II.

Bone and Joint Infections Bones and joints represent special problems for the host defense mechanisms. Normal bone has an excellent blood supply, although there is slowing of the circulation in the metaphyseal region in children. Once pus forms under pressure, the vascular supply to bone is lost because of its rigid structure, resulting in areas of infected, devitalized bone. Septic emboli in bone or vascular thrombosis can cause additional devascularization. Ligaments and tendons are relatively avascular structures and do not handle infection well. Joints, with their avascular cartilage and menisci, pose a particular problem. Local phagocytic function can be deficient, and it is often difficult to ensure adequate delivery of humeral factors (antibodies, opsonins, complement). In addition to the direct destructive effect of cell breakdown on cartilage, the pus under pressure interferes with cartilage nutrition and blood supply to the periarticular structures. At particular risk is the epiphyseal blood supply, and avascular neurosis may be the result. Antibiotics can inhibit or cure an infection only when they can reach the infecting organism in bacteriostatic or bactericidal concentrations. Infections producing pressure in a bone or joint as well as in relatively avascular tissues can impede or prevent antibiotics from reaching the primary site of infection. An acute infection of bone (hematogenous osteomyelitis), in its earliest phase, is a medical disease and can often be cured by prompt, appropriate antibiotic therapy. However, the time between initial infection and bone infarct is often short. If effective treatment is delayed and devascularization of the involved tissues results, then surgical treatment is a necessary adjunct to the antibiotic therapy. Even under the best of circumstances, late treatment (perhaps as early as 48 hours after the infection starts) may result in the loss of or abnormal function of the joint. Thus, appropriate antibiotic therapy must be initiated as early as possible. Appropriate therapy requires knowledge of the etiologic agent and its sensitivities. Every effort should be made to obtain a bacterial culture and determine sensitivity. Once the culture specimen is obtained, it is important to institute antibiotic therapy based on a probable diagnosis using the most effective broad-spectrum antibiotics. Diagnosis The earliest symptom or sign that may help differentiate a bone or joint infection is usually pain or localized tenderness in the periarticular region. In the infant, refusal to move or use an extremity may be noted first. The cardinal signs of infection redness, heat, and swelling may appear later than the pain and tenderness, or not at all. When examining a child with a fever of unknown origin, note any pain or alteration of the normal range of motions of a joint and carefully palpate all metaphyseal areas to determine local tenderness. Roentgenograms are of little value in making the early diagnosis, although careful comparison with the opposite side may show abnormal soft-tissue shadows. Roentgenographic evidence of bone or joint destruction is seen during the chronic phase of the disease. Osteomyelitis should always be included in the differential diagnosis for a patient with the radiographic appearance of a bone tumor (5). Radioisotopic bone scanning, especially indium imaging, is helpful in early localization of bone infection (6). Many authorities have advocated the use of magnetic resonance imaging in the diagnosis of osteomyelitis (7,8,9,10), but clinical context is of paramount importance in the evaluation of any abnormal findings. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) serum levels are useful in laboratory evaluations (11,12,13,14).

