Bacteremia due to Fusobacterium species

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Bacteremia Due to Fusobacterium Species SHARON HENRY, MD.* ALFRED DeMARIA, Jr., M.D. WILLIAM R. MCCABE, M.D. Boston, Massachusetts From tha Maxwell Finland Laboratory for Infectious Diseases and the Department of Medicine, Boston City Hospital, and the Departments of Medicine and Microbiology, Boston University School of Medicine, Boston, Massachusetts. Requests for reprints should be addressed to Dr. William R. McCabe, Maxwell Finland laboratory for Infectious Diseases, Boston City Hospital, 818 Harrison Avenue, Boston, Massachusetts 02118. Manu- script accepted November 1, 1982. l Current address: Squibb Institute for Medical Research, P.O. Box 4000, Princeton, New Jersey 08540. Twenty-six patients were identified as having bacteremia with Fu- sobacterium species over a five-year period at Boston City Hospital. They represented 0.9 percent of bacteremic patients and were equally divided as to sex. Bacteremia with Fusobacterium occurred primarily in young adults and in patients over 60 years of age and was not observed in children. In 16 patients (62 percent), Fuso- bacterium was the only blood culture isolate. The most common primary foci of tnfection were the female genital tract, the upper respiratory tract, the oral cavity, and the lower respiratory tract. Five patients had primary foci of infection that were initially occult. Three of these patients were found to have unappreciated oral and pha- ryngeal lesions, and one had a liver abscess; no primary infection was established in the remaining patient. Shock related to bacter- emia developed in six patients (23 percent), four of whom had Fu- sobacterium species as the only blood culture Isolate. Death oc- curred in three patients (12 percent), all of whom were over 60 years old. Metastatic infection occurred in only one patient in whom he- , matogenous osteomyelitis developed. Postpartum fusobacterial bacteremia was uniformly benign. Evaluation of bacteremia with Fusobacterium species in nonpostpartum patients, without an overt focus of infection, should be directed to a search for occult abscess, especially of the upper respiratory tract and oral cavity. Gram-negative, anaerobic bacilli of the genus Fusobacterium are normal inhabitants of the oral cavity, the female genital tract, and the alimentary tract [ 11. F. nucleatum and F. necrophorum are the species of Fusobacterium most frequently isolated from clinical specimens [2]. These species, and occasionally other species of Fusobacterium, are often implicated in infections arising from the respiratory tract, the pelvis, and the gastrointestinal tract [3,4]. The incidence and epidemiologic factors of bacteremia due to Fusobacterium species are difficult to determine from the available literature because of variations in nomenclature and anaerobic culture technique [3,5]. It has been common for fusobacterial bacteremias to be considered in series inclusive of other Bacteroidaceae. Recent observation of fu- sobacterial bacteremia in several patients with initially occult foci of infection led to this review of the epidemiology of bacteremia due to Fusobacterium species. Twenty-six patients were identified over a five-year period as having at least one blood culture that grew Fuso- bacterium, either alone or in combination with other organisms. The charts of these patients were reviewed as to the source of bacteremia, patient characteristics, clinical course, and outcome. August 1983 The American Journal of Medlclne Volume 75 225

Transcript of Bacteremia due to Fusobacterium species

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Bacteremia Due to Fusobacterium Species

SHARON HENRY, MD.* ALFRED DeMARIA, Jr., M.D. WILLIAM R. MCCABE, M.D.

Boston, Massachusetts

From tha Maxwell Finland Laboratory for Infectious Diseases and the Department of Medicine, Boston City Hospital, and the Departments of Medicine and Microbiology, Boston University School of Medicine, Boston, Massachusetts. Requests for reprints should be addressed to Dr. William R. McCabe, Maxwell Finland laboratory for Infectious Diseases, Boston City Hospital, 818 Harrison Avenue, Boston, Massachusetts 02118. Manu- script accepted November 1, 1982. l Current address: Squibb Institute for Medical Research, P.O. Box 4000, Princeton, New Jersey 08540.

