Douglas N. Fish and Susan L. Pendland
KEY CONCEPTS
Folliculitis, furuncles (boils), and carbuncles begin around hair follicles and are caused most often by Staphylococcus aureus. Folliculitis and small furuncles are generally treated with warm, moipruritic papules localizesdt heat to promote drainage; large furuncles and carbuncles require incision and drainage. A penicillinase-resistant penicillin such as dicloxacillin is commonly used for extensive or serious infections (e.g., fever). Empiric treatment of purulent infections that have a high suspicion for community-associated methicillin-resistant S. aureus (CA-MRSA) should include clindamycin, trimethoprim–sulfamethoxazole, a tetracycline, or linezolid.
Erysipelas, a superficial skin infection with extensive lymphatic involvement, is caused by Streptococcus pyogenes. The treatment of choice is penicillin, administered orally or parenterally, depending on the severity of the infection.
Impetigo is a superficial skin infection that occurs most commonly in children. It is characterized by fluid-filled vesicles that develop rapidly into pus-filled blisters that rupture to form golden-yellow crusts. Effective therapy includes penicillinase-resistant penicillins (dicloxacillin), first-generation cephalosporins (cephalexin), and topical mupirocin. S. aureus is the primary cause of impetigo, with infections caused by CA-MRSA emerging in recent years.
Lymphangitis, an infection of the subcutaneous lymphatic channels, is generally caused by S. pyogenes. Acute lymphangitis is characterized by the rapid development of fine, red, linear streaks extending from the initial infection site toward the regional lymph nodes, which are usually enlarged and tender. Penicillin is the drug of choice.
Cellulitis is an infection of the epidermis, dermis, and superficial fascia most commonly caused by S. pyogenes and S. aureus. Lesions generally are hot, painful, and erythematous, with nonelevated, poorly defined margins. Oral trimethoprim–sulfamethoxazole, doxycycline, minocycline, or clindamycin is used for initial treatment of suspected CA-MRSA in patients with purulent cellulitis (i.e., lesion with purulent drainage or exudate, or nondrainable abscess). Treatment of nonpurulent cellulitis generally consists of a penicillinase-resistant penicillin (dicloxacillin) or first-generation cephalosporin (cephalexin) for 5 to 10 days, with the option of adding coverage for CA-MRSA in certain patients. Severe infections in hospitalized patients should receive empiric therapy with vancomycin.
Necrotizing fasciitis is a rare but life-threatening infection of subcutaneous tissue that results in progressive destruction of superficial fascia and subcutaneous fat. Early and aggressive surgical debridement is an essential part of therapy for treatment of necrotizing fasciitis. Mixed infections are treated with broad-spectrum regimens that cover streptococci, gram-negative aerobes, and anaerobes. Infections caused by S. pyogenes or Clostridium species should be treated with the combination of penicillin and clindamycin.
Diabetic foot infections are managed with a comprehensive treatment approach that includes both proper wound care and antimicrobial therapy. Potential pathogens include staphylococci, streptococci, aerobic gram-negative bacilli, and obligate anaerobes. Antimicrobial regimens for diabetic foot infections are based on severity of the infection, expected treatment setting, and risk factors for infection with more resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa. Outpatient therapy with oral antimicrobials should be used whenever possible for less severe infections, while more severe infections initially require IV therapy.
Prevention is the single most important aspect in the management of pressure sores. After a sore develops, successful local care includes a comprehensive approach consisting of relief of pressure, proper cleaning (debridement), disinfection, and appropriate antimicrobial therapy if an infection is present. Good wound care is crucial to successful management.
All bite wounds (either animal or human) should be irrigated thoroughly with large volumes of sterile normal saline, and the injured area should be immobilized and elevated. Depending on the severity of the bite wound, amoxicillin–clavulanic acid or ampicillin–sulbactam is often used for treatment of animal bites because of their coverage of Pasteurella species, streptococci, S. aureus, and anaerobes typically present in the oral flora of dogs and cats.
Although antimicrobial prophylaxis of dog bites is not recommended routinely, patients with bite injuries caused by cats or humans should be given prophylactic antimicrobial therapy for 3 to 5 days. Infected bite wounds should be treated for 7 to 14 days with oral or IV antibiotics having activity against Eikenella corrodens, streptococci, S. aureus, and β-lactamase–producing anaerobes.
Skin and soft-tissue infections (SSTIs) may involve any or all layers of the skin (epidermis, dermis, subcutaneous fat), fascia, and muscle. They also may spread far from the initial site of infection and lead to more severe complications, such as endocarditis, gram-negative sepsis, or streptococcal glomerulonephritis. Sometimes the treatment of SSTIs may necessitate both medical and surgical management. This chapter presents details of the pathogenesis and management of some of the most common infections involving the skin and soft tissues, ranging in severity from superficial to life-threatening.
EPIDEMIOLOGY
Bacterial infections of the skin can be classified as primary or secondary (Table 88–1).1–3 Primary bacterial infections usually involve areas of previously healthy skin and are caused by a single pathogen. In contrast, secondary infections occur in areas of previously damaged skin and are frequently polymicrobic. SSTIs are also classified as complicated or uncomplicated. Complicated infections are those that involve deeper skin structures (e.g., fascia, muscle layers), require significant surgical intervention, or occur in patients with compromised immune function (e.g., diabetes mellitus, human immunodeficiency virus [HIV] infection).4 Other categories that are crucial for successful treatment are the differentiation of necrotizing versus nonnecrotizing, as well as purulent versus nonpurulent, SSTIs.4–7
TABLE 88-1 Bacterial Classification of Important Skin and Soft-Tissue Infections1–3
SSTIs are among the most common infections seen in community and hospital settings.8,9 However, most infections are believed to be mild and are treated in an outpatient setting, making it difficult to accurately quantify community-acquired SSTIs. SSTIs were diagnosed in 0.8% of physician office visits between 1993 and 2005; this corresponded to approximately 82 million diagnoses of SSTI, being more common among 70 years of age and older.3Emergency room visits for SSTIs have increased dramatically in recent years, attributed primarily to an increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) cellulitis and abscesses.10,11 A study of emergency department visit rates between 1997 and 2007 found a 3.1-fold increase (11% per year) for abscess SSTIs, with only a minimal increase in nonabscess SSTIs.11 According to an Agency for Healthcare Research and Quality (AHRQ) report, in 2007 SSTIs were responsible for over 600,000 hospitalizations and represented 2% of all admissions in males and 1.2% in females.9 Another study examined the rate and occurrence of infectious disease hospitalization using data from the Nationwide Input Sample for 1998 to 2006.12 A total of 10.1% of hospitalizations during that period were due to cellulitis.
While the exact incidence of SSTIs is unknown, the frequency of infections caused by drug-resistant gram-positive cocci has been increasing.4–7 While the high incidence of healthcare-associated MRSA (HA-MRSA) has been a major concern for many years,13 the emergence of CA-MRSA is even more problematic.5–7,13–19 CA-MRSA are characteristically isolated from patients lacking typical risk factors (e.g., prior hospitalization, long-term care facility) and are often susceptible to non–β-lactam antibiotics such as trimethoprim–sulfamethoxazole, doxycycline, and clindamycin.1,13,14,16,18,20 They also differ genetically from HA-MRSA with methicillin resistance carried on the type IV staphylococcal chromosomal cassette mec (SCCmec) element of the mecA gene.1,13 CA-MRSA strains often harbor genes for Panton-Valentine leukocidin (PVL), a cytotoxin responsible for leukocyte destruction and tissue necrosis. In contrast, HA-MRSA strains usually lack genes for PVL and are associated with SCCmec alleles I to III.1,13,16,16,19 While the incidence of HA-MRSA has declined in recent years,21 the incidence of CA-MRSA has dramatically increased.4–7,20 Clinicians should suspect CA-MRSA in geographic areas with a high prevalence of these strains, or in recurrent or persistent infections that are not responding to appropriate β-lactam therapy. Concerns for the future are the mixing of community and nosocomial strains, with HA-MRSA strains acquiring virulence genes (PVL) or CA-MRSA strains acquiring antimicrobial resistance via the SCCmec element.13
In addition to the emergence of CA-MRSA, treatment choices for SSTIs have been further complicated by the increased incidence of macrolide-resistant strains of S. aureus and Streptococcus pyogenes.16,20,22Data from the Minnesota Department of Health found erythromycin susceptibility among CA-MRSA strains decreased from 45% to 13% during the years 2000 to 2005.20 There is concern about the use of clindamycin for CA-MRSA infections due to the risk of inducible clindamycin resistance in S. aureus strains that are erythromycin-resistant, but clindamycin-susceptible.20 A double-disk test (D-zone test) is recommended to identify erythromycin-resistant strains with inducible clindamycin resistance if treatment with clindamycin is desired.6,7,13,23 A positive D-zone test, indicating the presence of the erm gene, suggests the possibility of the emergence of clindamycin resistance during therapy.13
ETIOLOGY
The majority of SSTIs are caused by gram-positive organisms present on the skin surface.7,24 Gram-positive bacteria (coagulase-negative staphylococci, diphtheroids) are the predominant flora of the skin, with gram-negative organisms being relatively uncommon (Table 88–2).1–3 S. aureus, as well as a variety of gram-negative bacteria, including Acinetobacter species, can be found in moist intertriginous areas (e.g., axilla, groin, and toe webs) of the body.1,2,25 Approximately 30% to 35% of healthy individuals are reported to be colonized with S. aureus on the skin or in the anterior nares.1,3 Colonization, whether transient or permanent, provides a nidus for infection should the integrity of the epidermis be compromised.1,2,10
TABLE 88-2 Predominant Microorganisms of Normal Skin1–3
CLINICAL PRESENTATION
Folliculitis
• Clustering, pruritic papules localized to hair follicles.
• Generally develop in areas subject to friction and perspiration.
• Papules are generally 5 mm or less in diameter and erythematous.
• Papules evolve into pustules that generally spontaneously rupture in several days.
• Systemic signs (fever, malaise) are uncommon.
