Hematogenous Osteomyelitis

A changing disease

Martin C. McHenry, M.D. Despite the availability of potent antimicrobial drugs, improved diagnostic techniques, and Department of Infectious Diseases effective surgical procedures, hematogenous osteo- Ralph J. Alfidi, M.D. myelitis continues to provide difficulties in diagnosis, complex problems in management, serious Department of Radiology morbidity and even mortality. In recent years, changes have occurred in the clinical setting, Alan H. Wilde, M.D. presenting manifestations and the types of causa- 1 2 Department of Orthopaedic Surgery tive microorganisms. - Microorganisms that rarely caused infection in the past have emerged William A. Hawk, M.D. as significant bone pathogens. New clinical syn- dromes, unusual locations of bone infection, and Department of Pathology additional pathogenetic mechanisms have been documented. Although chronic osteomyelitis has long been known to be a difficult lesion to produce in laboratory animals, recent experimental models of chronic osteomyelitis that mimic human disease have been devised.3-7 New informa- tion is available concerning defects in host resist- ance which may predispose to some forms of osteomyelitis. Furthermore, knowledge of some of the microbial factors related to virulence of certain bone pathogens is increasing. The purpose of this report is to review briefly, in view of current developments, selected aspects of the problem of hematogenous osteomyelitis.

General considerations Given the appropriate predisposing factors, osteomyelitis may develop in any bone of the body. In the human skeleton, at least 206 bones develop

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Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. 126 Cleveland Clinic Quarterly Vol. 42, No. 1 which vary in location, size, shape, bone, while much of the arch has the structure, and function. In general, configuration of a flat bone.8 bones are composed of a cortex of Although bone is the most solid of compact (lamellar) bone and a me- the organs of the body, it is permeated dulla of spongy or cancellous bone. with a system of channels that may With respect to general architecture, provide a reservoir for pathogenic Jaffe8 has grouped bones into four microorganisms—lacunae, canaliculae, categories: (1) tubular (long and Haversian or Volkmann's canals, and short), (2) short (cuboidal), (3) flat, the medullary cavity.9"11 and (4) irregular. The tubular bones include the humerus, radius, ulna, fe- Pathogenesis mur, tibia, fibula (the long tubular Microorganisms may reach bone bones), metacarpals, metatarsals and by one of three mechanisms: (1) direct phalanges (short tubular bones). The inoculation secondary to trauma or shaft of a tubular bone consists of a surgery, (2) contiguous spread from an cortex of compact osseous tissue sur- adjacent soft-tissue infection, or (3) rounding loosely meshed cancellous hematogenous spread from a distant tissue of the bone marrow cavity; in focus of infection. We will confine our the midportion of the shaft (di- remarks to the latter mechanism. aphysis), the cortex is thickest and Collins9 and Kahn and Pritzker10 there is the least amount of cancellous have emphasized some special charac- osseous tissue. The short (cuboidal) teristics of bone relevant to pyogenic bones comprise the carpals, tarsals, bacterial infection. These include a sesamoids, and certain anomalous relatively small volume of tissue space bones. The bulk of the short bones is surrounded by a rigid wall favoring composed of spongy osseous tissue, and the accumulation of exudate under where they are not covered by articular increased tension; an anatomical ar- cartilage they are enclosed only by a rangement of blood vessels that favors thin cortical shell. The flat bones com- massive bone necrosis in association prise the ribs, sternum, scapulae, and with increased tissue pressure; an in- many of the bones of the skull. These adequate mechanism for resorption of bones are thin in part or throughout, necrotic bone, which can lead to in- are composed primarily of cortical complete healing and recurrent in- bone, and contain relatively little fection; and the capacity for reactive spongy bone. The irregular bones in- ossification which may take place clude the innominate (ilium, ischium, readily in fibroblastic granulation tis- pubis), the vertebrae, and some of the sue of walls of abscesses. bones of the skull. These bones are classified as irregular because they do Acute hematogenous osteomyelitis not qualify for inclusion in the first Table 1 lists the site of bone in- three categories. Some of the irregular volvement in 1,865 patients with acute bones may have the characteristics of hematogenous osteomyelitis gathered more than one of those in the first from several reports of studies con- three categories. For example, the body ducted in the preantimicrobial,12-14 of a vertebra resembles that of a short and in the antimicrobial era.14-22 The

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Table 1. Site of bone involvement in acute hematogenous osteomyelitis based on review of studies conducted at various time periods12-22

Bones involved Femur 207 (24.4%) 29 (29.3%) 323 (35.5%) Tibia 214 (25.3%) 28 (28.2%) 293 (32.2%) Humerus 76 (8.9%) 20 (20.2%) 95 (10.4%) Foot 61 (7.2%) 17 (17.1%) 52 (5.7%) Galcaneous 29 4 24 Other tarsals 19 3 7 Metatarsals 13 6 6 Phalanges Unspecified Skull 59 (7%) 6 (6%) 3 (0.3%) Mandible 18 2 Frontal 13 4 Maxilla 12 Temporal 5 Cranium 4 1 Nasal 2 Sphenoid 2 Malar 1 Basiooccipital 1 Parietooccipital 1 Occipital 1 Parietal 1 Pelvis 58 (6.9%) 11 (11.1%) 38 (4.2%) Ilium 7 16 Ischium 2 8 Pubis 2 7 Unspecified 58 7 Fibula 51 (6%) 10 (10.1%) 61 (6.7%) Radius 29 (3.4%) 5 (5%) 29 (3.2%) Ulna 19 (2.2%) 9 (9.1%) 22 (2.4%) Clavicle 11 (1.3%) 5 (5%) 8 (0.9%) Rib 11 (1.3%) 6 (6.1%) 7 (0.8%) Patella 6 4 Scapula 6 3 1 Metacarpal 6 Carpal 3 Sternum 1 2 Phalanx-hand 5 (5%) 1 Phalanges unspecified 31 (3.7%) Unspecified bones 10 (1.1%) Multiple bony involvement 45 (5.3%) 24 (24%) 45 (4.9%)

1 Of the 99 patients, in 57, osteomyelitis was diagnosed before 1939. data are arbitrarily arranged into bial and antimicrobial era. Table 2 three time periods because one of the lists other data from these studies. studies14 overlapped the preantimicro- Acute hematogenous osteomyelitis is

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Table 2. Selected features of acute hematogenous osteomyelitis based on review of studies conducted at various time periods12-22

Time of studies 1919-1937 1924-1954 1948-1968 Number of patients 846 99* 911 Age of patients <21 yr (75%) <15 yr (100%) <21 yr (81-100%)f Male/female Î 584/262 58/41 503/253 Pathogens§ Staphylococcus aureus 418/560 (75%) 62/86 (72%) 567/672 (84%) Streptococcus pyogenes 75/560 (13.4%) 18/86 (20.9%) 28/672 (4.2%) Gram-negative bacilli 7/560 (1.3%) 3/86 (3.4%) 16/672 (2.4%) Mortality 12%-25.4% 21.2% 1% Some complications (survivors) Relapse or chronic osteomyelitis 23%-46% 28.2% 20% Adjacent pyoarthrosis 18.7% 1% 5.7% Pathologic fracture 0.4% ?2% 1% Amyloidosis 0.4%

* Of the 99 patients, in 57, osteomyelitis was diagnosed before 1939. t Ages not reported in one study of 110 patients. | Sex not reported in two studies (155 patients). § Based upon the number of cases in which the infecting organism was determined. caused most frequently by Staphylococ- phagocytes which may also favor de- cus aureus or by Group A streptococci. velopment of infection in that re- It occurs most frequently in long tu- gion.26 bular bones, but no bone is exempt. Initially, the acute inflammatory The majority of cases of acute hema- process behaves as a cellulitis of the togenous osteomyelitis occur in chil- bone marrow; it may be amenable to dren before the age of puberty; the appropriate antimicrobial chemother- initial lesion is usually located in the apy and resolve with minimal or no metaphyseal sinusoidal veins of the destruction of bone. When the infec- red bone marrow of long bones.9' 13' tion is uncontrolled, there is necrosis 23-25 The term metaphysis was first of marrow, osteocytes, and trabecular used by Kocher to denote the broad bone. Abscesses form, and tiny seques- cancellous end of the bone shaft which tra of necrotic trabeculae remain in a is adjacent to the epiphyseal growth pool of purulent exudate.9 26 plate. Branches of the nutrient ar- Accumulation of exudate under tery end in the metaphysis as narrow pressure results in spread of the infec- capillaries, which turn back on them- tion in the medullary cavity and into selves in acute loops at the growth the cortex through the Haversian and plate, and enter a system of large Volkmann's canals. In infants less than sinusoidal veins leading to the sinu- 1 year of age, nutrient metaphyseal 23 25 soids of the bone marrow. ' At this capillaries may still perforate the epi- 25 point, blood flow slows, presumably physeal growth plate; the infection allowing bacterial emboli to settle and may spread to affect the epiphysis and initiate the inflammatory process. The the adjacent joint. In children more sinusoids of the metaphyseal bone mar- than 1 year of age, the epiphyseal cir- row are said to have a paucity of culation is separated from the vascular

