Journal of the American Academy of Orthopaedic Surgeons 166 The annual rate of acute hematog- enous osteomyelitis in children under the age of 13 in the United States is estimated to be approxi- mately 1:5,000. 1 Population studies show a worldwide incidence rang- ing from 1:1,000 to 1:20,000, 2 making this an uncommon, but not a rare, problem. Half of all cases of acute hematogenous osteomyelitis occur in children under the age of 5. 3 Neo- natal osteomyelitis is estimated to occur in 1 to 3 infants per 1,000 intensive-care-nursery admissions. 3 Before the advent of antibiotics, bacterial osteomyelitis in children carried mortality rates of 20% to 50%. 2,4 Advances in antibiotic treatment, diagnostic modalities, and surgical management have made death uncommon, but mor- bidity due to delays in diagnosis and inadequate treatment continue to result in permanent sequelae and poor outcomes in as many as 6% of affected children. 4,5 Failure of cultures to demonstrate patho- genic bacteria in many patients, poor understanding of the patho- physiology of bone infections, and emerging antibiotic resistance have led to the development of many different empirical treatments. However, recent advances in the evaluation and management of acute hematogenous osteomyelitis and a thorough understanding of this disease entity will help to ensure accurate diagnosis and prompt treatment. Basic Science The etiology and pathophysiology of bone infections are still incomplete- ly defined. Introduction of bacteria into bone can occur by direct inocu- lation, hematogenous spread from bacteremia, or local invasion from a contiguous focus of infection. A his- tory of trauma is common. Most long-bone infections occur in the metaphyseal portions of tubular bones of the lower extremities (Fig. 1). The majority of infections involve only a single bone; involvement at two or more sites is very uncommon except in neonatal infections. Infection spreads via Volkmann’s canals or the haversian bone system through the metaphyseal bone to the subperiosteal space. Elevation of the periosteum can result in ab- scess formation. In severe cases, infarction of cortical bone may lead to the formation of a sequestrum and chronic osteomyelitis. Septic arthritis can occur in joints in which the metaphysis is intra- Dr. Song is Assistant Director of Orthopedic Surgery, Children’s Hospital and Regional Medical Center of Seattle, Seattle, Wash. Dr. Sloboda is Resident in Orthopaedic Surgery, Madigan Army Medical Center, Tacoma, Wash. Reprint requests: Dr. Song, Department of Orthopedic Surgery, Children’s Hospital and Regional Medical Center of Seattle, 4800 Sand Point Way NE, Seattle WA 98105. Copyright 2001 by the American Academy of Orthopaedic Surgeons. Abstract Acute hematogenous osteomyelitis in children is a relatively uncommon but potentially serious disease. Improvements in radiologic imaging, most notably magnetic resonance imaging, and a heightened awareness of this condition have led to earlier detection and resultant marked decreases in morbidity and mortal- ity. Staphylococcus aureus, which has the ability to bind to cartilage, pro- duce a protective glycocalyx, and stimulate the release of endotoxins, accounts for 90% of infections in all age groups. Infections with Haemophilus influen- zae have become rare in immunized children. A careful history and a thorough physical examination remain important. Positive cultures are obtained in only 50% to 80% of cases; the yield is improved by the use of blood cultures and evolving molecular techniques. Improvements in antibiotic treatment have lessened the role of surgery in managing these infections. Sequential intra- venous and high-dose oral antibiotic therapy is now an accepted modality. Evaluation of response to treatment by monitoring C-reactive protein levels has decreased the average duration of therapy to 3 to 4 weeks with few relapses. The emergence of antibiotic resistance, particularly resistance to methicillin and vancomycin by S aureus organisms, is of increasing concern. Long-term sequelae and morbidity are primarily due to delays in diagnosis and inadequate treatment. J Am Acad Orthop Surg 2001;9:166-175 Acute Hematogenous Osteomyelitis in Children Kit M. Song, MD, and John F. Sloboda, MD Kit M. Song, MD, and John F. Sloboda, MD Vol 9, No 3, May/June 2001 167 articular (e.g., hip, shoulder, and ankle). It has been estimated that 10% to 16% of cases of septic arthri- tis are secondary to bacterial osteo- myelitis. The avascular physis gen- erally limits extension of infection into the epiphysis except in neo- nates and infants. Blood vessels cross the physis until approximately 15 to 18 months of age, with the potential for concomitant septic ar- thritis. This may be present in as many as 75% of cases of neonatal osteomyelitis. 