Chapter 20 General Principles of Infection
Etiology
Surgeon-Dependent Factors
Skin Preparation
Hand washing is the most important procedure for prevention of nosocomial infections. Studies suggest that hand scrubbing for 2 minutes is as effective as traditional hand scrubbing for 5 minutes. The optimal duration of hand scrubbing has yet to be determined. Hand rubbing with an aqueous alcohol solution that is preceded by a 1-minute nonantiseptic hand washing for the first case of the day was found by Parienti et al. to be just as effective in prevention of surgical site infections as traditional hand scrubbing with antiseptic soap. The effectiveness of common antiseptics is summarized in Table 20-1.
Prophylactic Antibiotic Therapy
Methicillin-Resistant Staphylococcus Aureus
The evolution of S. aureus into a multiple-drug–resistant pathogen (methicillin-resistant S. aureus [MRSA]) has become a major health concern worldwide. Approximately 57% of S. aureus bacteria are methicillin resistant, and now vancomycin-resistant strains are being reported. This is probably one of the most worrisome problems in the fight against bacterial infections. Initially, MRSA was seen only in hospital settings and long-term care facilities; however, it is now becoming increasingly prevalent in young, healthy individuals in the community (Table 20-2; at-risk groups), and it is particularly virulent. The mortality rate associated with invasive MRSA infections is 20%.
TABLE 20-2 At-Risk Groups and Risk Factors for Community-Acquired Methicillin-Resistant Staphylococcus aureus
AT-RISK GROUPS | RISK FACTORS |
---|---|
From Marcotte AL, Trzeciak MA: Community-acquired methicillin-resistant Staphylococcus aureus: an emerging pathogen in orthopaedics, J Am Acad Orthop Surg 16:98, 2008.
Because of the prevalence of community acquired (CA)-MRSA, it is necessary to rapidly identify the organism, determine antibiotic sensitivity, and begin antibiotic therapy (for empirical coverage see Table 22-2). For invasive infections, intravenous vancomycin is recommended or, alternatively, daptomycin, gentamicin, and linezolid can be used. In cases of necrotizing fasciitis, clindamycin, gentamicin, rifampin, trimethoprim-sulfamethoxazole, and vancomycin are effective. Until a sensitivity determination can be made, antimicrobial coverage specifically of CA-MRSA is recommended. For deep subperiosteal abscess or superficial abscess, irrigation and débridement are necessary to reduce bacterial counts. Obtaining an infectious disease consult is highly recommended.
Diagnosis
Laboratory Studies
A complete blood cell count, including differential and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), should be obtained during initial evaluation of bone and joint infections. The white blood cell count is an unreliable indicator of infection and often is normal even when infection is present. The differential shows increases in neutrophils during acute infections. The ESR becomes elevated when infection is present, but this does not occur exclusively in the presence of infection. Fractures or other underlying diseases can cause elevation of the ESR. The ESR also is unreliable in neonates, patients with sickle cell disease, patients taking corticosteroids, and patients whose symptoms have been present for less than 48 hours. Peak elevation of the ESR occurs at 3 to 5 days after infection and returns to normal approximately 3 weeks after treatment is begun. CRP, synthesized by the liver in response to infection, is a better way to follow the response of infection to treatment. CRP increases within 6 hours of infection, reaches a peak elevation 2 days after infection, and returns to normal within 1 week after adequate treatment has begun. Other tests, such as the S. aureus surface antigen or antibody test and counterimmunofluorescence studies of the urine, are promising, but their usefulness in clinical situations has not been proved. Material obtained from aspiration of joint fluid can be sent to the laboratory for a cell count and differential to distinguish acute septic arthritis from other causes of arthritis. In septic arthritis, the cell count usually is greater than 80,000/mm3, with more than 75% of the cells being neutrophils (Table 20-3). Jung et al. devised an algorithm to predict the probability of septic arthritis in children (Table 20-4). A Gram stain also should be obtained. Gram stains identify the types of organisms (gram-positive or gram-negative) in about a third of bone and joint aspirates. Intraoperative frozen section also should be obtained in cases in which infection is suspected. A white blood cell count greater than 10 per high-power field is considered indicative of infection, whereas a count less than 5 per high-power field all but excludes infection.
