Infections of the Foot and Ankle

Classification

Infections are classified to assist with treatment selection. Classification is by host type, organism, or anatomic location. Host factors are the most significant. Hosts can be classified as normal or compromised. Compromised hosts include patients with systemic illness, poor nutritional state, peripheral vascular disease, trauma, and peripheral neuropathy. This changes both the differential diagnosis and the treatment of a foot infection. Diabetes is the most common systemic host factor in a patient with foot infection; these are considered in Chapter 32 .

It is convenient to separate infections by the offending organism. The organisms are broadly classified as bacterial, mycobacterial, and fungal. These broad categories are subdivided into numerous groups that determine effective treatment options. Selection of the appropriate antibiotic in particular depends on the involved organism.

Anatomic location determines access to the affected region by therapeutic agents and the body’s own defenses, as well as anatomic structures at risk from the infection. The necessity of surgical intervention is often dependent on location of the infection. The location can be classified as soft tissue, joint, or bone. A localized collection of purulent material, an abscess, is a special classification by anatomic location. This isolated space is addressed surgically.

Soft Tissue Infections

Soft tissue infections often present secondary to trauma to the protective stratum corneum of the epidermis ( Fig. 33-1 ). Surgery, injury, maceration, intravenous (IV) drug abuse, eczema, and constitutionally derived skin breaks can provide a portal of entry for the pathologic organism. Blisters, ulcers, and open wounds are often colonized with bacteria. In a compromised host these bacteria can spread, resulting in a localized and ultimately systemic infection. More virulent organisms can use a portal to spread within a normal host. The offending organism can often be deduced from the point of entry and host status. For example, postoperative wound infections in a normal host are often Group A streptococci.

Breaks in the epidermis are not necessary for soft tissue to become infected. Some virulent organisms possess toxins that weaken the skin’s defenses. These organisms are able to attack healthy hosts without an entry portal. Staphylococcus aureus is the primary pathogen to penetrate intact skin. It manifests as cellulitis or an abscess.

Erythrasma

Erythrasma is a superficial infection of the skin caused by Corynebacterium minutissimum . Normally found in the web space, it can also be found in a more generalized distribution. The scaly lesions vary from red to brown, are well defined, and have irregular borders ( Fig. 33-2 ). The lesions are most commonly asymptomatic but can be pruritic. The lesions can become fissured and macerated, creating breaks in the protective stratum corneum. These openings can result in more extensive infections.

Erythrasma is commonly confused with psoriasis, dermatophytosis, and candidiasis. Wood’s lamp examination can help distinguish erythrasma, because the colonies glow coral-red. Erythromycin (250 mg four times daily for 14 days) is the treatment of choice.

Cellulitis

Cellulitis is the acute inflammatory response to a pathogen, often bacterial. Aerobic gram-positive cocci, S. aureus , and streptococci are the most commonly involved pathogens. Cellulitis is characterized by superficial swelling, pain, erythema, and localized warmth ( Fig. 33-3 ). Proximal lymphadenopathy is common. Erythema streaking along the course of lymph drainage (lymphangitis) is common with streptococcal infections, while localized pus-producing lesions are staphylococcal. Cellulitis is limited to the dermis and subcutaneous tissues. The treatment of cellulitis uses empiric antibiotics directed against Staphylococcus and Streptococcus species. The affected limb should be elevated to help control swelling.

The rise of methicillin resistant S. aureus (MRSA) and other resistant organisms has complicated the selection of antibiotics. This organism is resistant to the β-lactam antibiotics including the penicillins and cephalosporins. MRSA is now found in both hospital-acquired and community-acquired infections. The risk factors for hospital-acquired MRSA are recent hospitalization, recent surgery, dialysis, residence in a long-term care facilityf, diabetes, and chronic or repeated courses of antibiotics. The risk factors for community-acquired MRSA are young age, socially disadvantaged environment, minority ethnicity, member of the armed forces, an athlete, and primary skin infections. MRSA transmission during team sports has been documented and should be considered in the differential diagnosis of clusters of skin abscesses in athletes. A community’s bacterial spectrum can assist in determining the risk of community-acquired MRSA in the general population.

