and two from empyemata associated with infections of the head and neck. T h e 37 peritoneal isolates of Fusobacteria sp. were recovered from a total of 35 children, 24 had a ruptured appendix, eight had rupture of a viscus after trauma, and three had perforation of a viscus associated with necrotising enterocolitis. T h e strains were mostly mixed with Peptostreptococcus sp., Bacteroides fragilis group and strains of Enterobacteriaceae. T h e most commonly associated organisms were Bacteroides fragilis group, anaerobic cocci and E. coli. T h e five strains of Fusobacteria sp. recovered from decubitus ulcers were isolated from such ulcers proximal to the head and neck. T h e I5 paronychia isolates were found to be mixed with S. aureus and pigmented Prevotella sp. and Porphyromonas sp. In one instance, the Fusobacteria sp. was also recovered from an associated digital osteomyelitis. T h e eight strains of Fusobacteria sp. isolated from sites of osteomyelitis were found to be mixed with Peptostreptococcus sp., pigmented Prevotella sp. and Porphyromonas sp. T h e y were isolated from one case each of osteomyelitis of the temporal bone (associated with mastoiditis), frontal bone (associated with frontal sinusitis), maxilla (associated with maxillary sinusitis), mandible (associated with periodontal abscess), occipital and temporal bone (associated with decubitus or diabetic ulcers), and metacarpal (associated with paronychia). Clinical and microbiological findings of the i6 patients whose cultures grew only Fusobacteria sp. are listed in Table III. T h e types of infection included

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eight abscesses; three each of conjunctivitis and bacteraemia, two of cervical lymphadenitis, and one each of osteomyelitis, aspiration pneumonia, sinusitis and paronychia. One patient (No. I I) with bacteraemia and sinusitis presented with periorbital ceUulitis and developed a subdural empyema. Of the three patients with conjunctivitis, one wore a contact lens while two did not have any known predisposing condition. T h e patient with aspiration p n e u m o n i a (No. 7) had D o w n ' s syndrome. One patient (No. I3) with a perirectal abscess, who also suffered from leukaemia, died of the infection. Antimicrobial therapy was administered to all patients. T h e r e was also surgical drainage or correction of the condition in 85 (4o %) instances. T h e antimicrobial agents administered were a penicillin in 8o cases, an aminoglycoside in 48, clindamycin in 4I, a cephalosporin in 34, erythromycin in 18, chloramphenicol in I6, metronidazole in I2, and co-trimoxazole in three. T w o (i %) patients died of their infection. T h e s e were one case each of perirectal abscess and aspiration p n e u m o n i a (also infected with P. intermedia and P. magnus). Discussion

This retrospective study demonstrates the prevalence of Fusobacteria sp. in a variety of infections in children. T h e 243 isolates of Fusobacteria sp. were recovered from 226 ( I 6 % ) specimens cultured for anaerobic bacteria. T h e importance of Fusobacteria sp. as a commonly encountered group of organisms in a variety of infections in children is confirmed. T h e species were especially prevalent in abscesses (mostly of the head and neck and intracranial), aspiration p n e u m o n i a and peritonitis. Although most strains of Fusobacteria sp. isolated were mixed with other aerobic and anaerobic bacteria, their recovery as the only isolate in I6 of the 213 (8%) patients (Table III) illustrates their potential virulence and clinical significance. Fusobacteria sp. are Gram-negative, non-sporulating, non-motile and, generally, moderately long filamentous organisms, sometimes slightly elongated rods, that belong to the family Bacteroidaceae. T h e ability of Fusobacteria sp. to produce butyric acid without isobutyric or isovaleric acids differentiates t h e m from the other Bacteroidaceae. T h e species of Fusobacteria seen most often in clinical infections include F. nucleatum, F. necrophorum, F. gonidiaformans, F. naviforme, F. mortiferum and F. varium. 1'~ Of these, F. nucleatum is best able to produce the enzyme beta-lactamase. Fusobacterium sp. are part of the normal oral, gastrointestinal and female genital tract flora. 2z,23 These sites, therefore, are the most c o m m o n origin of infections that involve these organisms. Fusobacteria sp. are often recovered mixed with other anaerobes and aerobes in polymicrobial infections. Fusobacteria sp. produce lipopolysaccharide, ~4 neutrophil-cytotoxic substances~5.26 and DNase 27 that have all been associated with virulence. Support for the pathogenic role ofFusobacteria sp. may be derived from in-vivo studies that have demonstrated their synergistic potential with other anaerobic and aerobic bacteria. 28-3~ With few exceptions, the presence of Fusobacteria sp. enhanced the growth of other aerobic and anaerobic bacteria. Bacterial synergy was demonstrated between Fusobacteria sp. and anaerobic cocci, Staphy-