Identification of the infecting organism is essential. In the early stages of the disease, particularly if there is a spiking temperature, blood cultures can often yield the organism. If acute metaphyseal tenderness is present, then the organism can frequently be obtained by inserting a needle into the site of maximum tenderness. A serrated biopsy needle is useful if subperiosteal pus is not P.41 encountered. If a joint is involved, then the effusion should be aspirated before joint lavage. Processing the aspirates should include the following: Immediate Gram stain. Inoculation of culture broth for aerobic and anaerobic cultures. White blood cell count. If thick, purulent material is encountered, then dilution in broth occasionally enhances the growth of organisms by decreasing the concentration of leukocytes and humeral antibacterial factors. This is done routinely in the microbiology laboratory with fluid aspirates. Determination of the character of the hyaluronic precipitate, the presence of fibrin clots, and any disparity between the glucose in the aspirate and blood glucose may prove helpful, but the Gram stain, culture, and cell count are most valuable (see Chap. 3). Differential diagnosis. Care must be taken to differentiate soft-tissue infection, or cellulitis, from an infection occurring in a bone or joint. This is a particularly important precaution when the infection overlies a joint because any aspiration of a reactive sterile effusion by passing a needle through the soft-tissue infection may create a pyarthrosis. Tenderness and swelling from unrecognized trauma over a bone, particularly with some periosteal reaction, can present a confusing picture, but the absence of fever and systemic signs is helpful. Nonbacterial inflammatory arthritis, including viral and toxic synovitis and rheumatoid arthritis, must be included in a differential diagnosis, but until proved otherwise, think first of septic arthritis. Spontaneous hemorrhages in patients with hemophilia and fractures in paraplegic patients, particularly patients with meningomyelocele, are special situations that can confuse the picture. Bacterial considerations (1,4,12) In acute hematogenous osteomyelitis, Staphylococcus aureus is the most common etiologic agent in all age groups. In recent years, an increasing number of isolated strains have been found to be methicillin resistant. In infants younger than 1 month, a diversity of other bacteria must also be considered. Group B streptococci and gram-negative organisms such as Escherichia coli, Proteus species, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Salmonella species are all suspect. In infants with a complicated medical history, particularly those who have had prolonged indwelling venous catheters, extensive surgery, or intensive prior antibiotic therapy, coagulase-negative staphylococci and rarely anaerobic organisms such as Bacteroides fragilis and fungal agents such as Candida albicans (hard to diagnose) must also be considered. In septic arthritis and osteomyelitis among infants younger than 1 month, S. aureus is the predominant etiologic agent. After the neonatal period and up to 4 years of age, Haemophilus influenzae is also a major cause of septic arthritis. In later childhood, the etiologic agents are the

same as for adults, with S. aureus predominating. Neisseria gonorrhoeae must be seriously considered, particularly among adolescents with single (especially the knee joint) or multiple joint findings. If there has been a preceding infection or if there is a concurrent infection in another organ system, one may suspect that the etiologic agent is the same as that from the initiating focus. But, because this is not always the case, direct culture from the bone or joint infection is advised. Special considerations Infections of the intervertebral discs, or acute discitis, may be encountered in children without antecedent infection or surgery (15). When organisms have been recovered, they have usually been staphylococcal. Infants may merely refuse to stand or walk, whereas older youngsters complain of pain in the back or lower extremity. The infection usually is low grade, particularly among children younger than 5 years of age. Roentgenograms reveal that the involved disc narrows rapidly over the first 2 to 3 weeks. A bone scan shows increased activity in the adjacent vertebrae. Although the process often appears self-limited, the symptoms and course of the disease can be improved by plaster immobilization and antistaphylococcal antibiotics. The difficulty in P.42 obtaining a bacterial diagnosis, even with needle biopsy, combined with the benign course of this condition, has led many clinicians to ignore efforts at establishing a bacterial diagnosis. The condition must, however, be differentiated from vertebral osteomyelitis with secondary disc destruction; in the latter condition, it is essential to obtain the bacterial diagnosis as an integral part of treatment of what can be a severe disease. The same precaution applies to disc infections following laminectomy. In these cases, an infection should be suspected when a postsurgical patient complains of increasing back pain starting 1 to 2 weeks postoperatively. Patients with hemolytic disorders, particularly those with sickle cell disease, are prone to the development of a subacute form of osteomyelitis. Salmonella infections are frequent, but other types of bacterial osteomyelitis are not uncommon (4). Because the diagnosis is usually made late, treatment is difficult and may require extensive surgical debridement and prolonged antibiotic therapy. Another special problem is presented by the patient who sustains a puncture wound in the sole of the foot. Despite initial cleansing and occasional debridement, cellulitis, arthritis, or osteomyelitis involving the foot develops in many patients (11). This occurrence is most commonly caused by P. aeruginosa. Early surgical debridement of the infected, including the plantar fascia, combined with preoperative and postoperative anti-P. aeruginosa antibiotics, has been the most effective method of management. For a serious infection, treatment is 5 days of antibiotic therapy with an aminoglycoside (e.g., tobramycin) or an antipseudomonal beta-lactam (e.g., ceftazidime) administered parenterally. Recently, ciprofloxacin has been used in gram-negative bone and joint infections (1); it must not be used in prepubertal children, however. Appropriate sensitivities guide antibiotic selection. Duration of therapy is empirical and may be guided by the clinical appearance and the CRP or ESR (11,15). Aminoglycoside doses need to be adjusted according to peak and trough serum levels and monitoring must include weekly Serum Creatinine (Cr) measurements and regular audiologist evaluation. Patients with human immunodeficiency virus or acquired immunodeficiency