For patients with mild cellulitis and no risk factors for MRSA, treatment involves oral first-generation cephalosporins such as cephalexin or clindamycin. For more severe cases, systemic involvement, or a compromised host, parenteral antibiotics are first-line agents. Cefazolin or ceftriaxone are often the primary agent. An aminoglycoside, gentamicin 5 mg/kg every day, should be added for diabetic patients and IV drug abusers to provide a broader coverage for possible gram-negative species. Alternative medications for infections at risk for both gram-positive and gram-negative organisms are β-lactams/β-lactamase inhibitory combinations, moxifloxacin, tigecycline, or trimethoprim-sulfamethoxazole.

For patients with risk factors for MRSA infections initial treatment of MRSA infections with β-lactams can exacerbate the infection or compromise outcomes by delaying appropriate treatment. For mild cases, clindamycin, a fluoroquinolone (moxifloxacin has extended gram-positive activity), doxycycline, or trimethoprim are acceptable choices. Selection of an antibiotic depends on resistance spectrums of the community and patient factors. For severe infections with suspected MRSA or failure of a β-lactam, parenteral treatment with linezolid, daptomycin, tigecycline, or vancomycin is appropriate. Due to concerns over the cost and the possibility of resistance to these agents, these antibiotics should be reserved for severe infections with a high clinical suspicion of MRSA.

The patient should be reevaluated at 48 hours after initiation of treatment. If there is poor clinical response, the antibiotic therapy should be changed. One should consider clindamycin or amoxicillin–clavulanate in these patients. The erythema can continue for days after the infection has been effectively treated. Desquamation of the skin is common as the localized edema resolves.

Necrotizing Fasciitis

Necrotizing fasciitis is a rapidly destructive infection of soft tissues with a high mortality rate. The lower extremity is the most affected region, and the foot is the second most common site in the lower extremity. Early diagnosis is the key to effective management. The infection rapidly spreads along the fascial planes and is associated with thrombosis of the cutaneous microcirculation. Early diagnosis is key to reducing mortality and morbidity and a high index of suspicion is necessary as most cases are not initially recognized. Most cases are polymicrobial and commonly associated with comorbidities. A portal of entry is found in only half of all patients. Risk factors include diabetes, obesity, peripheral vascular disease, intravenous drug use, alcohol abuse, malnutrition, smoking, corticosteroid therapy, immune suppression, cancer, chronic renal failure, and age. Nonsteroidal antiinflammatory drugs (NSAIDs) can delay the diagnosis of necrotizing fasciitis by reducing the symptoms but have not been shown to be a risk factor. The use of broad-spectrum antimicrobials can blunt the systemic effects without treating the underlying infection, reducing the ability to use fever and organ failure to aid in recognizing the severity of the infection.

The definitive signs of necrotizing fasciitis are hemorrhagic bullae, skin necrosis, fluctuance, crepitus, and neurologic deficits. These definitive signs are not found until late in the disease progression. The clinical presentation progresses through three stages listed in Table 33-1 . It has been recognized that some patients rapidly progress through the stages affecting the whole limb in 24 hours while others have a more indolent progression. Delay in treatment can significantly increase the risk of morbidity and mortality as the stage at time of initial treatment has been shown to be prognostic. The common early signs are swelling, pain, and erythema. Pain out of proportion is the key indicator especially if it extends past the margins of visible skin changes. The margins tend to be irregular. Failure of intravenous antibiotics in the treatment of cellulitis points to an early presentation of necrotizing fasciitis. Leukocytosis, weeping blisters, blue skin discoloration, sensory deficits, systemic sepsis, shock, and mental status changes are late manifestations. Fig. 33-4 shows the clinical appearance of necrotizing fasciitis.

