Anaerobic Osteomyelitis and Arthritis in a Military Hospital: A lo-Year Experience ITZHAKBROOK,M.D., ~&SC., EDITHH. FRAZIER,M.SC.,Bethesda, Mary/and
PURPOSE The methods of collecting, transporting, cultivating, and identifying aerobic bacteria in bone and joint infections have improved marhedly since the early 1930s.In addition, many of the anaerobes have been reclassified and renamed. The purpose of this study was to provide more current information regarding the incidence of recovery of anaerobic bacteria from clinical specimens of infected bone and joint. MATEEUAU3AND METHOD& Specimens from 73 infected bone specimens and 65 infected joints inoculated on media supportive for aerobic and anaerobic bacteria showed bacterial growth. RESULT& One hundred fffty-seven organisms (22 isolates/specimen), consisting of 122 anaerobit bacteria (1.7 isolates/specimen) and 35 facultative or aerobic bacteria (0.5 isolate/specimen), were recovered from the 73 bone specimens. Anaerobic bacteria were recovered with aerobe or facultative bacteria in 24 (333%)iustances. The predominant anaerobes were Bacteroides species (49 isolates), anaerobic cocci (45), IGsoImcterium species (ll), Frop~o&actetium acnes (7), and ClcnrtzWum species (6). Conditions predisposing to bone infections were vascular disease, bites, contiguous infection peripheral neuropathy, hematogenous spread, and trauma Pigmented I%voteBa and Porphyromonas species were mostly isolated in shull and bite infections (7 of 19), members of the Bacterokks fragilis group in hand and feet infection (12 of 16), and R~~~b~cteriun~ species in skull, bite, and hematogenous long bone infectio= Seventy-four organisms (1.1 isolates/specimen), consisting of 67 anaerobic bacteria (1.0 isolate/specimen) and 7 facultative or aerobic bacteria (0.1 isoJate/specimen), were isolated from 65 joint specimena The predominant anaerobes were I? acnes (24 isolates), anaerobic cocci (17), Jhcteroidee species
From the Department of Pediatrics and Infectious Diseases, Naval Medical Center, Bethesda, Maryland. The opinions and assertfons contained herein are the private ones of the writer and are not to be construed as official or reflecting the views of the Navy Department, the Naval services at large. or the Defense Nuclear Agency. Requests for reprints should be addressed to ltzhak Brook, M.D., MSc.. Armed Forces Radiobiology Research Institute. Bethesda, Maryland 20889-5145. Manuscript submitted October 15,1991, and accepted in revised form August 10. 1992.
(lo), and CIostMium species (5). Predisposing conditions to joint infection were trauma, prior surgery, presence of a prosthetic joint, and contiguous infection. I? acnedvisolates were associated with prosthetic joints, members of the Z3.fragirigroup with hematogenous spread, aud Ck#rti&un species with trauma The clinical presentation of these cases is disCW
CONCLUSION: These data highlight the importance of anaerobic bacteria in bone and joint infection.
A
naerobic bacteria have received increasing recognition in the etiology of osteomyelitis [l-4] and septic arthritis [5,6], although the exact prevalence of anaerobes in these infections is unknown. Evidence that anaerobic bacteria might be a primary cause of osteomyelitis and arthritis is provided by their established pathogenicity in bone and joint infections in animals [7] and humans [l-3,5]. More than 300 cases of bone infection and 200 cases of joint infection involving anaerobic bacteria have been reported in the literature. Most of these cases were reported in series that described patients with bone and joint infections diagnosed during the years 1970 to 1981 [3-51. Since the publication of most of these reports, the methods of collection, transportation, cultivation, and identification of anaerobic bacteria have improved markedly. Furthermore, many of the anaerobes have been reclassified and renamed according to newer identification criteria. Therefore, a more current evaluation of the incidence of recovery of anaerobic bacteria from clinical specimens is desirable. Such a study may better show the frequency of the recovery of anaerobes from clinical specimens of bone and joint today and may illustrate the effect of these improvements on the recovery of such organisms. This report describes over 10 years of experience (1976 to 1936) of a military hospital in the diagnosis of anaerobic bacterial etiology of bone and joint infections.