Twenty-six patients were identified as having bacteremia with Fu- sobacterium species over a five-year period at Boston City Hospital. They represented 0.9 percent of bacteremic patients and were equally divided as to sex. Bacteremia with Fusobacterium occurred primarily in young adults and in patients over 60 years of age and was not observed in children. In 16 patients (62 percent), Fuso- bacterium was the only blood culture isolate. The most common primary foci of tnfection were the female genital tract, the upper respiratory tract, the oral cavity, and the lower respiratory tract. Five patients had primary foci of infection that were initially occult. Three of these patients were found to have unappreciated oral and pha- ryngeal lesions, and one had a liver abscess; no primary infection was established in the remaining patient. Shock related to bacter- emia developed in six patients (23 percent), four of whom had Fu- sobacterium species as the only blood culture Isolate. Death oc- curred in three patients (12 percent), all of whom were over 60 years old. Metastatic infection occurred in only one patient in whom he-

, matogenous osteomyelitis developed. Postpartum fusobacterial bacteremia was uniformly benign. Evaluation of bacteremia with Fusobacterium species in nonpostpartum patients, without an overt focus of infection, should be directed to a search for occult abscess, especially of the upper respiratory tract and oral cavity.

Gram-negative, anaerobic bacilli of the genus Fusobacterium are normal inhabitants of the oral cavity, the female genital tract, and the alimentary tract [ 11. F. nucleatum and F. necrophorum are the species of Fusobacterium most frequently isolated from clinical specimens [2]. These species, and occasionally other species of Fusobacterium, are often implicated in infections arising from the respiratory tract, the pelvis, and the gastrointestinal tract [3,4]. The incidence and epidemiologic factors of bacteremia due to Fusobacterium species are difficult to determine from the available literature because of variations in nomenclature and anaerobic culture technique [3,5]. It has been common for fusobacterial bacteremias to be considered in series inclusive of other Bacteroidaceae. Recent observation of fu- sobacterial bacteremia in several patients with initially occult foci of infection led to this review of the epidemiology of bacteremia due to Fusobacterium species. Twenty-six patients were identified over a five-year period as having at least one blood culture that grew Fuso- bacterium, either alone or in combination with other organisms. The charts of these patients were reviewed as to the source of bacteremia, patient characteristics, clinical course, and outcome.

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FusoaAcTERruM BACTE~~EMIA--HENRY ET AL

METHODS

Records of all positive blood cultures processed by the Medical Microbiology Laboratory at Boston City Hospital were reviewed for the period of April 1975 through March 1980. The medical records of patients identified as having bacter- emia with Fusobacterium species were reviewed for patient characteristics and details concerning source of bacteremia, clinical features, underlying disease, and outcome. Shock was defined as a decrease of blood pressure to less than 90/60 mm Hg, or a 70 mm Hg or greater decrease in systolic or diastolic pressure in patients who were previously hy- pertensive. Underlying diseases were classified as rapidly fatal, ultimately fatal, and nonfatal by the standard criteria of McCabe and Jackson [6]. By definition, death due to bac- teremia occurred within seven days of onset, unless there was evidence of recovery from the bacteremic episode and a second event occurred that was considered fatal. The pe- riod between the time blood culture specimens were obtained and the time bacterial growth was first recognized in the blood culture bottles was also noted.

Indications and techniques for drawing blood culture specimens on the various services at Boston City Hospital remained constant through the period of this study. Brain- heart infusion broth, with or without 0.025 percent sodium polyanethol sulfonate, in commercially prepared, evacuated bottles was used for isolation of anaerobic bacteria. Blood culture bottles were incubated at 35’C and examined daily for evidence of turbidity, hemolysis, gas, and colony forma- tion. Positive specimens were smeared for Gram stain ex- amination and subcultured on prereduced Centers for Disease Control anaerobic blood agar or anaerobic blood agar (Scott, Fiskville, Rhode Island). The anaerobic bottles of blood culture sets received from the Obstetrics and Gynecology service were routinely subcultured at 24 or 48 hours, even without evidence of bacterial growth. All blood cultures were blindly subcultured for anaerobic bacteria at seven days. Subcultures were incubated for 48 hours at 35% in Gas-Pak (BBL, Cockeysville, Maryland) jars. Anaerobic, gram-negative bacteria were presumptively identified by the criteria of Dowell and Hawkins [7] and Dowell and Lombard [8]. Iden- tification was based on growth characteristics, cellular morphology, colonial morphology, antibiotic susceptibility by the paper disk method (kanamycin, 1,000 pg; vancomycin, 5 pg; and colistin, 10 pg), and growth in 20 percent bile. Results were reported as Bacteroides fragilis group, Bac- teroides non-fragilis group, and Fusobacterium species. A number of Fusobacterium species were identified as F. nucleatum on the basis of colony characteristics. Several of these isolates were confirmed as F. nucleatum by gas-liquid chromatography.

