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Janet Wong, M.D.
Acute Osteomyelitis - Microbial Etiology
Neonate Group B streptococcus S. aureus Candida sp. Enterobacteriaceae other streptococci Infant S. aureus S. pyogenes S. pneumoniae H. influenzae Older Chid S. aureus S. pyogenes Salmonella (SSA)
There are three different routes of infection in children. The most common seems to be the hematogenesis route, which gains entry into the bone from the blood stream. Less commonly is by direct inoculation and this can be a puncture wound, such as stepping on a nail or something. This can also occur following trauma or surgery. Finally, a particular spread, which is really rare in children and seems to be more common in adults with various disabilities, especially alterations in blood flow.
Unusual Organisms and Osteomyelitis
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Penetrating trauma: soil organisms, yeast, gram negative Hemoglobinopathies: salmonella Brucella: sacroiliitis IV drug abuse: P. aeruginosa Chronic Osteomyelitis: Gram negative enteric, Staphylococcus Fractures, surgery: chronic osteomyelitis Contiguous Infection: anaerobes (bite, ulcer, sinusitis, mastoiditis) Fungi: disseminated H. capsulatum, C. immitis
What is thought to happen from the hematogenesis standpoint is that the during a course of bacteremia, as the organisms enter into the bone through the nutrient artery towards the growth plate, there are these loose capillaries that are said to have sluggish blood flow in them. It is also thought that maybe there is a fully developed reticulum within this system. There does seem to be evidence of low oxygen within the metaphysis, and we always hear about this preceding history of trauma as a possibly predisposing factor. Perhaps this is simply disruptive blood flow, but the history of trauma to children is common, and it is hard to know what really this is contributing to the pathogenesis. The nutrient artery penetrates into the diaphysis of the bone, moving up into the metaphysis and making a hairpin turn at the epiphysis. This is why it is in a long individual, at least for the tubular long bones, that osteomyelitis is more common at the ends of the bones because of these here hairpin turns. More recently there is some evidence in animals, specifically chickens, who actually can develop osteomyelitis spontaneously. A chicken strain of Staphylococcus aureus that appears at the endothelium within the capillaries of bones have gaps, and it looks as if the organisms can actually access the capillary system to these particular gaps. If you take a Staph aureus and inject it into the blood of the chicken, within 12 hours you can see bacteria in some of these capillaries, and subsequently a day or two later, evidence of infection at the metaphyseal epiphyseal junction. So this is sort of an interesting animal experiment, perhaps showing that these epithelial gaps, at least in chickens, play some role. Another factor in the development of osteomyelitis, at least relating to Staphylococcus aureus, is the organism that produces this sort of slimy stuff seems to make it more adherent to various portions of the bones and thus more commonly associated with osteomyelitis than those other organs. Microbial etiology of osteomyelitis. In the neonate, the organisms most commonly associated with osteomyelitis are typically Group B streptococcus and Staphylococcus aureus. Very small babies may involve for various gram negative bacteria and certainly cause osteomyelitis as well as some other bacteria. In the infant and older child, Staphylococcus aureus is the most common cause. Streptococcus is the second most common. Highly encapsulated organisms are unusual causes of osteomyelitis, but 3 to 5% of patients with acute osteomyelitis will have pneumococcus as the etiology. In the older child, the same types of organisms are seen. Salmonella is an important pathogen in patients with sickle cell anemia. With penetrating injuries, organisms associated with the soil or the skin or on clothes can of course lead to infection. Some of these injuries, such as injuries associated with lawn mower trauma, can grind the soil-type organism into the skin and ultimately into the bone. Now, sacroiliitis is not necessarily specifically an osteo, it is an osteo-like illness we must keep in mind, especially in dealing with certain populations, especially those who are likely to ingest under pasteurized or nonpasteurized dairy products. IV drug abuse is associated with P. aeruginosa, hopefully not a major problem in kids, but it certainly is something that is seen in adults. Chronic osteomyelitis is associated with gram negative organ-
Clinical Manifestations of Osteomyelitis
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isms. With fractures, this may lead to a chronic infection. Contiguous infections which are not that common in pediatric patients may be associated with anaerobic organisms. Perhaps it is a decubitus ulcer, perhaps sinusitis, and after that may lead to osteomyelitis of facial or scalp or skull bones. Finally, certain fungi can disseminate and cause infection on the bone. The clinical manifestations of osteomyelitis include fever and limitation of the extremity or the part of the body that is involved. Localized swelling, warmth, erythema, and point tenderness especially would be major clinical findings suggesting osteomyelitis. Now, outside of the extremities it could sometimes be very difficult to pinpoint or even think about osteomyelitis. It could be a subtle finding. For example, patients with pelvic osteomyelitis may have a slight abdominal pain, perhaps they have some hip pain or have some trouble walking, but when you examine their extremities you really cannot pinpoint anything. It is not until you do some more specific physical examinations, perhaps even a rectal examination, that they sort of come up on this diagnosis. Vertebral osteomyelitis typically occurs in older children with back pain and tenderness when you palpate or stretch over the spinal processes. Finally, in neonates, one may see osteomyelitis in association with septic arthritis because of the way the epiphysealmetaphyseal junction is actually positioned inside the joint, so that the organism is able to rupture through the bone, it will rupture into the joint space. In older children, typically if there is a rupture through the periosteum; it will not rupture into the joint space. Also, in contrast to what might happen in older children where a single bone is what is most typically seen), in the neonate, multiple bones are commonly infected.