MATERIALS AND METHOOS The diagnosis of osteomyelitis or arthritis was established in each patient either by diagnostic asJanuary 1993
The American Journal ol Medicine
Volume 94
21
ANAEROBIC OSTEOMYELITIS AND ARTHRITIS / BROOK AND FRAZIER
piration or by surgical dbbridement and drainage of infected material. All patients had roentgenographic evidence of bone or joint infection and had pathologic confirmation of the diagnosis of osteomyelitis and arthritis. Specimens that did not have such a confirmation were not included in the study. Between June 1976 and June 1987,73 specimens of an established infection of the bone and 65 specimens of an established infected joint submitted to the Clinical Microbiology Laboratories at the Naval Hospital in Bethesda, Maryland, for the isolation of aerobic as well as anaerobic bacteria showed bacterial growth. These included the following bone infections: 8 skull, 3 mastoid or ethmoid, 2 vertebra, 26 long bones, 31 hands and feet, and 3 pelvis or sacrum. The joint infections included 2 of the cervical spine, 4 sternoclavicular, 6 elbow, 2 shoulder, 1 wrist, 26 hip, 17 knee, 3 ankle, and 4 sacroiliac. These 138 cases represent only those specimens that were submitted for identification of anaerobic as well as aerobic bacteria. Ninety-eight of the 138 patients from whom these specimens were obtained were male. Patients’ ages ranged between 12 weeks and 79 years (mean age: 36 years and 8 months). Prior to the collection of samples, antimicrobial therapy was administered to 28 (38%) of the patients with osteomyelitis and to 16 (25%) of those with arthritis. Specimens submitted to the microbiology laboratory were obtained using aseptic procedures by either biopsy of tissue (including bone) or aspiration of loculated joint fluid or pus adjacent to an area of osteomyelitis. Fluid or pus specimens were transported to the laboratory within 30 minutes of collection in a syringe sealed with a rubber stopper after evacuation of the air. Specimens of tissue or bone were transported in an anaerobic transport tube (Port-A-Cub Be&n Dickinson Company, Cockeysville, MD). The time between the collection of materials and the inoculation of specimens generally did not exceed 2 hours. Sheep blood (5%), chocolate, and MacConkey’s agar plates were inoculated for the isolation of aerobic organisms. The plates were incubated at 37OC aerobically (MacConkey) and under 5% carbon dioxide (blood and chocolate) and examined at 24 and 48 hours. For the isolation of anaerobes, the specimens were plated onto prereduced vitamin Kl-enriched Brucella blood agar, an anaerobic blood agar plate containing kanamycin and vancomycin, an anaerobic blood plate containing colistin and nalidixic acid, and inoculated into enriched thioglycolate broth. The plated media were incubated in GasPak jars (BBL Microbiology Systems, Cockeysville, MD) and examined at 48, 96, and 120 hours. The
22
January 1993
The American Journal of Medicine
Volume 94
thioglycolate broth was incubated for 14 days. Anaerobes were identified by previously described techniques [8,9]. Aerobic bacteria were identified using conventional methods [lo]. The data were organized according to anatomic locations. Five milliliters of blood was collected aseptically from 33 patients with osteomyelitis and from 26 with arthritis and was inoculated (lo%, vol/vol) into 1 bottle each of aerobic and anaerobic BACTEC media (Johnson Laboratories, Cockeysville, MD). Anaerobic bottles were examined visually on Days 1 through 7, read on a BACTEC 640 reader on Days 2 and 4 through 7, and blindly subcultured on Day 3. Statistical analysis was done using the Student’s ttest.