RESULTS

Twenty-six patients were identified as having bacter- emia with Fusobacterium species. In 16 patients (62 percent), only Fusobacterium organisms were isolated from the blood. Of the remaining 10 patients with polymicrobial bacteremia, including Fusobacterium, five had one other species isolated (two with Peptostrep-

tococcus, two with Staphylococcus epidermidis, and one with an alpha-hemolytic Streptococcus); two had two other organisms present (group B beta-hemolytic Streptococcus and Peptostreptococcus; Peptostrep- tococcus and a gram-positive anaerobic bacillus, not Clostridium); two had three other organisms present (S. epidermidis. Peptostreptococcus, and Bacteroides species; group C Streptococcus, Streptococcus bovis, and Staph. epidermidis); and one patient had multiple blood cultures that grew Fusobacterium species, Escherichia coli, Aeromonas hydrophilia, Klebsiella species, and Clostridium perfringens. During the same five-year period, 100 patients were identified as having bacteremia due to Bacteroides species, 68 as the only organism isolated and 32 with polymicrobial bacter- emia. In Table I, the incidence of bacteremia due to Fusobacterium species is compared with the incidence of several other organisms that are frequent blood cultures isolates. The yearly incidence of fusobacterial bacteremia was fairly constant for the entire period.

The mean of the elapsed time between collection of blood for culture and recognition of the presence of organisms subsequently identified as Fusobacterium was 4.3 f 2.9 (k standard deviation) days. In eight of the 26 patients (31 percent), the organisms were rec- ognized on routine seven-day subculture. The median time to recognition was three days. The recognition time was not significantly different in those patients with polymicrobial bacteremia inclusive of Fusobacterium species (mean 4.6 days, median three days). Seven of the 26 bacteremias (27 percent) with Fusobacterium were recognized in two days or less. In 53 percent of the bacteremias with Bacteroides species, blood culture results were positive in two days or less. Similar data in bacteremia due to aerobic organisms over the same period are 80 percent for E. coli, 67 percent for Staph. aureus, and 92 percent for Strep. pneumoniae. The one third of staphylococcal isolates obtained beyond 48 to 72 hours of blood culture incubation consisted primarily of single bottle isolates of questionable clinical signif- icance.

The 26 patients with fusobacterial bacteremia ranged in age from 17 to 82 years (mean 43 years). The group was equally divided by sex. No cases of fusobacterial bacteremia occurred in any patient younger than 17 years. The age distribution of cases was bimodal, with 14 patients (54 percent) under 40 years of age and nine (35 percent) older than 60 years. The source of bac- teremia was the upper respiratory tract in seven (oro- pharyngeal lesions in four, sinusitis in two, and dental disease in one), pelvic infection in nine (puerperal in six, postoperative in two, and related to malignancy in one), aspiration pneumonitis and lung abscess in five, biliary tract in one, and liver abscess in one. Two patients had concomitant pulmonary lesions and decubitus ulcers

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TABLE I Occurrence of Bacteremia Due to Fusobacterlum Species at Boston City Hospital from April 1975 Through March 1980 as the Incidence In Patients with Bacteremla and the Proportion Per 1,000 Hospital Admlssions

Cause of Bacteremia’ Number of Patients

Percentage of Incidence per Patients with 1,000 Hospital Bacieremiat Admissions

Fusobacterium species 26 0.9 0.33 1975-76 3 0.9 1976-77 4 1.0 1977-76 6 1.1 1978-79 5 0.6 1979-80 8 1.0

Bacteroides species 100 3.5 1.26 Escherichia coli 255 8.8 3.22 Staphylococcus aureus 298 10.3 3.76 Streptococcus pneumoniae 297 10.2 3.75 Anaerobic cocci 50 1.7 0.63

l Incidence of bacteremia for other selected organisms is given for comparison. 1 Includes all patients with a positive blood culture report, including those with isolates of uncertain clinical significance and probable con- taminants.

at the time of bacteremia. A source of bacteremia was not established in one patient. Table II demonstrates the distribution of age and sex of patients by source of bacteremia. Nine of the 13 female patients (69 percent) had a pelvic source of bacteremia, and two thirds of these patients were under 40 years of age. All male patients under 40 years of age had a respiratory source of bacteremia, the upper respiratory tract being the source in five. Polymicrobial bacteremia occurred in five females with a pelvic source of infection, in two patients with upper respiratory tract infection, in one of the patients with pulmonary and skin lesions, in the patient with the biliary tract infection (with five organ- isms isolated from the blood), and in the patient with the occult source.