Furuncles
• Inflammatory, draining nodule involving a hair follicle.
• Generally develop in areas subject to friction and perspiration.
• Lesions are discrete, whether occurring as singular or multiple nodules.
• Lesion starts as a firm, tender, red nodule that becomes painful and fluctuant.
• Lesions often drain spontaneously.
• Lesions caused by CA-MRSA often have necrotic centers characteristic of “spider bites.”
• Systemic signs are uncommon.
Carbuncles
• Formed when adjacent furuncles coalesce to form a single inflamed area.
• Form broad, swollen, erythematous, deep, and painful follicular masses.
• Commonly develop on the back of the neck and are more likely to occur in patients with diabetes.
• Commonly associated with systemic signs (fever, chills, malaise).
• Bacteremia with secondary spread to other tissues is common.
S. aureus and S. pyogenes account for the majority of community-acquired SSTIs.1,10,24 Data from large surveillance studies showed S. aureus to be the most common cause (45%) of SSTIs in hospitalized patients.26 Also of note in these studies was the 36% incidence of methicillin resistance among strains of S. aureus. Other common nosocomial pathogens included Pseudomonas aeruginosa (11%), enterococci (9%), and Escherichia coli (7%).26
PATHOPHYSIOLOGY
The skin serves as a barrier between humans and their environment, therefore functioning as a primary defense mechanism against infections. The skin and subcutaneous tissues normally are extremely resistant to infection but may become susceptible under certain conditions. Even when high concentrations of bacteria are applied topically or injected into the soft tissue, resulting infections are rare.1–3,27,28Several host factors act together to confer protection against skin infections. Because the surface of the skin is relatively dry and has a pH of approximately 5.6, it is not conducive to bacterial growth.1,3Continuous renewal of the epidermal layer results in the shedding of keratocytes, as well as skin bacteria.2 In addition, sebaceous secretions are hydrolyzed to form free fatty acids that strongly inhibit the growth of many bacteria and fungi. Conditions that may predispose a patient to the development of skin infections include (a) high concentrations of bacteria (>105 microorganisms), (b) excessive moisture of the skin, (c) inadequate blood supply, (d) availability of bacterial nutrients, and (e) damage to the corneal layer allowing for bacterial penetration.2,3,27,28
The best defense against SSTI is intact skin.2,27 The majority of SSTIs result from the disruption of normal host defenses by processes such as skin puncture, abrasion, or underlying diseases (e.g., diabetes).1,2,27,29 The nature and severity of the infection depend on both the type of microorganism present and the site of innoculation.
FOLLICULITIS, FURUNCLES, AND CARBUNCLES
Folliculitis is inflammation of the hair follicle and is caused by physical injury, chemical irritation, or infection. Infection occurring at the base of the eyelid is referred to as a stye. While folliculitis is a superficial infection with pus present only in the epidermis,10,24 furuncles and carbuncles occur when a follicular infection extends from around the hair shaft to involve deeper areas (subcutaneous tissue) of the skin.29 A furuncle, commonly known as an abscess or boil, is a walled-off mass of purulent material arising from a hair follicle.10 The lesions are called carbuncles when adjacent furuncles coalesce to form a single inflamed area.10 This aggregate of infected hair follicles forms deep masses that generally open and drain through multiple sinus tracts.13,29 S. aureus is the most common cause of folliculitis, furuncles, and carbuncles.13,29 Inadequate chlorine levels in whirlpools, hot tubs, and swimming pools have been responsible for outbreaks of folliculitis caused by P. aeruginosa.1,29 Outbreaks of furunculosis caused by S. aureus and CA-MRSA have been reported in settings involving close contact (e.g., families, prisons), especially when skin injury was common (such as with sports).13,29 In addition, some individuals experience repeated episodes of furunculosis.24 The major predisposing factor in recurrent infection is the presence of S. aureus in the anterior nares.16,24,29
TREATMENT
Folliculitis, Furuncles, and Carbuncles
Desired Outcomes
The goals of treatment include relieving discomfort, preventing further spread of the infection, and preventing recurrence. Controlling recurrent furunculosis is key due to the difficulty in treating chronic furunculosis.24 Treatments should be effective and inexpensive and have minimal adverse effects.
Treatment
Table 88–3 summarizes evidence-based treatment recommendations from clinical guidelines for SSTIs.5,6,16,30–33 Treatment of folliculitis generally requires only local measures, such as warm moist compresses or topical therapy (e.g., clindamycin, erythromycin, mupirocin, or benzoyl peroxide).29,31 Topical agents generally are applied two to four times daily for 7 days. Small furuncles generally can be treated with moist heat, which promotes localization and drainage of pus.29,31 Large and/or multiple furuncles and carbuncles require incision and drainage.4,13,16,31,32 Systemic antibiotics are usually not necessary unless accompanied by fever or extensive cellulitis.4,16 Treatment of more severe infections generally consists of a penicillinase-resistant penicillin (such as dicloxacillin) or a first-generation cephalosporin (such as cephalexin) for 5 to 10 days (refer to Table 88–4 for adult and pediatric doses). An alternative agent for penicillin-allergic patients is clindamycin. Empiric treatment of purulent infections that have a higher suspicion for CA-MRSA should include clindamycin, trimethoprim–sulfamethoxazole, a tetracycline, or linezolid.4,6,24,32 For individuals with nasal colonization, application of mupirocin ointment twice daily in the anterior nares for the first 5 days of each month decreases recurrent furunculosis by almost half.16,24 In addition, a single oral daily dose of clindamycin 150 mg for 3 months or 500 mg of azithromycin weekly for 3 months reduced recurrent infections caused by susceptible strains of S. aureus by approximately 80%.24
TABLE 88-3 Evidence-Based Recommendations for Treatment of Skin and Soft-Tissue Infections5,6,16,30–33
TABLE 88-4 Recommended Oral Drugs or Outpatient Treatment of Mild–Moderate Skin and Soft-Tissue Infections
Evaluation of Therapeutic Outcomes
Many follicular infections resolve spontaneously without medical or surgical intervention. Lesions should be incised if they do not respond to a few days of moist heat and nonprescription topical agents. Following drainage, most lesions begin to heal within several days without antimicrobial therapy. Any patient who is unresponsive to several days of therapy with a penicillinase-resistant penicillin or first-generation cephalosporin should have a culture and sensitivity performed because of the increasing frequency of CA-MRSA.
ERYSIPELAS
Erysipelas is a distinct form of cellulitis involving the more superficial layers of the skin and cutaneous lymphatics.5,13,24,34 The intense red color and burning pain associated with this skin infection led to the common name of “St. Anthony’s fire.” The infection is almost always caused by β-hemolytic streptococci, with the organisms gaining access via small breaks in the skin. Group A streptococci (S. pyogenes) are responsible for most infections.16,24,31Infections are more common in infants, young children, the elderly, and patients with nephrotic syndrome.6,31 Erysipelas also commonly occurs in areas of preexisting lymphatic obstruction or edema.13,31 Diagnosis is made on the basis of the characteristic lesion.
CLINICAL PRESENTATION
General
• Lower extremities are the most common sites.
Symptoms
• Flu-like symptoms (fever, chills, malaise) common prior to the appearance of the lesion
• Infected area described as painful or as a burning pain
Signs
• Lesion is intensely erythematous and edematous, often with lymphatic streaking.
• Lesion has raised border, which is sharply demarcated from uninfected skin.
• Temperature is often mildly elevated.
Laboratory Tests
• Causative organism usually cannot be cultured from the surface skin.
• Needle aspiration or punch biopsies occasionally identify organism.
• Cultures considered for more severe cases (e.g., atypical clinical findings such as fluid-filled blisters).
Other Diagnostic Tests
• A complete blood count is often performed because leukocytosis is common.
• C-reactive protein is also generally elevated.
TREATMENT
Erysipelas
Desired Outcomes
The goal of treatment of erysipelas is rapid eradication of the infection, thereby providing relief of symptoms (pain, tenderness, fever).34 Preventing recurrent infection is also important, as recurrence is a primary complication, occurring in approximately 20% of patients.24,34 Treatments should be effective and inexpensive and have minimal adverse effects.
Treatment
Mild to moderate cases of erysipelas are treated with intramuscular procaine penicillin G or penicillin VK for 7 to 10 days (see Table 88–4).24,31 Recommended doses and monitoring parameters for selected antibiotics are given in Tables 88–5 and 88-6. Penicillin-allergic patients can be treated with clindamycin. For more serious infections, the patient should be hospitalized and aqueous penicillin G administered IV.24,31 Marked improvement usually is seen within 48 hours, and the patient often may be switched to oral penicillin to complete the course of therapy. Although one study has shown that the median time for cure, IV antibiotics, and hospital stay was reduced in patients receiving prednisolone in addition to antibiotics, further studies are needed before corticosteroids can be recommended for routine use.16,31,35
TABLE 88-5 Drug Dosing Tablea
TABLE 88-6 Drug Monitoring
CLINICAL PRESENTATION
General
• Exposed skin, especially the face, is the most common site.
Symptoms
• Pruritus is common.
• Systemic signs and symptoms of infection are minimal.
• Weakness, fever, and diarrhea occasionally seen with bullous form.
Signs
Nonbullous:
• Lesions start as small, fluid-filled vesicles.
• Vesicles rapidly develop into pustules that rupture readily.
• Purulent discharge dries to form characteristic golden-yellow crusts.
Bullous:
• Lesions start as vesicles that rapidly progress into bullae containing clear yellow fluid.
• Bullae soon rupture, forming thin, light brown crusts.
• Regional lymph nodes may be enlarged.
Laboratory Tests
• Cultures should be collected.
• Crusted tops of lesions should be raised to obtain purulent material at the base for culture.
• Open, draining pustules should not be cultured as they may be colonized with skin flora.
Other Diagnostic Tests
• Complete blood count often performed as leukocytosis is common
Evaluation of Therapeutic Outcomes
Erysipelas generally responds quickly to appropriate antimicrobial therapy. Temperature and white blood cell count should return to normal within 48 to 72 hours. Erythema, edema, and pain also should resolve gradually.