syndrome can have septic joints, which frequently may be missed because of the relatively weak immune response to the infectious agent. Joint aspiration should be performed in this setting (16). Lyme arthritis. Lyme arthritis, the most common vectorborne infection in the United States, is caused by the spirochete Borrelia burgdorferi, which is transmitted to humans primarily via the Ixodes scapularis tick from its natural hosts, deer and white-footed mice (17). Arthritis, the most common form of late Lyme disease (other forms being encephalopathy and polyneuropathy), can occur weeks to months after the original infection. Approximately 60% of untreated primary disease will develop arthritis (18). Clinical presentation includes fever and joint effusion, which may be confused with acute septic arthritis, especially in children (19). Treatment with oral antibiotics such as doxycycline for 4 weeks or the parenteral agent ceftriaxone for 2 weeks usually results in lasting cure. However a small percentage of patients experience ongoing symptoms despite antibiotic therapy. Possible reasons include persistent infection, residual joint damage, or a chronic autoimmune synovitis (20). Requirements and characteristics of appropriate antibiotic treatment (1,4,21) For initial treatment of bone or joint infection, choose a bactericidal antibiotic effective against the suspected organism and a route of administration that ensures delivery of therapeutic levels to the infected site. The intravenous (IV) route is generally preferred for initial treatment [although some agents such as gentamicin and tobramycin are effective given intramuscularly (IM)]. Recent studies (1) have indicated that oral antibiotics appear in therapeutic concentrations in bones and joints and, if given properly, can substitute for parenteral therapy in children. Most authorities, however, prefer the IV route. The duration of parenteral treatment is 3 to 4 weeks for septic arthritis and 4 to 6 weeks for osteomyelitis (the longer duration for infections caused by S. aureus). In adults with selected organisms, the treatment may be completed using P.43 oral quinolones after the initial pain, swelling, and fever have resolved with IV antibiotics. Quinolone antibiotics (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin) have allowed oral therapy against a broad spectrum of bacteria including Pseudomonas (1). In treating children with osteomyelitis, treatment may be initiated with an IV agent such as nafcillin (Nafcil or Unipen), and the 4- to 6-week treatment course may be completed with oral dicloxacillin (Dynapen) or trimethoprim (Bactrim or Septra). For all ages the dosage of antibiotics (oral or parenteral) is at the upper therapeutic level. When appropriate, adequate bactericidal drug levels for both oral as well as parenteral agents should be documented. Providing parenteral antibiotics through home health care teams greatly reduces the cost of treatment. The differentiation between a mild, well-localized infection and a localized bone tumor can sometimes require a surgical biopsy (5). The CRP or ESR is also a helpful guideline to determine the duration of treatment (11). A summary of antimicrobial agents commonly used in acute bone and joint infections is presented in Table 3-1. These agents are known to enter bone and joint sites readily when given in adequate doses.