All patients were febrile at the time of the bacter-

emia. Twenty-one of the 26 patients had signs and symptoms referrable to a focus of infection or had just given birth. In the remaining five patients, a source of bacteremia was not identified at the time the laboratory reported Fusobacterium in the blood. All of these pa- tients had culture of blood for evaluation of fever. Work-up prompted by the report of the positive blood culture results revealed occult oropharyngeal infection in two, dental infection in one, and liver abscess in one, but failed to establish a source of bacteremia in the fifth patient.

Eleven patients had no significant underlying disease before the development of bacteremia. Six of these patients were postpartum females, three had an upper respiratory tract infection, and two had undergone gynecologic surgery. Three patients had malignancy.

TABLE II Distribution of Patients with Bacteremla Due to Fusobacterium Species by Age, Sex, and Source

Source Upper Respiratory Female lower Gastrointestinal Tract, CHher,

Tract, Oral Genital Respiratory Biliary Tract, Unknown, Age and Sex Cavity Tract Tract Liver Uncertain Total

I39 years 6 6 2 0 0 14 Male 5 - 2 - - 7 Female 1 6 0 - - 7

40-59 years 0 1 1 1’ 0 3 Male - - 0 1 - 1 Female - 1 1 0 - 2

I60 years 1 2 2 1+ 3t 9 Male 1 1 1 2 5 Female 0 2 1 0 1 4

Total 7 9 5 2 3 26

l Liver abscess. t Biliary tract. t One with unknown source, and two with simultaneous lung infections and infected decubitus ulcers.

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TABLE Ill Distribution of Cases of Bacteremia Due to Fusobacterium Species and Fatality Rates in Respect to Presence of Shock, Age, Underlying Diseases, Source of Bacteremia, and Nature of Blood Culture Isolates

Number of Fatality

Patients Rate’

All categories 26 3/26 (12%)

Patients with shock 6 2/6 (33%)

Age (years) <17 0 -

17-40 14 o/14

41-59 3 013

60 or greater 9 3/9 (33%)

Underlying disease Rapidly fatal 0 -

Ultimately fatal 5 2/5 (40%) Nonfatal or none 21 l/21 (5%)

Source of bacteremia Pelvis 9 o/9

Upper respiratory tract 7 o/7

Lower respiratory tract 5 2/5 (40 %)

Lower respiratory tract 2 l/2 (50%)

versus skin Other 3 o/3

Bacteremia Fusobacterium species alone 16 2/16 (13%)

Polymicrobial 10 l/10 (10%)

l Deaths/number at risk (percent).

Four patients had acute and chronic alcoholism, and three of these had pulmonary infection (that is, aspira- tion pneumonitis) related to altered mental status and alcohol withdrawal seizures. Only two patients had hepatic disease. Underlying diseases in three young males with respiratory tract infection were limited to intravenous drug abuse, asthma, and hypertension. Four of the elderly patients had severe central nervous sys- tem disease, diabetes mellitus, renal insufficiency, and heart disease. The patient with liver abscess had a polyclonal gammopathy. Categorized by severity of underling disease, none of the patients had rapidly fatal disease, five had ultimately fatal disease, and 21 had nonfatal or no underlying disease.

Results of laboratory examination were consistent with the patients’ underlying diseases and infections. No characteristic hematologic abnormalities were noted. White blood cell counts ranged between 7,700 to 38,700/mm3. Ten of 22 patients for whom data were available had serum bilirubin levels of 1.8 mg/dl or greater.

Patients received a variety of antimicrobial agents. Twelve patients with an immediately appreciated, nonpelvic source of bacteremia all promptly received

antibiotics generally considered active against Fuso- bacterium species (penicillin G, ampicillin, oxacillin, a cephalosporin, clindamycin, chloramphenicol. or tet- racycline). Among the nine patients with a pelvic source of infection, five postpartum patients were well and either were ready for discharge from the hospital or had been discharged at the time the positive blood culture result was reported. They had received a variety of antimicrobial agents, often orally, usually of a short duration. Four of the five patients with an initially occult source of infection had begun receiving an antimicrobial agent expected to be active against Fusobacterium before receipt of the blood culture result. The fifth pa- tient with an unappreciated dental abscess began re- ceiving penicillin two days after the first culture-positive specimen was drawn. This patient had persistent bac- teremia despite penicillin therapy until surgical drainage was performed. This was the only patient with persistent bacteremia, but his course was otherwise uncompli- cated.