Table 33-1

Staging of Necrotizing Fasciitis

Stage	Signs
1	Pain Warm skin
2	Blisters Bullae
3	Hemorrhagic bullae Skin anesthesia Skin gangrene

Laboratory data may be useful in identifying high-risk patients presenting with cellulitis but should never delay surgical treatment of patients with clinical presentation consistent with necrotizing fasciitis. Table 33-2 lists the components of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC). Patients with a score greater than 5 should be considered moderate risk and greater than 7 should be considered high risk. The LRINEC score is not sensitive in immunocompromised patients and intravenous drug users. The LRINEC score becomes more sensitive as the disease progresses. Interventions to correct laboratory disturbances can reduce the accuracy of the score, but an increasing score despite antibiotics may indicate the presence of necrotizing fasciitis. The sensitivity of the LRINEC score is reported from 43% to 80%.

Table 33-2

LRINEC Scoring

Modified from Wong C, Khin L, Heng K, et al: The LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections, Crit Care Med 32:1535–1541, 2004.

Sum of the Score for the Six Components
0–5	Low risk	<50%
6–7	Moderate risk	50%–75%
8–13	High risk	>75%
Laboratory Test	Value	Score
C-reactive protein (mg/L)	<150	0
	≥150	4
White blood cell count (cells/µL)	<15,000	0
	15,000–25,000	1
	>25,000	2
Hemoglobin (g/dL)	>13.5	0
	11–13.5	1
	<11	2
Sodium (mmol/L)	>135	0
	<135	2
Creatinine level (mg/dL)	≤1.58	0
	>1.58	2
Glucose (mg/dL)	<180	0
	>180	1

LRINEC , Laboratory Risk Indicator for Necrotizing Fasciitis.

Treatment of necrotizing fasciitis involves early surgical debridement and broad-spectrum antibiotics. Due to the thrombosis of microcirculation, antibiotics alone are ineffective. In suspicious cases, a limited biopsy is often warranted. A 2-cm incision is made under local anesthesia. The surgeon bluntly dissects down to the deep fascia. Biopsy specimens are sent for cultures and pathologic examination. Histology demonstrates necrosis of fascia and necrosis of the arterial walls. A lack of bleeding, dishwater-colored drainage, or minimal resistance to finger dissection along the facial plane are signs of necrotizing fasciitis. An aggressive surgical debridement should be extended until the skin and subcutaneous tissue appear viable and firmly adherent to the underlying fascia ( Fig. 33-5 ). All necrotic skin, subcutaneous tissue, fascia, and muscle should be removed. Repeat debridement should be carried out at 48-hour intervals. Hydrogel or negative pressure therapy dressings are used to promote granulation tissue.

Medical treatment with antibiotics starts empirically based on infection classification ( Table 33-3 ). Type 1 polymicrobial infections are treated with a combination of ampicillin-sulbactam and clindamycin. Clindamycin and linezolid inhibit M protein and exotoxin production facilitating phagocytosis and suppressing the production of tumor necrosis factor alpha. For type 2 monomicrobial infections, a first-generation cephalosporin is used unless there is suspicion of methicillin resistance, where vancomycin is utilized. Culture results are used to modify the antibiotic regimen. Antibiotic therapy typically continues for 4 to 6 weeks. Coagulopathy, cardiopulmonary collapse, and acute renal failure are seen in the more advanced stages of necrotizing fasciitis. Blood component therapy, dialysis, and cardiopulmonary support should be used aggressively when indicated. A patient’s metabolic requirements are doubled during the treatment period. Supplemental feedings or total parenteral nutrition should be considered.