3 Fewer than 20% of infections occur in nontubular bones. The cal- caneus and pelvis are the most com- mon sites. Infections in the flat bones (e.g., the skull, scapula, ribs, and sternum) and the spine are rare. 2 Staphylococcus aureus is by far the most common pathogen causing acute hematogenous osteomyelitis in all age categories. It has been im- plicated in as many as 89% of all in- fections. Streptococcus pneumoniae, group A Streptococcus, and coagulase- negative staphylococci are more age- and disease-specific. Group B strepto- cocci have been found with greater frequency in neonates, but account for only 3% of infections in this age group. 3 Infections with these patho- gens generally result in a single focus of infection, unlike neonatal infec- tions with group A streptococci and S aureus. The introduction of a vac- cine against Haemophilus influenzae type b has led to a marked decline in the incidence of infections by this organism from 2% to 5% of all bone infections to nearly 0% in immu- nized children. 1-3,5-7 Avian models of bone infection most closely mimic what is observed in humans and have provided infor- mation about the pathophysiology of bone infections. Gaps in the en- dothelium of growing metaphyseal vessels allow the passage of bacteria that then adhere to type I collagen in the hypertrophic zone of the growth plate. Staphylococcus aureus surface antigens appear to play a key role in this local adherence, while endotox- ins suppress local immune response. An extensive glycocalyx surround- ing each bacterium enhances adhe- sion of other bacteria and may be protective against antibiotic treat- ment. Bacterial proliferation then occurs, occluding vascular tunnels within 24 hours. Abscesses appear after 48 hours, with local tissue necrosis and extension beyond the calcifying area of the growth plate. Four to eight days after infection, localized sequestra of dead cartilage are formed, and infection extends beyond the metaphysis. Further bone destruction may be mediated by prostaglandin production as a result of S aureus infection. 8,9 Diagnosis Bacterial osteomyelitis in children must be differentiated from the wide range of conditions that may present with clinical symptoms and signs mimicking infection (Table 1). Figure 1 Sites of acute osteomyelitis in 657 children with single-site involvement. (Adapted with permission from Gutierrez KM: Osteomyelitis, in Long SS, Pickering LK, Prober CG [eds]: Principles and Practice of Pediatric Infectious Diseases. New York: Churchill Livingstone, 1997, p 529.) Ulna 3% Pelvis 9% Radius 4% Humerus 12% Tibia 22% Fibula 5% Femur 27% Hands and feet 13% Table 1 Differential Diagnosis of a Painful, Swollen Extremity in a Child Systemic conditions Acute rheumatic fever Chronic recurrent multifocal osteomyelitis Fungal arthritis Gaucher’s disease Henoch-Schönlein purpura Histiocytosis Leukemia Primary bone malignant tumors Reactive arthritis Reiter’s syndrome Round cell tumors Sarcoidosis Septic arthritis Sickle cell disease Systemic juvenile rheumatoid arthritis Tuberculosis Nonsystemic conditions Cellulitis Fracture/nonaccidental trauma Hemangioma/lymphangioma Histiocytosis Legg-Perthes disease Osteochondrosis Overuse syndromes Reactive arthritis Reflex neurovascular dystrophy Slipped capital femoral epiphysis Stress fracture/toddler’s fracture Subacute osteomyelitis Transient synovitis Acute Hematogenous Osteomyelitis in Children Journal of the American Academy of Orthopaedic Surgeons 168 The history and physical examina- tion findings associated with acute hematogenous osteomyelitis are sen- sitive but rarely specific. The most frequent clinical findings are fever, pain at the site of infection, and lim- ited use of the affected extremity. Constitutional symptoms, such as lethargy and anorexia, are less com- mon. The degree of abnormality does not correlate with the extent of infection, and older children will often have more subtle symptoms. Most patients will have had symp- toms for less than 2 weeks. On physical examination, signs are often age-dependent. Neonates have a thin periosteum that is easi- ly penetrated by infection and as a result frequently have swelling at the affected site and irritability on movement of the limb. Infants and young children will have point ten- derness with limited ability to bear weight or use the extremity. Older children, with their thicker metaph- yseal cortex and densely adherent periosteum, will generally have point tenderness and a mild limp. Cellulitis is occasionally present and may be a manifestation of an underlying abscess. 