In an acute infection in which the organism is not immediately identified, the choice of therapy is determined by the organisms most commonly expected in the various age groups, along with the other factors previously listed. General guidelines are presented in Table 3-2. A local instillation or continuous irrigation with an antibiotic solution is almost never indicated. Systemic antibiotics, properly administered, achieve adequate levels in viable tissues (1,4). In many posttraumatic conditions, delivery of local antibiotics in methyl methacrylate beads is worthwhile (21). This treatment is indicated especially when a delayed bone graft or soft-tissue muscle flap is planned. Some favorable reports have been published about an implantable pump with a reservoir for antibiotic (generally amikacin). Continue antibiotics until the infection has been eliminated. A normal or declining ESR or CRP is one of the most helpful laboratory tests to indicate control of infection. Adjunctive treatment. Most orthopaedists believe that the healing process is aided by immobilizing the infected area. There is disagreement over casting or splinting. Undoubtedly, however, patients are more comfortable when the infected area is immobilized. If damage to the bone is significant, cast immobilization may be important to prevent a pathologic fracture. If damage to articular cartilage is suspected, motion of the involved joint is recommended after a brief 1- to 2-day period of immobilization. Surgical intervention. Appropriate antibiotic treatment instituted within the first 48 hours of acute osteomyelitis or septic arthritis is usually satisfactory. However, early diagnosis is rarely the case. If treatment is initiated over 48 hours after onset, it is important to determine whether medical treatment alone is adequate. Err on the side of more aggressive operative drainage. If the patient has been on an appropriate antibiotic for more than 24 hours without significant resolution of pain and temperature, then surgical intervention is indicated. In a bone infection, metaphyseal or subperiosteal abscesses must be drained. If metaphyseal point tenderness is present, and there is doubt whether this represents significant metaphyseal or subperiosteal pus, then it is safer to err on the side of a small surgical exploration or aspiration with a biopsy needle. If pus is encountered, then open surgical drainage is indicated. Joints In joint infections, satisfactory evacuation of pus can be achieved by needle aspiration. When the joint is easily visible and palpable, such as with the knee joint, repeated needle aspiration is usually adequate to keep the joint decompressed. Aspiration should be done with a 16- to 18-gauge needle. Irrigation of the joint to ensure removal of as much cellular debris as possible is helpful (12). The hip joint presents special problems (12). The blood supply to the femoral head is intraarticular; hence, any increase in pressure can deprive the entire femoral head of its circulation. Because hip P.44

P.45

P.46

P.47 joint effusions are not readily palpable, it is difficult to be certain that repeated aspirations decompress the joint. For this reason, most authorities believe that immediate surgical drainage of a septic hip is indicated, and some believe that the shoulder should be treated similarly. The possible exception is in gonococcal arthritis (22). The hip joint can be drained anteriorly between muscle planes or posteriorly with a muscle-splitting incision. The capsule and synovium are opened and drains are inserted. TABLE 3-1 Antimicrobial Agents Commonly Used Initially in Acute Bone and Joint Infections Antibiotic Usual susceptible organisms Daily dosage (IV route) Comment Cefazolin (cephalosporins) Penicillinase-producing Staphylococcus aureus; will also treat streptococci, pneumococci, nonpenicillinase-producing staphylococci, and Klebsiella pneumoniae 07 d: 40 mg/kg divided doses q12h Infant: 60 mg/kg divided doses q8h Child: 80 mg/kg divided doses q6h Adult: 36 g divided doses of 8h A drug of choice; IV route preferred, but may be given IM. Adjust adult dosage according to blood urea nitrogen or, preferably, the creatinine clearance Nafcillina Same as cefazolin 07 d: 50 mg/kg divided doses q12ha 7 d6 wk: 75 mg/kg divided doses q8h 6 wk3 y: 80 mg/kg divided doses q6h Child: 150 mg/kg divided doses q6h Adult: 212 g divided doses of 46 h A drug of choice Methicillin Same as cefazolin and nafcillin No longer commonly used; too many problems Monitor patients for proteinuria: drug has occasionally been implicated in adverse renal side effects Clindamycin S. aureus, pneumococci, streptococci (not enterococci), and many Bacteroides fragilis strains Pediatric: 1020 mg/kg PO or IV or IM in 34 doses Adult: 600900 mg of 68 h Considered an excellent agent for B. fragilis infections Penicillin G (aqueous) Streptococci (not enterococci), pneumococci, gonococci, and penicillinsusceptible staphylococci 07 d: 50,000 unit/kg divided dose q12h greater than 7 d: 75,000100,000 unit/kg IV or IM divided doses q8h