Table 33-3

Microbiological Classification of Necrotizing Fasciitis

Type	Pathogens	Site of Infection	Comorbidities
I Polymicrobial	Anaerobes	Trunk Perineum	Diabetes Mellitus
II Monomicrobial	Beta-hemolytic Streptococcus A Staphylococcus aureus	Extremities
III	Clostridium Gram-negative bacteria Vibrios s. Aeromonas hydrophila	Extremities Trunk Perineum	Trauma Seafood consumption
IV Fungal	Candida spp. Zygomycetes	Extremities Trunk Perineum	Immunosuppression

Hyperbaric oxygen is used as an adjunctive treatment at some medical centers. Hyperbaric chambers come in single and multiple place systems ( Fig. 33-6 ). Studies have demonstrated a beneficial trend, but there is no conclusive evidence for the effectiveness of hyperbaric oxygen. Prompt surgical debridement continues to be the most important factor in reducing mortality.

Abscesses

An abscess is a collection of purulent material and infection in a closed space. In the foot, the infection is usually an extension of a subcutaneous infection or penetrating wound. Often abscesses involve the deep spaces of the foot ( Fig. 33-7 ). With a plantar deep space infection, the patient presents with pain and swelling along the instep. Examination demonstrates a loss of the longitudinal arch. Patients often become bedridden due to the pain of weight bearing.

The infection is often polymicrobial. Without treatment, the infection will spread along the flexor tendons extending into the deep compartment of the leg. Surgical debridement is essential in the treating the abscess. Appropriate antibiotics are based on intraoperative cultures. If the infection appears to be localized more medially, a medial single-incision fasciotomy can be used to expose the infected compartment. Most deep abscesses of the foot occur in the central plantar space. If the infection appears to localize more dorsally in the forefoot, a two-incision fasciotomy approach allows ready exposure to the more dorsal spaces.

NATIVE JOINT INFECTIONS

An infected joint can develop from an adjacent infection, direct traumatic inoculation, or hematogenous spread. Septic arthritis is recognized clinically by the abrupt appearance of redness, swelling, and tenderness about the joint. Fever is not a prerequisite for the diagnosis of septic arthritis. Infection should be a primary consideration in any acute monoarticular arthritis, followed by crystal arthropathy, Reiter syndrome, or a neuropathic joint. Adjacent soft tissue swelling and increased joint fluid can be detected on imaging studies. The diagnosis is made by joint aspiration prior to antibiotic treatment. The ankle is the third most commonly affected. Multiple joints are involved in 20% of cases.

S. aureus is the most common organism in septic joints. In children younger than 2 months, group B streptococci is the most likely pathogen. Neisseria gonorrhoeae is a common pathogen in the sexually active young adult. In these patients, an enriched agar with high carbon dioxide culture should be included in the joint aspirate studies. Puncture wounds can inoculate the joint with anaerobic and gram-negative species. Diabetes mellitus, joint prosthesis, inflammatory arthritis (rheumatoid), osteoarthritis, crystal arthropathy, cutaneous ulcers, and alcoholism predispose a patient to septic arthritis. Antitumor necrosis factor therapy doubles the risk of septic arthritis.

Treatment of suspected septic arthritis begins with aspiration of the joint. The fluid obtained is analyzed for color, Gram stain, cultures, glucose, protein, crystals, and cell count with differential. Aspiration through an area of cellulitis should be avoided. Other studies to consider include peripheral blood cell count, C-reactive protein, erythrocyte sedimentation rate, uric acid, and blood cultures. One third of patients with septic arthritis will have bacteremia and helps identify the pathogen. Joint fluid analysis generally shows leukocyte counts greater than 100,000/mm ³ , 90% polymorphonuclear leukocytes, elevated protein, and glucose below that of serum.

The standard definition of a positive joint aspiration is a leukocyte count greater than 50,000, though consideration of the complete clinical picture must be made. Using that standard, the sensitivity of the exam is only 64%. Any leukocyte counts greater than 10,000 cells/mm ³ should be considered suspicious of a joint infection and the patient closely monitored. Gram stain has a sensitivity of 50%. Cultures are generally positive unless the organism is N. gonorrhoeae or the patient received antibiotics before the aspiration. The yield of joint fluid cultures is enhanced by utilization of blood culture bottles. Table 33-4 provides a guideline for interpreting laboratory studies. The joint fluid should also be examined under polarized microscopy for crystals. Both gout and pseudogout can mimic a septic joint. Cell count alone cannot distinguish gout from a septic joint.