Fever, limitation of use of involved extremity or area. Localized swelling, warmth, erythema and pain (point tenderness) Pelvic osteomyelitis: hip and/or abdominal pain, difficulty walking, rectal mass Vertebral osteomyelitis: back pain, tenderness over spinal processes Neonates- frequently accompanied by septic arthritis since epiphyseal, metaphyseal junction within joint capsule; multiple bones Infected, pseudoparalysis (high risk for sequelae
Pseudomonas osteochondritis: foot puncture wound followed by local findings in 48-96h; fever not prominent
Differential Diagnosis of Osteomyelitis and Septic Arthritis
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Rheumatic fever Cellulitis Skeletal Neoplasia (Ewing's sarcoma, leukemia) Bone Infarction in hemoglobinopathy Hemophilia Thrombophlebitis Child Abuse/Trauma Toxic synovitis Appendicitis, UTI, Psoas abscess (Pelvic osteomyelitis)
Diagnosis of Osteomyelitis
Laboratory • ESR or CRP elevated • Blood and bone aspirate cultures
Diagnosis of acute osteomyelitis. The erythrocyte sedimentation rate is generally elevated. Other people like to get the C-reactive protein and other nonspecific inflammatory laboratory tests. CRP seems to come down more rapidly than the ESR. If there sed rate is coming down slower, maybe I can draw out the therapy a little bit longer. From a radiographic standpoint, plain films are frequently helpful, but generally they are useful later in the course because we know they will not show specific changes for 7, 10 or 14 days. This is how long it takes for decrease in bone mass to occur, and that will show on your x-ray. Periosteal new bone formation may also not be apparent for about 10 or 14 days. The indications to undergo a technician bone scan. This is abnormal in the vast majority of patients. It is not helpful in the neonate, it is not helpful in those patients who have a fracture or surgery. It is not helpful to patients with hemoglobinopathies where an infarction and an infection cannot really be distinguished by a typical bone scan. In special situations, a CT and MRI could be particularly helpful. This is especially true in patients that have pelvic osteomyelitis, perhaps those with vertebral osteomyelitis. Then, many times when it is not clear what is going on, you really would like to have an organism, an actual bone biopsy as opposed to aspiration. A biopsy where one can look at the bone under the microscope as well as get a good culture can be very helpful. I think these are most useful in the usual cases. The inflamed bone is typically of osteomyelitis, for vertebral osteomyelitis they are very helpful. CT scans are very helpful. MRIs seems to be getting more popular, and surgeons particularly like to obtain these types of radiographic imaging prior to surgical approaches, so I think we are going to see more MRI evaluations.
Radiology • Plain films - typical changes occur in 10-21 days (bone destruction, periosteal new bone) • Tc99m Bone Scan - abnormal in over 90% (not as useful in neonates or following fracture or surgery) • CT/MRI - may be helpful in unusual cases (pelvic, vertebral, skull) • Bone biopsy and culture - useful in unusual or chronic cases
Antibiotic Management of Osteomyelitis
Organism S aureus Agent Nafcillin/oxacillin Alternatives: clindamycin or cefazolin Streptococci P aeruginosa osteochondritis Salmonella penicillin Ticarcillin/Piperacillin + aminoglycoside ampicillin if susceptible; cefotaxime, ceftriaxone, TMP-SMX as above 7-10 days if adequate debridement 3-4 weeks Duration (minimum) 3 weeks and ESR <2030 mm/h Neonate - 4 weeks
Antibiotic management of acute osteomyelitis. I think that for the straight forward cases, related especially to Staph aureus, a typically nafcillin or oxacillin is initially provided and that can be a good initial therapy. Antibiotics should be continued either IV or orally for a minimum of three weeks, and shows that treatment for less than three weeks in acute osteomyelitis will lead to more relapses. So, greater than three weeks is what is recommended, and typically four to six weeks is what is provided. I like to see the sed rate below 30 mL per hour before I discontinue therapy. I think that whether you should provide therapy intravenously or orally is somewhat up to each individual and the parents, and what their home situation is like, what can be done from the home IV therapy standpoint, and whether the organism has been isolated.