12 yadult: 1224 million units of 46 h Useful for open fractures contaminated with barnyard waste and for treatment of clostridia infection Ampicillin Same as penicillin G; also Haemophilus influenzae, some strains of Escherichia coli, Proteus, and Salmonella 07 d: 50 mg/kg divided doses q12h 7 d6 wk: 75 mg/kg divided doses q8h Infant: 100 mg/kg divided doses q6h Child: 150 mg/kg divided doses q6h 12 yradult: 812 g H. influenzae now shows a 10%20% ampicillin resistance in some areas. Empirin therapy must therefore be with ceftriaxone or cefuroxime Ceftriaxone Select gram-negative organisms or mixed infections 012 yr: 50 mg/kg once daily 12 yradult: 2 g q24h Generally reserved for resistant or mixed infections Cefuroxime Select gram-negative organisms or mixed infections greater than 3 mo-12 yr: 75 mg/kg divided doses q8h Generally reserved for resistant or mixed infections Ceftazidime Select gram-negative organisms including Pseudomonas or mixed infections 12 yradult: 1.5 g q8h less than 12 yr not indicated 12 yradult: 1 g q812h Same as cefuroxime Gentamicin Gram-negative infections less than 12 yr: 67.5 mg/kg in three equal doses Agent of choice for suspected gram-negative infections Tobramycin 12 yradult: 35 mg/kg in three equal doses (dose adjusted based on peak and trough levels) can be given as a single daily dose May be given either IV or IM. Renal function must be carefully checked, and therapy beyond 10 days must be administered cautiously because of potential nephrotoxicity and ototoxicity. May be synergistic with carbenicillin against some strains of Pseudomonas aeruginosa; also usually synergistic with penicillin against enterococci. Reduce dosage to 3 mg/kg/d as soon as clinically indicated. Follow with peak and trough serum levels if available aSome authorities recommend that nafcillin not be used in 0- to 7-day-old infants because of poor pharmacokinetics. From Hansen ST Jr, Ray CG. Antibiotics in orthopaedics. In: Kagan BM, ed. Antimicrobial therapy, 3rd ed. Philadelphia, PA: WB Saunders, 1980, with permission.

TABLE 3-2 Tentative Selection of Therapy When Organisms Are Not Immediately Identified Situation Organisms suspected Suggested antibiotic choice

Newborn (1 mo) Staphylococcus aureus Nafcillin plus gentamicin or tobramycin Osteomyelitis Streptococci Gram-negative bacteria including Escherichia coli, Klebsiella pneumoniae, Proteus group, Pseudomonas aeruginosa Septic arthritis S. aureus 1 mo4 yr Osteomyelitis S. aureus Second-generation cephalosporin to cover H. influenzae Septic arthritis Haemophilus influenzae S. aureus Streptococci Second-generation cephalosporin to cover H. influenzae 4 yr12 yr Osteomyelitis Septic arthritis S. aureus First- or second-generation cephalosporin 12 yradult Osteomyelitis S. aureus A cephalosporin (first- or second-generation agent) or nafcillin Septic arthritis S. aureus A cephalosporin or nafcillin (ceftriaxone if gonococcus is strongly suspected) Special considerations Chronic hemolytic disorders Osteoarthritis S. aureus A cephalosporin (second-generation if salmonella is suspected) or nafcillin until sensitivity results are available Septic arthritis Pneumococci Salmonella groupa Infections following puncture wounds of the foot Pseudomonas aeruginosa Ceftazidime actually achieves better drug levels than aminoglycosides (gentamicin or tobramycin) Infections following trauma or surgery S. aureus Streptococci Gram-negative organisms A first- or second-generation cephalosporin (or nafcillin) plus gentamicin or tobramycin