Drainage of purulent material from the joint is essential in the treatment of septic arthritis. This may be by open surgical procedure or aspiration. The method chosen is controversial. There is little evidence to support open surgical drainage of an infected joint in the foot. Daily aspiration of the affected joint is often sufficient in combination with antibiotic therapy. Indications for surgical intervention include failure to clinically respond within 48 hours of therapy, persistence of pyarthrosis beyond 48 hours, inaccessibility of the joint for aspiration, viscous material that defies attempts at aspiration, and radiographic changes affecting bone. Many surgeons do not feel they can adequately drain the joints in the foot by aspiration alone and prefer open drainage for all septic joints in the foot.

Surgical decompression requires adequate exposure of the joint, a synovectomy, and a thorough irrigation with saline. The joint is allowed to continue to drain using suction or a Penrose drain for 24 to 48 hours. The foot should be splinted to allow relative rest and for patient comfort. If the symptoms have not resolved, repeat irrigation and debridement should be undertaken at 48 hours. The use of antibiotics in the irrigation has not been shown to have superior results to saline alone.

Broad-spectrum empiric antibiotics should be administered parenterally. Nafcillin combined with third-generation cephalosporins will cover most infections. For patients with a penicillin allergy, levofloxacin is an accepted substitute. Patients at risk for MRSA (nursing home residents, recent inpatients, or if community-associated MRSA is more than 10%) should be treated with vancomycin. The choice of antibiotic is adjusted depending on the pathogen isolated from the aspirate. Therapy should continue for 4 weeks.

Total Ankle Replacement Infections

The last 20 years has shown substantial growth in the incidence of total ankle replacement(TAR). As this procedure becomes more common, treatment of prosthetic joint infections (PJI) at the ankle will increase. The incidence of infection of a total ankle, 2.4% for primary and 4% for revision, is higher than for total hip or knee prosthesis. Risk factors for PJI at the ankle include prior surgery, wound healing problems more than 14 days postoperatively, low functional preoperative score, and diabetes. Due to the relative recent increase in TAR, the diagnosis and treatment of PJI at the ankle is based on hip and knee literature.

PJI is classified as early, chronic, and hematogenous seeding. The clinical presentation of PJI is often not specific and can be confused with cellulitis, gout, or aseptic loosening. The International Consensus Meeting on PJI defined the criteria ( Table 33-5 ) for PJI, which has been modified as new tests have become available. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are common early tests that are not very specific, but if both are normal they are very effective are ruling out PJI. In immunocompromised patients and infections with low virulent pathogens, CRP and ESR may not be effective. Imaging studies are not very specific and are not supported in the literature. Joint aspirations for white blood cell count, neutrophil percentage, cultures, alpha-defensin, and leukocyte esterase test are used to help determine if PJI is present. Avoidance of antibiotics prior to the aspiration is important to prevent false negative results. The sensitivity of aspiration was shown to be improved by saline lavage and use of blood culture system. Interoperative tissue specimens for frozen section and cultures should be obtained from multiple intraarticular sites at the time of surgery.

Treatment of PJI is often dictated by the classification of the infection, soft tissue envelope, and patient comorbidities. For early infections, irrigation and debridement with exchange of the polyethylene can be considered. For chronic infections, a two-stage revision with antibiotic spacer and 6 weeks of culture specific antibiotics is appropriate. If the bone stock is insufficient for revision TAR, ankle arthrodesis is indicated. Arthrodesis can be accomplished either as a two-stage procedure with internal implants or a single stage using external fixation. Amputation should be considered an appropriate surgical treatment for patients with significant comorbidities, a compromised soft tissue envelope, or failure of reimplantation of TAR.