LEUKOCYTES | NEUTROPHILS (%) | |
---|---|---|
Normal | <200 | <25 |
Traumatic | <5,000 | <25 |
Toxic synovitis | 5,000-15,000 | <25 |
Acute rheumatic fever | 10,000-15,000 | 50 |
Juvenile rheumatoid arthritis | 15,000-80,000 | 75 |
Septic arthritis | >80,000 | >75 |
From Morrissy RT: Septic arthritis. In Gustilo RB, Genninger RP, Tsukayama DT, editors: Orthopaedic infection: diagnosis and treatment, Philadelphia, 1989, WB Saunders.
Imaging Studies
Radiographic studies are helpful but are not as useful in the diagnosis of acute bone and joint infections as they are in following responses to treatment. Plain radiographs show soft tissue swelling, joint space narrowing or widening, and bone destruction (Fig. 20-1). Bone destruction is not apparent on radiographs, however, until an infection has been present for 10 to 21 days. In addition, 30% to 50% of the bone matrix must be lost to show a lytic lesion on radiographs (Fig. 20-2). Wheat found that fewer than 5% of plain radiographs were initially abnormal in bone and joint infections, and fewer than 30% were abnormal at 1 week; however, 90% were abnormal at 3 to 4 weeks. If initial radiographs are normal in the evaluation of bone and joint infections, other imaging methods that show soft tissue swelling and loss of normal fat planes around the involved bone or joint should be used.

FIGURE 20-1 A, Radiographic evidence of acute bone and joint infection. B, Treatment with antibiotic cement spacer.
(Courtesy of Andrew Crenshaw.)
Conventional tomography can be useful in identifying a sequestrum or subchondral bony plate destruction, although it has largely been replaced with more conventional radiographic methods. Arthrography helps document proper aspiration of a suspected septic joint. Dye should be injected only after fluid is obtained from the joint because the bactericidal effect of iodinated contrast material can cause a false-negative culture result. CT can help determine the extent of medullary involvement. Pus within the medullary cavity replaces the marrow fat, causing an increased density on the CT scan. Adjacent soft tissue abscesses also are seen easily (Fig. 20-3). CT diagnosis of acute osteomyelitis is based on detection of intraosseous gas, osteolysis, soft tissue masses, abscesses, or foreign bodies. Additionally, increased vascularity after administration of a contrast agent also can aid in the diagnosis. Narrowing of the medullary cavity by granulation tissue and new bone is readily shown during the healing phase of osteomyelitis. CT identifies sequestra in chronic osteomyelitis (Fig. 20-4). It also is helpful in identifying alterations in areas poorly seen on plain films, such as the sternoclavicular joint, sacroiliac joint, and spine. Contrast material can be used to delineate abscesses in necrotic tissue that does not enhance from surrounding hyperemic tissue.
A major disadvantage of three-phase 99mTc phosphate bone scintigraphy is that the increased uptake caused by osteomyelitis is difficult to distinguish from that caused by degenerative joint disease or posttraumatic or postsurgical changes. The relative activity in each of the three phases may be helpful in differentiating other causes of increased uptake. Cellulitis causes increased activity during the flow and equilibrium phases and a decreased or normal uptake in the delayed phase. Osteomyelitis causes increased uptake in all three phases (Fig. 20-5). Increased uptake in the delayed phase but not in the flow or equilibrium phase suggests degenerative joint disease (Table 20-5). 99mTc phosphate bone scans are unreliable in neonates (<6 weeks old) and usually are negative in 60% of these patients with bone or joint infections.