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lococcus aureus and Pseudomonas aeruginosa by means of a subcutaneous abscess model in mice. 32 In this model, Fusobacteria sp. enhanced the formation of abscesses and mortality when inoculated with the other organisms. As was found with other anaerobic bacteria, the ability of Fusobacteria sp. to induce subcutaneous abscesses was correlated with the presence of a mucopolysaccharide layer in the cell wall. 3' T h e production of subcutaneous abscesses in experimental animals could, therefore, be an indication of the organism's virulence, as has been noticed with other anaerobic strains. 33 Factors associated with infections involving Fusobacteria sp. include breakup of the normal cutaneous and mucosal defenses as may occur in Epstein-Barr virus pharyngitis, 34'35 tissue injury caused by surgery or trauma, and impaired blood supply caused by microvascular disease. Moreover, the production of proteolytic enzymes by Fusobacteria sp. may allow early invasion of regional veins, even without tissue necrosis. 3~ F u r t h e r m o r e the low oxidation-reduction potential and oxygen-free environment of devitalised tissue allows growth of these organisms. Fusobacteria sp. may be isolated from a variety of infections in h u m a n beings. T h e y have been recovered from 5 - I 0 % all anaerobic infections in children 37-39 and 3 % cases of anaerobic bacteraemia, v T h e infections they commonly cause in children are located in the u p p e r respiratory tract and the head and neck. In older persons, however, they tend to induce lower respiratory tract infection as a result of aspiration. T h e spectrum of infections in which Fusobacteria sp. play a pathogenic role include bacteraemia, head and neck infections (such as chronic otitis media, sinusitis and mastoiditis, peritonsillar and retropharyngeal abscesses, Vincent's angina, gingival and dental infections), p u l m o n a r y infections (aspiration pneumonia, lung abscesses and empyema), intracranial infections (meningitis and intracranial abscesses), gastrointestinal infections (peritonitis, hepatic and abdominal abscesses), osteomyelitis, urogenital (prostatic and female genital abscesses, amnionitis) as well as skin and soft tissue infections especially around the oropharyngeal area. 1, 2 Fusobacteria sp. have been generally associated with bacteria of primarily oropharyngeal origin, 4°'41 that may accompany t h e m in cervical septic thrombophlebitis, 36 necrotising p n e u m o n i a or metastatic infection 42 known as Lemierre's disease. 41'4a Even so, primary fusobacterial bacteraemia has also been observed. 44 T h e m a n a g e m e n t of Fusobacterial infections includes medical and surgical treatment. W h e n needed, surgical drainage of pus and debridement of necrotic tissue are an integral part of therapy and should accompany administration of appropriate antimicrobial agents. Fusobacteria sp. are generally susceptible to a variety of antimicrobial agents that include penicillins and cephalosphorins. Most Fusobacteria sp., however, are resistant to erythromycin and rifampicin. For beta-lactamase-producing Fusobacteria sp., addition of a beta-lactamase inhibitor such as clavulanic acid to a penicillin renders the penicillin effective against these organisms. 4~ Other antimicrobial agents effective against beta-lactamase-producing Fusobacteria sp. include clindamycin, metronidazole, chloramphenicol, and imipenem. 1'2

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(I thank L. C o l h o u n , P. Y o c u m , J. Perry, a n d E. H. Frazier for the technical s u p p o r t as well as Sarah T h o r p e for secretarial assistance.) References

x. Brook I. Pediatric anaerobic infections, diagnosis and management. 2nd Ed. St. Louis : CV Mosby, I989. 2. Finegold SM. Anaerobic Bacteria in Human Disease. New York: Academic Press, I977. 3. Turner K, Nord CE. Beta-lactamase-producing micro-organisms in recurrent tonsillitis. ScandJ Inf Dis I983; 39 (suppl): 83-85. 4. Brook I, Finegold SM. Bacteriology and therapy of lung abscess in children. J Pediatr 1979; 94: io--i2. 5. Brook I. Microbiology of chronic otitis media with perforation in children: microbiologic studies. Am ff Dis Child I98o; t34: 564-565. 6. Brook I. Bacteriologic features of chronic sinusitis in children, ffAMA I981 ; e46: 967-969. 7. Brook I, Controni G, Rodriguez W, Martin W. Anaerobic bacteremia in children. Am J Dis Child 198o; I34: IO52-IO56. 8. Brook I, Grimm S, Kielish RB. Bacteriology of acute periapical abscess in children. J Endodont I98I; 7: 378-380. 9. Brook I. Aerobic and anaerobic bacteriology of peritonsillar abscess in children. Acta Pediatr Scand I981; 7o: 831-835. Io. Brook I. Aerobic and anaerobic bacteriology of chronic mastoiditis in children. Am J Dis Child I98I ; 135 : 478-479. I I. Brook I. Aerobic and anaerobic bacteriology of cervical adenitis in children. Clin Pediatr. I98O; I9: 693-696. I2. Brook I. Bacteriology of intracranial abscess in children, ff Neurosurg 1981 ; 54:484-488. I3. Brook I. Aerobic and anaerobic bacteriology of cholesteatoma. Laryngoscope I98I; 91: 250--255.

I4. Brook I. Microbiology of retropharyngeal abscesses in children. A m J Dis Child I987; I4I : 202-204 .