1-4,6,10 Serologic Studies Serologic studies that should be ordered when evaluating a child with possible acute hematogenous osteomyelitis include a complete blood cell (CBC) count with differ- ential and peripheral smear, eryth- rocyte sedimentation rate (ESR), C- reactive protein (CRP) determina- tion, and blood cultures. As most blood counts are automated, in- spection of the peripheral smear can be helpful in eliminating the possibility of leukemia. The white blood cell (WBC) count will be ele- vated in 31% to 40% of patients with acute hematogenous osteomyeli- tis 6,11,12 ; the ESR, in up to 91%. 6,11-13 Several authors have reported on the usefulness of the CRP level in making the diagnosis and fol- lowing response to treatment of acute hematogenous osteomye- litis. 12-14 On presentation, it is ele- vated in as many as 97% of pa- tients. The degree of rise of the CRP has not been correlated with severity of infection. The CRP rises more rapidly than the ESR after onset of infection, with synthesis beginning within 4 to 6 hours after injury and peaking after 24 to 72 hours (Fig. 2). Failure of the CRP level to fall rapidly after initiation of treatment has been predictive of long-term sequelae. 15 Unlike the ESR, the CRP concentration is inde- pendent of the physical properties of cells and is a direct quantitative measurement. Similar to the ESR, it will rise and fall after surgery, trauma, or systemic illnesses, as well as in patients with benign and malignant tumors, thereby limiting its usefulness in some situations. 16,17 Both the ESR and CRP are frequently elevated in neonatal infections, 18 but the response to treatment of these indices has not yet been doc- umented. Radiologic Evaluation Radiography remains an essential tool for diagnosing and managing osteomyelitis in children and should be performed in every case of sus- pected infection. The sensitivity and specificity of radiographs range from 43% to 75% and from 75% to 83%, 19 respectively (Fig. 3). Soft- tissue swelling will be evident with- in 48 hours of the onset of infection. Periosteal new-bone formation may be evident by 5 to 7 days. Osteolytic changes require bone mineral loss of at least 30% to 50% and may take 10 days to 2 weeks after the onset of symptoms to develop. 19,20 Technetium-99m bone scintigra- phy is useful in the setting of nor- mal radiographs and clinical suspi- cion of osteomyelitis (Figs. 4, A; 5, B). It can be positive within 24 to 48 hours of the onset of symptoms. The reported sensitivity ranges from 84% to 100% for detection of osteomyelitis; the specificity, from 70% to 96%. 19 Aspiration of bone has not been shown to create a false-positive result if bone scintig- 100 160 140 120 80 60 40 20 0 0 Days Days Osteomyelitis alone Osteomyelitis with adjacent arthritis CRP, mg/L ESR, mm/hr CRP, mg/L ESR, mm/hr 5 10 15 20 25 30 100 160 140 120 80 60 40 20 0 0 5 10 15 20 25 30 CRP ESR CRP ESR Figure 2 Rise and fall of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in 50 patients with osteomyelitis with and without associated septic arthritis. Shaded areas indicate the normal range of values. Bars indicate 1 SD. (Reproduced with permission from Unkila-Kallio L, Kallio MJT, Peltola H: The usefulness of C-reactive pro- tein levels in the identification of concurrent septic arthritis in children who have acute hematogenous osteomyelitis: A comparison with the usefulness of the erythrocyte sedi- mentation rate and the white blood-cell count. J Bone Joint Surg Am 1994;76:848-853.) Kit M. Song, MD, and John F. Sloboda, MD Vol 9, No 3, May/June 2001 169 raphy is carried out within 24 hours of aspiration. The use of pinhole- collimated views and single-photon- emission computed tomography (SPECT) (Fig. 5, C) can increase both sensitivity and specificity. 