Shock occurred in six patients. Five of these patients were more than 60 years old, and the sixth was the 50-year-old man with a liver abscess. Shock occurred in four of the five patients with ultimately fatal underlying disease. Bacteremia was caused by Fusobacterium species alone in four. Blood culture from one of the others grew Staph. epidermidis, and the sixth was the patient with polymicrobial bacteremia including aerobic gram-negative bacilli and C. perfrigens. Shock did not occur in any patient under 50 years old. Three patients died, two with shock and one with severe pulmonary disease. The two patients who died in shock had Fu- sobacterium as the only blood culture isolate. Mortality by underlying disease, age, source of bacteremia, and blood culture isolate is summarized in Table Ill. The three deaths related to infection occurred in patients with pulmonary infection who were more than 60 years old. Two of the three deaths occurred among the five patients with ultimately fatal underlying disease. The one death in the group with nonfatal underlying disease occurred in a 68-year-old woman with diabetes and a history of congestive heart failure. Two of the deaths occurred among the 16 patients in whom Fusobacter- ium was the only blood culture isolate. Among surviving patients in whom shock did not develop, only one had a significant complication, and that was a 17-year-old man with bacteremia with Fusobacterium nucleatum (confirmed by gas-liquid chromatography) secondary to a pharyngeal abscess in whom multifocal os- teomyelitis developed. One postpartum patient treated with ampicillin returned to the hospital one week after discharge with renewed fever; blood culture revealed Mycoplasma hominus, which responded to therapy with tetracycline.

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COMMENTS

Fusobacterium species have long been recognized as pathogens in humans, as evidenced by the historic term “fusospirochaetal” infection. Organisms of the genus Fusobacterium have been isolated from infections of the oropharynx, lung, female genital tract, abdomen, and a number of other sites [3]. The difficulty in as- sessing the precise role of anaerobic, gram-negative bacilli in human infection related to the technical as- pects of culture methods and identification has been emphasized [2,3]. Increased recognition of the role of anaerobic bacteria in infection and progress in tech- niques of isolation and identification occurred just be- fore the period of the present study (1975 to 1980). Blood culture specimens were collected and processed with attention to the isolation of anaerobes. Identification of anaerobic gram-negative bacilli was based on pub- lished guidelines [7,8]. Although identification must be considered presumptive because of the lack of routine use of gas-liquid chromatography, all of the isolates of Fusobacterium species did meet cellular and colonial morphologic criteria and diagnostic antimicrobic disk susceptibility testing criteria (sensitive to kanamycin and colistin, resistant to vancomycin) characteristic for the genus. Several stains were confirmed as F. nucle- atum by gas-liquid chromatography and fermentation studies.

The family Bacteroidaceae includes the genera Bacteroides and Fusobacterium, as well as other bac- teria rarely encountered in bacteremia. At Boston City Hospital over a five-year period, bacteremia due to members of this family was recognized in 126 of 2,839 patients with bacteremia (4.4 percent). This incidence is consistent with other recent reports [5,9]. The 4: 1 ratio of Bacteroides to Fusobacterium among cases of gram-negative, anaerobic bacteremia observed in the present study is similar to that observed among blood culture isolates submitted to the Centers for Disease Control [ lo].

Fusobacterium was observed in approximately 1 percent of cases of bacteremia at Boston City Hospital, without a significant change in incidence over the five years of the study. The similarity of the incidence of fusobacterial bacteremia observed in the present study compared with that in earlier reports suggests com- parable success rates in isolation and identifica- tion.