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. Spring 1975 Hematogenous osteomyelitis 129 system of the metaphysis by an avas- direct involvement of the joint may de- cular barrier, the epiphyseal growth velop from extension of the meta- plate.25'26 The epiphyseal growth physeal infection through the peri- plate acts as a barrier to spread of in- osteum without passage through the fection, preventing epiphysitis and in- epiphyseal cartilage.27 fection of the adjacent joint.25 The Pyoarthrosis of an adjacent joint is infection spreads laterally through the a relatively frequent complication of cortical canals; this causes ischemia acute hematogenous osteomyelitis even and focal necrosis of cortical bone in the antimicrobial era (Table 2). It nourished by blood vessels in the Hav- most frequently involves the hip, ersian and Volkmann canals. Subperi- shoulder, or knee; but other joints may osteal infection follows escape of the be involved. exudate through the cortex in the re- Figure 1 is a roentgenogram of the gion of the metaphysis, probably because the cortical bone of the metaphysis is thinner than that of the diaphysis.27 In children, the periosteum is loosely attached to bone and may become elevated by subperiosteal abscesses. This, in turn, may cause dis- ruption of periosteal blood vessels that supply the underlying cortical bone and infarction of large portions of the cortex, resulting in the formation of very large bony sequestra. Eventually these sequestra become separated from viable bone and are surrounded by purulent exudate. If the patient sur- vives, fibrous tissue and new bone may be produced in the medullary cavity and subperiosteal new bone (involucrum) will be formed.10

Bacteria invade the bony substance of nearly all sequestra and remain there as long as the sequestra persist.28 Sequestra serve as a potential source for reinfection because they have no blood supply, and neither antimicrobial drugs nor antibodies pene- trate well into them.10' 29 When exudate perforates through Fig. I. Roentgenogram of the left femur and the periosteum, subcutaneous ab- tibia-fibula of a 5-week-old infant, revealing scesses and chronic draining sinuses de- soft tissue swelling about the knee, a radiolu- velop. In joints such as the hip or cent defect in the metaphyseal region of the distal femur, and periosteal elevation and new shoulder, where the joint capsule sur- bone formation on the lateral aspect of the rounds a portion of the metaphysis, femur and medial aspect of the tibia.

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. 130 Cleveland Clinic Quarterly Vol. 42, No. 1 left femur and tibia-fibula of a 5-week- periosteal space. The periosteum may old infant taken on the day of admis- rupture early with the formation of sion for acute hematogenous osteomy- soft tissue abscesses. This rapid de- elitis. This infant had evidence of os- compression prevents the vascular phe- teomyelitis of the femur and tibia as nomena which are responsible for well as infection of the knee joint. A bony infarction and sequestra forma- hemolytic streptococcus was isolated tion in older infants and children. from the knee joint. This patient il- Qureshi and Puri35 reported the oc- lustrated many of the unique features currence of hematogenous osteomye- of neonatal hematogenous osteomyelitis in two infants after umbilical litis.27, 30-32 Pyoarthrosis and multiple catheterization for exchange transfu- bone involvement are more common sion and were unable to find similar in hematogenous osteomyelitis in ne- cases reported in the literature. On onates than in older infants and chil- the other hand, umbilical infection dren.25, 27' 30 Although the long tubu- has appeared to be an important pre- lar bones are most frequently involved disposing factor to neonatal osteomy- in neonates,33 there is an increased in- elitis in some series,34 but not in oth- cidence of involvement of membra- ers.30 Respiratory and cutaneous in- nous bones such as the maxilla.31' 32 fections have also been found to be Systemic manifestations frequently are important predisposing factors in minimal or absent despite multiple many cases. In some series, group A bony involvement. The most common streptococci have been the most presenting problem is swelling and frequent causative organisms,27'34 pain or loss of movement of an ex- whereas in others staphylococci pre- tremity. If the epiphysis and joints dominate.30' 32' 33 are not involved in the neonate and In the preantimicrobial era, acute bacteremia is controlled, prognosis for hematogenous osteomyelitis was un- recovery without sequellae is unusu- common in adults.24 When it occur- ally good. Sequestra, chronic infection, red, it usually involved the vertebrae, and draining sinuses rarely develop af- presumably because they are one of ter hematogenous neonatal osteomye- the most active sites of hematopoiesis litis.27' 31 Although there is consider- in adults.36 Acute hematogenous os- able roentgenographic evidence of per- teomyelitis of long bones in adults ap- iosteal reaction, infarction of the bony pears to be extremely rare,38' 37 prob- cortex does not occur.25'34 ably because the marrow cavities of Certain anatomic factors appear to the limbs in adults are filled with ad- contribute to the different nature of ipose tissue, with the exception of tiny the disease in neonates.27 The cancel- foci of red marrow in the extreme lous spaces of the metaphysis are proximal portions of the humeri and larger, the bone is of a more spongy femora. Zadek37 and Wiley and Tru- texture, the cortex is thinner, and the eta36 reported a total of 22 cases of periosteum is more loosely attached to acute hematogenous osteomyelitis in bone of neonates than in older infants long bones of adults. Recently King and children.25' 27 This allows the in- and Mayo38 described the findings in fection to pass more easily from the six additional cases. The lesion usu- medulla to the cortex and to the sub- ally begins around the nutrient artery

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. Spring 1975 Hematogenous osteomyelitis 131 in the diaphysis of long bone.38 The pathologic changes are principally periosteal and central.37 When the infection is uncontrolled, the sup- purative process spreads primarily through marrow cavity. Because the periosteum is more firmly adherent to the adult bone, subperiosteal abscess formation occurs less frequently than in children; the large cortical sequestra of osteomyelitis in children do not develop in the long bones of adults. When the infection progresses to the end of the long bone of adults, neigh- boring joints may become involved. Figure 2 shows the excretory urogram of a diabetic woman with a soli- tary, mildly hydronephrotic kidney and a functioning ureterosigmoidostomy. A Charnley-Mueller prosthesis had been inserted in the right hip because of disabling osteoarthritis. Several days Fig. 2. Intravenous urogram revealing a soli- postoperatively, a rectal tube was re- tary, mildly hydronephrotic kidney and a quired and severe rectal bleeding de- functioning ureterosigmoidostomy; a Charn- ley-Mueller prosthesis is present in the right veloped. This was followed by bactere- hip. mia due to Klebsiella type 32, probably arising from infection of the Klebsiella. In each of the cases, the urinary tract. This in turn, was com- femur was involved. The association plicated by Klebsiella type 32 infection of this type of hematogenous osteomy- of the hip and femur, which pro- elitis with urologic procedures or pel- gressed to involve the entire femur vic operations was emphasized.39 Re- and the right knee joint (despite ap- cently, Irvine et al40 and Hall41 have propriate therapy). Figure 3 shows the noted an association between geni- lateral roentgenogram of the femur tourinary tract infections and deep in- taken 24 days after the onset of bac- fections after total hip or knee re- teremia and before pyoarthrosis of the placements. All of the serious infec- knee was evident clinically. There was tions reported by those physicians gas in the tissues of the thigh and evi- were caused by enteric gram-negative dence of extensive osteomyelitis of the bacilli. femur. Since 1944, the incidence of acute In 1966, Smith39 reported a case of hematogenous osteomyelitis of chil- acute hematogenous Klebsiella osteo- dren has been descreasing.1 In some myelitis of the femur in an adult; his medical centers, the relative propor- search of the literature produced only tion of cases caused by S. aureus has nine other reported cases of acute hem- diminished;1 however, the staphylo- atogenous osteomyelitis caused by cocci that cause disease have become