21 In the early stages of an infection, scintig- raphy may show decreased uptake because of the relative ischemia caused by the increased pressure from the presence of purulent mate- rial (Fig. 3). Such “cold” scans have been reported to have a positive pre- dictive value of 100%, compared with a positive predictive value of 83% for “hot” scans. 21,22 Scintigraphy is of more limited use in neonatal in- fections, with reported sensitivity ranging from 30% to 86%; radiogra- phy may be more sensitive in this setting. 2,3,10 Gallium scanning, although more sensitive for infection than Tc-99m scanning, delivers a higher amount of radiation, may take up to 48 hours to perform, and is not specific for infection. Scanning with indium- 111–tagged WBCs can be helpful in those rare situations in which osteomyelitis is suspected but the Tc-99m scan appears normal. 2,19 It requires preparation time and can take as long as 24 hours to perform. Monoclonal antibody scans have been investigated, but are as yet of unproven benefit. 2 Magnetic resonance imaging has a reported sensitivity of 88% to 100% and a specificity of 75% to 100% in the detection of osteomye- litis. The positive-predictive values for MR imaging and Tc-99m scin- tigraphy are comparable (85% and 83%). 20 However, MR imaging can provide biplanar images of the in- fected site and is superior to scintig- raphy and CT for depicting the marrow cavities of long bones and adjacent soft tissues. It is most use- ful for detecting spinal and pelvic infections (Fig. 5, D) and for plan- ning surgical approaches for de- bridement when a subperiosteal or soft-tissue abscess may be pres- ent. 19-21,23,24 Characteristic T1- and T2-weighted images can be used to differentiate acute, subacute, and chronic osteomyelitis. 24 T1-weighted and short-tau inversion recovery (STIR) images are most useful for the detection of acute osteomyelitis (Fig. 4). The use of gadolinium en- hancement can aid in identifying sinus tracts and distinguishing cel- lulitis from abscess. 19 Like scintig- raphy, MR imaging is limited by a lack of specificity; the signal pat- terns seen with fractures, bone infarction, tumors, postsurgical changes, bone contusions, and sym- pathetic edema are similar. 24 Computed tomography has been most useful in the detection of gas in soft-tissue infections and in the identification of sequestra in cases of chronic osteomyelitis. 19,21 It is also useful in diagnosing and accu- rately defining the location of pelvic and spinal infections after localiza- tion with scintigraphy (Fig. 5). For deep infections, needle localization prior to biopsy or debridement can be helpful. Ultrasonography is attractive for evaluating the possibility of bone and joint infections in children because of its low cost, relative avail- ability, and noninvasive nature, as well as because there is no ionizing radiation involved and no need for Figure 3 A, Radiograph of a child with a swollen forearm, elevated temperature, and elevated CRP value. B, Technetium bone scan per- formed on day of presentation was interpreted as normal, although it shows a “cold” left radius (i.e., area of decreased radionuclide uptake). C, Follow-up radiograph at 6 weeks shows periosteal elevation of the entire radius. D, Follow-up radiograph at 3 months demonstrates seg- mental bone loss in the radius. A B C D Acute Hematogenous Osteomyelitis in Children Journal of the American Academy of Orthopaedic Surgeons 170 sedation. It has been used to detect intra-articular, soft-tissue, and sub- periosteal fluid collections prior to their appearance on plain radio- graphs. However, the lack of speci- ficity, dependence on operator skill, and inability to image marrow or show cortical detail of bone have limited the usefulness of ultrasound compared with MR imaging or CT. An algorithm for radiologic evaluation of suspected bone infec- tions is shown in Figure 6. Radiog- raphy should be the initial study. If positive, MR imaging, CT, or ultrasonography can be used to de- fine the infected area and to plan surgical approaches if needed. If the results of any of those studies are negative, scintigraphy can be very helpful in isolating the infected area, after which one of the other modalities can be used to provide additional information for treat- ment planning. Bacterial Cultures Obtaining cultures of organisms directly from sites of bone infection in order to focus antibiotic treat- ment is critical to effective manage- ment. 2,3,25 However, direct culture of the affected bone results in isola- tion of the bacterial agent in only 48% to 85% of cases. 