Osteomyelitis

Osteomyelitis is the infection of bone. It is characterized by acute inflammation, vascular engorgement, edema, cellular infiltration, and abscess formation. The infective agents can be bacteria, fungi, or mycobacteria. The source of the infection can be hematogenous, an adjacent infection, or direct inoculation by trauma or surgery. The infection can be acute or chronic. The clinical presentation varies based on the organism, location, and host factors. A conclusive diagnosis is made with a bone biopsy. The diagnosis of osteomyelitis is clinically important due to the length of therapy required for the treatment of bone infections and the necessity for surgical debridement. Sickle cell anemia, chronic granulomatous disease, and diabetes mellitus predispose a patient to develop osteomyelitis.

Hematogenous infections are most common in children and can affect any of the bones of the foot. The calcaneus and talus are the most commonly involved sites in the foot, with 7% and 4% of all hematogenous infections, respectively. S. aureus is the usual pathogen.

Brodie’s abscess is a particular form of chronic osteomyelitis found in the lower portion of the tibia, talus, or forefoot. These “subacute” abscesses have a sclerotic wall and contain purulent material ( Fig. 33-8 ) but typically have no systemic symptoms, and laboratory studies are often normal. Treatment of Brodie’s abscess is debridement and antibiotics.

The clinical presentation of acute osteomyelitis includes fever, local pain, swelling, and tenderness. Laboratory studies may show an elevated white blood cell count, ESR, and CRP. In compromised hosts and in patients with involvement of the small bones of the foot, the laboratory studies may not be abnormal. Blood cultures are positive in half of patients. Cultures obtained from sinus tracts are often unreliable. Identification of the pathogen requires bone aspiration or biopsy. Bone biopsy and culture has a sensitivity of 95% and specificity of 99% if taken before antibiotics are administered.

Radiographic changes include osteolysis, periosteal reaction, cortical erosion, and formation of sequestra and involucrum ( Figs. 33-9 and 33-10 ). The early signs of soft-tissue swelling, periosteal thickening and elevation, and osteopenia are subtle and are often missed. Bone mineral loss of 30% is required for radiographic change to be visible. These changes take 10 to 14 days to appear. The radiographic findings resemble malignancy, fractures, and neuropathic conditions. Because of these problems, radiographs have a sensitivity of 43% to 75% and specificity of 75% to 83%. During treatment, radiographic findings often lag clinical response.

MRI can detect changes in the bone earlier than plain films. Osteomyelitis is identified by alteration of bone marrow signal that results in a loss of the normal marrow signal on T1 and the enhancement of edema on T2 images. MRI can also demonstrate secondary signs such as cellulitis, fluid collection, cortical interruption, and sinus tract formation. The presence of secondary signs can increase the sensitivity of a scan. The scan provides precise anatomic details showing adjacent abscess formation, sinus tracts, and the extent of osseous involvement. MRI has a sensitivity of 77% to 100% and specificity of 80 to 100%. Gadolinium enhancement can improve the detection of adjacent soft tissue disease. The use of contrast is particularly helpful in the diabetic foot and postsurgery patient. The presence of surgical implants reduces the effectiveness of MRI. Neuropathic disease, altered weight bearing, and surgery can cause marrow changes consistent with osteomyelitis.

Fast spin-echo short T1 inversion recovery (FSE STIR) images are useful for initial screening. Their high sensitivity and rapidity of scan can detect small marrow changes. Patients with positive scans can then undergo additional imaging using gadolinium-enhanced fat-suppressed T1-weighted sequences. The increased specificity of these examinations helps to eliminate false positives. In cases with discordant marrow signs, secondary signs can be used to determine the presence of osteomyelitis. The secondary signs with highest positive predictive value are cortical interruption, a cutaneous ulcer, and a sinus tract.