RESULTS Osteomyelitis MICROBIOLOGY: One hundred fifty-seven organisms (2.2 isolates/specimen), consisting of 122 anaerobic bacteria (1.7 isolates/specimen) and 35 facultative or aerobic bacteria (0.5 isolate/specimen), were recovered from the 73 bone specimens. Anaerobic bacteria recovered from all specimens were mixed with facultative or aerobic bacteria in 24 cases (33%) (Tables I and II). The predominant anaerobic organisms were Bacteroides species (23 isolates, including 16 isolates of members of the Bacteroides fragilis group), Prevotella species (21 isolates), anaerobic gram-positive cocci (45 isolates, including 12 Peptostreptococcus magnus isolates and 9 Peptostreptococcus prevotii isolates), Fusobacterium species (11 isolates), Propionibacterium acnes (7 isolates), and Clostridium species (6 isolates). The most frequently recovered facultative or aerobic bacteria were Staphylococcus aurew (10 isolates) and Streptococcus species (6). Several correlations were found between the site of infection, the predisposing conditions, and the organisms isolated (Tables I and II). These were the increased rate of recovery of pigmented Prevotella and Porphyromonas species in skull and bite infections (7 of the 19 members of this group) (p <0.05), the higher rate of recovery of members of the B. fragilis group in infections of the hands and feet associated with vascular disease or neuropathy (12 of the 16 members of the B. fragilis group) (p <0.05), the recovery of most Fusobacterium isolates from skull infections, bites, and hematogenous long-bone infections, and the paucity of anaerobic gram-positive cocci in skull infections. The highest isolation rate of aerobic or facultative organisms was in long-bone infections associated with trauma or contiguous foci (6 of 10 infec-
I
Similar organisms Mated in blood
Total
Hands/feet Vascular disease/ neumpathy Bites Unknown Pelvislsarcrum
Long bones Hematogenous source Trauma or contiguous foci Vascular disease or peripheral neuropathy Implants Unknown etiology
Skull Mastoid ethmoid Vertebra
lnfcctedBale/ m
Anaerobic Organisms
TABLE
1
3
1
1
1
-
8
-
2
-
2
_
!
-
f
1
1
4
7
-
-
2
111
-
-
1
-
1
-
z
1
--
2
_
-
__
-_T17;
1
_
P. anae P. m&us pfii
-
1
_
-
_
P. asacchamty. P. ticus micms
2
! 1
i
14
PM* sbwpfo- TotalNo. coccus OlbJlaespnies mbes
-
1
-
1
-
-
1
----
3
6-_.-_ll__-
73
2
1
:Tr_rr____,r_,zi__1___Iz2
11
18
:_r_r__i_rrrI_12--~II1IIl
-
2
-
-
5
-
5
9
3
-
-
--
-
1
]
1
4
-
3
6
-
1-
-
5
T----_--_-l_l____
11
-
-
6
-
-
6
-
2
_.
7
--
2
-
-
1
-
3
1
1
_
4
1
2
12
3
6
l-
2
--
-
9
1
3
2
1
2
-
2
-
-
-
14
i
2
1
1
122
;
19
33
:
a
16
-
11
1
5. intw P. mcdius maps
1
-
1
‘-
ki/bda panda
--
r
-
Elktaium Mum
5
-
z
7
-
Back f. Fuse. cbstdmides numb Lwctmium dium P. 8. fragilis specks atum speck species acne
10
-
3
2
P. asacP. P. E. cham ink+ metan 6. theta* /yikd media ncgmica ovatus bomkmn
8
I’_!-_! -----
P. orisP. P. “L. biria ma/is @%us hocue
6__--11__-21122-_---_--_.---
; 2
$zs Is&ted)
Totd No.