I5. Brook I, Friedman E, Rodriguez WJ, Controni G. Complications of sinusitis in children. Pediatrics I98O; 66:568-572. I6. Brook I. Aerobic and anaerobic bacterial isolates of acute conjunctivitis in children: a prospective study. Arch Ophthal I98o; 98: 833-835. I7. Brook I. Bacterial studies of peritoneal cavity and postoperative surgical wound drainage following perforated appendix in children. Ann Surg I98O; I92: 2o8-212. I8. Brook I, Finegold SM. Bacteriology of aspiration pneumonia in children. Pediatrics I98o;

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19. Brook I, Randolph J. Aerobic and anaerobic flora of burns in children. J Traum I98I ; eI : 313-318. 20. Sutter VL, Citron DM, Edelstein MAC, Finegold SM. Wadsworth anaerobic bacteriology manual 4th Ed. Belmont CA: Star Publishing, 1985. 2I. Holdeman LV, Cate EP, Moore WEC. Anaerobe laboratory manual 4th Ed. Blacksburg: Virginia Polytechnic Institute and State University, I977. 22. Socransky SS, Manganiello SD. The oral microbiota of man from birth to senility. J Periodontal I971 ; 42 : 485-496. 23. Rosebury T. Microorganisms indigenous to man. New York: McGraw-Hill, I966. 24. Hase S, Hofstad T, Rietschel ET. Chemical structure of the lipid A component of lipopolysaccharide from Fusobacterium nucleatum. J Bacteriol I977; I29: 9-I4. 25. Van Dyke TE, Bartholomew E, Genco RJ, et al. Inhibition of neutrophil chemotaxis by soluble bacterial products. J Periodontol I982; 53:502--5 ° 8 . 26. Garcia MM, Alexander DC, McKay HA. Biological characterization of Fusobacterium necrophorum cell fractions in preparation for toxin and immunization studies. Infect Immun I975; n : 6o9-616. 27. Porschen RK, Sonntag S. Extracellular deoxyribonuclease production by anaerobic bacteria. Appl Microbiol I974; 27: 1o31-Io33. 28. Abe PM, Lennard ES, Holland JW. Fusobacterium necrophorum infection in mice as a

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model for the study of liver abscess formation and induction of immunity. Infect Immun 1976; 13: I473-I478. Conlon PJ, Hepper KP, Teresa GW. Evaluation of experimentally induced Fusobacterium necrophorum infections in mice. Infect Immun I977; 15: 5IO-517. Hill GB, Osterhut S, Pratt PC. Liver abscess production by non-spore-forming anaerobic bacteria in a mouse model. Infect Immun I974; 9: 599-603. Brook I, Walker RI. The relationship between Fusobacterium species and other flora in mixed infection. J Med Microbiol 1986; 21 : 93-xoo. Brook I, Hunter V, Walker RI. Synergistic effect ofBacteroides, Clostridium, Fusobacterium, anaerobic cocci, and aerobic bacteria on mortality and induction of subcutaneous abscesses in mice. J Infect Dis I984; 149: 924-928. Kasper DL. The polysaccharide capsule of Bacteroides fragilis subspecies fragilis: Immunochemical and morphologic definition. J Infect dis I976; 133 : 79-89. Portman M, Ingall D, Westenfelder G, Yogev R. Peritonsillar abscess complicating infectious mononucleosis. J Pediatr I984; lO4: 742-744. Dagan R, Powell KR. Postanginal sepsis following infectious mononucleosis. Arch Intern Med 1987; 14'7: I58I--I583. Goldhagen J, Alford BA, Previtt LH, et al. Suppurative thrombophlebitis of the internal jugular vein: report of three cases and review of the pediatric literature. Pediatr Infect Dis J 1988; 7:41°-414 • Dunkle LM, Brotherton TJ, Feigin RD. Anaerobic infections in children: a prospective study. Pediatrics 1976; 57: 311-32o. Thirumoorthi MC, Keen BM, Dajani AS. Anaerobic infections in children: a prospective survey. J Clin Microbiol 1976; 3: 318-323. Brook I, Martin WJ, Cherry JD, Finegold SM. Recovery of anaerobic bacteria from pediatric patients. Am J Dis ChiM I979; I33:IO20--IO24. Seidenfeld SM, Sutker WL, Luby JP. Fusobacterium necrophorum septicemia following oropharyngeal infection. J A M A I982; 248: I348-I35O. Moreno S, Altozano JG, Pinilla B, et al. Lemierre's disease: postanginal bacteremia and pulmonary involvement caused by Fusobacterium necrophorum. Rev Infect Dis 1989; xI: 3 I9-324. Vogel LC, Boyer KM. Metastatic complications of Fusobacterium necrophorum sepsis. Am J Dis Child 198o; 134: 356-358. Lemierre A. On certain septicemias due to anaerobic organisms. Lancet I936; x : 7oi-7o3. Bouvier DP, Armstrong RD, Bradshaw DM, et aL Fusobacterium necrophorum septicemia without a primary focus. S Med J I985; 78 : I52I-I522. Appelbaum PC, Spangler SK, Jacobs MR. Susceptibilities of 394 Bacteroidesfragilis, nonB. fragilis group Bacteroides species, and Fusobacterium species to newer antimicrobial agents. Antimicrob Agents Chemother I99I ; 35: I212-I214.