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acute hematogenous osteomyelitis of children has changed since the advent of antibiotics.1, 2'38-45-47 More severe forms of the disease were observed in the preantimicrobial era when the mortality rate was as high as 25% (Ta- ble 2). Severe shaking chills, fever, and bone pain were characteristic; death usually could be attributed to septicemia and, in about two thirds of the patients, occurred within 2 weeks of the onset of the illness.13 After 1944, the mortality fell to 1% or less. Fur- thermore, the fulminating type of infection is now rarely seen and the incidence of acute systemic illness with the disease has diminished.1' 2•3S-45-47 The onset of the illness is more frequently gradual and insidious, bone lesions remain localized and may be mistaken for benign or malignant tu- mors or other conditions. Before the introduction and use of antimicrobial drugs, hematogenous osteomyelitis of the spine was considered an uncommon condition.13 In the last 3 decades, the incidence appears to have increased.1 Hematogenous spinal osteomyelitis is a disease primarily of Fig. 3. Lateral roentgenographic view of the adults; the majority of cases occur after right femur from the same patient as in Figure the third decade of life, when the 2, taken 24 days after the onset of Klebsiella spine is completely formed.48 Accord- type 32 bacteremia. There is gas in soft tissues. 48 The bony cortex is thinned and eroded and ing to Kulowski, the predilection for there are focal areas of periosteal reaction. hematogenous osteomyelitis to involve vertebrae of adults (in contrast to os- increasingly resistant to antibiotics.42 teomyelitic involvement of long tubu- Gram-negative bacilli have been cited lar bones in children) may be at- more frequently as being bone path- tributed in part to lack of true epiphy- ogens.1- 43 In a recent study from Aus- seal growth of vertebrae, persistence of tralia,44 gram-negative bacilli ac- rich, cellular, red bone marrow, and counted for 8% of cases of acute a sluggish voluminous blood supply. hematogenous osteomyelitis, which is The latter condition might favor lo- considerably higher than that re- calization of bacteria in the vertebral corded in previous years (Table 2). body. There are also indications that the Table 3 lists some of the pertinent type of clinical illness associated with features of hematogenous osteomyelitis

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Table 3. Nontuberculous hematogenous osteomyelitis of the spine of adults: selected features based on review of reported cases36, 49-67

Number of patients 86 Age range, yr 26-79 (mean 58.6 yr, ±11.3 SD) Men/women 56/30 Antecedent urinary tract or jjelvic infec- 38 44.2% tion Pathogen* Staphylococcus aureus 28/55 50.9% Gram-negative bacilli 17/55 30.9% Streptococci 4/55 7.3% Mortality from infection 5/86 5.8% Complications Paralysis 7/86 8.1% Temporary 5 Permanent 2 Paravertebral abscess 6/86 6.9% Epidural abscess or granuloma 5/86 5.8% Retropharyngeal abscess 2/86 2.3% Endocarditis 2/86 2.3% Vertebra involved Cervical 8 Thoracic 35 Thoracolumbar 2 Lumbar 35 Lumbosacral 7 > 1 interspace 9

* Based upon the number of cases in which a pathogen was isolated from the involved bone or blood or both. of the spine in 86 adult cases gathered portant predisposing factors in more from several reports in the litera- than 40% of the cases. Organisms ture.36- 49-57 Data from other reports1' may reach the spine directly through

48,58-ao were not included because it the nutrient branches of the posterior was not always possible to separate spinal artery during bacteremia36 or adult from childhood cases, to differ- by retrograde spread through the para- entiate between cases caused by hema- vertebral venous plexus of Batson. Ac- togenous spread from those produced cording to Wiley and Trueta,36 the by other mechanisms, or to tabulate all earliest lesion is in the body of the the bones involved. vertebrae close to the anterior longi- S. aureus, various enteric gram-nega- tudinal ligament. The lesion spreads tive bacilli, and streptococci are most across the periphery of the interverte- frequently responsible for hematoge- bral disc in a system of freely anasto- nous spinal osteomyelitis in the adult mosing venous channels to involve the (Table 3). Infections of the urinary body of the adjacent vertebrae. More tract or pelvis, particularly those de- than one vertebral body is involved as veloping after a surgical or instru- a rule, at least in the later stages of mental procedure, appear to be im- the disease. Extension to the contigu-

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. 134 Cleveland Clinic Quarterly Vol. 42, No. 1 ous disc and vertebral body is abetted bacilli, and fungi. This can be accom- by the absence of a circumferential plished either by percutaneous (Craig cartilaginous plate and the lack of needle) biopsy under fluoroscopic con- definite protective subchondral layer trol or by open surgical biopsy when of compact bone.48 Rapid progression this seems indicated. It is extremely of the infection in the spongy verte- important to remember to obtain cul- bral bone and in the intervertebral tures for acid-fast bacilli because it disc may cause significant destruction may be difficult or impossible to dif- of these structures. ferentiate tuberculous from pyogenic The lumbar vertebrae are involved infection of the spine (Fig. 4 A, B). most commonly by hematogenous os- Positive blood cultures usually es- teomyelitis, followed in order of fre- tablish the cause of hematogenous ver- quency by the thoracic and cervical tebral osteomyelitis, but rarely they vertebrae. Extension of infection an- may be misleading. For example, dur- teriorly to the spine occurred com- ing our study of gram-negative bacte- monly in the preantibiotic era.48 De- remia,72 we treated a patient with re- pending upon the location, anterior current urinary tract infection and extension of infection may cause a Proteus mirabilis bacteremia at the retropharyngeal abscess, mediastinitis time when signs, symptoms, and roent- with pleural or pericardial involve- genographic changes of vertebral oste- ment, subphrenic and retroperitoneal omyelitis and disc-space infection abscess, or a psoas abscess. The tend- were evolving. Culture of the affected ency of these abscesses to gravitate vertebral interspace yielded Mycobac- or migrate is well known. terium tuberculosis rather than P. mi- The infection may also extend pos- rabilis. Thus, whenever possible, cul- teriorly and invade the spinal canal ture of the involved bone or interspace causing an extradural abscess or gran- should be obtained. uloma; this may lead to compression More recently, new pathogenic of the spinal cord and paralysis. When mechanisms for acute hematogenous the infection perforates the dura, men- osteomyelitis in adults have been de- ingitis results. There were no exam- scribed. Since 1971, 59 cases of acute ples of meningitis in the 86 cases in- hematogenous osteomyelitis have been cluded in Table 3, but meningitis de- reported in adults who are addicted veloped in four patients in Kulow- to or abuse drugs by taking them in- 48 ski's series and in one patient in the travenously.61-69 Pertinent clinical and 1 series of Waldvogel et al. One of the microbiologic data from those 59 pa- goals of antimicrobial chemotherapy tients are summarized in Table 4. for vertebral osteomyelitis is to try to Most of the patients were heroin ad- prevent extension of the process and dicts who took the drug intravenously. associated complications. Each of the patients complained of Because vertebral osteomyelitis may pain, but most were remarkably free be produced by a wide variety of or- of systemic illness. Vertebrae and ganisms, we routinely recommend ob- pelvic bones were most frequently taining material from the involved affected, but a wide variety of other bone or interspace for smears and cul- bones and joints were involved in some tures for aerobes, anaerobes, acid-fast patients. Diagnosis frequently was