5,6,26,27 Given the potentially low yield from cul- tures and the reluctance to perform invasive procedures on distressed children, it may be tempting not to perform bone aspiration. Neverthe- less, concerns about emerging anti- biotic resistance by bacteria make the identification of pathogens and the use of organism-specific treat- ment desirable. Aspiration is easily performed through thin metaphyseal bone with an 18-gauge spinal needle, and the central trocar can be used to dis- engage any bone plugs created by passage through the cortex. Local infiltration of lidocaine into the tis- sues combined with intravenous sedation is generally effective. The aspiration of bone through an over- lying area of cellulitis has not been shown to cause osteomyelitis. Direct culture of cellulitic areas yields a positive culture in fewer than 10% of cases, 28 with Staphylococcus and Streptococcus species being most commonly isolated. Blood cultures are positive in 30% to 60% of cases of acute osteomye- litis in children. 1,4,6,27 The use of multiple blood cultures has not been shown to increase the likelihood of having a positive culture, especially if the samples were drawn after the initiation of antibiotic treatment. The combination of blood and direct cultures provides the highest yield, but in many cases treatment of pre- sumed infections will be empirical, based on clinical and radiographic criteria. Most bacterial cultures will be positive within 48 hours of speci- men collection. However, fastidi- ous organisms may take as long as 7 days to become positive. A survey of hospitals in one area showed that cultures are held an average of 5 days before being discarded. A B C D Figure 4 A, Technetium bone scan shows acute osteomyelitis in the distal left femur. B, T1-weighted MR image also demonstrates acute osteomyelitis, which was confirmed by biopsy and treated with intravenous antibiotics. C, A STIR MR image further demon- strates acute osteomyelitis. D, Gradient-echo MR image illustrates growth arrest due to the infection. Kit M. Song, MD, and John F. Sloboda, MD Vol 9, No 3, May/June 2001 171 The relatively low yield of stan- dard bacterial cultures has stimulated interest in using molecular tecniques for detection and speciation of bacte- rial and viral infections. Molecular methods have been shown to be more sensitive than standard culture techniques for detecting pathogens and can do so even in the absence of viable organisms. These techniques fall into two broad categories: non- amplified and amplified. With non- amplified techniques, direct binding of a target molecule is done with a labeled oligonucleotide probe or monoclonal antibody, followed by detection of the probe agent with radiolabeling, enzyme-linked immu- nosorbent assay, or chemolumines- cence. These methods are specific and applicable when looking for a particular organism. With amplified techniques, geo- metric amplification of the target molecule is achieved by using enzyme-driven reactions. The most common of these techniques is the polymerase chain reaction (PCR). The basis of these methods is to tar- get a portion of bacterial DNA or RNA that is not present in human cells. A probe or primer specific to that region of DNA or RNA is in- troduced, which on binding pro- motes binding of a polymerase that replicates the target region in a series of temperature-dependent cycles. The amplified products are then identified by gel electrophoresis. Much recent work has focused on the highly conserved area of DNA that codes for the 16s ribosomal RNA subunit. There is enough gene se- quence variation within this area to allow differentiation among bacterial species and from human DNA. 29,30 Polymerase chain reaction has produced some promising results in diagnosing periprosthetic infec- tions and septic arthritis, but a high false-positive rate has been ob- served. 