Infections caused by anaerobic bacteria are common, and may be serious and life-threatening. Anaerobes predominant in the bacterial flora of normal human skin and mucous membranes, and are a common cause of bacterial infections of endogenous origin. Infections due to anaerobes can evolve all body systems and sites. The predominate ones include: abdominal, pelvic, respiratory, and skin and soft tissues infections. Because of their fastidious nature, they are difficult to isolate and are often overlooked. Failure to direct therapy against these organisms often leads to clinical failures. Their isolation requires appropriate methods of collection, transportation and cultivation of specimens. Treatment of anaerobic bacterial infection is complicated by the slow growth of these organisms, which makes diagnosis in the laboratory only possible after several days, by their often polymicrobial nature and by the growing resistance of anaerobic bacteria to antimicrobial agents.

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Joint and Bone Caused by Anaerobes


SEPTIC ARTHRITIS


Septic arthritis is defined as a purulent infection in a joint cavity. The infection commonly reaches the joint by hematogenous spread or by direct extension of pathogenic bacteria.


Septic arthritis




Staphylococcus aureus and Group A Streptococcus are the most common etiologic agent. Other organisms include Gram negative aerobic bacilli, Neisseria gonorrhoeae, Neisseria meningiditis, Salmonella spp., H. influenzae, Kingela kingae, and anaerobic bacteria.In intravenous drug addicts, enteric bacteria, Pseudomonas aeruginosa and Candida spp. can cause septic arthritis, especially in the sternoclavicular joint and intervertebral disk space. Rare causes of septic arthritis include mycobacteria, Mycoplasma pneumoniae, and fungi such as histoplasmosis and Candida albicans.1
The predominante anaerobes recovered in arthritis include anaerobic Gram-negative bacilli including Bacteroides fragilis group, Fusobacterium, Clostridium and Peptostreptococcus spp. 2 Most of the cases of anaerobic arthritis, in contrast to anaerobic osteomyelitis, involved a single isolate. The joints most frequently involved with anaerobic infection were the larger ones, especially the hip and knee, and less frequently the elbow and shoulder. 

The major aerobic and facultative organisms isolated from prosthetic joint are  staphylococci, streptococci and select aerobic Gram-negative bacteria. The predominate anaerobic organisms arePropionibacterium acnes, Clostridium spp. ( Clostridium perfringens, Clostridium difficile, Clostridium septicum and Clostridium cadaveris.), Peptostreptococcus spp. and Finegoldia magna, Actinomyces spp., Bacteroides spp.

P. acnes infection often presents late, occurring more than 3 months after the joint implantation, with some infections presenting beyond 36 months from the date of implantation; Clostridium infection tends to present early, within three months after the initial implantation of hardware ; Actinomyces spp. generally appear after a year of implantation.
  

Pathogenesis

Most anaerobic arthritis are secondary to hematogenous spread. Predisposing conditions to joint infection are trauma, prior surgery, presence of a prosthetic joint, and contiguous infection.2 Propionibacterium acnes isolates are associated with prosthetic joints and performance of an arthroscopy3, B. fragilis group with hematogenous spread, and Clostridium spp. with trauma. 2
The presence of multiple septic joints is seen after spread from a primary site or in endocarditis.


Diagnosis

Fever, malaise, and vomiting may be present. Pain may be severe; motion is limited, and the joint is splinted by muscular spasm. An effusion develops and the overlying tissues become swollen, tender, and warm. As the infection progresses, contractures and muscular atrophy may result. Radiographic examination may reveal joint capsule distention and subsequent narrowing of the cartilage space, erosion of the subchondral bone, irregularity and fuzziness of the bone surfaces, bone destruction, diffuse osteoporosis, and associated osteomyelitis. CT can be helpful in the diagnosis of arthritis of the shoulder, hip, and sacroiliac joint. MRI is very sensitive in the early detection of joint fluid and  can delineate abnormalities of soft tissue adjacent bone, and the extent of cartilage destruction.
C-reactive protein and peripheral leukocytes count may be elevated. Culture of the blood may recover the causative organisms.

Arthrocentesis can provide a rapid diagnosis. The joint fluid glucose is generally reduced compared to serum levels and leukocytes are above 50,000 cells/mm3.33 Gram stain and aerobic and anaerobic cultures should be done.