IMPETIGO
Impetigo is a superficial skin infection that is seen most commonly in children.6,24,36,37 The infection is generally classified as bullous or nonbullous based on clinical presentation.10,36,37 Impetigo is most common during hot, humid weather, which facilitates microbial colonization of the skin.6,31,36 Minor trauma, such as scratches or insect bites, allows entry of organisms into the superficial layers of skin, and infection ensues.29,31,37 Impetigo is highly communicable and readily spreads through close contact, especially among siblings and children in daycare centers and schools.31,36
CLINICAL PRESENTATION
General
• Lymphadenitis (acute or chronic inflammation of the lymph nodes) may occur when microorganisms reach the lymph nodes.
Symptoms
• Systemic signs and symptoms (i.e., fever, chills, malaise, and headache) often develop rapidly before any sign of infection is evident at the initial site of inoculation, or after the initial lesion has subsided.
• Systemic signs and symptoms often are more profound than would be expected based on examination of the cutaneous lesion.
Signs
• Peripheral lesion associated with proximal red linear streaks directed toward the regional lymph nodes is diagnostic of acute lymphangitis.
• Lymph nodes usually are enlarged and tender.
• Peripheral edema of the involved extremity often is present.
• Thrombophlebitis and acute lymphangitis in the lower extremities may be confused because both are associated with red linear streaking and tender areas; however, in thrombophlebitis, no portal of entry is identifiable.
Laboratory Tests
• Cultures of the affected lesions often yield negative results.
• Pathogens often identified by Gram stain of the initial lesion if done early in the course of the disease.
Other Diagnostic Tests
• Complete blood count often performed as leukocytosis is common
Although historically caused by S. pyogenes, S. aureus has emerged as a principle cause of impetigo (either alone or in combination with S. pyogenes).24,36,37 The bullous form is caused by strains of S. aureuscapable of producing exfoliative toxins.24,36 The bullous form most frequently affects neonates,36 and accounts for approximately 30% of all cases of impetigo.31,36 Similar to other SSTIs, impetigo has been reported to be increasingly due to CA-MRSA.24,37
TREATMENT
Impetigo
Desired Outcomes
The goals of treatment include relieving discomfort, improving the cosmetic appearance of lesions, preventing further spread of the infection, and preventing recurrence. Preventing transmission to others is also important.36,37Treatments should be effective and inexpensive and have minimal adverse effects.36
Treatment
Although impetigo may resolve spontaneously, antimicrobial treatment is indicated to relieve symptoms, prevent formation of new lesions, and prevent complications such as cellulitis. Penicillinase-resistant penicillins (such as dicloxacillin) are preferred for treatment because of the increased incidence of infections caused by S. aureus.16,24 First-generation cephalosporins (e.g., cephalexin) are also commonly used.24 Penicillin, administered as a single intramuscular dose of benzathine penicillin G or as oral penicillin VK, is effective for infections known to be caused by S. pyogenes. Penicillin-allergic patients can be treated with clindamycin. The duration of therapy is 7 to 10 days. A 7-day course of topical therapy with mupirocin ointment or retapamulin ointment is also effective for mild cases.16,24 With proper treatment, healing of skin lesions generally is rapid and occurs without residual scarring. Removal of crusts by soaking in soap and warm water also may be helpful in providing symptomatic relief.24,31
A review of interventions for impetigo by the Cochrane Collaboration found that topical mupirocin and oral antibiotics (except penicillin and erythromycin) were equally effective for the treatment of impetigo.38 Conclusions for extensive impetigo could not be made due to lack of data. Adverse effects were more commonly reported with oral antibiotics (GI) than for topical agents. In addition, disinfectant solutions did not show evidence of benefit.
Evaluation of Therapeutic Outcomes
Clinical response should be seen within 7 days of initiating antimicrobial therapy for impetigo. Treatment failures could be a result of noncompliance or antimicrobial resistance. A followup culture of exudates should be collected for culture and sensitivity, with treatment modified accordingly.
LYMPHANGITIS
Acute lymphangitis is an inflammation involving the subcutaneous lymphatic channels. Lymphangitis usually occurs secondary to puncture wounds, infected blisters, or other skin lesions. Most infections are caused by S. pyogenes.39
TREATMENT
Lymphangitis
Desired Outcomes
The goal of treatment of lymphangitis is rapid eradication of the infection, thereby providing relief of symptoms (pain, tenderness, fever). Prevention of systemic complications is also an important goal as thrombophlebitis and abscess formation are possible. Treatments should be effective and inexpensive and have minimal adverse effects.
Treatment
Penicillin is the antibiotic of choice. Because these infections are potentially serious and rapidly progressive, initial treatment should be with IV penicillin G 1 to 2 million units every 4 to 6 hours. Parenteral treatment should be continued for 48 to 72 hours, followed by oral penicillin VK for a total of 10 days.39 Nondrug therapy includes immobilization and elevation of the affected extremity and warm-water soaks every 2 to 4 hours.39 For penicillin-allergic patients, clindamycin may be used.
Evaluation of Therapeutic Outcomes
Lymphangitis usually responds rapidly to appropriate therapy; signs and symptoms often are decreased markedly or absent within 24 hours of starting antibiotics.
CELLULITIS
Cellulitis is an acute infectious process that represents a serious type of SSTI. It initially affects the epidermis and dermis and may spread subsequently within the superficial fascia.10 Cellulitis is considered a serious disease because of the propensity of the infection to spread through lymphatic tissue and to the bloodstream. S. pyogenes and S. aureus are the most frequent bacterial causes.5,7,13,22,29However, many bacteria have been implicated in various types of cellulitis (Table 88–1). Approximately 4 million patients were hospitalized for cellulitis between 1998 and 2006, representing 10% of all infection-related admissions.12,40 The rising incidence of infections caused by methicillin-resistant S. aureus (MRSA) is a major concern in both the community and hospital settings.14–19,26
Injection drug users are predisposed to several infectious complications, including abscess formation and cellulitis at the site of injection.16 These SSTIs are often polymicrobic in nature and are believed to originate from the skin and/or oropharynx, as well as from contaminated needles, syringes, and diluents.16 S. aureus is the most common pathogen isolated from injection drug users; the incidence of MRSA is also rising.14,16,41 Anaerobic bacteria, especially oropharyngeal anaerobes, are also found commonly, particularly in polymicrobic infections.16 Outbreaks caused by Clostridium species have also been reported in injection drug users, particularly in association with contaminated black tar heroin.16
Acute cellulitis with mixed aerobic and anaerobic pathogens may occur in diabetics, following traumatic injuries, at sites of surgical incisions to the abdomen or perineum, or where host defenses have been otherwise compromised (vascular insufficiency).6,10,29 In older patients, cellulitis of the lower extremities also may be complicated by thrombophlebitis. Other complications of cellulitis include local abscess, osteomyelitis, and septic arthritis.16,42
TREATMENT
Cellulitis
Desired Outcomes
The goals of therapy of acute bacterial cellulitis are rapid eradication of the infection and prevention of further complications. Effective treatment of cellulitis includes avoidance of unnecessary antimicrobials that contribute to increased resistance, and minimizing toxicities and cost of therapy.
Drug and Nondrug Management of Cellulitis
Local care of cellulitis includes elevation and immobilization of the involved area to decrease swelling.5,43 Cool sterile saline dressings may decrease pain and can be followed later with moist heat to aid in localization of the cellulitis. Surgical intervention (incision and drainage) as a mode of therapy is rarely indicated in the treatment of uncomplicated cellulitis, but may play an important role in management of more severe or complicated cases. Antimicrobial therapy is directed against the type of bacteria either documented or suspected to be present based on the clinical presentation. Particular attention must be paid to patients with risk factors for more atypical or resistant bacterial pathogens when selecting antibiotics for treatment of cellulitis. Such organisms include particularly CA-MRSA, but also aerobic gram-negative bacteria and anaerobes.
CLINICAL PRESENTATION
General
• Usually a history of an antecedent wound from minor trauma, abrasion, ulcer, or surgery
Symptoms
• Patients often experience fever, chills, or malaise and complain that the affected area feels hot and painful.
• Systemic findings such as hypotension, dehydration, and altered mental status are common.
Signs
• Characterized by erythema and edema of the skin.
• Lesions are nonelevated and have poorly defined margins.
• Affected areas generally are warm to touch.
• Inflammation generally is present with little or no necrosis or suppuration of soft tissue.
• Lesions may be associated with purulent drainage, exudates, and/or abscesses.
• Tender lymphadenopathy associated with lymphatic involvement is common.
Laboratory Tests
• Cultures should be collected when possible.
• Gram stain of fluid obtained by injection and aspiration of 0.5 mL of saline (using a small 22-gauge needle) into the advancing edge of the lesion may aid the microbiologic diagnosis but often yields negative results.
• Diagnosis usually is made on clinical grounds rather than by culture.