31 The PCR method has been found to be very sensitive for the detection of infection when a primer for a specific organism is used. In cases of polymicrobial infection or infection due to an unknown bacter- ial strain, the use of universal prim- ers that amplify all bacterial species present is being developed. Identi- fication of the amplified genetic ma- terial remains difficult. Treatment The management of acute hematog- enous osteomyelitis is largely non- operative. The role of surgery is to improve the local environment by removing infected devitalized bone and soft tissue, decompressing a Acetabular roof Proximal femur A B C D E Figure 5 A, AP radiograph of a 15-year-old girl with right hip pain. B, Technetium bone scan of hips with pinhole collimation. C, SPECT images of the right hip show lesion in the supra-acetabular area. D, MR image depicts pelvic osteomyelitis. E, Brodie’s abscess of the acetabulum was localized on this CT scan prior to biopsy. large abscess cavity, and facilitating antibiotic delivery. If antibiotic treatment is initiated before signifi- cant bone and soft-tissue necrosis has occurred, it is more likely to be successful without the need for sur- gical treatment. Antibiotic Therapy Most recent studies of antibiotic treatment of acute hematogenous osteomyelitis have emphasized a sequential parenteral-oral antibiotic regimen. 2,3,5,12,13 Due to the low yield of culture techniques, empirical treatment based on known epidemi- ologic trends in different age groups and at-risk populations will often be necessary (Table 2). Empirical antibiotic coverage should always include coverage for S aureus, as this is the most common pathogen in all age groups. For neo- natal osteomyelitis, treatment tar- geting group B streptococci and Gram-negative rods should be added. Children less than 4 years of age need antibiotic coverage for H in- fluenzae type b if the immunization program has not been completed or the history is uncertain. For fully immunized children, the most likely pathogens are S aureus, Streptococcus pyogenes, and S pneumoniae. For im- munocompromised children with sickle cell disease, broad-spectrum coverage to include Salmonella spe- cies should be included. Children with human immuno- deficiency virus (HIV) infection have a propensity for infection by S pneumoniae. However, to date, there is no evidence to suggest that pre- senting signs and symptoms or re- covery from infection are affected by coinfection by HIV. Broad-spectrum coverage is suggested for HIV- positive children due to the wide range of organisms reported. 2 Antibiotic selection should sub- sequently be altered according to the results of culture and sensitivity testing. There are concerns about emerging antibiotic resistance. Methicillin- and cephalosporin- resistant S aureus organisms have been reported in as many as 20% of community-acquired bone and joint infections. 32,33 Recently, emergence of vancomycin-resistant S aureus in Japan and parts of the United States has raised the specter of emerging bacterial strains for which there are no known antibiotic treatments. 34 The duration and route of ad- ministration of antibiotic treatment have previously been empirical, with the length of intravenous therapy ranging from 4 to 8 weeks. The du- Acute Hematogenous Osteomyelitis in Children Journal of the American Academy of Orthopaedic Surgeons 172 Negative Bone scan Positive Negative Positive Negative Positive Positive Negative Radiographic evaluation Antibiotic therapy Antibiotic therapy Antibiotic therapy Biopsy, surgical debridement Biopsy, surgical debridement Consider aspiration Suspicion of osteomyelitis (clinical/serologic evidence) No clinical improvement in 48 hr MR imaging, CT, or ultrasound; reassess diagnosis MR imaging, CT, or ultrasound for abscess/sequestrum Figure 6 Algorithm for radiologic evaluation and treatment when acute hematogenous osteomyelitis is suspected. Kit M. Song, MD, and John F. Sloboda, MD Vol 9, No 3, May/June 2001 173 ration of antibiotic treatment has not been related to the presence or absence of positive blood or direct cultures; antibiotic sensitivity or resistance of the bacteria; degree of elevation of the WBC count, CRP, or ESR; presence or absence of puru- lent material; or symptoms at pre- sentation. Authors of earlier studies suggested that a total duration of treatment of less than 3 weeks is associated with a higher rate of re- lapse. 35 Although previously con- troversial, the need to complete at least a 3-week oral antibiotic regi- men has become accepted. 5,6,12-14,25 Success of treatment correlates most closely with an adequate serum level of the antibiotic, rather than the route of administration. 25 Doses that are two to three times the package recommendation are generally necessary to ensure a peak serum titer greater than or equal to 1:8. 