Radionuclide bone scans are extensively used in diagnosing osteomyelitis. The three-phase bone scan changes take only 2 days to appear. Osteomyelitis is characterized by accumulation of the tracer in all three phases of the scan. This relatively inexpensive test has a very low false-negative rate, though are not specific. Fracture, neuropathic joints, trauma, surgery, and hyperemia can result in positive test results for three-phase bone scan. The sensitivity of the study ranges from 69% to 100% and specificity from 38% to 82%. Three-phase bone scans combined with labeled white blood cells increases the specificity. This combination improves the sensitivity to 73% to 100% and specificity to 55% to 100%. The test is complicated and requires an additional hospital day to perform. The combined tests are generally more expensive than MRI.

Another option for evaluating musculoskeletal infections is 18F-fluorodeoxyglucose positron emission tomography (PET). PET evaluates cellular glucose metabolism to identify increased use by activated neutrophils and macrophages. The sensitivity is 91% to 100% and specificity is 88% to 91%. An advantage of PET is the ability to differentiate between Charcot’s lesions and osteomyelitis. PET is particularly useful around metal implants, which limit the usefulness of MRI. The studies are limited to facilities with a PET scanner and are expensive. Elevated blood glucose can result in false negative results. PET should be considered for differentiating Charcot’s lesions and osteomyelitis or for detecting osteomyelitis near metallic implants.

The treatment of osteomyelitis depends upon surgical debridement. Antibiotics are less effective in acidic, anaerobic, hypercapnic, and poorly perfused regions. Excision of necrotic bone, removal of purulent material, and elimination of any dead space is essential to the success of antibiotic treatment. The surgical debridement is more important than serum levels of antibiotics or duration of treatment. Care should be taken during the debridement to ensure all dysvascular bone is removed. Punctate bleeding should be visible on all bone surfaces. An expendable bone can be completely resected and the wound treated as a soft tissue infection, substantially decreasing the duration of treatment. After debridement a combination of local tissue closure, drains, local antibiotic delivery devices, and tissue transfer procedures may be necessary to fill the dead space and cover exposed bone. Adequate coverage of bone is required to treat osteomyelitis.

The selection of antibiotic is initially governed by the suspected pathogen. This choice is modified by sensitivity testing. A peak minimum serum bactericidal dilution of 1 : 8 is the goal of therapy. Typically treatment is 4 to 6 weeks of antibiotic therapy after the last debridement. Intravenous therapy is expensive and inconvenient for patients requiring outpatient services, peripheral inserted central catheter (PICC), and portable infusion pumps. For some antibiotics (fluoroquinolones, linezolid, and trimethoprim), the oral and parenteral forms result in similar serum concentrations and favorable bone penetration. β-lactam antibiotics do not reach these levels and are not appropriate for oral administration. Recent studies have demonstrated equivalent results for oral and intravenous antibiotics. Rifampin is frequently added to the primary antibiotic for its effectiveness against biofilms.

Sedimentation rate and C-reactive protein levels are used to monitor the efficacy of the treatment. The return of these studies to normal during the course of therapy is a favorable prognostic sign. The sedimentation rate, C-reactive protein, and leukocyte counts can become elevated after each surgical debridement. The use of these laboratory studies in treating chronic osteomyelitis or a host compromised by systemic disease is limited. In these patients, the studies might not be elevated prior to treatment.

Biofilms

When treating infections involving bone or surgical implants, one should consider the concept of a biofilm. A biofilm is a hydrated matrix of proteins and polysaccharides that encompass a polymicrobial collection of cells. Bacterial cells can exist both in a free-floating platonic state or as one of these polymicrobial communities ( Fig. 33-11 ). Most bacteria exist in nature as biofilm communities adherent to inert surfaces. The cells within these communities may exist in a different phenotypical state from the platonic cells. The characteristics of a biofilm makes eradicating an infection difficult.