Other Diagnostic Tests
• Complete blood count often performed as leukocytosis is common
• Blood cultures often useful because bacteremia may be present in up to 30% of cases
Because staphylococcal and streptococcal cellulitis are indistinguishable clinically,22,42 and because of concern regarding appropriate recognition and treatment of MRSA infections, guidelines from the Infectious Diseases Society of America provide detailed recommendations for empiric antibiotic therapy of cellulitis.32 Infection with CA-MRSA should be considered in patients with skin abscesses, subjective history of insect bites, or more severe infections.32,42 Appropriate clinical specimens for culture and susceptibility testing should be collected whenever possible in such patients.5,32,42 Incision and drainage is the primary therapy for infections such as small abscesses and furuncles, and in otherwise uncomplicated patients with mild infections. Systemic antibiotic therapy is often unnecessary in such cases.32 Antibiotic therapy is recommended along with incision and drainage in patients with more complicated abscesses associated with the following: severe or extensive disease involving multiple sites of infection; rapidly progressive infection in the presence of associated cellulitis; signs and symptoms of systemic illness; complicating factors such as extremes of age, comorbidities, or immunosuppression; abscesses in areas that are difficult to drain, such as hands, face, and genitalia; or lack of response to previous drainage alone.32,42,44–47
Antibiotic selection for outpatient treatment of cellulitis is chiefly determined by clinical findings such as appearance of the infected lesion and presence of more severe systemic illness. Purulent cellulitis is defined as infection associated with purulent drainage or exudate in the absence of a drainable abscess.32 Empiric antibiotics for purulent cellulitis in outpatients should include an orally administered agent with activity against CA-MRSA such as trimethoprim–sulfamethoxazole, a tetracycline, or clindamycin (Table 88–7); infection due to streptococci is less likely in this situation and specific coverage is not required.32,48–50 Oral linezolid is also recommended in such cases but is significantly more expensive and no more efficacious than other treatment options.32
TABLE 88-7 Initial Treatment Regimens for Cellulitis and Necrotizing Fasciitis
Clinical Controversy…
The most appropriate dose of trimethoprim–sulfamethoxazole for the treatment of CA-MRSA is not known. Although higher doses (e.g., two double-strength tablets orally twice daily) have been recommended,32 a prospective observational study of high dose versus standard dose of trimethoprim–sulfamethoxazole for treatment of SSTIs caused by MRSA found no clinically or statistically significant differences in rates of clinical resolution of infections.51Although trimethoprim–sulfamethoxazole is an inexpensive and generally well-tolerated drug, whether higher doses have any true clinical benefit and should be routinely used in most patients remains to be established.
Nonpurulent cellulitis is defined as cellulitis without purulent drainage or exudate and no associated abscess. The role of MRSA in these types of infection is not clear, so empiric therapy of nonpurulent cellulitis is directed primarily against Group A β-hemolytic streptococci. Recommended empiric therapy consists of an orally administered β-lactam such as cephalexin or dicloxacillin, or clindamycin.32 Oral cephalosporins, such as cefadroxil, cefaclor, cefprozil, cefpodoxime proxetil, and cefdinir, are also effective in the treatment of cellulitis but are more expensive.16,42 In penicillin-allergic patients, oral or parenteral clindamycin may be used.32,42 Alternatively, a first-generation cephalosporin may be used cautiously for patients without a history of immediate or anaphylactic reactions to penicillin. In severe cases in which cephalosporins cannot be used because of suspected and/or documented MRSA or severe β-lactam allergies, vancomycin should be administered.16,32
Empiric treatment of CA-MRSA should be considered for patients with nonpurulent cellulitis if they have not responded appropriately to β-lactam therapy alone, or if patients exhibit signs of more severe infection with systemic toxicity.32 Recommended drugs for coverage of CA-MRSA in this setting are the same as those for purulent cellulitis. Clindamycin has reasonably good activity against β-hemolytic streptococci, but the activities of trimethoprim–sulfamethoxazole and the tetracyclines against this organism are not well defined.32 Therefore, if empiric coverage of both MRSA and β-hemolytic streptococci is desired for patients with nonpurulent cellulitis, it is recommended that they receive clindamycin alone or amoxicillin in combination with trimethoprim–sulfamethoxazole, doxycycline, or minocycline.32Although often used for treatment of uncomplicated outpatient cellulitis, fluoroquinolones (e.g., levofloxacin, moxifloxacin) are not recommended for routine use due to their unnecessarily broad spectrum of activity, concerns for resistance, and higher cost compared with other preferred options.
Clinical Controversy…
Whether antibiotic coverage for both β-hemolytic streptococci and CA-MRSA is required during the initial treatment of nonpurulent cellulitis is controversial. The great majority of nonpurulent cellulitis appears to be caused by β-hemolytic streptococci, and hospitalized patients treated with β-lactam antibiotics alone were reported to have excellent clinical response rates.52 However, the high prevalence of CA-MRSA has prompted some clinicians to empirically cover this pathogen as part of routine therapy because of benefit-versus-risk considerations.32,52 Whether the addition of antibiotics having activity against CA-MRSA should be done routinely, or in which specific patients such coverage should be considered, is not known.
Patients in whom specific pathogens have been identified by culture should have empiric antibiotics narrowed according to susceptibility test results. If documented to be a mild cellulitis secondary to streptococci, oral penicillin VK or intramuscular procaine penicillin G may be administered. Since S. aureus susceptibilities are more variable, treatment of documented staphylococcal infections will depend on test results for specific isolates. The usual duration of therapy for outpatient therapy of cellulitis, either purulent or nonpurulent, is 5 to 10 days.16,31,42
More severe infections should be treated initially with IV antibiotic regimens (Table 88–7). The classification of infections as either purulent or nonpurulent is again useful in the selection of appropriate initial therapy in these patients. Hospitalized patients with more severe or complicated purulent cellulitis should be empirically treated with an antibiotic having activity against MRSA. Vancomycin, linezolid, daptomycin, telavancin, and clindamycin are all acceptable treatment options with comparable efficacy in adults.31,32,53 In children, vancomycin, linezolid, or clindamycin is the preferred treatment option. Hospitalized patients with nonpurulent cellulitis may be initially treated with IV cefazolin or nafcillin, with change to an agent with activity against MRSA if there is unsatisfactory clinical response.32Ceftriaxone 50 to 100 mg/kg as a single daily dose has also been efficacious in the treatment of cellulitis in pediatric patients.31,43 The recommended duration of therapy for cellulitis in hospitalized patients is 7 to 14 days, but this should be individualized based on patient response.32
Linezolid, quinupristin–dalfopristin, daptomycin, ceftaroline, and telavancin all exhibit excellent activity against resistant gram-positive pathogens.44–47,53 However, significantly higher cost compared with vancomycin, as well as lack of demonstrated advantages in efficacy, makes them most appropriate for treatment of complicated or refractory infections, or those documented as caused by multidrug-resistant pathogens, rather than as initial therapy. The availability of orally administered linezolid may provide a cost-effective “step-down” option as an alternative to prolonged treatment with parenteral agents for many patients with more complicated infections and/or those patients who require initial hospitalization.48
Carbapenems (i.e., imipenem, meropenem, ertapenem, and doripenem) and the β-lactam–β-lactamase inhibitor combination antibiotics (ampicillin–sulbactam, ticarcillin–clavulanate, and piperacillin–tazobactam) appear to be equivalent to standard therapies in adults.5,16,31,42 However, the greater cost of these agents without increased efficacy compared with other reliable regimens, particularly given the increasing problem of MRSA, makes them less desirable for empiric therapy except in serious polymicrobic infections.5,16,42
For cellulitis caused by gram-negative bacilli or a mixture of microorganisms, immediate antimicrobial chemotherapy, as determined by Gram stain, is essential (Table 88–7). Surgical debridement of necrotic tissue and drainage also may be appropriate. Gram-negative cellulitis may be treated appropriately with an aminoglycoside (such as gentamicin or tobramycin), or a first- or second-generation cephalosporin (e.g., cephalexin, cefaclor, or cefuroxime). Ceftriaxone, ceftazidime, and the fluoroquinolones are also effective in the treatment of cellulitis caused by both gram-negative and gram-positive bacteria.5,16,31,42 If gram-positive aerobic bacteria are also present on Gram stain, an additional agent such as penicillin G or a penicillinase-resistant penicillin may need to be added to provide coverage against staphylococci or streptococci as appropriate.32 Addition of an agent active against MRSA (e.g., vancomycin) may need to be considered for severe, complicated infections in hospitalized patients.5,16,31,32,42
Because some polymicrobic infections may also involve anaerobic bacteria, antibiotic therapy may need to be broadened to include agents with good activity against these organisms. Many different treatment regimens are possible depending on the bacteriology of the lesion (Table 88–7). Orally administered antibiotics, as monotherapy or in combination regimens, may be appropriately used in the treatment of mild to moderate infections in outpatients. Monotherapy or combination regimens of IV antibiotics may be necessary for more severe infections in hospitalized patients. Therapy should be 10 to 14 days in duration.16,31,42
Because gram-negative and mixed aerobic–anaerobic cellulitis can progress quickly to serious tissue invasion, therapeutic intervention should be immediate.16,31,42 If treated early, a rapid response can be seen. Unfortunately, because these infections often occur in patients with compromised immune defenses, they may still progress, even with therapeutic intervention. If the infectious process is secondary to a systemic cause (e.g., diabetes), the treatment course often is prolonged and may be associated with high morbidity and mortality.16,31,42
Infections in injection drug users generally are treated similarly to those in other types of patients.16,31,42 It is important that blood cultures be obtained in these cases because 25% to 35% of patients may be bacteremic.16,31 Also, patients should be assessed for the presence of abscesses; incision, drainage, and culture of these lesions are of extreme importance.16 Initial antimicrobial therapy while awaiting culture results of abscesses should include broad coverage for gram-negative and anaerobic organisms, in addition to S. aureus (including MRSA in areas with high prevalence) and streptococci.16,31,42
Evaluation of Therapeutic Outcomes
If treated promptly with appropriate antibiotics, the majority of patients with cellulitis are cured rapidly. Culture and sensitivity results should be evaluated carefully for both the adequacy of culture material and the presence of resistant organisms. Additional high-quality samples for culture may be needed for microbiologic analysis. Failure to respond to therapy also may be indicative of an underlying local or systemic problem or a misdiagnosis.