2,25 Inability to reliably take oral medications, poor oral absorption, poor response to intra- venous therapy, inadequate moni- toring of antibiotic levels, and inad- equate improvement of the local environment by surgery have been implicated in treatment failures using this approach. 2,6,25 Early treat- ment protocols suggested transition to oral antibiotics once clinical im- provement was observed, with treat- ment continuing until normalization of the ESR. 25 Peltola et al 12 documented suc- cessful treatment of acute hematog- enous osteomyelitis in children from 3 months to 14 years old with a very short course of intravenous antibiotics followed by oral therapy. The authors utilized changes in the CRP level to guide treatment. Ini- tiation of oral treatment resulted in a rapid fall in the CRP and an im- provement in the clinical course. Treatment was discontinued when the CRP level and ESR normalized. The average length of intravenous treatment was 5 days, and the total duration of treatment averaged 23 days. A more controversial issue in this study was the absence of serum monitoring of antibiotic levels. The authors used very high doses of cefadroxil (150 mg per kilogram of body weight per day in four doses) or clindamycin, which is readily absorbed. No failures of treatment were seen in this study with a mini- mum follow-up period of 1 year. In our institution over the past 5 years, we have utilized a protocol whereby empirical treatment is started with high-dose intravenous cefazolin after obtaining local and/or blood cultures for all bone and joint infec- tions. A regimen of 100 to 150 mg/ kg/day is started, with doses admin- istered every 8 hours. Serial values for CRP are checked. Once clinical improvement is seen and the CRP level approaches normal, oral cepha- lexin therapy is started at a dosage of 150 mg/kg/day, with doses every 6 hours. Peak serum levels are checked after the fourth dose. If the response is adequate, the patient is discharged, and antibiotic treatment is continued until the ESR normalizes. A weekly outpatient CBC count with differential is obtained to monitor for the develop- ment of antibiotic-induced neutrope- nia. In our series of 40 consecutive patients treated in this manner, the average length of antibiotic treatment was 21 days. There were no relapses. There are no reports of neonates with osteomyelitis being treated by intravenous-oral regimens. Serious permanent sequelae occur in 6% to 50% of affected children due to the multiple sites of involvement (in Table 2 Common Pathogens and Recommended Antibiotic Therapy Age Likely Organisms Intravenous Antibiotic Treatment Oral Antibiotic Therapy (in 4 doses) Neonate Staphylococcus aureus Nafcillin, 150-200 mg/kg/day and Dicloxacillin, 75-100 mg/kg/day or Beta-hemolytic Streptococcus Gentamicin, 5.0-7.5 mg/kg/day or Cephalexin, 100-150 mg/kg/day or (group A, group B) Cefotaxime, 150 mg/kg/day Clindamycin, 30 mg/kg/day Gram-negative rods Infant/ S aureus Non-Hib-immunized: Dicloxacillin, 75-100 mg/kg/day or toddler Haemophilus influenzae Nafcillin, 150 mg/kg/day and Cephalexin, 100-150 mg/kg/day or <3 yr old type b (Hib) Cefotaxime, 100-150 mg/kg/day Clindamycin, 30 mg/kg/day Pneumococci Single-agent treatment: Streptococci Cefuroxime, 150-200 mg/kg/day Child S aureus Hib-immunized: Dicloxacillin, 75-100 mg/kg/day or ≥3 yr old Cefazolin, 100-150 mg/kg/day or Cephalexin, 100-150 mg/kg/day or Nafcillin, 150-200 mg/kg/day or Clindamycin, 30 mg/kg/day Clindamycin, 30-40 mg/kg/day Acute Hematogenous Osteomyelitis in Children Journal of the American Academy of Orthopaedic Surgeons 174 20% to 50% of cases) and the high rate of concomitant septic arthritis. Because neonates are more prone to generalized sepsis, have less consis- tent oral antibiotic absorption, and have a less predictable radiographic and serologic response to treatment, it has generally been recommended that the entire course of treatment be intravenous. 3,4,10 Uncomplicated pelvic and verte- bral osteomyelitis or diskitis 2-4,36 and calcaneal osteomyelitis 37 in chil- dren have been successfully treated with antibiotics without surgical in- tervention. The necessary duration of antibiotic treatment regimens is frequently longer than for osteomy- elitis in an extremity, although the surgical indications are the same. Surgical Treatment The indications for surgical inter- vention have been controversial. 