Twenty-six patients were identified as having bac- teremia due to Fusobacterium species. The age distri- bution correlated with the portal of entry, with 88 per- cent of patients under 40 years old having an upper respiratory tract source (five of six were males) or pelvic source (all female), whereas patients over 40 years old

FUSOBACTERIUM BACTEREMIA-HENRY ET AL

were distributed among those having intraabdominal and lower respiratory sources, as well as upper respiratory and pelvic portals of entry. Nine of the 13 females with fusobacterial bacteremia had a pelvic source of bac- teremia, most often representing puerperal bacteremia. Eight of the 13 males had a respiratory tract source of bacteremia. Among 50 patients with fusobacterial bacteremia reported by Felner and Dowell [lo], 48 percent were younger than 40 years old. The most common portals of entry were the upper and lower respiratory tracts (46 percent), the gastrointestinal tract and liver (38 percent), and the pelvis (10 percent). Since all of their cases were based on submissions of isolates to the Centers for Disease Control, the distribution of portals of entry may not be reflective of this disease as seen in a general hospital. Among cases of sepsis due to Fusobacterium reported before 1960, Tynes and Utz [4] found that 43 percent arose in the gastrointestinal tract, 34 percent in the lung, 15 percent in the upper respiratory tract, and only 4 percent from the geni- tourinary tract. Among six cases of bacteremia reported by Chow and Guze [5], four originated in the female genital tract.

Five of 26 patients had a source of fusobacterial bacteremia that was not appreciated until the blood culture report was received from the laboratory. In one of these patients, the source was never defined. In one, an occult liver abscess was found on radionuclide liver scanning carried out because of anaerobic bacteremia. In the remaining three patients, unappreciated oral and oropharyngeal suppurative infection was found. Four of the five initially unexplained cases of fusobacterial bacteremias were monobacteremic; in the exception, Staph. epidermidis grew in one blood culture. Unex- plained fusobacterial bacteremia should prompt im- mediate evaluation for an occult upper respiratory le- sion. Further evaluation should be directed primarily to the abdominal cavity and the pelvis.

Ten of 22 patients (45 percent) for whom data were available had hyperbilirubinemia (serum bilirubin level of 1.8 mg/dl or higher) in the present series. Only two of these patients had underlying liver disease (related to alcoholism), and the third was the patient with liver abscess. Similar rates of hyperbilirubinemia have been described in patients with bacteremia due to anaerobic, gram-negative bacilli [3,5,10-121. Hyperbilirubinemia in this setting has not been adequately explained. It has been suggested that toxicity to the hepatobiliary system is responsible [5].

Metastatic abscesses have been associated with bacteremia from Fusobacterium species and Bacter- oides species [4,5,10]. In all but one of our 26 patients, suppurative lesions appeared to be primary. In one patient, liver abscess appeared to be the source of the

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recognized bacteremia, but the source of the liver ab- scess was never established. The one patient with clear-cut metastatic infection was a 17-year-old black male, with normal hemoglobin electrophoretic results, who had a pharyngeal abscess, F. nucleatum bacter- emia, and multiple foci of osteomyelitis. Hematogenous osteomyelitis due to Fusobacterium and other Bacter- oidaceae has been described previously [ 5,12,13]. Septic thrombophlebitis and endocarditis have been associated with bacteremia due to anaerobic, gram- negative bacilli [3,5,10,14] but were not clinically ev- ident in any of our patients.

The most common source of fusobacterial bacter- emia in females in the present series was the pelvis. When good techniques of anaerobic bacteriology are applied, fusobacteria are commonly isolated from fe- male pelvic infections [ 15,161. The outcome of fuso- bacterial bacteremia in our nine patients with puerperal bacteremia and pelvic infection was uniformly good despite therapy or lack of it. In five of these patients, bacteremia was polymicrobial, usually including an- aerobic streptococci. Chow and Guze [5] reviewed Bacteriodaceae bacteremia in 154 obstetric patients described in the literature and added 30 cases of their own; they found only one death in these 184 patients (0.5 percent). A similar benign course in obstetric and gynecologic patients with bacteremia due to Bacter- oidaceae, including Fusobacterium species, has been reported by others [9,17] r including patients who also had simultaneous bacteremia with anaerobic strepto- cocci [ 181.

In the present series, shock related to fusobacterial bacteremia developed in six of 26 patients (23 percent). All of the patients with shock were aged 50 years or older, and four were among the five patients with ulti- mately fatal underlying diseases. Only one of these patients had concomitant bacteremia with another aerobic or anaerobic gram-negative organism, and four had Fusobacterium as the only blood culture isolate. This rate of shock is very similar to the 21 percent in- cidence observed in patients with ultimately fatal and nonfatal underlying disease with aerobic, gram-negative bacteremia receiving appropriate antibiotics [ 191. Rates of shock of 18 to 35 percent have been reported in series of bacteremia due to unspeciated Bacter- oidaceae [5,12,20,21], with a similar higher rate of shock in patients with ultimately fatal underlying dis- eases 151.