NECROTIZING SOFT-TISSUE INFECTIONS
Necrotizing soft-tissue infections consist of a group of extremely severe infections, associated with high morbidity and mortality, that require early and aggressive surgical debridement in addition to appropriate antibiotics and intensive supportive care.4,7,54–57 Different terms have been used to classify necrotizing infections based on factors such as predisposing conditions, onset of symptoms, pain, skin appearance, etiologic agent, gas production, muscle involvement, and systemic toxicity.5,29,55 However, while many types of necrotizing soft-tissue infections have been designated as unique infectious processes, they all share similar pathophysiologies, clinical features, and treatment approaches.54–57 The major clinical entities of necrotizing infections are necrotizing fasciitis and clostridial myonecrosis (gas gangrene).54–56
Necrotizing fasciitis is a rare but severe infection of the subcutaneous tissue that may be caused by aerobic and/or anaerobic bacteria and results in progressive destruction of the superficial fascia and subcutaneous fat.5,13,31,55,56 Type I necrotizing fasciitis is the most common type and accounts for approximately 80% of necrotizing soft-tissue infections.55,56 It generally occurs after trauma or surgery and involves a mixture of anaerobes (Bacteroides, Peptostreptococcus) and facultative bacteria (streptococci and Enterobacteriaceae) that act synergistically to cause destruction of fat and fascia.7,55 Type I necrotizing fasciitis is also reported more commonly among injection drug users.54–57 In type I infections, the skin may be spared, and the speed at which the infection spreads (3 to 5 days) is somewhat slower than that in type II.29 Necrotizing fasciitis affecting the male genitalia is termed Fournier’s gangrene.55 Type II necrotizing fasciitis is caused by virulent strains of S. pyogenes and is commonly referred to as streptococcal gangrene.7,55 This type of infection has often been called “flesh-eating bacteria” by the lay press. Unlike previous reports of streptococcal gangrene that affected older individuals with underlying diseases, recent reports have occurred primarily in young, previously healthy adults following some type of minor trauma. It differs from type I infections in its clinical presentation. Type II infections have rapidly extending necrosis (i.e., 24 to 72 hours) of subcutaneous tissues and skin, gangrene, severe local pain, and systemic toxicity.29,54–57 They are also highly associated with an early onset of shock and organ failure and are present in approximately half the cases of streptococcal toxic shock-like syndrome.29,54,55 Of note, CA-MRSA is increasingly reported in type II infections, either as a single organism or in combination with streptococci.9,55,56 Clinicians should consider CA-MRSA in areas that are endemic for CA-MRSA or if patients have risk factors for these organisms.
CLINICAL PRESENTATION
General
• Most frequently involve the abdomen, perineum, and lower extremities.
• Predisposing factors such as diabetes mellitus, local trauma or infection, or recent surgery often present.
• Rapid diagnosis is critical due to the aggressive nature and high associated mortality (20% to 50%).
Symptoms
• Systemic symptoms generally are marked (e.g., fever, chills, and leukocytosis) and may include shock and organ failure, especially in patients with type II infections.
• Pain in the affected area and systemic toxicity are characteristically more pronounced than with cellulitis.
Signs
• May be difficult to differentiate between necrotizing fasciitis and cellulitis early in infection.
• Affected area is initially hot, swollen, and erythematous without sharply demarcated margins.
• Affected area is often shiny, exquisitely tender, and painful.
• Diffuse swelling of the area is followed by the appearance of bullae filled with clear fluid.
• Rapidly progressive infection with the frequent development of a maroon or violaceous color of the skin after several days.
• Infection may rapidly evolve into a frank cutaneous gangrene, sometimes with myonecrosis.
Laboratory Tests
• Tissue samples should be obtained for histologic examination, and culture and susceptibility testing.
• Clostridial myonecrosis shows little inflammation on histologic examination.
Other Diagnostic Tests
• Surgical exploration is the best and most rapid diagnosis of necrotizing infections; computed tomography and magnetic resonance imaging may also be helpful.
• Blood samples should be collected for complete blood count and chemistry profile, as well as for bacterial culture.
• Laboratory tests that may aid in the diagnosis of necrotizing infections (LRINEC score) include C-reactive protein, white blood cell count, hemoglobin, sodium, creatinine, and glucose.
Clostridial myonecrosis (type III necrotizing fasciitis) is a necrotizing infection that involves the skeletal muscle.9,55 Type III infections account for less than 5% of necrotizing infections.55 Gas production and muscle necrosis are prominent features of this infection, which readily explains why this infection is commonly referred to as gas gangrene.54–56 The infection advances rapidly, often over a matter of a few hours.54–56 Most infections occur after surgery or trauma, with Clostridium perfringens identified as the most common etiologic agent.55
TREATMENT
Necrotizing Soft-Tissue Infections
Desired Outcomes
The goals of therapy of acute bacterial cellulitis are rapid eradication of the infection, prevention of further complications, and reduction in mortality. Effective treatment of necrotizing soft-tissue infections includes avoidance of unnecessary antimicrobials that contribute to increased resistance, and minimizing toxicities and cost of therapy.
Management of Necrotizing Infections
On diagnosis, immediate and aggressive surgical debridement of all necrotic tissue is essential.9,54–57 Initial surgical debridement performed greater than 14 hours after the diagnosis of necrotizing infection was independently associated with increased patient mortality, including a 34-fold increased risk of death in patients with septic shock.58 Patients often require further surgical intervention following initial debridement to ensure that all necrotic tissue has been removed.16,54–58 Type I necrotizing fasciitis must be empirically treated with broad-spectrum antibiotics that include coverage against streptococci, Enterobacteriaceae, and anaerobes. A number of antibiotic regimens are recommended to successfully treat necrotizing soft-tissue infections (see Table 88–5); these are generally similar to regimens used for polymicrobic cellulitis.31,54–57 Antibiotic therapy can be modified after Gram stain and culture reports are available.
If a diagnosis of type II necrotizing fasciitis is established, broad-spectrum empiric therapy should be replaced with the combination of penicillin and clindamycin.55,56 Although S. pyogenes remains susceptible to penicillin, clindamycin is more effective.54,56 Several factors have been postulated to explain the greater efficacy of clindamycin, including the mechanism of action (inhibition of protein synthesis) that may cause decreased production of bacterial exotoxins.54–57 In addition, clindamycin has immunomodulatory properties that may account for the higher efficacy.54,56 Clindamycin is also effective against strains of CA-MRSA.55 The combination of penicillin and clindamycin is also recommended for treatment of clostridial myonecrosis.16,54,55 Hyperbaric oxygen also may be of some benefit for clostridial myonecrosis.54–57
Evaluation of Therapeutic Outcomes
Because of the high mortality associated with necrotizing infections, rapid and complete debridement of all devitalized and necrotic tissue is essential. Surgical debridement, coupled with appropriate antimicrobial therapy and supportive measures for management of shock and organ failure, should stabilize the patient. Vital signs and laboratory tests should be monitored carefully for signs of resolution of the infection. Change in antimicrobial therapy or additional surgical debridement may be needed in patients who do not show signs of improvement.
DIABETIC FOOT INFECTIONS
Three major types of foot infections are seen in diabetic patients: deep abscesses, cellulitis of the dorsum, and mal perforans ulcers.59,60 Most deep abscesses involve the central plantar space (arch) and are caused by minor penetrating trauma or by an extension of infection of a nail or web space of the toes. Infections of the dorsal area generally arise from infections in the toes that are related to routine care of the nails, nail beds, and calluses of the toes. Mal perforans ulcer is a chronic ulcer of the sole of the foot. The ulcer develops on thickened, hardened calluses over the first or fifth metatarsal. Mal perforans ulcers are associated with neuropathic changes, which are responsible for the misalignment of the weight-bearing bones of the foot.59,60 Osteomyelitis is one of the most serious complications of diabetic foot infection (DFI) and may occur in 30% to 40% of infections.30,59
Epidemiology
DFI is among the most common complications of diabetes, accounting for as many as 20% of all hospitalizations in diabetic patients at an annual cost of $200 to $350 million.30,59,61 Approximately 15% of diabetic patients experience significant soft-tissue infection during their lifetime.61 Approximately 71,000 lower-extremity amputations, often sequelae of uncontrolled infection, are performed each year on diabetic patients; this represents up to 70% of all nontraumatic amputations in the United States.30,59,61 Approximately 20% of diabetics will undergo additional surgery or amputation of a second limb within 12 months of the initial amputation.30,59
Etiology
Mild cases of DFI are often monomicrobial. However, more severe infections are typically polymicrobic; up to 60% of hospitalized patients have polymicrobial infections (Table 88–8).30,59,60,62–67 Wide ranges in the frequency of various bacteria in DFI reflect differences in culture techniques as well as variation among different types and severity of infections. Staphylococci and streptococci are the most common pathogens, although gram-negative bacilli and/or anaerobes occur in up to 50% of cases.30,62–67 Although P. aeruginosa is an important pathogen in DFI, it is usually reported to occur in <10% of wounds and is most commonly associated with more severe infections.30,63Obligate anaerobes are also more commonly associated with severe infections in patients with chronic foot ischemia.30,62,63 MRSA is increasingly important in DFI and has been reported in from 10% to 30% of infected wounds.30,63,64,67–69 The presence of MRSA in DFI has been associated with increased risk of treatment failure and worse patient outcomes, but these findings have not been consistent among studies and the clinical relevance of MRSA in this setting is still unclear.30,60,68
TABLE 88-8 Bacterial Isolates from Foot Infections in Diabetic Patients30,59,60,62–68,71
Identifying causative pathogens from cultures of diabetic wounds is often difficult. The chronic nature of DFI means that these wounds are often heavily colonized by organisms not playing a role in the infection. Superficial swab cultures are not as reliable as culture specimens obtained from deep tissues via biopsy, tissue scraping (curettage), or needle aspiration of drainage or abscess fluid.64,67,70 Therefore, cultures and sensitivity tests should be done with specimens obtained from a deep culture of the wound base whenever possible. Before the wound is cultured, it should be scrubbed vigorously with saline-moistened sterile gauze to remove any overlying necrotic debris and further debrided as necessary.30,64 Bone cultures should also be performed when there is diagnostic uncertainty regarding the presence of osteomyelitis or when therapeutic decisions are dependent on knowing the exact etiology of infection.30,64
Pathophysiology
Three key factors are involved in the development of diabetic foot problems: neuropathy, angiopathy and ischemia, and immunologic defects. Any of these disorders can occur in isolation; however, they frequently occur together.61
Neuropathic changes to the autonomic nervous system as a consequence of diabetes may affect the motor nerve supply of small intrinsic muscles of the foot, resulting in muscular imbalance, abnormal stresses on tissues and bone, and repetitive injuries.59,61 Diminished sensory perception causes an absence of pain and unawareness of minor injuries and ulceration. The sympathetic nerve supply may be damaged, resulting in an absence of sweating that may lead to dry cracked skin and secondary infection.30,59,61
Atherosclerosis is more common, appears at a younger age, and progresses more rapidly in the diabetic than in the nondiabetic. Diabetics may have problems with both small vessels (microangiopathy) and large vessels (macroangiopathy) that can result in varying degrees of ischemia, ultimately leading to skin breakdown and infection.