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. Spring 1975 Hematogenous osteomyelitis 135 delayed and initially mistaken for other conditions. Pseudomonas aeruginosa and other gram-negative bacilli were the pathogens in the majority of cases. Of the 59 patients, only two had endocarditis and there were no deaths reported. Leonard et al70 reported the development of acute hematogenous osteomyelitis in five patients receiving intermittent hemodialysis for chronic renal failure. Of the five patients, in four, repeated intravenous cannula infections occurred and Staphylococcus epidermidis and S. aureus were cultured from the blood on different oc- casions. The fifth patient had a subcutaneous arteriovenous fistula and the source of osteomyelitis was not defined. Staphylococci were the most common etiologic organisms, but P. aeruginosa was the pathogen in one patient. The thoracic spine and ribs were the bones most commonly involved, but the tibia, toes, and clavicle were affected in some patients. One patient had bacterial endocarditis. The overall mortality was 60%. In 1974, we treated a patient with Fig. 4A, B. Posteroanterior and lateral roent- chronic renal failure (who was being genograms of the thoracolumbar region maintained on intermittent hemo- showing evidence of destruction of large por- dialysis) for an infected subcutaneous tions of the bodies of the first and second lum- arteriovenous fistula and bacteremia bar vertebrae and collapse of the interverte- caused by S. aureus. Bacteremia was bral disk space. Mycobacterium tuberculosis eradicated promptly and appropriate was cultured from specimens obtained by aspi- ration biopsy of the affected area. The patient antimicrobial therapy was adminis- recovered after a long course of antitubercu- tered for an extended period of time. lous therapy. Figures 5 to 7 are roentgenograms of the thoracic spine taken 50, 63, and 83 tic levels of vancomycin had been days after the day of staphylococcal present in the blood for several weeks. bacteremia. Needle biopsy and aspira- Because of the patient's cachectic state tion of the interspace between the 11th and hopeless prognosis, surgery to re- and 12th thoracic vertebrae was per- lieve the spinal cord compression was formed on the 74th day after the day not undertaken and hemodialysis was of bacteremia; the culture yielded 5. discontinued at the request of his fam- aureus, despite the fact that therapeu- ily. The patient died from his under-

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Table 4. Selected features of acute hematogenous osteomyelitis in drug addicts or abusers based on review of reported cases (1971-1974)61"69 *

Number of patients 59 Age 18-50 yr (mean 33 yr ± 8.9 SD) Sex Man/woman = 50/9 Pathogen (s)f Pseudomonas aeruginosa 47 Pseudomonas aeruginosa and other pathogen(s)| 3 Klebsiella (3)—Enterobacter (1) 4 Pseudomonas sp 2 Candida stellatoidea 1 Candida guillermondi 1 Staphylococcus aureus 1 Bone and joints involved Vertebra 40 Cervical 7 Thoracic 2 Lumbar 22 Lumbosacral 8 Nonspecified 1 Sacroiliac Symphysis pubis Radial styloid Sternoclavicular Ischium Humerus Rib(s) Hip Femur Clavicle Scapula Knee Shoulder Acromioclavicular Costochondrals Pain 59/59 Systemic illness 5/59 § Endocarditis 2/59 Mortality reported 0

* Heroin addicts (57) or abusers (2); pentazocine and methalphenidate hydrochloride (1); all patients took drugs intravenously. t Diagnosis was established by culture of the bony lesion, interspace, or joint in 57 patients and by blood culture alone in 2 patients. t Klebsiella (1), Staphylococcus aureus (1), Enterobacter cloacae and Streptococcus fecalis (1). § Fever, chills, and other symptoms or signs of acute infection were absent in most cases. lying renal disease. At autopsy, there Baker et al71 reported the develop- was no evidence of endocarditis. Fig- ment of acute hematogenous osteomy- ure 8 is a photomicrograph of a his- elitis in three adults with severe neu- tologic section of the skeletal infection tropenia and were unable to find re- obtained at autopsy. ports of similar cases in the literature.

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tients with Salmonella septicemia.73' 74 The risk for hematogenous Salmo- nella osteomyelitis in patients with sickle cell disease and related hemo- globinopathies is several hundred times that seen in the normal popula- tion.74-78 This complication occurs primarily in infants and young chil-

Fig. 6. Lateral roentgenogram of the involved thoracic region taken 63 days after the day of bacteremia. This shows further progression of the disease with obliteration of the interspace.

Figs. 5A, B. Posteroanterior and lateral tomograms showing decrease in vertical height of the 11th thoracic vertebra, narrowing of the subjacent vertebral interspace, and loss of the normal architecture of the vertebral end plates of the 11th and 12th thoracic vertebrae. (Tomograms taken 50 days after the day of staphylococcal bacteremia).

Recently, during a study of gram-negative bacteremia,72 members of our group treated an adult patient with neutropenic leukemia for hematogenous pyoarthrosis of the hip and oste- Fig. 7. Thoracic myelogram with patient in omyelitis of the femur due to£. coli. the head-down position showing marked extradural constriction behind the T11-T12 Hematogenous osteomyelitis in sickle disk space. (Myelogram was done 83 days after cell disease and related anemias the day of staphylococcal bacteremia. Staphy- lococcus aureus was isolated from the involved Salmonella osteomyelitis is uncom- spinal interspace on the 74th day after the on- mon, occurring in less than 1 % of pa- set of bacteremia.)

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Fig. 8. This photomicrograph was prepared from the Tll-12 lesion demonstrated in Fig- ure 7. The process appears to be in a subsidiary phase and formed largely of granulation tissue containing fragments of necrotic bone and modest numbers of inflammatory cells. At autopsy, there was considerable destruction of interspace tissues with encroachment on the spinal cord by the process (hematoxylin-eosin, XlO).

dren, but cases in adults have been re- cell crisis. Eventually the diagnosis ported.78 may become apparent, particularly in The infection begins in the medulla those patients who have persistent of the diaphysis of long and short tu- fever, continued leukocytosis, and bular bones.76'77 Multiple bony in- roentgenographic changes that are far volvement is common. The phalanges more severe than those secondary to of the hands and feet may become in- bone marrow thromboses in sickle cell volved78 producing an illness resem- disease.74,77 According to Engh et al,77 bling the "hancl-foot" syndrome of the most frequent distinguishing sickle cell disease.78 The clinical and roentgenographic findings are longi- roentgenographic features of Salmo- tudinal intracortical diaphyseal fissur- nella osteomyelitis may be very diffi- ing, overabundant involucrum forma- cult or impossible to differentiate from tion, and involvement of multiple and those of a sickle cell crisis, especially often symmetrical diaphyseal sites. in the earliest stages of the illness; The linear structures in the cortical therefore, blood cultures should be ob- diaphysis have been termed "cortical tained from all patients with sickle Assuring," but probably represent a

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. Spring 1975 Hematogenous osteomyelitis 139 layer of purulent exudate beneath the Staphylococci and other gram-positive involucrum and between it and the cocci have caused hematogenous oste- dead bone.74 omyelitis less frequently in patients The pathogenesis of hematogenous with sickle cell disease than in other 74 Salmonella osteomyelitis is a complex children, and the reasons for this are phenomenon and may be related to not clear. several factors. Salmonella organisms Studies of antibacterial host factors are widely present in the environ- in patients with sickle cell disease ment,80 providing ample opportunity failed to reveal immunoglobulin defi- for exposure and colonization of the ciencies, and the response to Salmo- intestinal tract with or without pro- nella vaccine in those patients was the ducing overt illness. Some strains of same as that in normal controls.89 Par- Salmonella have the capacity per se to adoxically, although pneumococcal os- cross the intestinal mucosal barrier teomyelitis is quite rare in patients and gain access to the systemic circu- with sickle cell anemia,90 a wide vari- lation.81' 82 However, injuries to the ety of abnormalities have been deter- intestinal mucosa from localized mined which may help to explain the thrombosis in sickle-hemoglobinopa- significantly increased incidence of se- thies and impairment of the hepatic rious pneumococcal infections in pa- reticuloendothelial system may facili- tients with sickle cell anemia. These tate invasion of the bloodstream by include functional asplenia,91 im- those organisms.73 Hemolytic crises of paired antibody response to intrave- sickle cell disease and related hemo- nous immunization,92 a defect in se- globinopathies may decrease the abil- rum opsonizing activity against the ity of macrophages of the spleen and pneumococcus,93 and an abnormality other sites to phagocytize circulating in the alternate pathway of comple- bacteria because of engorgement of ment activation.94 The apparent rar- reticuloendothial cells with hemolyzed ity of pneumococcal osteomyelitis in erythrocytes.83 Bone marrow throm- patients with sickle cell disease may boses and infarction that occur in be due to the frequent, rapidly lethal sickle cell crises may favor localization nature of pneumococcal infections in of circulating bacteria in bone. In- patients with this hemoglobinopa- creased concentrations of bilirubin or thy.90 other breakdown products of erythrocytes in the bone marrow may provide Osteomyelitis in chronic granuloma- an environment favorable to Salmo- tous disease of childhood nella organisms.77-84 Of 28 patients with chronic gran- Shigella and certain strains of E. ulomatous disease of childhood re- coli may also invade the intestinal ported by Wolfson et al,95 eight pa- mucosal barrier81 and occasionally tients had evidence of osteomyelitis cause bacteremia.85'86 In patients with involving 19 bones. Some of these le- sickle cell disease, hematogenous oste- sions may have been the result of hem- omyelitis has been produced by E. atogenous spread of infection and oth- coli,85 Shigella sonnet,86 Serratia mar- ers from contiguous spread of an ad- cescens,81 and Arizona hinshawii.88 jacent focus of soft tissue infection;