38,39 The primary aim of surgery is to im- prove the local environment for anti- biotic delivery. A “hole-in-bone” ap- pearance has not been shown to mandate surgical intervention un- less there is aspiration of purulent material. Rates of surgical interven- tion have decreased with the advent of better antibiotic treatment for os- teomyelitis, the heightened aware- ness that has led to earlier detection of infections, and a shift toward more subacute forms of osteomyelitis, which do not routinely require sur- gical debridement. 40 The cited rates of surgical intervention in earlier studies ranged from 22% 39 to as high as 83%, 25 compared with 8% to 45% in more recent series. 6,12,38 The presence of subperiosteal, associated soft-tissue, or bone abscess on aspi- ration; an obvious osseous seques- trum; failure to respond to antibiotic therapy; and concomitant septic arthritis in a deep joint are generally recognized indications for surgical intervention. 2,4,6,12,25,38,39 Complications Major complications related to os- teomyelitis are becoming less com- mon. Recurrent infection, chronic osteomyelitis, pathologic fracture, and growth disturbance have been linked to late recognition and inad- equate treatment of acute hematog- enous osteomyelitis. 5 Children who present with combined osteomye- litis and septic arthritis have been observed to have a more prolonged course of recovery 13 and a greater potential for growth disturbance and long-term sequelae. 2,3 Excessive surgical debridement can also cause pathologic fracture and growth arrest with subsequent limb- length discrepancy or angular defor- mity. 4 Complications associated with antibiotic treatment have been few. Diarrhea, nausea, rash, thrombocyto- sis, transient changes in liver en- zymes, and antibiotic-induced neu- tropenia have been observed with high-dose oral antibiotic therapy. 25 Summary The management of acute hematog- enous osteomyelitis has been greatly improved by enhanced imaging capabilities and advances in antibi- otic therapy. Early recognition and prompt intervention will decrease the morbidity associated with this condition. Initial evaluation should include plain radiography; serologic studies, including ESR, CRP, CBC count with differential and smear; blood cultures; and, when possible, aspiration of the suspected site. Empirical intravenous treatment based on the known epidemiology of age-specific pathogens should be started, with antibiotic selection modified on the basis of the culture results. Sequential intravenous-oral therapy is now accepted, with tran- sition based on the clinical and/or CRP response to treatment. Moni- toring of serum antibiotic levels is controversial, but may be helpful to ensure adequate treatment. Surgical treatment is warranted if there is aspiration of purulent material from the suspected site, an obvious area of necrotic bone, or failure to rapidly respond to antibi- otic therapy. Generally good out- comes with few long-term compli- cations can be expected. References 1. 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Dich VQ, Nelson JD, Haltalin KC: Osteomyelitis in infants and children: A review of 163 cases. Am J Dis Child 1975;129:1273-1278. 36. Highland TR, LaMont RL: Osteomye- litis of the pelvis in children. J Bone Joint Surg Am 1983;65:230-234. 37. Jaakkola J, Kehl D: Hematogenous calcaneal osteomyelitis in children. J Pediatr Orthop 1999;19:699-704. 38. LaMont RL, Anderson PA, Dajani AS, Thirumoorthi MC: Acute hematoge- nous osteomyelitis in children. J Pediatr Orthop 1987;7:579-583. 39. Cole WG, Dalziel RE, Leitl S: Treatment of acute osteomyelitis in childhood. J Bone Joint Surg Br 1982;64:218-223. 40. Hamdy RC, Lawton L, Carey T, Wiley J, Marton D: Subacute hematogenous osteomyelitis: Are biopsy and surgery always indicated? J Pediatr Orthop 1996;16:220-223. . ma- terial remains difficult. Treatment The management of acute hematog- enous osteomyelitis is largely non- operative. The role of surgery is to improve the local environment by removing infected. acute hematogenous osteomyelitis have emphasized a sequential parenteral-oral antibiotic regimen. 2,3,5,12,13 Due to the low yield of culture techniques, empirical treatment based on known epidemi- ologic. 9% Radius 4% Humerus 12% Tibia 22% Fibula 5% Femur 27% Hands and feet 13% Table 1 Differential Diagnosis of a Painful, Swollen Extremity in a Child Systemic conditions Acute rheumatic fever Chronic