Diabetic patients typically have normal humoral immunity, normal levels of immunoglobulins, and normal antibody responses. Patients with diabetes, however, have impaired phagocytosis and intracellular microbicidal function as compared with nondiabetics; this may be related to angiopathy and low tissue levels of oxygen.30,59,61 These defects in cell-mediated immunity make patients with diabetes more susceptible to certain types of infection and impair the patients’ ability to heal wounds adequately.59,60,61
TREATMENT
Diabetic Foot Infections
Desired Outcomes
The goals of therapy in the management of DFI include the following: (a) successfully treat infected wounds by using effective nondrug and antibiotic therapy; (b) prevent additional infectious complications; (c) preserve as much normal limb function as possible; (d) avoid unnecessary use of antimicrobials that contribute to increased resistance; and (e) minimize toxicities and cost while increasing patient quality of life.
CLINICAL PRESENTATION
General
• Infections are often much more extensive than they appear initially.
Symptoms
• Patients with peripheral neuropathy often do not experience pain; simple complaints of swelling or edema are common.
Signs
• Clinical signs of infection may not be present secondary to angiopathy and neuropathy.
• Lesions vary in size and clinical features (e.g., erythema, edema, warmth, presence of pus, draining sinuses, pain, and tenderness).
• Foul-smelling odor suggests the presence of anaerobic organisms.
• Temperature may be mildly elevated or normal.
Laboratory Tests
• Specimens for culture and sensitivities should be collected.
• Deep-tissue samples obtained during surgical debridement are most useful for culture and susceptibility testing.
• Wounds must be cultured for both aerobic and anaerobic organisms.
Other Diagnostic Tests
• Possible presence of osteomyelitis also must be assessed via radiograph, bone scan, or both, as appropriate.
Management
Up to 90% of infections can be treated successfully with a comprehensive treatment approach that includes both wound care and antimicrobial therapy.30,60,64,65 After carefully assessing the extent of the lesion and obtaining necessary cultures, necrotic tissue must be thoroughly debrided, with wound drainage and amputation as required. Wounds must be kept clean and dressings changed frequently (two to three times daily). Because of the relationship between hyperglycemia and immune system defects, glycemic control must be maximized to ensure optimal wound healing. In addition, the patient’s activities should be restricted initially to bedrest for leg elevation and control of edema, if present. Adequate pressure relief from a foot wound (i.e., off-loading) is crucial to the healing process.30,61,64 Finally, appropriate antimicrobials must be initiated.30,60,61,64,65 However, the optimal antimicrobial therapy for DFI has yet to be defined. Empiric therapy that is totally comprehensive in its coverage of all possible pathogens does not seem to be necessary unless the infection is life- or limb-threatening, assuming that adequate wound care is also being performed.30,60,64,65 This is particularly true regarding MRSA, P. aeruginosa, and anaerobes; the perceived need for empiric coverage of these organisms often leads to use of excessively broad-spectrum drug regimens. Several studies have shown good treatment efficacy despite the fact that treatment regimens did not have consistently good activity against these particular organisms.30,64,66–68,71
Proper selection of empiric antibiotics for DFI begins with thorough patient assessment and classification of the severity of the infection. Specific drug regimens, route of administration, and duration of therapy are all then largely dependent on the severity of infection. Although a number of classification systems are available, the most recent DFI treatment guidelines use those summarized in Table 88–9.30,64Wounds with no local signs of infection often do not require antibiotic therapy, and the majority of mild, uncomplicated infections can be managed successfully on an outpatient basis with highly bioavailable oral antimicrobials and good wound care (Tables 88–9 and 88-10).30,60,64,65 Antibiotics for treatment of mild infections should be largely limited to those with activity against skin flora such as streptococci and methicillin-susceptible S. aureus (MSSA), except in those patients with risk factors for infection with other types of pathogens (Fig. 88–1).30,64 Patients with specific risk factors for MRSA (Table 88–10) should empirically receive trimethoprim–sulfamethoxazole or doxycycline orally, while those who have received antibiotics within the past month should also receive empiric antibiotics that provide activity against gram-negative bacilli. Oral antimicrobials should be used cautiously in DFI complicated by osteomyelitis, extensive ulceration, areas of necrosis, or a combination of these. The use of topical antimicrobials, including medical-grade honey, has been advocated for the treatment of DFI in an attempt to minimize the cost of therapy and systemic antibiotic exposure leading to adverse effects and resistance. Although the most recent guidelines allow for consideration of topical therapy in mild infection in selected patients, use of topical agents is quite controversial and not routinely recommended.30,60,64,72,73
TABLE 88-9 Classifications and Treatment Strategies for Diabetic Foot Infections of Varying Severity
TABLE 88-10 Suggested Antibiotic Regimens for Empiric Treatment of Diabetic Foot Infections
FIGURE 88-1 Recommended treatment algorithm for initial management of mild to moderate diabetic foot infections. (GNR, aerobic gram-negative rods; GPC, aerobic gram-positive cocci; MRSA, methicillin-resistant Staphylococcus aureus; TMP-SMX, trimethoprim–sulfamethoxazole.)
Appropriate initial therapy for patients with moderate to severe infection is also dependent on the presence of specific risk factors that increase the likelihood of infection with more resistant pathogens such as P. aeruginosa and MRSA (Table 88–10).30,64 Many moderate infections can be successfully treated with orally administered antibiotics that provide activity against MSSA, streptococci, and gram-negative aerobic bacilli; coverage of obligate anaerobes may also be considered in patients with chronic or previously treated wounds (Fig. 88–2).30,64 The addition of orally administered agents with activity against MRSA is recommended in patients with moderate or severe infection and specific risk factors for MRSA; such patients may also be considered for hospitalization and initial treatment with parenteral antibiotics in order to ensure adequate antibiotics for potentially more complex infections.30,64 Patients with more extensive or chronically unhealed wounds, even though assessed as moderate in severity, may also be more appropriately treated initially with parenteral antibiotics in the hospital setting.30,64 All patients with severe DFI should be hospitalized initially and treated with broad-spectrum IV antibiotics (Table 88–10 and Fig. 88–2).30,64 Severe infection is considered a risk factor for P. aeruginosa, so most patients with severe DFI will be initially started on antipseudomonal antibiotics.30,64 Many patients will also be initially started on antibiotics that provide activity against MRSA due to risk-versus-benefit considerations, but assessment of risk factors in individual patients should still be performed in order to minimize the use of excessively broad-spectrum antibiotics when possible.
FIGURE 88-2 Recommended treatment algorithm for initial management of severe diabetic foot infections. (GNR, aerobic gram-negative rods; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible S. aureus.)
Current guidelines for management of DFI include options for both monotherapy and combination regimens (Table 88–10).30 Monotherapy, along with appropriate medical or surgical management, or both, is often effective in treating DFI, including those in which osteomyelitis is present.30,60,65,66 Monotherapy is particularly attractive because of the potential advantages of convenience, cost, and avoidance of toxicities. Microbiologic and clinical cure rates ranging from 60% to 90% may be expected from any of these agents.66 Selection of a specific regimen is determined by patient-specific factors including allergies, renal function, history of previous antibiotic use, and cost. In penicillin-allergic patients, metronidazole or clindamycin plus a fluoroquinolone, aztreonam, or possibly a third- or fourth-generation cephalosporin is appropriate.30,60,65 Vancomycin also is used frequently in severe infections because of its excellent activity against gram-positive pathogens. Linezolid, daptomycin, and tigecycline are specifically recommended alternatives for treatment of this pathogen.30,60,64,65 Tigecycline may be particularly useful in this setting because of its activity against gram-negative aerobes and anaerobic bacteria, thus allowing it to be used as monotherapy for the treatment of mixed infections in patients where coverage of P. aeruginosa is not of great concern. A newer agent, ceftaroline fosamil, has in vitro activity that is suitable for DFI but has not been studied for this indication and its role is not yet defined. Because many patients already have some degree of diabetic nephropathy that may place them at higher risk of nephrotoxicity, strong recommendations have been made against the use of aminoglycoside antibiotics unless no alternative agents are available.30,60 When an aminoglycoside is used, care must be taken to avoid further compromising renal function. All antibiotic regimens should be adjusted as necessary for renal dysfunction.
Duration of therapy for DFI depends on the severity of the infection, ranging from 1 to 2 weeks for mild infections up to 2 to 4 weeks or more for severe infections.30,60 In cases of underlying osteomyelitis, treatment should continue for 6 to 12 weeks.30,60,65 After healing of the infection has occurred, a well-designed program for prevention of further infections should be instituted. The use of adjunctive agents such as colony-stimulating factors, growth factors, and hyperbaric oxygen for either prevention or treatment of DFIs is controversial and not widely recommended.30
Evaluation of Therapeutic Outcomes
Therapy should be reevaluated carefully after 48 to 72 hours to assess favorable response. Change in therapy (or route of administration, if oral) should be considered if clinical improvement is not observed at this time. For optimal results, drug therapy should be appropriately modified according to information from deep-tissue culture and the clinical condition of the patient. Infections in diabetic patients often require extended courses of therapy because of impaired host immunity and poor wound healing.
PRESSURE SORES
The terms decubitus ulcer, bed sore, and pressure sore are used interchangeably.74–76 The decubitus ulcer and the bed sore are types of pressure sores. The term decubitus ulcer is derived from the Latin word decumbere, meaning “lying down.” Pressure sores, however, can develop regardless of a patient’s position.