A biofilm is closely adherent to any inert material, such as necrotic bone or surgical implants. The ability of a biofilm to adhere to a surgical implant depends on the material of the implant as well as surface characteristics. Titanium has a lower adherence rate and has been recommended over stainless steel for high risk cases. Preexisting organic material on implants increases the susceptibility of an implant to colonization by a biofilm. Once established, biofilms can last a lifetime. For purposes of clinical treatment, one should consider biofilms permanent until the affected surface is removed.

Bacteria in a biofilm are more resistant to antibiotics and host defenses. Antibiotics are much more effective against isolated free-floating, platonic, cells. The matrix itself can limit access or inactivate antibiotics. The bacteria may exist in spore-like state that is resistant to antibiotics beyond any native resistance of the organism. The host reaction to the biofilm can result in significant collateral damage to native tissues due to chronic inflammatory response. Low-grade biofilm infection may be misdiagnosed as aseptic implant loosening.

The concept of biofilms gives us a paradigm to explain clinical experience with surgical treatment of infections and loosening of surgical implants. In the presence of an infection, all structures composed of inert material should be removed. Perioperative antibiotics should be directed against the platonic bacteria released from the biofilms by the mechanical action of removing the affected surface. Cultures will often only show one species of polymicrobial matrix. Biofilm bacteria may be better detected by polymerase chain reaction, fluorescence in situ hybridization, or DNA microarrays. Local antibiotics may be effective in preventing biofilms from being reestablished.

Local Antibiotics By Implantable Device

Local antibiotic administration in infected wounds can achieve high concentrations of antibiotic without high systemic levels. This minimizes the systemic sides effects and maximizes the effective concentration in the local wound bed. Depending on the application, minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), or minimum biofilm eradication concentration (MBEC) may be the goal of local delivery of antibiotics. The MBEC is lower when antimicrobial exposure is continuous and prolonged. The MBEC may be a thousand times higher than the MIC. This very high concentration makes local delivery desirable.

Polymethyl methacrylate beads impregnated with tobramycin have been shown to be effective in reducing the infection rates in the treatment of open fractures ( Fig. 33-12 ). The most commonly used antibiotics in beads are vancomycin, tobramycin, daptomycin, and gentamicin. The beads are placed into a wound and a bead pouch created by wound closure or application of an impermeable membrane. The accumulated fluid bathes the wound with a high concentration of antibiotic. Calcium sulfate–impregnated beads may also be used but the antibiotic is rapidly released. Calcium phosphate-calcium sulfate composite beads elute the antibiotics over a longer period.

When it is necessary to preserve the alignment of the extremity during an extended treatment of an infection, an antibiotic spacer is effective. These devices are often constructed out of polymethyl methacrylate impregnated with antibiotics. They can maintain the relationship between bones, allowing for later reconstruction. Fig. 33-13 shows the use of an antibiotic spacer used to treat a total ankle infection. The ankle eventually was successfully fused using external fixation.

The elution of antibiotic declines over a period of weeks, leaving a foreign body in the wound that can serve as a nidus for secondary infection. However, there are reports of patients functioning for long periods of time with retained methacrylate spacers without recurrence of the infection. Removal of the antibiotic carrier normally accompanies additional surgical treatment. Care should be taken to ensure nonabsorbable implants are fashioned to allow complete removal. The use of very high dose antibiotics, greater than 3 g per batch of vancomycin or aminoglycoside, has been associated with increased rates of acute kidney injury, which is more common in patients with underlying chronic kidney dysfunction.

Biodegradable antibiotic delivery systems currently commercially available are calcium sulphate and calcium sulfate/hydroxyapatite composites. These products can incorporate all water-soluble antibiotics and their mild exothermic reactions allow use of temperature sensitive drugs. While developed to stimulate bone formation, little evidence supports the osteoinduction. The calcium sulfate products have been noted to more rapidly and complete absorb than hydroxyapatite. Their use has been extended to use adjacent to prosthetic joints, but concern exists over the mechanical effect of the material on joint wear.

Common Organisms