In the pre-antibiotic era, mortality rates of 80 percent were observed in patients with bacteremia due to Bacteroides and Fusobacterium [4,1 I]. In the antibiotic era, an overall mortality of approximately 30 percent in patients with bacteremia due to members of the Bacteroidaceae has been observed [ 591. Feiner and Dowell [lo] reported an overall mortality of 12 percent

in 50 patients with bacteremia due to Fusobacterium species, the same incidence in the present series of 26 patients. All three deaths in the present series occurred in patients with acute lung infection; one also had a decubitus ulcer. The importance of age and severity of underlying disease in mortality observed in bacteremia due to members of the Bacteroidaceae [9,10,12,18,22] was confirmed. The three deaths occurred in the nine patients older than 60 years. Two of the three deaths occurred in patients with ultimately fatal diseases. Fu- sobacteriaf bacteremia alone, or even as part of poly- microbial bacteremia, had a relatively benign course in 14 patients under 40 years of age.

Infections due to anaerobic bacteria are character- istically polymicrobial, often including aerobic bacteria [3]. Bacteremia may represent only part of the flora involved at the primary site of infection, and although therapy directed at organisms isolated from the blood is of significant importance, patients often require therapy directed against other suspected pathogens. Chow and Guze [5] have noted that appropriate anti- biotic therapy in patients with bacteremia due to the Bacteroidaceae as defined by in vitro susceptibility studies, significantly improves outcome in terms of fatality, primarily in patients with ultimately fatal underlying diseases. They also established a critical role for drainage of suppurative infection. The worst prog- nosis was in patients who received inappropriate drugs and no drainage. Similar data on outcome related to appropriate or inappropriate therapy have been reported in other series [ 9, lo]. Recognition of the resistance of many strains of B. fragilis to penicillin had led to a general acceptance of clindamycin as the drug of choice for infections with anaerobes. Resistance of Fusobacterium species to penicillin has been observed [23], but such resistance is unusual in the most com- monly isolated species, F. nucleatum and F. necro- phorum [ 24,251. Fusobacterium species have been reported to be uniformly susceptible to clindamycin, chloramphenicof, and metronidazole, but activity of the cephalosporins, tetracyclines, and erythromycin is variable [23-251, Most of the patients in the present series received appropriate antimicrobial therapy with either penicillin for upper and lower respiratory infection or a regimen including clindamycin for intraabdominal infection. Patients with postpartum bacteremia and infection of the female genital tract received a variety of antibiotics, usually ampicillin, clindamycin, or a tet- racycline, and in some instances, no therapy, with a uniformly good outcome.

Fusobacterium species accounted for 1 percent of the cases of bacteremia observed at Boston City Hos- pital over a five-year period. The incidence of bacter- emia with Bacteroides was approximately four times that with Fusobacterium. Relatively longer incubation

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periods were required to isolate Fusobacterium from upper respiratory tract, as it did in the pre-antibiotic era blood specimens compared with other more common [4,5,11,26]. The occurrence of unexpected fusobac- pathogens, as has been previously reported [ 1,221. terial bacteremia should lead to a careful search for Thirty-eight percent of patients with Fusobacterium occult abscess, especially in the upper respiratory isolated from the blood had polymicrobial bacteremia. tract. Patients with fusobacterial bacteremia tended to fall into two groups-young patients (less than 40 years old) with upper respiratory and pelvic sources of bacteremia who had a uniformly good outcome, and elderly patients with a variety of portals of entry. Death occurred in the latter group only. Although bacteremia due to anaerobic, gram-negative bacilli in the antibiotic era usually arises from the gastrointestinal tract [3], fusobacterial bac- teremia still commonly results from infection in the

ACKNOWLEDGMENT

We are grateful to Dr. Kurt Stottmeier, Ms. Kathleen Browne, and the staff of the Medical Microbiology Laboratory, Boston City Hospital, for advice and iden- tification of bacteria, to Mr. David Hardy for the provision of statistical data, and to Ms. Raquel Rodriguez for her expert assistance in the preparation of the manu- script.

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