Recovered From 73 Bones
TABLE II
-
3
11
24 _-
73
-
Srmilar organisms isolated in blood
$
5
1
-
2
z
-
T
;
:
ia
i -
; 2
;r1zr1
:
-
Others
6 10 5
2
a
Total
Hands/feet Vascular disease/ neumpathy Bites Unknown etiology Pelvis and sacrum
Long bones Hematogenous source Trauma or contiguous foci Vascular disease or peripheral neuropathy implants Unknown etiology
Skull Mastoid ethmoid Vertebra
Mected Bowl Predisposing Conditii
Total No.of Bones
Total No. of Bones Merdm Mated)
Aerobicand Facultative OrganismsRecoveredFrom 73 Bones
-
3
-<
-
1
x
r -
1
species
P%?lJdommas
-
2
1
-
1
1
5 1
-
species
PrOkUS
I
1
-
-
-1
;-
-
species
Entern bactef
-
r
-
-
I
1
7 -
-
species
Kkbsiella
-
-
1
-
-
6
1
T
1
2
-
3
2
-
-
7 -
-
1
1
StreptOcoccus species
-
1
-
r -
-
1 -
-
Eschetichia co/i
Streptococcus faecalis
-
r
-
-
-
5 -
-
1
species B_ hernolytic
COCCUS
Sttepfo-
-
-
-
5
1
1
.! -
!
e$!$
.
Slaphyb coccus
1
2
: 1
2
10
-
r
r
1
aureus
COCCUS
Sfaphyb
and
35
2
4
7
!
2”
3
4 2 1
Facultatives
Total No. d Aerobes
ANAEROBIC
tions) (p <0.05) and in hand and feet infections associated with vascular disease or neuropathy (5 of 18) (Table II). Organisms similar to those isolated in the bone were also recovered in the blood in six instances (Table I). CLINICAL FEATURES: The duration of symptoms before diagnosis varied from 5 to 41 days (mean: 24 days). Thirty-three infections were classified as acute osteomylitis and 40 as chronic osteomylitis. Etiologic factors predisposing to bone infection were present in 62 (85%) cases (7 patients had 2 predisposing conditions) and were as follows: vascular insufficiency (13), bites (ll), peripheral neuropathy (lo), trauma (7), diabetes (4), periodontal disease (4)) decubitus ulcers (3)) fractures (3)) prosthesis (3), chronic sinusitis (3), chronic mastoiditis (2), foreign body (2), steroid therapy (2), sickle cell anemia (2), ethmoiditis (l), and scalp infection (1). Sixty-two (85%) of the patients had fever (above 37.7OC) on admission. Leukocytosis (greater than 10,000 cells/ml) was observed in 68 (93%) patients. The erythrocyte sedimentation rate was increased (above 15 mm/h) in 43 of the 58 (74%) patients in whom it was measured. Pain was present in 70 (96%) patients. A technetium-99m bone scan was obtained in 21 patients, and the results were positive in 6 (21%). The pus had a foul odor in 35 (48%) patients. However, since the pus was not smelled routinely, the exact prevalence of a foul odor is unknown. Four patients died during the course of therapy of their infection: two with decubitus ulcers, one with vascular insufficiency and sepsis, and one with diabetes. All patients were treated with parenteral antibiotic therapy directed against all organisms. The antimicrobials used were ampicillin, penicillin G, cefoxitin, oxacillin, chloramphenicol, clindamycin, metronidaxole, and aminoglycosides. Antimicrobial therapy was administered for 3 to 6 weeks. In addition to diagnostic aspiration, extensive surgical drainage or debridement was performed in 64 (88%) patients. Amputation of the feet was performed in four patients with severe vascular insufficiency. Fifty-seven (78%) patients were followed in the outpatient clinic for a period of 8 to 31 months after completion of therapy. Forty-six (81%) completely recovered from the infection, 8 (14%)had a recurrence of the osteomyelitis, and 3 (5%) had recurrence of the primary infection 4 to 7 months later. Arthritis MICROBIOLOGY: Seventy-four
lates/specimen),
organisms (1.1 isoconsisting of 67 anaerobic bacteria
OSTEOMYELlTlS
AND ARTHRITIS
/ BROOK AND FRAZIER