Management of Osteomyelitis
For Group A Streptococcus I think penicillin alone is fine. Osteochondritis should be treated with a combination of antibiotics, but an surgical debridement is most important.
Indications for Surgery • Drain purulent material from subperiosteal space or other tissue planes • Remove sequestra or infected foreign material • Débride and drain puncture associated infection • In neonate early drainage of bone and joint is critical • Chronic osteomyelitis
Serum titers, we are saying that we are taking a specimen of blood at some point around the dose of an antibody before a dose which would be the trough level or right after a dose IV, perhaps an hour and a half after an oral dose would typically represent the peak in the serum concentration and therefore test the inhibition of the organism. You simply take the organism which you hopefully have identified and have isolated in the micro lab, and inoculate that into serial 2-fold solutions of this serum. As I mentioned, typically you like to treat these patients for four to six weeks; either IV or orally depending on the organism and the situations. Now, there are some times when you want to perform surgical drainage; I think that if the surgeon went in to aspirate the region or he might even see it on an MRI scan or CT scan, there is an actual subperiosteal abscess that should be drained. If there is a sequestra or there is swollen material within the bones, that needs to be drained. In the neonate, these need to be drained. For Salmonella, ampicillin is generally the treatment of choice if the organism is susceptible to this antibiotic.
Etiology of Septic Arthritis and Age
Organism S. aureus Neonate +++ +++ -+ 2-36 months >36 months +++ ++ + +++ ---+ ++ + ++ ++ ++ –
Organisms that cause septic arthritis in children. Again, in the neonate, Staph aureus and Group B streptococcus are going to be the leading organisms. Candida albicans and gram negative are also apparent in premature infants. In the child between 2 and 36 months of age, Staph aureus is the most common. The second most common is going to be pneumococcus. Salmonella is something to think about in patients with hemoglobinopathies. In older individuals Staph aureus, Group A strep, and pneumococcus are the leading causes of septic arthritis. Puncture wounds of the foot frequently are caused by nail injuries through the tennis shoe or some other shoe penetration and inoculation of the bones. The majority of the patients have Pseudomonas aeruginosa isolated either by itself or combination of Staph aureus or streptococci. When the surgeons explored the wounds, osteochondritis was noted in all of the patients. There was also some septic arthritis and some cutaneous abscesses also noted. So, the course of exploration clearly is important. I think it is a conclusion that in this infection, which is a infection of cartilage, that it is important to perform the optimum surgery which would be to débride and devitalize the infected soft tissue cartilage and bone. You need to drain these joints. Then when you do that, one may only have to treat with antibiotics for perhaps seven to ten days. So, this is in contrast to what we are typically taught in treating osteomyelitis for a prolonged period.
S ,pneumoniae S. pyogenes --
Group B streptococcus N. gonorrhoeae Candida sp. ++ H Influenzae – (unimmunized) Salmonella (SSA) Kingella kingae + -– ----
Clinical Manifestations of Septic Arthritis
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Acute onset fever, refusal to walk or limp Large joints (knee, hip, ankle) most common Swelling, warmth, erythema of joint with decreased mobility Abduction and external rotation is typical with hip In neonate systemic symptoms may be minimal In neonate multiple joints and contiguous osteomyelitis are common Small joints tend to be involved with gonococcal infection
Clinical manifestations of septic arthritis. We have the acute onset of fever, refusal to walk, a limp would be the classic manifestation in a baby. Perhaps the parents indicate that when they change the diaper the baby is crying. Most of the time large joints are involved. You might see a swelling, warmth, erythema, and decreasing mobility in the joint. In the hip, the classic presentation would be abduction and external rotation. In the neonate, however, the symptoms may be very minimal. You might have multiple joints involved and many bones infected as well, and it is more or less hip. When you look at this baby you might see that there is a slight dyssymmetry, and, in the baby, you may illicit some pain on movement but it may be very subtle.