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. 140 Cleveland Clinic Quarterly Vol. 42, No. 1 the authors did not specify. Members of the onset of the illness.16 When the of the family Enterobacteriaceae, S. patient presents with a typical history aureus, and Aspergillus fumigatus were of chills, fever, pain in one site in a the offending organisms. These orga- limb, and localized tenderness to pal- nisms produce catalase, are phagocy- pation, a provisional diagnosis can be tized normally by the patient's poly- made and therapy started after ap- morphonuclear leukocytes, but they propriate pretreatment cultures are survive and persist within the abnor- obtained. Detection of localized ten- mal phagocytes. Osteomyelitis in the derness is the most significant early patients with chronic granulomatous clinical finding and indicates that the disease was manifested by granuloma- periosteum has been involved.14 When tous inflammation and did not present therapy is started more than 3 days af- with pain, fever, or local signs of in- ter the onset of the illness, persistence flammation. The most frequent sites of infection, sequestra formation, and of involvement were the metatarsals, chronic osteomyelitis is much more tarsals, and metacarpals; but the tibia, likely. It is somewhat discouraging to fibula, humerus, femur, ribs, and tho- note that approximately 20% of pa- racic vertebrae were involved in some tients with acute hematogenous osteo- patients. Roentgenographic changes myelitis in the antibiotic era have in some small bones (increased breadth relapses or progress to chronic osteo- and lack of acute destruction) simu- myelitis (Table 2). The roentgeno- lated tuberculous dactylitis. In other graphic changes of chronic osteomye- small bones, there was marked destruc- litis are shown in Figures 9 to 12. Al- tion and widening concomitantly. Ab- though the changes were observed on scesses and sequestra rarely occurred. the roentgenograms of a patient in Long-term antimicrobial therapy with- whom osteomyelitis developed after out surgical intervention usually was internal fixation of a comminuted frac- all that was required for cure. Of the ture, the changes are illustrative of se- eight patients, a surgical procedure vere chronic osteomyelitis: sequestra- was required for cure in two. tion in a radiolucent cavity, periosteal elevation with extensive subperiosteal Diagnostic considerations new bone formation. One of the major problems in es- Patients who have hematogenous os- tablishing an early diagnosis of acute teomyelitis in certain locations may hematogenous osteomyelitis is that present unusual diagnostic difficulties. roentgenographic examination is nor- For example, patients with osteomye- mal in the early stages of the disease. litis of the pelvis may be misdiagnosed Bone changes may be demonstrated as having acute appendicitis on the earlier in acute osteomyelitis by right, paracolic abscess on the left, means of radioisotope scanning than pyelonephritis, arthritis of the hip, by conventional roentgenography,63'65 pelvic tumor, sciatica, or other con- 96 and should be used when indicated. ditions. Some patients with hema- Available data indicate that persist- togenous osteomyelitis of the ilium ence of infection, sequestra formation, have had a normal appendix removed 97 and chronic osteomyelitis rarely de- because of a mistake in diagnosis. velop when appropriate antimicrobial Hematogenous osteomyelitis of the therapy is initiated within 3 days metatarsal sesamoids may masquerade

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osseous infection are essential for optimal therapy. In patients with chronic draining sinuses, care must be taken to avoid contamination of specimens with members of the normal body flora. After cleansing the surrounding skin with isopropyl alcohol, material should be obtained for culture by aspi- ration or with a swab under aseptic technique. Whenever possible, necrotic or infected tissue from the depth of the wound should be obtained. Often this can be best accomplished at the time of surgery. The material should be placed in a suitable container and transported to the laboratory with an j| -»jH - /4 mm•

Fig. 9. Roentgenogram of the left femur, Oc- tober 27, 1969, showing marked periosteal reaction, four radioopaque sequestra and a radiolucent area of cortical destruction lateral to the largest of the sequestra. under the guise of cellulitis, trauma, or gout.98 Hematogenous sternal osteomyelitis may present as a mass lesion with the differential diagnosis includ- ing perforating aneurysm, tuberculosis, carcinoma, and mediastinal abscess.99 Osteomyelitis of a rib may be mistaken for bone tumor, particularly Ewing's sarcoma.100

Microbiologic considerations Since hematogenous osteomyelitis Fig. 10. Sinogram of the left femur on Octo- may be produced by a wide variety of ber 27, 1969. The contrast material outlines pathogens, adequate pretreatment cul- the lateral and central sequestrum and par- tures of blood and accessible sites of Itially outlines the large mediaIl sequestrum . Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. 142 Cleveland Clinic Quarterly Vol. 42, No. 1

chronic osteomyelitis, L-form vari- ants107 or protoplasts108 have been recovered from lesions using special hy- pertonic media. In recent years, anaerobic bacteria have received increased attention as being causes of bone infection.101-103 It is of interest in this regard, that before 1920, Taylor and Davies28 regu- larly cultured anaerobic bacteria from sequestra of patients with chronic osteomyelitis secondary to trauma. An- aerobic bacteria frequently participate in mixed infections with other organisms and usually occur in cases of os-

Fig. 11. Sinogram on November 4, 1969, after sequestrectomy, showing contrast material in the surgical space. informative requisition without delay. Special techniques are required for isolation of anaerobes101 and other fastidious organisms. Gram-stained smears of exudates, abscesses, or infected tissues should always be obtained simultaneously with the cultures. They may be extremely helpful in evaluating the results of cultures.102 When routine aerobic cultures of bone are sterile in cases of osteomyelitis, anaerobic bacteria,101- 103 acid- fast bacilli,104- 105 actinomyces, fungi, or other unusual pathogens106 should Fig. 12. Roentgenogram of the femur taken in the healing phases of the chronic osteomye- be considered. In cases of recurrent or litis.

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certainty in this case whether Bacte- roides osteomyelitis resulted directly from trauma or from hematogenous spread from a focus of infection in the abdomen.

Fig. 13. Roentgenogram of right femur and upper tibia-fibula, showing compound fracture of distal femur and gas in soft tissues. The roentgenogram was taken before the onset of Bacteroides fragilis bacteremia which lasted 24 days.

teomyelitis resulting from trauma or spread of contiguous soft tissue infection.101- 103 However, cases of hematogenous osteomyelitis due to anaerobic bacteria have been reported. Figures 13 to 15 are roentgenograms of the femur from a patient with osteomyelitis due to Bacteroides fragilis. This patient had abdominal and skeletal trauma, abdominal infection, and B. fragilis bacteremia that persisted for 24 days de- Fig. 14. Roentgenogram taken later in clinical course shows area of cortical destruction and spite parenteral clindamycin therapy. periosteal reaction in the diaphysis of femur It was not possible to determine with laterally and medially.

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the infected joint space yielded the same organisms. Hematogenous osteomyelitis has resulted rarely from smallpox112 and BCG vaccination.113- 114 Hematoge- nous skeletal tuberculosis does not occur as frequently as in the past, but still causes significant diagnostic and therapeutic problems.104

Microbial determinants The properties of microorganisms which determine their ability to cause disease of bone are not well defined. Some of the properties of gram-negative bacilli relevant to their pathogenicity have been reviewed elsewhere115' 116 and will not be repeated here. We will confine ourselves to some brief remarks about the Staphylococcus, since it is still the organism most commonly responsible for hematogenous osteomyelitis. Recent studies indicate that a muco- peptide of the cell wall of virulent

Fig. 15. Roentgenogram of the femur on June 4, 1974, showing further evidence of osteomyelitis.

With the increased use of prolonged intravenous therapy and immunosup- pressive drugs, unusual organisms such as fungi109' 110 or atypical acid-fast bacilli111 may cause hematogenous osteomyelitis. Figure 16 is the roentgenogram of a patient with hematogenous osteomyelitis of the phalanx.