(1.0 isolate/specimen) and 7 facultative or aerobic bacteria (0.1 isolate/specimen), were isolated from 65 joint specimens (Table III). Anaerobic bacteria recovered from all specimens were mixed with facultative or aerobes in 7 (11%) cases. The predominant anaerobic organisms were P. acnes (24 isolates), anaerobic gram-positive cocci (17 isolates, including 6 P. mugnus isolates), and Bacteroides species (10, including 9 isolates from the B. frugilis group). The facultative or aerobic bacteria were four S. uureus isolates, two Stuphylococcus epidermidis isolates, and one Escherichiu coli isolate. Several correlations were found between the site of infection, the predisposing conditions, and the organisms isolated. Of the 24 P. acnes isolates, 13 were recovered from the knee and 10 from the hip (p <0.05). Of these 24 instances, the infection was associated with a prosthetic joint in 8 cases, previous surgery in 4, trauma in 3, and prior administration of steroids in 1. Isolates from the B. frugilis group were recovered in nine instances, five in association with a distant site of infection. In three of five cases in which Fusobucterium species were recovered, oropharyngeal infection was present. Clostridium species were associated with trauma in four of the five instances of recovery and with needle aspiration in one instance. Of the six isolates of P. mugnus, three were recovered in a prosthetic joint. Organisms similar to those isolated in the joints were also recovered in the blood of five patients. CLINICAL FEATURES: The duration of symptoms before diagnosis varied from 1 to 23 days (mean: 4.5 days), and all but six infections were diagnosed as acute arthritis. Etiologic factors predisposing to arthritis were noted in 49 (75%) cases and were as follows: trauma (14 patients, 8 of whom had fractures), prior surgery (ll), prosthetic joint (lo), contiguous infection (5), prior needle aspiration (4), diabetes (3), and malignancy (2). Fifty-two (80%) of the patients had fever (above 37.7OC) on admission. Leukocytosis (greater than 10,000 cells/ml) was observed in 48 (74%) patients. The erythrocyte sedimentation rate was increased (above 15 mm/h) in 30 of the 43 (70%) patients in whom it was measured. Swelling and pain were present in 62 (95%) patients. Blood cultures were obtained in 14 patients, and results were negative in all cases. The pus had a foul odor in 24 (37%) patients. One patient with a chronic debilitating disease died of the infection. All patients were treated with parenteral antibiotic therapy directed against all isolated organisms. The antimicrobials used were ampicillin, penicillin G, fl-lactam-resistant penicillins,
January
1993
The American
Journal
of Medlclne
Volume
94
25
I----I------
9
-
L9 I_---_-__--__--_
-
P
-
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s
2
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ANAEROBIC OSTEOMYELITIS AND ARTHRITIS / BROOK AND FRAZIER
erythromycin, clindamycin, metronidazole, and aminoglycosides. Therapy was administered for 2 to 7 weeks. In addition to diagnostic aspiration, extensive surgical dbbridement and drainage was performed in 31 (48%) patients. Fifty-one (78%) patients were followed in the outpatient clinic for a period of 4 to 28 months after completion of therapy. Complete eradication of the infection was documented in 37 (73%) of these patients. However, despite the eradication of the infection, serious bone and joint changes occurred in 22 of these 37 (60%) patients, and 15 required further surgical procedures to correct or replace the joints. The infection persisted in 14 patients: 12 responded to repeated surgical dbbridement and extended courses of antimicrobial therapy, and chronic infection persisted in 2 patients.