Differential Diagnosis of Septic Arthritis
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Nonbacterial infection- virus, hepatitis, Tb, fungi, Lyme disease Juvenile rheumatoid arthritis, other collagen vascular disease Acute rheumatic fever Inflammatory bowel disease Leukemia Toxic synovitis, psoas abscess, pelvic osteomyelitis (when unable to bear weight) Reactive arthritis (Shigella, Yersinia, Salmonella; Endocarditis Trauma (hemarthrosis) Cellulitis
Evaluation- Septic Arthritis
1. 2. Blood cultures positive in approximately 40% of cases Synovial fluid - culture and Gram-stain WBC count/mm3 %PMN Fluid: blood glucose Septic arthritis JRA >50,000 <15-20,000 90% 60%
In the evaluation of septic arthritis, a blood culture is very helpful and in some studies it has been positive in up to 40% of patients., what you want to get is a sample of the synovial fluid, a blood culture, and a gram stain. Classically, if the white blood cell count of the synovial fluid is greater than 50,000 with predominance of polys, then this most likely a bacterial infection. If the count is between 15,000 to 20,000, maybe less than 10,000, with a smaller proportion of polys and the glucose limit is normal, this is more likely to be a juvenile rheumatoid arthritis or some other collagen vascular disease. If we are dealing with an adolescent, and GC is a consideration, then vaginal or urethral cultures should be obtained. Sometimes the plain radiography can give you some additional clues as to the foreign body scenario and a bone joint scan can sometimes be useful as well.
normal to 9 (75%)
3. 4. 5.
Vaginal or urethral culture if appropriate Plane Radiograph: soft tissue swelling, joint space widening, osteomyelitis Bone joint Tc-99m Scan
Empiric Antibiotics for Septic Arthritis Age Neonate Agents Nafcillin/Vancomycin + aminoglycoside/ cefotaxime Infant or child Nafcillin/oxacillin add cefotaxime/ ceftriaxone if no Hib vaccine (cefuroxime) Adolescent with presumed GC Immunocompromised child Nafcillin/oxacillin plus aminoglycoside or extended spectrum cephalosporin 3 weeks Ceftriaxone 7 days 3 weeks S. aureus 2 weeks H. Influenzae Duration 3 weeks
Empiric antibiotics for septic arthritis. Nafcillin is the drug that we would use in the nursery now. Vancomycin might be started initially because of what is going on in your nursery with the aminoglycoside or cefotaxime. In the infant or child this should read Nafcillin or oxacillin, plus cefotaxime regardless of Hib immunization, because of the problem with penicillin is just a pneumococcus. If one should have the organism then, I think you can tailor the treatment more readily. In the adolescent, ceftriaxone should be the drug.
Septic Arthritis: Indications for Surgery
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Join remains swollen and erythematous after repeat needle aspiration Removal of foreign material secondary to penetrating Hips should be drained surgically In neonate surgical drainage of most joints indicated Arthroscopic lavage of knee alternative to arthrotomy
Indications for surgery. If you have repeat aspiration of the joint and it remains swollen and erythematous, surgery of the joint is indicated to remove foreign material, certainly all hips should be drained. Some people might say all shoulder infections as well. In some situations you can actually do arthroscopy rather than surgical incision and drainage. It depends on the site and size of the joint. There are some risk factors for outcome for septic arthritis that I have also provided for you.
Risk Factors for Sequelae of Septic Arthritis
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Young age <6-12 months (especially neonate) Prolonged duration of symptoms prior to treatment Hip and shoulder infection (especially with S. aureus Sequelae • Cartilage damage, stiff joint with poor mobility, abnormal bone growth if epiphysis involved, unstable joint, chronic dislocation
Discitis - Clinical Manifestations
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Low-grade fever Infants: Refusal to sit, pain when changing diaper Young child: Hip or leg complaints, and refusal to walk or limps; irritable Older child with back pain, abdominal pain Pain on palpation over vertebral processes Paraspinal muscle spasm Differential diagnosis: Toxic synovitis, vertebral osteomyelitis, epidural abscess, pelvic osteomyelitis, sacroiliitis (Brucellosis)
Discitis or disc space infection. This is more common in young children. The history can be one of nominal pain, a back pain, or difficulty walking, and a child not wanting to sit. The diagnosis is typically made on plain film and bone scans. If you do an MRI or CT on a patient, it can look terrible. Management is with an oral antistaphylococcal agents and let the child ambulate as tolerated, usually in their own room with bed rest.
Discitis- Diagnostic Evaluation and Management
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Plan radiographs: disc space narrowing Bone scan: abnormal uptake in disc space and adjacent vertebral bodies MRI or CT are necessary if clinical and initial radiographic findings are not typical Management: Rest and oral antistaphylococcal antibiotic for 34 weeks and ESR <20 mm/hr
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