MRI has been used for evaluating bone and joint infections. MRI is a complex imaging method that aligns the body’s protons along the axis of a powerful external magnetic field and records the motion of the protons as they return to the magnetic field alignment after absorbing energy from a radiofrequency-generating coil. Each type of tissue has its own unique signal characteristics. Two parameters are evaluated. The first is the echo time (TE), which is the time that elapses between the initial radiofrequency pulse and its return back to the radio antenna (akin to a sonar ping). The second is repetition time (TR), which is the time between the applied consecutive radiofrequency pulses to the patient (the frequency of pings). When the TR and TE are short, a T1 image is produced that shows fat as a high, bright signal. When the TR and TE are long, a T2 image is obtained that shows water as a bright signal. An additional signal is obtained by suppressing the fat signal; this is called short tau inversion recovery (STIR). STIR signals have a high negative predictive value for osteomyelitis of almost 100%; however, STIR cannot be used to differentiate fluid collections (e.g., abscesses) from circumscribed soft tissue edema. The reported abnormal images reflect an increase in water content, resulting from edema in the marrow cavity. Marrow fat is replaced by edema and cellular infiltrates that are lower in signal than fat on T1 images and higher in signal than fat on T2 and STIR images. The classic findings of osteomyelitis on MRI are a decrease in the normally high marrow signal on T1 images and a normal or increased signal on T2 images (Fig. 20-6). According to Boutin et al., MRI is the most appropriate tool to rule out cartilaginous epiphyseal infection. Mazur et al. showed that MRI was superior in sensitivity (97%) and specificity (92%) to 99mTc phosphate bone scintigraphy for detection of osteomyelitis. MRI detects changes (e.g., lytic areas) much earlier in the course of disease than radiographs because it shows the condition of the intramedullary cavity. The signal changes seen on MRI are nonspecific, and anything that causes edema or hyperemia (e.g., fractures, tumors, and inflammatory processes) produces signal changes similar to that of osteomyelitis. Although MRI is good for detailing marrow involvement and discitis, it does little to detect early cortical bone involvement.
1. Patients suspected of musculoskeletal infection should have plain radiographs of the area in question.
2. CT is useful in detecting bone abnormalities such as sequestra.
3. Ultrasonography helps to establish if a joint effusion is present and to localize needle aspiration to diagnose septic arthritis.
4. A three-phase bone scan accurately detects osteomyelitis in nonviolated bone. If hardware is in place or if there has been previous trauma to the bone or a Charcot joint for instance is present, a three-phase bone scan is only useful as a screening test. A white blood cell–labeled bone scan helps with detection of complicated osteomyelitis, and combining this with a colloid scan maximizes accuracy. This is especially useful in total joint infections and diabetic feet but less so in neuropathic joints. It is not helpful with spinal osteomyelitis.
5. MRI shows surrounding tissue and is excellent in detecting osteomyelitis. Adding gallium improves detection of spinal osteomyelitis.
6. FDG-PET also is helpful in the diagnosis of spinal infection and chronic osteomyelitis but is not readily available in all health care institutions.
Treatment
Several routes of antibiotic treatment exist. Oral antibiotics are still the most commonly used. Intravenous application may be required for more serious infections that do not respond to oral antibiotics. Local delivery of antibiotics also can be beneficial. Polymethyl methacrylate (PMMA) beads impregnated with heat-stable antibiotics (tobramycin, vancomycin, and gentamicin) have been used since the early 1970s. A 2- to 3-cm area around each bead has a high concentration of antibiotic. With tobramycin and vancomycin, the peak concentration of antibiotic delivered to local tissue occurs on the first day and lasts for only approximately 1 week. This local delivery system avoids systemic toxicity; however, it requires removal (usually surgical) within 4 weeks. A more attractive biodegradable system is the collagen-gentamicin sponge, which obviates the need for surgical removal and delivers higher concentrations of antibiotics than PMMA beads. It has been suggested that antibiotic release by this method may be complete within 4 days. Lactic acid polymerase may be the next step in local biodegradable antibiotic delivery systems. This system delivers a high concentration of quinolines (bactericidals for probable pathogens of chronic osteomyelitis) for 60 days, with a peak release of antibiotics at day 15. An additional method of local antibiotic delivery is that of mixing autogenous iliac crest bone graft with piperacillin or vancomycin. Antibiotics must be chosen carefully. For example, heat-stable antibiotics are required for PMMA applications; quinolones have shown detrimental effects on chondrocytes and fracture healing; and tobramycin at intermediate levels of concentration (400 µg/mL) can decrease cell replication. In general, vancomycin is less toxic to osteoblasts at high local concentrations than other aminoglycosides and rifampin and the quinolones should not be administered when bone regeneration is an issue. An infectious disease consult can help guide the appropriate antibiotic in each patient and can be especially useful with the ever-changing microbial picture. Even though many surgical techniques have been described for the treatment of osteomyelitis (see Chapter 21), prevention is still the best course, and adherence to the basic principles of treatment of infections helps achieve success.