Numerous systems for classification of pressure sores have been described. The 2007 recommendations of the National Pressure Ulcer Advisory Panel are shown in Table 88–11 and illustrate the various stages of progression through which a pressure sore may pass.77
TABLE 88-11 Pressure Sore Classification
Complications of pressure sores are not uncommon and may be life-threatening. Infection is one of the most serious and most frequently encountered complications of pressure ulcers.75,76 Although most pressure sore wounds are heavily colonized, the majority of these eventually heal.78–80 When true infection is present, however, there is bacterial invasion of previously healthy tissue. Without treatment, an initial small, localized area of ulceration can rapidly progress to large ulcers within days. The visible ulcer is just a small portion of the actual wound81; up to 70% of the total wound is below the skin. A pressure-gradient phenomenon is created by which the wound takes on a conical nature; the smallest point is at the skin surface, and the largest portion of the defect is at the base of the ulcer (Fig. 88–3).
FIGURE 88-3 Distribution of forces involved with sore formation in a conical fashion.
Epidemiology
Pressure sores are most common among chronically debilitated persons, the elderly (70% involve persons greater than 70 years of age), and persons with serious spinal cord injury.28,75,76,81,82 Generally, patients who are at risk for pressure sores are elderly or chronically ill young patients who are immobilized, in either bed or a wheelchair, and who may have altered mental status and/or incontinence.75,76,81,82
Etiology
Similar to DFIs, a large variety of aerobic gram-positive and gram-negative organisms, as well as anaerobes, frequently are isolated from wound cultures.28 Most pressure sores are colonized with microorganisms, making assessment for infection a clinical challenge.28,78 Curettage of the ulcer base after debridement provides more reliable culture information than does needle aspiration.78–80 Biopsy specimens give the most reliable data but may not be practical to obtain. Deep-tissue cultures from different sites may give different results. Cultures collected from pressure ulcers reveal polymicrobial growth. A culture collected by swab is likely to identify surface bacteria colonizing the wound rather than to diagnose the infection.78
Pathophysiology
Many factors apparently predispose patients to the formation of pressure sores: paralysis, paresis, immobilization, malnutrition, anemia, infection, and advanced age. Factors thought to be most critical to their formation are pressure, shearing forces, friction, and moisture28,75,83; however, there is still debate as to the exact pathophysiology of pressure sore formation.83
Pressure is the essential element in the formation of pressure sores.28,76,81,83 The areas of highest pressure are generated most often over the bony prominences.28,74–76,78,82,83 Both the degree of pressure and the length of time that the pressure is applied are important.75,76,83
Shearing occurs when two surfaces move in opposite directions.28,83 This situation can occur when the head of a bed is raised, causing the upper torso to slide downward, transmitting pressure to the sacrum and other areas. This effect results in occlusion or distortion of vessels, leading to compromise of the dermis. At the same time, sitting and gravity create shearing forces; the posterior sacral skin area can become fixed secondary to friction with the bed. The effects of friction and shearing forces combine, resulting in transmission of force to the deep portion of the superficial fascia and leading to further damage of soft-tissue structures.28,75,78,83
Compounding the problems of shearing and friction forces are the macerating effects of excessive moisture in the local environment, resulting from incontinence and perspiration. This factor is of critical importance because when combined with the other forces, it increases the risk of pressure sore formation fivefold.28,75,79,83
TREATMENT
Pressure Sores
Desired Outcomes
The primary goal for pressure sores is prevention. Once a pressure sore has developed, the goals of therapy are prevention of complications (i.e., infections), preventing sores from growing larger, and preventing the development of sores in other locations.81 Eradication of infection should include good wound care and topical therapies, and avoidance of broad-spectrum antimicrobials unless guided by results from appropriately collected cultures or in patients with bacteremia, sepsis, cellulitis, or osteomyelitis.
CLINICAL PRESENTATION
General
• Most pressure sores are in the pelvic region and lower extremities; see Figure 88–4.
• Most common sites: sacral and coccygeal areas, ischial tuberosities, and greater trochanter.
Symptoms
• Patients commonly have other medical problems that may mask signs and symptoms of infection.
• Pain may be present with or without infection; continuous pain may indicate infection.
Signs
• A dark red color on the surface of a pressure sore may indicate local infection.
• Surrounding erythema, swelling, and heat are commonly present with infection.
• Purulent discharge, foul odor, and systemic signs (e.g., fever and leukocytosis) of infection may be present.
Laboratory Tests
• Cultures should be collected from either a biopsy or fluid obtained by needle aspiration.
Other Diagnostic Tests
• Complete blood count often performed for assessment of potential infection.
• Consider magnetic resonance imaging if suspicious of underlying osteomyelitis.
FIGURE 88-4 Supine view of areas where pressure sore formation tends to occur.
Drug and Nondrug Management
Prevention is the single most important aspect in the management of pressure sores. Skin surveillance and frequent repositioning (i.e., pressure reduction) are key in preventing pressure sores.76,81Prevention is far easier and less costly than the intensive care necessary for the healing and eventual closure of pressure sores. Of primary importance, then, is the ability to identify patients who are at high risk so that preventive measures may be instituted. Relief of pressure through proper positioning, and periodic repositioning, is probably the single most important factor in preventing pressure sore formation. Relief for a period of only 5 minutes once every 2 hours is believed to give protection against pressure sore formation.75,78–81 Repositioning seated patients every 15 to 60 minutes is also recommended.28,81Pressure relief devices such as mattresses or overlays filled with air, water, gel, or foam are helpful in preventing pressure sores.84 Cushions and ankle or heel protectors should also be encouraged.75,76,78 Skin care and prevention of soilage are also important, with the intent being to keep the surface relatively free of moisture. Patients with problems of incontinence should be cleaned frequently, and efforts should be made to keep the involved areas dry.75
The medical approach to the treatment of pressure sores depends on the stage of the disease. Medical management generally is indicated for lesions that are of moderate size and relatively shallow depth (stage 1 or 2 lesions) and are not located over a bony prominence. Depending on their location and severity, from 30% to 80% of these ulcers will heal without an operation. Surgical intervention is almost always necessary for ulcers that extend through superficial layers or into bone (stage 3, stage 4, and unstageable lesions).77
The goal of therapy is to clean and decontaminate the ulcer in order to permit formation of healthy granulation tissue that promotes wound healing or prepares the wound for an operative procedure. The main factors to be considered for successful topical therapy (local care) are (a) relief of pressure, (b) debridement of necrotic tissue as needed, (c) wound cleansing, (d) dressing selection, and (e) prevention, diagnosis, and treatment of infection.28,75,76,78,81,82
Relief of pressure is important once a pressure sore has developed. The same repositioning methods and pressure-reducing devices used for preventive care also apply to treatment.28,76
The goals of debridement and cleansing measures are removal of devitalized tissue and reduction of bacterial contamination, which can slow granulation time and impede healing.28,75,76 Debridement can be accomplished by surgical, mechanical, or chemical means.28,75,76 Surgical debridement rapidly removes necrotic material from the wound and is recommended for urgent situations (e.g., cellulitis and sepsis).78–80 Mechanical debridement generally involves wet-to-dry dressing changes. Saline-soaked gauze is applied to the wound; after drying, the gauze is removed and with it any adherent necrotic tissue. Other effective mechanical therapies include hydrotherapy (use of the whirlpool [Hubbard tank] to remove necrotic tissue and debris), wound irrigation, and dextranomers (beads placed in the wound to absorb exudate and bacteria).28,76 Chemical debridement includes enzymatic and autolytic agents. Enzymatic debridement involves application of topical debriding agents to remove devitalized tissue. This method is recommended for patients who cannot tolerate surgery or are in a long-term care or home setting.28,76 Autolytic debridement involves the use of synthetic dressings that allow devitalized tissue to self-digest via enzymes present in wound fluids. Autolytic debridement is contraindicated in the treatment of infected pressure sores.28
Pressure sore wounds should be cleaned with normal saline.76 No cleansing solution or technique has demonstrated greater efficacy on healing.84 Cleansing agents that are cytotoxic, such as povidone–iodine, iodophor, sodium hypochlorite solution, hydrogen peroxide, and acetic acid, should be avoided.75,76,79,80 Many of these agents destroy granulation tissue and impair healing. Many different types of dressings are available for pressure sores.28 Wound dressing materials should keep the wound moist, allow free exchange of air, act as a physical barrier to bacteria, and prevent physical damage.28,76 Controlled studies of the various types of wound dressings have shown no significant differences in healing outcomes.70 Occlusive dressings (hydrocolloid, such as DuoDERM™ or Tegaderm™) and transparent dressings (e.g., 3M Tegaderm™) are not recommended for infected wounds.28,76 If occlusive dressings are used, any infection should be controlled or the dressing frequency increased.
A 2-week trial of topical antibiotics (silver sulfadiazine or triple antibiotic) may be considered for a clean ulcer that is not healing or is producing a moderate amount of exudate despite appropriate care.79Systemic treatment of pressure ulcers is generally for infections associated with bacteremia, sepsis, cellulitis, or osteomyelitis.79,80 Empiric therapy for infected pressure sores or associated infectious complications should cover MRSA, anaerobes, enterococci, and more resistant gram-negative bacteria such as Pseudomonas (see Table 88–5).76 Thereafter, antibiotics should be guided by results from appropriately collected cultures.
Other nonpharmacologic approaches to shortening the healing time have included the use of hyperbaric oxygenation, hydrotherapy, high-frequency/high-intensity sound waves, and electrotherapy.79,80,84Electrical stimulation is the only adjunctive therapy that is proven effective.79,80 Various comorbid conditions (diabetes mellitus, smoking, peripheral vascular disease, malnutrition) may impair wound healing. Eliminating or optimizing these factors is recommended, although studies have not demonstrated benefit.28,75,76,81–83
Evaluation of Therapeutic Outcomes
With appropriate wound care and antimicrobial therapy, infected pressure sores can heal. A reduction in erythema, warmth, pain, and other signs and symptoms should be seen in 48 to 72 hours.