COMMENTS This retrospective study demonstrates the importance of anaerobic bacteria in bone and joint infection. The true incidence of osteomyelitis and arthritis, however, can be determined only in prospective studies. The lower mean age of our patient population as compared with that of community hospital patients probably accounts for the good response to therapy. The improved culture techniques and the increased awareness of anaerobic infection have led to the recognition of the important role of these organisms in osteomyelitis and septic arthritis [5]. The importance of anaerobes in bone infection was especially notable in osteomyelitis of the long bones after trauma and fracture [3-51, osteomyelitis related to peripheral vascular disease, and osteomyelitis of cranial and facial bones [3-51. The role of anaerobes in joint infection was especially obvious in arthritis following hematogenous and contiguous spread of infection, in trauma, and in arthritis associated with prosthetic joints [6,11]. Several reports that used methods adequate for the recovery of anaerobic bacteria have described the role of anaerobes in osteomyelitis [3-5,12,13]. The microbiology of anaerobic osteomyelitis depends on the location of the bone and the underlying sources of the infection. Anaerobic osteomyelitis of cranial and facial bones is generally due to spread of infection from a contiguous soft-tissue source or from sinus, ear, or dental infection. The high concentration of anaerobic bacteria within the normal oral flora accounts for their importance in cranial osteomyelitis. The importance of intestinal anaerobes in pelvic osteomyelitis has been related to their spread from decubitus ulcers [14]. The role of anaerobes in osteomyelitis associated with peripheral vascular disease is through their access
from soft-tissue ulcers adjacent to the involved bone. Osteomyelitis of long bones is generally due to hematogenic spread, trauma, or the presence of a prosthetic device. The bacteriology of nonactinomycotic bone infection has been reviewed by Lewis et al [2]. Like Lewis et al [2], we found anaerobic streptoccoci and Bacteroides species to be the most common organisms at all sites, including bites and cranial infection. Pigmented Prevotella and Porphyromonus species were especially prevalent in skull and bite infections, whereas members of the B. fragilis group were associated with vascular disease or neuropathy. Fusobacterium species, which are members of the oral flora, were most frequently isolated from bites and from cranial and facial infections. Clostridium species were most often found in long bones, especially in association with environmental wound contamination after trauma. Because clostridial species are inhabitants of the lower gastrointestinal tract, these organisms may contaminate compound fractures of the lower extremities. Septic arthritis due to anaerobic bacteria is uncommon. Finegold [5], who reviewed the literature up to 1977, located 180 cases of septic arthritis due to obligate anaerobic nonspore-forming bacteria, 3 cases due to Actinomyces species, and 13 cases due to Clostridium species. Of interest is that no bacterial growth was noted in 18% of the cases, despite a clinical picture of septic arthritis. It is possible that a number of these cases represented anaerobic infection that was not documented because of inadequate culture methodologies. The organism most commonly observed in previous studies [5] has been Fusobacterium necrophorum. However, most reported cases date from before the antibiotic era, when Fusobacterium sepsis was more common. In this report, there were only five cases of Fusobacterium infection. Anaerobic cocci were the next most common isolate in our study, which parallels the results reported by Finegold [5]. Like Fitzgerald et al [6] and Bourgault et al [15], we found that the most common anaerobic coccal isolate was P. magnus (three isolates were recovered in prosthetic joint infections). Finegold [5] reported 20 cases of joint infections caused by members of the B. fragilis group-half of which occurred as the result of hematogenic spread. We isolated nine B. fragilis group organisms, five of which were associated with possible hematogenic spread. As in previous reports [5,16], we also observed that Clostridium species were associated with trauma. In contrast to bone infection caused by anaerobic bacteria, most cases of septic arthritis due to anaerobic organisms were not polymicrobial.