Human Immunodeficiency Virus
Four stages of HIV infection have been identified, although not all individuals infected with HIV go through all four stages. The stages are (1) acute primary HIV infection, (2) chronic asymptomatic HIV infection, (3) symptomatic HIV infection, and (4) advanced HIV-associated opportunistic disease or AIDS. Acute primary HIV infection appears clinically similar to infectious mononucleosis and occurs 2 to 6 weeks after viral transmission. Clinical features include pharyngitis, dysphagia, lymphadenopathy, rash, fever, fatigue, hepatosplenomegaly, and leukopenia. This stage is self-limiting, and most patients do not seek medical attention. Within 3 months after viral transmission, most patients develop positive serology, and virtually all patients seroconvert by 6 months, although delayed seroconversion 1 year after infection has been reported. After acute infection, a prolonged period ranging from 5 to more than 15 years of symptomless, chronic infection ensues. In the third stage (AIDS-related complex) the HIV-infected patient is no longer symptom free but has not yet developed AIDS-defining opportunistic infection as defined by the CDC or an absolute CD4 cell count of less than 200/mm3. In the final stage, a potentially life-threatening opportunistic disease develops as a result of the severe cell-mediated immunodeficiency. The epidemiological data on HIV transmission overwhelmingly indicate that the virus is transmitted through sexual, parenteral, and maternal-infant routes. HIV has been isolated from many organs and tissues, including bone. Blood, semen, vaginal secretions, bone, breast milk, and possibly saliva have been implicated in HIV transmission. With current screening of donors and HIV testing techniques, the risk of HIV infection per unit of blood transfused is 1 in 2 million. Although the risk from any single transfusion is low, each transfusion has the potential to be fatal. This potential has increased physician awareness and decreased the elective use of allogeneic blood. When an individual does become infected from a transfusion, the development of AIDS seems to be more rapid than with other forms of transmission. In the United States, two donors were responsible for the transmission of HIV in four musculoskeletal grafts in 1985 and 1988. No further transmissions of HIV through allografts have been reported since 1988. However, the risk of transmission of HIV through allografts is estimated to be 1 in 1.6 million (one to two cases every 2 years) related to the fact that a window period still exists between testing methods and the patient having detectable viral antibodies. Nucleic antibody testing has a window period for HIV and hepatitis C of 7 days and 8 days for hepatitis B. Additionally, there has been one reported case of hepatitis B and two of hepatitis C, with the most recent occurring in 2002. With better screening techniques including patient history and serological and nucleic acid testing, rates remain low. Additionally, chemical sterilization techniques have also decreased the opportunity for disease transmission through allografts. The current risk of acquiring an infection from the allograft remains well below the overall perioperative nosocomial risk. Intraoperative culturing of the allograft has a low sensitivity and is generally not recommended. However, it is important that each surgeon knows the specifications of the tissue bank that he or she uses and to ensure that it is American Association of Tissue Banks (AATB) accredited (Table 20-6).
Adapted from Azar FM: Tissue processing: role of secondary sterilization techniques, Clin Sports Med 28:191, 2009.
Musculoskeletal Syndromes in Human Immunodeficiency Virus–Infected Patients
The most common musculoskeletal syndromes in HIV-infected patients are manifestations of drug toxicity, reactive arthritis, infectious arthritis, myositis, tendinitis, and bursitis. General principles to be kept in mind when evaluating an HIV-infected patient with musculoskeletal problems include the following: (1) Any musculoskeletal syndrome that occurs in non–HIV-infected patients can occur in HIV-infected patients; (2) HIV infection can alter the clinical presentation, severity, and course of musculoskeletal problems; and (3) early diagnosis of infections is especially important to prevent their spread in an immunocompromised patient (Table 20-7).