Clues to purulent arthritis involving anaerobes include a foul odor in the joint fluid, and gas under pressure, failure to recover organisms on routine culture, Gram stain of the joint fluid showing organisms with the unique morphology, and evidence of anaerobic infection elsewhere.


Treatment

Parenteral antibiotic therapy is initiated immediately after joint aspiration, and should be guided by the results of Gram-stain and bacterial cultures. Adequate penetration into the joint is essential.
Therapy of anaerobic arthritis is not different from that required for arthritis caused by aerobes, including treatment of any underlying disease, appropriate drainage and debridement, and temporary joint immobilization.
Beta-lactamase-resistant penicillin derivative, first generation cephalosporins, vancomycin or lenizolid covers S. aureus infection. The last two agents are also effective against methicillin resistant S. aureus (MRSA).  Clindamycin, cefoxitin, carbapenems, or the combination of a penicillin plus beta-lactamase inhibitor are active against S. aureus and most anaerobic bacteria. Metronidazole is only effective against anaerobic bacteria. Antimicrobial are given for at least 3 to 4 weeks in mild cases. Orally administered antibiotics can substitute parenteral treatment after adequate control of infection and inflammation, if compliance and monitoring are possible.
Surgical drainage may be required when rapid re-accumulation of fluid occurs after the initial drainage. Drainage of pus may be intermittent aspiration or by open incision and drainage followed by continuous suction irrigation. Debridement by arthroscopy can be done in some cases of pyogenic arthritis of the knee. 


OSTEOMYELITIS

Osteomyelitis can involve all parts of a bone, although the initial focus usually involves the metaphysis. Recovery requires early diagnosis and intensive therapy.


Osteomyelitis of femur 

S. aureus is the commonest isolate from infected bones.4 Other causative agents are beta-hemolytic streptococci, Gram-negative enteric bacteria, Streptococcus pneumoniae, Haemophilus influenzae type-b, Kingella kingae, Bartonella henselae and Borrelia burgdorferi. Rare causes of osteomyelitis are mycobacteria, actinomycosis, and fungi.5
The predominant anaerobes are Bacteroides, Peptostreptococcus , Fusobacterium, and Clostridium spp, and Propionibactrium acne.2,6,7 Most specimens that yield anaerobes had polymicrobial flora, except for infections involving actinomyces.


Pathogenesis

When anaerobes are present in combination with aerobic organisms, they may act synergistically in producing disease.
Conditions predisposing to bone infections due to anaerobes are vascular disease, burns, bites, diabetes mellitus, human bites, contiguous infection, peripheral neuropathy, fractures and trauma. The organisms generally reflected the microbial flora of the mucus surface adjacent to the infected site. Pigmented Prevotella and Porphyromonas spp. are mostly isolated in skull and bite infections, B fragilis group in hand and feet infection, Fusobacterium spp. in skull, bite, and hematogenous long bone infections, Peptostreptococcus spp. in small bones of the extremities, Clostridium spp. in long bones, and actinomyces in the vertebra. 2,6,7
osteomyelitis is often an anaerobic infection elsewhere in the body. Spread to bone is by contiguous or hematogenic route. The original infection often shows characteristic of anaerobic infection such as abscess, septic thrombophlebitis, production of foul odor and gas, and tissue necrosis. Some patients have arthritis involving anaerobic bacteria, usually in an adjacent joint.

Osteomyelitis proximal tibia

Diagnosis 

Local inflammatory signs may be absent in the early stages. Later, there usually is localized erythema, warmth, tenderness, swelling, fever, elevated pulse, throbbing pain over the end of the shaft; and limitation of joint motion. Laboratory findings may reveal leukocytosis, elevated sedimentation rate and CRP. Blood cultures are generally positive early in the course. Aerobic and anaerobic cultures and staining should be performed of bone aliquots.
Radiographs may show spotty rarefaction and demineralization followed by periosteal new bone formation. Radionuclide scanning with technetium may be positive before bony changes are seen on the radiograph. MRI can differentiate cellulitis from osteomyelitis, and differentiate acute from chronic osteomyelitis.8
Although the clinical presentation of anaerobic osteomyelitis may not differ markedly from that of aerobic osteomyelitis, it should be suspected in particular clinical settings: Hand infections occurring as a result of bites, osteomyelitis of the pelvis or ilium after intraabdominal sepsis, osteomyelitis following decubitus ulcers, osteomyelitis of the skull and facial bones, chronic non-healing indolent ulcers of the foot, particularly in diabetics or in patients with associated vascular insufficiency who have underlying foci of bony involvement, presence of foul-smelling exudates and sloughing of necrotic tissue, gas in soft tissues, or black discharge from a wound or both, Gram stains of clinical material that reveals multiple organisms having different morphologic characteristics, failure to grow organisms from clinical specimens, particularly when the results of the Gram-stain has shown organisms but also with negative Gram-stains, the presence of sequestra in the bone and exacerbation of chronic osteomyelitis of long bones.