This patient was receiving therapy for Fig. 16. Roentgenograms of the right middle Hodgkin's disease when pulmonary in- finger of a patient with Hodgkin's disease. filtrates and pain and swelling of the They show soft tissue swelling, periosteal re- finger developed. Material aspirated action, and erosion of the bony cortex of the directly from the lung yielded Myco- middle phalanx with narrowing of the joint space. Material aspirated from the infected bacterium kansasii and Cryptococcus joint space yielded Mycobacterium kansasii neoformans. Material aspirated from and Cryptococcus neoformans.

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. Spring 1975 Hematogenous osteomyelitis 145 strains of S. aureus inhibits chemotaxis predominantly to phage groups I and of polymorphonuclear leukocytes, sup- II; most were lipase-positive and all presses inflammatory edema formation, produced protein A. They suggested and enables the bacteria to produce that a possible host-parasite interac- more severe lesions presumably as a tion takes place in the bone marrow in result of their unbridled multiplica- which lipids and staphylococcal lipases tion in the early stages of established may play a role analogous to that sug- infection.117 Another constituent of gested for furunculosis. the cell wall of S. aureus, protein A, reacts with the Fc fragment of normal Therapeutic considerations and immune IgG immunoglobulin.118 Patients with acute hematogenous The main opsonic site of the immu- osteomyelitis should be on bed rest noglobulin G is located on the Fc with immobilization of the affected region.119'120 Evidence suggests that part. Appropriate antimicrobial ther- protein A of staphylococci inhibits apy alone may be sufficient to cure phagocytosis by competing with poly- this infection if treatment is started morphonuclear leukocytes for the Fc within 72 hours after the onset of the sites.119 Thus, it is possible that pro- disease.15 Whenever possible, a Gram- tein A may enhance survival of stained smear of an aspirate from the staphylococci in tissues and may be affected area should be used as a guide another virulence factor, along with to initial therapy. When this is not leukocidins, hemolysins, coagulase, possible, initial therapy must be based and penicillinase.119 It also has been upon an educated guess as to what is shown that a considerable number of the most likely etiologic organism. staphylococci isolated from human Knowledge of the age of the patient, sources are capable of producing cap- the location of the infection, the pres- sules which may enhance their viru- ence of underlying predisposing dis- lence.120 It is known that extracellular eases and circumstances involved in staphylococcal toxins may cause capil- development of the infection may per- lary vasospasm with thrombosis,121 mit an educated guess as to the etio- which might contribute to the develop- logic organism. For example, in an ment of the acute lesion in staphylo- otherwise healthy child with a history of a recent furuncle and a presumptive coccal osteomyelitis. clinical diagnosis of acute hematoge- An attribute of osteomyelitis caused nous osteomyelitis of the distal femur, by S. aureus is its tendency to recur, parenteral antistaphylococcal therapy often at some time remote from the with therapeutic doses of a penicil- initial episode.11'13 Cases are on rec- linase-resistant penicillin should be ord in which recurrences occurred af- administered after appropriate pre- ter quiescent periods of 40 to 70 treatment cultures are obtained (pro- years.11'13 The ability of staphylococci vided there is no history of penicillin to persist in bone remains unex- allergy). Definitive antimicrobial plained. Recently, Hedstrom and 122 chemotherapy depends upon the Kronvall showed that strains of identity of the pathogen, its in vitro staphylococci responsible for chronic susceptibility and the patient's ability hematogenous osteomyelitis belonged

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Table 5. Currently preferred antimicrobial drugs for initial presumptive therapy of acute hematogenous osteomyelitis*

Suspected etiologic organism Currently preferred drugs f Staphylococcus aureus 1) Oxacillin, methicillin, or nafcillin 2) A cephalosporin 3) Vancomycin 4) Clindamycin Streptococcus pyogenes 1) Penicillin G 2) A cephalosporin 3) Erythromycin 4) Clindamycin Salmonellae 1) Chloramphenicol 2) Ampicillin 3) Trimethoprim-sulfamethoxazole Pseudomonas aeruginosa 1) Carbenicillint and gentamicin§ E. coli, Klebsiella-Enterobacter, Proteus, Ser- 1) Gentamicin ratia Bacteroides 1) Clindamycin 2) Chloramphenicol

* Definitive antimicrobial therapy is determined subsequently from the results of in vitro susceptibility tests and the patient's response to treatment. Initial therapy of acute hematogenous osteomyelitis is administered by the parenteral route. f Numeral 1 represents the drug(s) of first choice, numerals after 1 represent alternative drugs that may be used when circumstances indicate. Î Should not be used in penicillin-allergic patients. § Tobramycin, amikacin, or sisomicin are investigational aminoglycoside antibiotics that maybe effective against gentamicin-resistant strains of Pseudomonas aeruginosa. to tolerate the drug. Table 5 lists some technique in the operating room, an of the preferred antimicrobial drugs incision of the skin is made over the for initial presumptive therapy of area of maximum tenderness. The acute hematogenous osteomyelitis for periosteum is incised in order to drain various suspected pathogens. We be- the subperiosteal abscess. In some in- lieve that antimicrobial therapy stances, it may be necessary to drill should be administered for at least 4 one or more small holes in the bony to 6 weeks in cases of uncomplicated cortex to decompress the medullary acute hematogenous osteomyelitis. cavity, allowing an abscess to drain When the patient with acute hema- and prevent infarction of the bony togenous osteomyelitis does not re- cortex. We now prefer to close the spond to treatment within 48 to 72 operative wound to prevent secondary hours (lysis of fever, decreased pain, infection. Suction drainage tubes are increased appetite and sense of well- utilized for a short period of time. being, sterile blood cultures), surgery When hematogenous osteomyelitis becomes mandatory. When the roent- in the neck of the femur is strongly genogram and bone scan reveal no suspected, arthrotomy for decompres- diagnostic changes, the surgeon has to sion and for culture is mandatory. The rely on his judgment as to the probable neck of the femur lies within the syno- location of the lesion. Under aseptic vial capsule of the hip joint. A sub-

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. Spring 1975 Hematogenous osteomyelitis 147 periosteal abscess in that region may is of little consequence. However, oc- rupture into the joint causing septic casionally it may give rise to serious arthritis. This can be complicated by gram-negative bacillary infection. Fig- necrosis of the head of the femur and ures 17 and 18 are roentgenograms of dislocation of the hip—a disaster for the hip region of a patient who re- a young child. quired suction-irrigation after removal The therapy of chronic hematoge- of an infected total hip prosthesis nous osteomyelitis is a complex sub- (staphylococcal pyoarthrosis). The ject and will be considered only postoperative hip wound became con- briefly. Bed rest, immobilization of the taminated with gram-negative bacilli, affected part, and administration of leading to recurrent episodes of gram- specific antimicrobial chemotherapeu- negative bacteremia. Fortunately, with tic agents are extremely important. appropriate surgical and medical man- However, because of the nature of the agement, the patient survived. It is our lesion itself, surgical procedures are policy to utilize the suction-irrigation mandatory in order to accomplish the apparatus for less than 10 days when- following: excise sinus tracts down to ever possible, and to obtain cultures of the involved bone, culture and biopsy the effluent solutions at frequent in- the infected bone, remove all seques- tervals. tra, drain abscesses, and debride all in- Recently, Hedstrom127 showed that fected granulation tissue and bone if prolonged antibiotic treatment of feasible. The surgeon attempts to re- chronic staphylococcal osteomyelitis move all ischemic bone and soft tissue for at least 6 months, significantly leaving a well-vascularized wound lowered the frequency of recurrences 123-125 bed. Other more complicated during the first year after the end of measures such as insertion of autoge- treatment than did shorter courses of nous bone grafts and application of split thickness skin grafts may be required in some patients. Under ideal conditions, postoperative treatment of patients with chronic osteomyelitis with the closed suction- irrigation technique serves to elimi- nate dead space by allowing healthy granulation tissue to obliterate the cavity occasioned by the infection and the surgical procedure.126 This has been responsible for improved results of surgical therapy of chronic osteomyelitis.124' 126 However, optimal use of the suction-irrigation apparatus requires meticulous nursing care to maintain continuous flow and to avoid contamination of the system. Even with the best technique, con- Fig. 17. Film taken following removal of in- tamination may occur, but usually it fected Charnley-Mueller prosthesis, showing suction-irrigation tube and gas in soft tissues.

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with Jordan and Kirby52 that immobilization in a body cast is not necessary for treatment of vertebral osteomyelitis.