TABLE 20-7 Musculoskeletal Syndromes in Human Immunodeficiency Virus–Infected Patients
CONDITION | COMMENTS |
---|---|
Arthralgias | Causes include systemic bacterial infection, inflammation, drug toxicity |
Reactive arthritis (Reiter syndrome) | Possibly more severe in HIV disease |
Psoriatic arthritis | Most commonly Staphylococcus aureus or Streptococcus pneumoniae |
Osteomyelitis | Reported in HIV disease as a result of extension of infection from septic joint |
Myositis | |
Pyomyositis | Focal pain, tenderness |
Idiopathic | Focal pain, tenderness |
From zidovudine | Usually resolves when zidovudine is discontinued |
From Lane N: HIV disease and arthritis: diagnostic and therapeutic dilemmas. In Cohen PT, Sande MA, Volberding PA, editors: The AIDS knowledge base, Boston, 1994, Little, Brown.
Risks and Prevention
During orthopaedic surgical procedures, contact with blood and other body fluids containing blood in gross or microscopic amounts is frequent (3.7%). Lacerations from bone fragments and edges and cuts and needle sticks must be avoided. The estimated risk after a mucocutaneous exposure was reported to be 0.09% based on one seroconversion in six studies. The American Academy of Orthopaedic Surgeons (AAOS) has developed several basic recommendations for procedures in the operating room (Box 20-1). These precautions involve wearing surgical gowns that offer protection against contact with blood, using nontouch techniques for surgery and suturing, not passing sharp instruments from hand to hand (establishing a “hands-free” zone), and proper removal of contaminated gowns and postoperative scrub. Specific recommendations by the AAOS can be found in their information statement Preventing the Transmission of Bloodborne Pathogens (2008).
Box 20-1
American Academy of Orthopaedic Surgeons Recommendations for Operating Room Procedures
1. Avoid the use of sharp instruments if possible.
2. Avoid direct passing of sharp instruments between team members.
4. Use a scalpel for skin incisions only, then scissors and electrocautery.
5. Avoid simultaneous suture of the same layer by two members of a team.
6. Preferably use blunt suture needles.
8. Comply with regulations for elimination of disposable material.
9. Always wear gloves when handling material covered with blood.
Adapted from Lemaire R, Masson JB: Risk of transmission of blood-borne viral infection in orthopaedic and trauma surgery, J Bone Joint Surg 82B:313, 2000.
After exposure of a health care worker to blood, a rapid HIV test should be performed on the source. If it is negative, no chemoprophylaxis should be offered. However, if it is positive, chemoprophylaxis should be offered. The rapid HIV test does have a low false-positive rate; therefore, all positive results should be followed with standard enzyme immunoassay and a Western blot assay. The test also will not identify HIV-positive patients if they have been infected less than 3 months. A decrease in seroconversion rates of 79% has been shown with the use of chemoprophylaxis after exposure using zidovudine and lamivudine, chain terminators for reverse transcriptase. Adding a protease inhibitor, indinavir, further decreases antiretroviral activity. These drugs should be started within 2 hours of exposure and generally are recommended for at least a 4-week course. In 2005, the CDC updated U.S. Public Health Service Guidelines for the management of occupational exposures to hepatitis B virus, hepatitis C virus, and HIV; recommendations for chemoprophylaxis can be found in Table 20-8. The most current postexposure prophylaxis (PEP) drug regimen can be found at the National HIV/AIDS Clinicians Consultation Center (http://www.ucsf.edu/hivcntr). Also questions about PEP can be answered at National Clinicians postexposure prophylaxis hot line (PEPline) at (888) HIV-4911. Most exposures to HIV-infected blood do not cause seroconversion, and toxicity of a chemoprophylactic regimen must be considered before the initiation of treatment. If available, consultation with infectious disease is recommended.
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