aInfections caused by Salmonella should be documented first by culture and sensitivity testing before empirical treatment with agents such as ampicillin (or chloramphenicol) is initiated. From Hansen ST Jr, Ray CG. Antibiotics in orthopaedics. In: Kagan BM, ed. Antimicrobial therapy, 3rd ed. Philadelphia, PA: WB Saunders, 1980, with permission.

At times, the fibrin entering the joint as a transudate forms clots and isolates segments of the joint from decompression. Hypertrophy of synovium and adhesions may also affect the ability of the surgeon to decompress the joint adequately. Under these circumstances, it is advisable to debride the joint arthroscopically or with an open procedure. Joints amenable to arthroscopic lavage are the knee, shoulder, and ankle. Chronic osteomyelitis presents a different problem from acute infection. Acute infection in the earliest phase is primarily a medical disease, with surgical techniques used as an adjunct. In chronic infection, the primary problem is surgical removal of all dead and poorly vascularized tissue. If this removal is properly done under appropriate antibiotic therapy, it is possible to eradicate most sites of chronic osteomyelitis. The operation must be carefully planned because it often involves significant removal of bone and surrounding tissues. In the case of chronic joint infections, it may mean complete resection of the joint with the creation of a pseudarthrosis or an arthrodesis. Rotational muscle flaps or free-tissue transfer may be required to cover areas of viable but poorly covered bone. Intravenous and oral antibiotics serve as valuable adjuncts. Patient quality of life can be profoundly impacted by chronic osteomyelitis (23); treatment leading to resolution of the infection does improve this impact. Gas gangrene Gas gangrene can be a fatal process. Prevention can be achieved by thorough debridement and removal of all devitalized tissue, delayed wound closure when in doubt, and antibiotic treatment as recommended previously. Clostridium perfringens infections carry a 65% overall mortality rate, which increases to 75% in infants and elderly patients. The diagnosis should be suspected when the patient is pale, weak, perspiring, and more tachycardiac than the degree of fever warrants. The patient frequently complains of severe pain. Mental confusion and gas in the tissues are late signs, as are the characteristic mousy odor, jaundice, oliguria, and shock. Other gas-producing species in addition to C. perfringens (ten isolated toxins), include E. coli, Enterobacter aerogenes, anaerobic streptococci, B. fragilis, and K. pneumoniae. Antitoxin does not appear to help much because it is neutralized as rapidly as it reaches muscle. Treatment consists of debridement and high doses of antibiotics. Penicillin is usually the best for the C. perfringens group; it should be given in amounts of 20 to 50 million units/day. Clindamycin or metronidazole are good alternative antibiotics in patients who are allergic to penicillin. Some clostridia are resistant to clindamycin, making it necessary to check sensitivities carefully. Hyperbaric oxygen is only an adjunct

to surgery. Its use allows the surgeon to save more tissue than might otherwise be possible, and it does lower the mortality rate slightly. Although exceedingly uncommon, group A streptococcal myonecrosis can have a similar course and results in death in a high percentage of cases. It must be treated with aggressive surgical debridement or amputation in addition to appropriate antibiotic therapy. Toxic shock syndrome has also been noted in orthopaedic patients and is caused by unique staphylococcal strains with unusual phage types. Toxic shock syndrome is also a surgical condition, but it carries a more favorable prognosis. Necrotizing fasciitis can be caused by several bacterial types (most commonly group A streptococcus) and often requires debridement combined with appropriate antibiotic therapy. Infectious disease consultation is indicated for each of these infectious conditions.