Summary and conclusions Hematogenous osteomyelitis is a disease with protean manifestations. The presenting illness and location of bone infection vary with the age of the patient, the nature of predisposing factors, and the pathogen. Data indicate that the incidence of acute hematogenous osteomyelitis of children is decreasing, that in neonates it may be increasing, and that in adults, it is increasing. The clinical picture of the condition has been modified from a frequently fulminating or acute illness with high mortality in the preantimicrobial era to a more insidious disease with a considerably lower mortality. Fig. 18. Same patient as in Figure 17. Film Hematogenous osteomyelitis now pre- taken approximately 2 months later, show- sents considerable diagnostic difficul- ing periosteal elevation and subperiosteal new bone formation indicative of osteomyelitis. ties and often is mistaken initially for a wide variety of unrelated illnesses. therapy. We routinely treat such pa- New mechanisms for hematogenous os- tients with an initial course of paren- teomyelitis include intravenous her- teral oxacillin therapy for from 4 to 6 oin abuse, infections of intravenous weeks, followed by oral administration cannulas or subcutaneous arterio- of cloxacillin or dicloxacillin for 1 to venous fistulas in hemodialysis pa- 2 years. We monitor them at periodic tients, parenteral hyperalimentation, intervals to make sure that they are and umbilical catheterization. It oc- tolerating the drug without side ef- curs with unusual frequency in pa- fects. tients with sickle cell hemoglobinopa- thies and chronic granulomatous Vertebral osteomyelitis is treated disease of childhood. It has been re- with bed rest, analgesics, appropriate ported in leukopenic patients and in antibiotics based upon the results of those with other disorders of leuko- susceptibility tests of isolates from the cytes. Although staphylococci are still affected intervertebral disc space or the most common causative organisms, bone (or blood cultures when the lat- an expanding number of cases are be- ter are unavailable). Therapy is ad- ing caused by gram-negative bacilli ministered for 4 to 6 weeks. Sponta- and more unusual pathogens. Despite neous intervertebral fusion usually the availability of potent antimicro- occurs. Surgery is not indicated unless bial drugs, 20% of children with acute a complication intervenes. We agree

Downloaded from www.ccjm.org on October 2, 2021. For personal use only. All other uses require permission. Spring 1975 Hematogenous osteomyelitis 149 hematogenous osteomyelitis contract tal during the years 1919-37. Br J Surg chronic or recurrent disease. 28: 261-274, 1940. 13. Wilensky AO: Osteomyelitis; Its Patho- Hematogenous osteomyelitis is not genesis, Symptomatology and Treatment. yet a disease of the past. Although it New York, MacMillan Co, 1934. accounts for only one fifth of all the 14. Green M, Nyhan WL Jr, Fousek MD: cases of osteomyelitis in the United Acute hematogenous osteomyelitis. Pedi- States, there is an urgent need for ad- atrics 17: 368-382, 1956. 15. Harris NH: Some problems in the diag- ditional studies of pathogenesis and nosis and treatment of acute osteomyeli- improved methods of management. tis. J Bone Joint Surg 42-B: 535-541, 1960. 16. Trueta J, Morgan JD: Late results in the References treatment of one hundred cases of acute haematogenous osteomyelitis. Br J Surg 1. Waldvogel FA, Medhoff G, Swartz MN: 41: 449-456, 1954. Osteomyelitis; a review of clinical fea- 17. Winters JL, Cahen I: Acute hematoge- tures, therapeutic considerations and un- nous osteomyelitis; a review of sixty-six usual aspects. N Engl J Med 282: 198- cases. J Bone Joint Surg 42-A: 691-704, 206,260-266, 316-322, 1970. 1960. 2. Leading article: Changed character of 18. Lowe RW, Brooks AL: Hematogenous osteomyelitis. Br Med J 3: 255-256,1967. osteomyelitis. South Med J 63: 1183-1189, 3. Norden CW: Experimental osteomyelitis 1970. I. A description of the model. J Infect 19. Caldwell GA, Wickstrom J: The closed Dis 122: 410-418, 1970. treatment of acute hematogenous osteo- 4. Norden CW: Experimental osteomyelitis myelitis; results in 67 cases. Ann Surg II. Therapeutic trials and measurement 131: 734-742, 1950. of antibiotic levels in bone. J Infect Dis 20. Altemeier WA, Largen T: Antibiotic and 124: 565-571, 1971. chemotherapeutic agents in infections of 5. Norden CW, Dickens DR: Experimental the skeletal system. JAMA 150: 1462- osteomyelitis III. Treatment with cepha- 1468, 1952. loridine. J Infect Dis 127: 525-528, 1973. 21. Blockey NJ, Watson JT: Acute osteomye- 6. Andriole VT, Nagel DA, Southwick WO: litis in children. J Bone Joint Surg 52-B: A paradigm for human chronic osteomye- 77-87, 1970. litis. J Bone Joint Surg 55-A: 1511-1515, 22. Shandling B: Acute hematogenous osteo- 1973. myelitis; a review of 300 cases treated 7. Andriole VT, Nagel DA, Southwick WO: during 1952-1959. S Afr Med J 34: 520- Chronic staphylococcal osteomyelitis; an 524, 1960. experimental model. Yale J Biol Med 47: 23. Hobo T: Zur Pathogenese der akuten 33-39, 1974. haematogenen Osteomyelitis mit Berück- 8. Jaffe HL: Metabolic, Degenerative and sichtigung der Vitalfarbungslehre. Acta Inflammatory Diseases of Bones and Sch Med Univ Kioto 4: 1-29, 1921-1922. Joints. Philadelphia, Lea 8c Febiger, 1972. 24. Starr CL: Acute hematogenous osteomye- 9. Collins DH: Pathology of Bone. London, litis. Arch Surg 4: 567-587, 1922. Butterworths, 1966, pp 209-227. 25. Trueta J: The three types of acute hema- 10. Kahn DS, Pritzker KPH: The pathophys- togenous osteomyelitis. J Bone Joint Surg iology of bone infection. Clin Orthop 96: 41-B: 671-680, 1959. 12-20, 1973. 26. Hart VL: Acute osteomyelitis in children. 11. Frost HM: Pyogenic osteomyelitis; the JAMA 108: 524-528, 1937. normal bone spaces as a bacterial reser- 27. Green WT, Shannon JG: Osteomyelitis voir. Henry Ford Hosp Med Bull 8: 263- of infants; a disease different from osteo- 266, 1960. myelitis of older children. Arch Surg 32: 12. Butler ECB: The treatment, complica- 462-493, 1936. tions and late results of acute haematoge- 28. Taylor K, Davies M: Persistence of bac- nous osteomyelitis based on a study of teria within sequestra. Ann Surg 66: 522- 500 cases admitted to the London Hospi- 528, 1917.