January 1993
The Amerkan Journal of Medklne
Volume 94
27
ANAEROMC DSTEOMYEUTIS
AND ARl’HRlTlS
/ BROOK AND FRAZIER
The organism that we most commonly isolated from infected joints was P. acnes. A third of the P. acnes isolates were recovered from prosthetic joints. This finding confirms the observation of Launder and Hungerford (111 and signifies the recent emergence of this organism as a pathogen. The majority of isolates were recovered in specimens from the hip and knee, where acquisition of the organisms is most likely due to direct inoculation during surgery. The growing recognition of the importance of anaerobic bacteria in bone and joint infection highlights the importance of isolating and identifying these organisms. In osteomyelitis, the most reliable source of culture would be bone biopsy obtained through uninfected skin and subcutaneous tissue [ 171. It is recommended that all biopsy specimens of infected bones be processed for the recovery of aerobic and anaerobic bacteria. When an anaerobic isolate is recognized as a major or sole pathogen, therapy should also be directed against this organism. The therapeutic approach should include management of the underlying disease, use of antimicrobial therapy directed against all major isolates based on their individual susceptibility, and removal of infected prostheses or internal fixation devices. Surgical drainage and dbbridement may be essential for removal of necrotic tissue that can BUBtain the anaerobic conditions. Meet anaerobic isolates are susceptible to penicillin or cephalosporina. However, members of the B. fragilis group and several other species of Prevotella and Porphyromonus are resistant to these agents, mostly through the production of @-lactamasea [18]. When choosing an antimicrobial agent for the treatment of infections involving @-la&mase-producing anaerobic bacteria, the pathogen should be completely identified and tested for antimicrobial susceptibility and &lactamase production. Antimicrobials that provide adequate coverage for resistant Bacteroides species as well as most other anaerobic bacteria include clindamycin, metronidaxole (excluding P. acnes), imipenem, and
28
January 1993
The An&can
Journal of Yedlclne
Volume 94
the combination of a /?-lactamase clavulanic acid) and a penicillin.
inhibitor
(e.g.,
ACKNOWLEDGMENT We acknowfedge the efforts of the staff of the Clinical Microbiology Laboratories at the Naval Medical Center and the secretarial Bar&o
assistance of Mrs. Minerva G.
and Ms. Sarah Thorpe.
REFERENCES 1. Waldvogel F4 Medoff G. Swartz MN. Osteomyelitis: tures, therapeutic 198-206.
considerations
a revfaw of clinical fea-
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2. Lewis RP, Sutter VL. Finegold SM. Bone infections invotving anaerobic bacte ria. Medicine (Baltimore) 1978; 57: 297-305. 3. RaftMJ. MeloJC. Anaerobicosteomyelitis.Medicine(t3attimore)1978; 57: 83-103. 4. Ptchichero ME, Friesen AH. Poiymicrobiil osteomyelitis: report of three cases and review of the literature. Rev Infect Dii 1982; 4: 86-96. 5. Fmegold SM. Anaerobic bacteria in human disease. New York: Academic Press, 1977. 6. Fitzgerald RA. Rosenbfatt J. Tenney JH, Bourgauft AM. AMerobic thritis. Ctin Orthop 1982; 1641 141-B. 7. Heinrich S. Putverer G. Den Nachweis U. Des &cferoi&s und Krankheitsporzessen
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me/anincgenicus
bei Mensch und Tier. Zeitschrift
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146: 331-B. 8. Holdeman LV. Cato EP. Moore WEC. editors. Anaarobe laboratory manual, 4th ed. Blacksburg. VA: Vlrgnia Polytechnic Institute and State University. 1977. 9. Sutter VL. Citron DM, Edatstein MAC, Finagokl SM. Wadsworth manual. 4th ed. Belmont, CA: Star PvMisfting. 1985.
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10. Lennette EH. Balows 4 Hausfer WJ. Shadomy CH. Manual of dinical micrcbiology. 4th ed. Washiion.
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DC American
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DS. Late infectton of total hip arthroptasty
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with
Ctin Ortftop
1981; 157: 170-6. l2 Templeton WC, Wawrukiewicz 4 Meb JC. Schiller MLG. Raff MJ. Anaerobic osteomyelitis
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Pircher F. Ostecmy-
elitfs beneath pressure sores. Arch Intern Med 1983; 143: 683-8. 11 Bourgault AM, Rosenbtatt JE. Fitzgerald RH. Peptococcus cant human pathogen. Ann Intern Med 1980: 93: 244-B. 16. Harrirtgton TM. Torretti
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D. Vicuzi FJ. Davis DE. Ckxtridium pfringns:
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an
Ann Errwrg Med 1981: 10: 31!S6.
17. Kamme C. Lindberg L Aerobic and anaerObiC bacteria in deep infections after total hi
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Differential
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18. Brook I. Pediitrfc anaerobic infection: diagnosis and management. book. St. Louis: CV Mosby Company, 1989.
A text-