MRI of osteomylitis in spine

Treatment


Treatment includes symptomatic therapy, immobilization in some patients, adequate drainage, and parenteral antibiotic therapy. Antibiotic therapy is often started before cultures results are available, but is adjusted to the sensitivities of the isolate(s).



Penicillins, cephalosporins, clindamycin and vancomycin achieve effective bone concentrations. For S. aureus, the preferred drug is a penicillinase resistant penicillin. Vancomycin or lenizolid are effective against MRSA.  Alternatives are the cephalosporins, clindamycin, and vancomycin. Other Gram-positive organisms such as groups A and B streptococci, S. pneumoniae, Clostridium, Actinomyces, and Peptostreptococcus spp. usually are penicillin sensitive. Aerobic and facultative Gram-negative organisms should be treated with a third-generation cephalosporin, quinolone, or aminoglycoside.
Agents effective against beta-lactamase producing anaerobes ( i.e. B. fragilis group, pigmented Prevotella and Porphyromonas and Fusobacterium spp.) are clindamycin,  chloramphenicol, cefoxitin, a carbapenem, metronidazole, or the combination of a beta-lactamase inhibitor and a penicillin.
Surgical intervention often is required to establish a diagnosis and to remove foreign material. Otherwise, surgery is limited therapeutically to those who require drainage of a subperiosteal collection or debridement of necrotic or devitalized bone. Failure to respond to appropriate treatment, coupled with continued pain, swelling, fever, and elevated leukocyte count and sedimentation rate are indications for surgery.



The usual duration of therapy is 4 to 8 weeks of parenteral agent(s) and depends on the etiology, extent of infection, and clinical and laboratory responses. A change to oral route can be made when pain, fever, and signs of local inflammation have resolved, and depends on the likelihood of adherence to the oral regimen.
Hyperbaric oxygen also may be considered as adjunctive therapy for anaerobic osteomyelitis.9


REFERENCES

1.   Dubost JJ, Soubrier M, Sauvezie B. Pyogenic arthritis in adults.
Joint Bone Spine.;67:11-21. 2000.
2.   Brook, I., Frazier, E.H.: Anaerobic osteomyelitis and arthritis in a military hospital: a 10-year experience. Am J Med 94:21–8, 1993.
2a. Shah NB, Tande AJ, Patel R, Berbari EF. Anaerobic prosthetic joint infection. Anaerobe. 2015 ;36:1-8.
3.   Sulkowski, M.S., Abolnik, I.Z., Morris, E.I., Granger, D.L.: Infectious arthritis due to Propionibacterium acnes in a prosthetic joint. Clin Infect Dis 19:224–5, 1994.
4. Ray PS, Simonis RB. Management of acute and chronic osteomyeliti
Hosp Med.;63:401-7. 2002.
5.   Waldvogel, F.A., Papageorgiou, P.S.: Osteomyelitis: the past decade. N Engl J Med 303:360-70, 1980.
6.   Lewis, R.P., Sutter, V.L., Finegold, S.M.: Bone infections involving anaerobic bacteria, Medicine 57:279-305, 1978.
7.   Raff, M.J., Melo, J. C.: Anaerobic osteomyelitis, Medicine 57:83-103, 1978.
8.   Tehranzadeh, J., Wang, F., Mesgarzadeh, M.: Magnetic resonance imaging of osteomyelitis. Crit Rev Diagn Imaging 33:495-534, 1992.
9.   Sheridan, R.L., Shank, E.S.: Hyperbaric oxygen treatment: a brief overview of a controversial topic. J Trauma 4:426–35, 1999.