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29. Frost HM, Villaneuva AR, Roth H: Pyo- myelitis and acute septic arthritis in chil- genic osteomyelitis; diffusion in live and dren. Med J Aust 2: 703-705, 1974. dead bone with particular reference to 45. Harris NH, Kirkaldy-Willis WH: Pri- the tetracycline antibiotics. Henry Ford mary subacute pyogenic osteomyelitis. J Hosp Med Bull 8: 255-262, I960. Bone Joint Surg 47-B: 526-532, 1965. 30. Weissberg ED, Smith, AL, Smith DH: 46. Robertson DE: Primary acute and sub- Clinical features of neonatal osteomyeli- acute localized osteomyelitis and osteo- tis. Pediatrics 53: 505-510, 1974. chondritis in children. Can J Surg 10: 31. Fardon DF: Osteomyelitis of the scapula 408-413, 1967. in an infant. Mo Med 67: 299-302, 1970. 47. Primary subacute hematogenous osteo- 32. Ek J: Acute hematogenous osteomyelitis myelitis. Br Med J 3: 728-729, 1969. in infancy and childhood; early clinical 48. Kulowski J: Pyogenic osteomyelitis of the diagnosis and effect of treatment. Clin spine; an analysis and discussion of 102 Pediatr 10: 377-379, 1971. cases. J Bone Joint Surg 18: 343-364, 1936. 33. Lindblad B, Ekengren K, Aurelius G: 49. Ambrose GB, Alpert M, Neer CS: Verte- The prognosis of acute hematogenous os- bral osteomyelitis; a diagnostic problem. teomyelitis and its complications during JAMA 197: 619-622, 1966. early infancy after the advent of antibi- 50. Stone DB, Bonfiglio M: Pyogenic verte- otics. Acta Paediatr Scand 54: 24-32, 1965. bral osteomyelitis; a diagnostic pitfall for 34. Einstein RAJ, Thomas CG Jr: Osteomye- the internist. Arch Intern Med 112: 491— litis in infants. Am J Roentgenol Radium 500, 1963. Ther Nucl Med 55: 299-314, 1946. 51. Genster HG, Anderson MJF: Spinal os- 35. Qureshi ME, Puri SP: Osteomyelitis after teomyelitis complicating urinary tract in- exchange transfusion. Br Med J 2: 28-29, fection. J Urol 107: 109-111, 1972. 1971. 52. Jordan CM, Kirby WMM: Pyogenic ver- 36. Wiley AM, Trueta J: The vascular anat- tebral osteomyelitis; treatment with an- omy of the spine and its relationship to timicrobial agents and bed rest. Arch In- pyogenic vertebral osteomyelitis. J Bone tern Med 128: 405^10, 1971. Joint Surg 41-B: 796-809, 1959. 53. Freehafer AA, Furey JG, Pierce DS: Pyo- 37. Zadek I: Acute osteomyelitis of the long genic osteomyelitis of the spine resulting bones of adults. Arch Surg 37: 531-545, in spinal paralysis. J Bone Joint Surg 1938. 44-A: 710-716, 1962. 38. King DM, Mayo KM: Subacute hema- 54. Henriques CQ: Osteomyelitis as a com- togenous osteomyelitis. J Bone Joint Surg plication in urology. Br J Surg 46: 19-28, 51-B: 458-463, 1969. 1958-59. 39. Smith AG: Hematogenous Friedlander's 55. Bruno MS, Silverberg TN, Goldstein DH: bacillus osteomyelitis. JAMA 195: 1060- Embolic osteomyelitis of the spine as a 1061, 1966. complication of infection of the urinary 40. Irvine R, Johnson BL Jr, Amstutz HC: tract. Am J Med 29: 865-878, I960. The relationship of genitourinary tract 56. Leigh TF, Kelly RP, Weens HS: Spinal procedures and deep sepsis after total hip osteomyelitis associated with urinary replacements. Surg Gynecol Obstet 139: tract infections. Radiology 65: 334-342, 701-706, 1974. 1955. 41. Hall AJ: Late infection about a total 57. Henson SW Jr, Coventry MB: Osteomye- knee prosthesis; report of a case second- litis of the vertebrae as a result of infec- ary to urinary tract infection. J Bone tion of the urinary tract. Surg Gynecol Joint Surg 56-B: 144-147, 1974. Obstet 102: 207-214, 1956. 42. Some problems of acute osteomyelitis. Br 58. Guri JP: Pyogenic osteomyelitis of the Med J 4: 317-318, 1972. spine; differential diagnosis through 43. Gerszten E, Allison MJ, Dalton HP: An clinical and roentgenographic observa- epidemiologic study of 100 consecutive tions. J Bone Joint Surg 28: 29-39, 1946. cases of osteomyelitis. South Med J 63: 59. Wear JE, Baylin GJ, Martin TM: Pyo- 365-367, 1970. genic osteomyelitis of the spine. Am J 44. Nade S, Robertson FW, Taylor TKF: An- Roentgenol Radium Ther Nucl Med 67: tibiotics in the treatment of acute osteo- 90-94, 1952.

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60. Griffiths HED, Jones DM: Pyogenic in- 75. Specht EE: Hemoglobinopathy salmo- fection of the spine. J Bone Joint Surg nella osteomyelitis. Clin Orthop 79: 110— 53-B: 383-391, 1971. 118, 1971. 61. Holzman RS, Bishko F: Osteomyelitis in 76. Barrett-Connor E: Bacterial infection heroin addicts. Ann Intern Med 75: 693- and sickle cell anemia; an analysis of 250 696, 1971. infections in 166 patients and a review 62. Lewis MA, Gorbach S, Altner P: Spinal of the literature. Medicine 50: 97-112, Pseudomonas chondro-osteomyelitis in 1971. heroin users. N Engl J Med 286: 1303, 77. Engh CA, Hughes JL, Abrams RC, et 1972. al: Osteomyelitis in the patient with 63. Kido D, Bryan D, Halpern M: Hematog- sickle-cell disease. J Bone Joint Surg 53- enous osteomyelitis in drug addicts. Am A: 1-15, 1971. J Roentgenol Radium Ther Nucl Med 78. Constant E, Green RL, Wagner DK: Sal- 118: 356-363, 1973. monella osteomyelitis of both hands and 64. Selby RC, Pillay KV: Osteomyelitis and the hand-foot syndrome. Arch Surg 102: 148-151, 1971 disc infection secondary to Pseudomonas aeruginosa in heroin addiction; case re- 79. Watson RJ, Burko H, Megas H, et al: port. J Neurosurg 37: 463-466,1972. The hand-foot syndrome in sickle-cell disease in young children. Pediatrics 31: 65. Salahuddin NI, Madhavan T, Fisher EJ, 975-982, 1963. et al: Pseudomonas osteomyelitis; radio- 80. Bowmer EJ: The challenge of salmonello- logic features. Radiology 109: 41-47, 1973. sis; major public health problem. Am J 66. Light RW: Vertebral osteomyelitis due to Med Sei 247: 467-501, 1964. Pseudomonas in the occasional heroin 81. Grady GF, Keusch GT: Pathogenesis of user. JAMA 228: 1272, 1974. bacterial diarrheas. N Engl J Med 285: 67. Bryan V, Franks L, Torres H: Pseudomo- 831-841, 1971. nas aeruginosa cervical diskitis with chon- 82. Hornick RB, Greisman SE, Woodward droosteomyelitis in an intravenous drug TE, et al: Typhoid fever; pathogenesis abuser. Surg Neurol 1: 142-144, 1973. and immunologic control. N Engl J Med 68. Wiesseman GJ, Wood VE, Kroll LL: 283: 686-691, 1970. Pseudomonas vertebral osteomyelitis in 83. Kaye D, Hook EW: The influence of he- heroin addicts; report of 5 cases. J Bone molysis or blood loss on susceptibility to Joint Surg 55-A: 1416-1424,1973. infection. J Immunol 91: 65-75, 1963. 69. O'Connell CJ, Cherry AV, Zoll JG: Os- 84. Kaye D, Palmieri M, Rocha H: Effect of teomyelitis of cervical spine; Candida bile on the action of blood against Salmo- guilliermondii. Ann Intern Med 79: 448, nella. J Bacteriol 91: 945-952, 1966. 1973. 85. Greenberg LW, Haynes RE: Escherichia 70. Leonard A, Comty CM, Shapiro FL, et al: coli osteomyelitis in an infant with sickle- Osteomyelitis in hemodialysis patients. cell disease. Clin Pediatr 9: 436-438, 1970. Ann Intern Med 78: 651-658, 1973. 86. Rubin HM, Eardley W, Nichols BL: Shi- 71. Baker LRL, Brain MC, Miller JK, et al: gella sonnei osteomyelitis and sickle-cell Osteomyelitis; an unusual sequel to anemia. Am J Dis Child 116: 83-87, 1968. neutropenia. Br Med J I: 722-725, 1967. 87. Fonk J, Coonrad DJ: Serratia osteomyeli- 72. McHenry MC, Gavan TL, Hawk WA, tis in sickle cell disease. JAMA 217: 80- et al: Gram-negative bacteremia; vari- 81, 1971. able clinical course and useful prognostic 88. Hruby MA, Honig GR, Lolekha S, et factors. Cleve Clin Q 42: 15-32, 1975. al: Arizona hinshawii osteomyelitis in 73. Widen AL, Cardon L: Salmonella typhi- sickle cell anemia. Am J Dis Child 125: murium osteomyelitis with sickle cell- 867-868, 1973. hemoglobin C disease; a review and 89. Robbins JB, Pearson HA: Normal re- case report. Ann Intern Med 54: 510-521, sponse of sickle cell anemia patients to 1961. immunization with Salmonella vaccines. 74. Diggs LW: Bone and joint lesions in Pediatrics 66: 877-882, 1965. sickle-cell disease. Clin Orthop 52: 119— 90. Seeler RA, Reddi CU, Kittams D: Diplo- 143, 1967. coccus pneumoniae osteomyelitis in an

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