ANIMAL AND HUMAN BITE WOUNDS
Approximately half the population in the United States will be bitten by either an animal or another human sometime during their lifetimes.85,86 Animal bites (typically from dogs or cats) are common causes of injury, particularly to children, and are associated with significant risk of infection without prompt attention to appropriate management. Likewise, human bite wounds are often deceptively severe and frequently require aggressive management to reduce the risk of infectious complications. If left untreated, soft-tissue infection and osteomyelitis may occur, possibly requiring extensive debridement or amputation.
Epidemiology
Dog bites account for approximately 60% of all animal bite wounds requiring medical attention.85 The Centers for Disease Control and Prevention reports that 386,000 individuals seek emergency room attention for dog bites annually.86 The rate of dog bite–related injuries is highest in children aged 5 to 9 years. Most dog bites are to the extremities,85 but the majority of bites to children less than 5 years of age are to the face and neck.86 Cat bites are the second most common cause of bite wounds in the United States, accounting for up to 20% of all animal bites.85 Cat bites occur most commonly on the upper extremities and face, with most injuries reported in women and the elderly.85,87 Human bites are the third most frequent type of bites requiring medical attention.
Infection rates after dog and cat bites are estimated at 20% overall. However, infection may occur in up to 30% to 80% of serious cat bites, a rate more than double those seen with dog bites.87 Also, bite wounds to the hands become infected in 30% to 40% of cases.85 Patients at greatest risk of acquiring animal bite–related infection have had a puncture wound (usually to the hand), have not sought medical attention within 8 hours of the injury, and are older than 50 years of age.85,87
Infected human bites can occur as bites from the teeth or from blows to the mouth (clenched-fist injuries). Bites by others can occur to any part of the body, but most often involve the hands. Infectious complications occur in 10% to 50% of patients with human bites.87
Etiology
Infections in bite wounds are caused predominantly by mouth flora from the animal or human biter, and from the victim’s own skin flora (Table 88–12).85,87–91 Most infections are polymicrobial, with a median of three to nine bacterial isolates per culture.85,87–91 Pasteurella is the most frequent isolate from both dog and cat bites. Pasteurella multocida is part of the normal oral flora of up to 90% of cats; dog bites more commonly involve P. canis(approximately 26% of infections).87,89 Tularemia (Pasteurella tularensis) and cat scratch disease (Bartonella henselae) have also have been transmitted by cat bites, while rabies is associated with dog bites, particularly in developing countries.89,90,97 Human bite wounds are notable for potential involvement of Eikenella corrodens in approximately 30% of infections.
TABLE 88-12 Bacterial Isolates from Infections in Animal and Human Bite Wounds85,87–90
Pathophysiology
The potential for infection from an animal bite is great owing to the pressure that can be exerted during the bite and the vast number of potential pathogens that make up the normal oral flora.85,87–90 Cats’ teeth are slender and extremely sharp. Their teeth easily penetrate into bones and joints, resulting in a higher incidence of septic arthritis and osteomyelitis.85,87–90 Although a dog’s teeth may not be as sharp, they can exert a pressure of 200 to 450 lb/in2(~1,400 to 3,100 kPa) and therefore result in a serious crush injury with much devitalized tissue.85,87–90 In addition, the polymicrobic (aerobic and anaerobic) nature of animal bites provides a synergistic relationship, thus making an infection harder to eradicate.88
Human bites generally are more serious and more prone to infection than animal bites, particularly clenched-fist injuries.88 While the force of a punch may sever a tendon or nerve or break a bone, it most often causes a breach in the capsule of the metacarpophalangeal joint, leading to direct inoculation of bacteria into the joint or bone.88,90 When the hand is relaxed, the tendons carry bacteria into deeper spaces of the hand, resulting in more extensive infection.88,90
TREATMENT
Desired Outcomes
The goals of therapy of bite wounds, whether caused by animals or humans, are twofold: to provide effective prophylaxis against infection, when appropriate, and to achieve rapid eradication of established infection and prevent further complications. Effective treatment of bite wounds includes avoidance of unnecessary antimicrobials that contribute to increased resistance, and minimizing toxicities and cost of therapy.
Management of Bite Wounds
Bite wounds should be irrigated thoroughly with a copious volume of sterile water or saline, and the wound washed vigorously with soap or povidone–iodine in order to reduce the bacterial count in the wound.87,90 Surgical debridement and immobilization of the affected area is often required in dog and human bites associated with more extensive tissue injury. Clinical failures due to edema have occurred despite appropriate antibiotic therapy.85Therefore, it is important to stress to patients that the affected area should be elevated for several days or until edema has resolved. In the case of animal bites, an immunization history of the animal should be obtained. It is also important for the patient’s tetanus immune status to be determined. Because transmission of viruses (HIV, herpes, hepatitis B and C) is a possibility with human bites, information about the biter is important. Although the possibility of acquiring HIV through saliva alone is believed to be unlikely, the presence of virus-containing blood in the saliva makes disease transmission possible.92,93 Bite victims exposed to blood-tainted saliva may be offered antiretroviral chemoprophylaxis, but each case should be individually assessed based on the potential for significant exposure and potential risks and benefits of antiretroviral therapy.92,93
CLINICAL PRESENTATION
General
Animal bites:
• Only general wound care is required for most patients with dog bites who present early (<12 hours) after injury; infection is more likely in patients presenting late (≥12 hours) after injury.
Human bites:
• Most patients with clenched-fist injuries present for medical care after infection is already established.
Symptoms
• Patients often seek medical care for infection-related complaints (i.e., pain, purulent discharge, and swelling) at the site of the injury.
• Wounds often have a purulent discharge, and decreased range of motion may be present.
Signs
• Erythema, swelling, and clear or purulent discharge at site of infected wound.
Animal bites:
• If P. multocida is present, a rapidly progressing cellulitis is observed within 24 to 48 hours of initial injury.
• Fever is uncommon.
• Adenopathy or lymphangitis is uncommon.
Human bites:
• Lymphadenopathy is common.
• In clenched-fist injuries, edema may limit the ability of tendons to glide in their sheaths, thereby limiting a joint’s range of motion.
Laboratory Tests
• Samples for bacterial cultures (aerobic and anaerobic) should be obtained from infected wounds.
• Wounds seen less than 8 hours or more than 24 hours after injury that show no signs of infection may not need to be cultured.
• White blood counts should be monitored for resolution of infection if initially elevated.
Other Diagnostic Tests
• Radiographic evaluation should be performed if damage to a bone or joint is suspected.
Patients with clenched-fist injuries should be seen by a specialist in hand care to evaluate for penetration into the synovium, joint capsule, and bone.16,88 Primary closure for human bites generally is not recommended. Tetanus toxoid and antitoxin may be indicated.
All patients with human bite injuries should receive prophylactic antibiotic therapy for 3 to 5 days due to high infection risk (Table 88–4).90,91,93 Prophylactic antimicrobial agents should be given as soon as possible to all patients, regardless of the appearance of the wound, unless it can be documented that the wound does not involve hands, feet, or joints and penetrates no deeper than the epidermis.16,79,90
The role of prophylactic antimicrobial therapy for early, noninfected animal bite wounds remains controversial.85,87,88,90 However, prophylactic antibiotics are generally advised unless the wound is very superficial and easily cleaned,85,87,88 or unless the patient presents 72 hours or more after injury and has no clinical signs of infection.88 Prophylaxis is more strongly recommended in patients with moderate to severe wounds, or if the wound is considered at high risk for infection. Factors associated with increased risk include the following: age greater than 50 years, immunocompromised patients, chronic comorbidities (e.g., diabetes), cat bites, deep puncture wounds beyond the epidermal layer, and wounds to the face, hands, feet, genitalia, or over joint surfaces.87,88,90 A 3- to 5-day course of prophylactic antibiotics is recommended.16,87,88,90
Clinical Controversy…
The question whether to provide antibiotic prophylaxis for animal bites, particularly those caused by dogs, remains controversial. Controlled studies have not definitively shown reduction in infection rates through use of prophylactic antibiotics for uninfected bites; however, such studies are few and recommendations are largely based on uncontrolled data. Recommendations in favor of antibiotic prophylaxis are based on the relatively high infection rates and the potential for severe complications such as osteomyelitis and septic arthritis. If used, prophylaxis should be kept to a short duration (i.e., 3 to 5 days) to minimize concerns related to cost, adverse effects, and antibiotic resistance.
Empiric antibiotics for treatment of established infection of bite wounds should be directed at a variety of aerobic and anaerobic flora (Table 88–4). Amoxicillin–clavulanic acid is most commonly recommended for oral outpatient therapy due to excellent activity against all likely pathogens, including Pasteurella and Eikenella.16,85,87,88,90 Alternative oral agents include moxifloxacin or doxycycline alone, or trimethoprim–sulfamethoxazole, levofloxacin, ciprofloxacin, or a second- or third-generation cephalosporin in combination with metronidazole or clindamycin to provide activity against oropharyngeal anaerobes. Although the combination of penicillin VK plus dicloxacillin has been recommended traditionally for treatment of bite wounds, its use has become less common in favor of other alternatives. Failure to provide adequate initial treatment of bite wounds results in treatment failures and increased need for hospitalization for parenteral antibiotics.16,85,87–90
Hospitalization for minor wounds is unnecessary if surgical repair of vital structures has not been performed. Patients with clenched-fist or other serious bite injuries and severe resultant infection may be considered for IV antibiotics. Treatment options for patients requiring IV therapy include β-lactam–β-lactamase inhibitor combinations (ampicillin–sulbactam, piperacillin–tazobactam), second-generation cephalosporins with antianaerobic activity (e.g., cefoxitin), and ertapenem.16,90 The combination of doxycycline or a fluoroquinolone with metronidazole or clindamycin may be used in patients with severe β-lactam allergies. The length of antimicrobial therapy depends on the severity of the injury/infection. However, therapy should generally be continued from 7 to 14 days.16,85,88–90
Tetanus does not occur commonly after dog bites; however, it is possible. If the immunization history of a patient with anything other than a clean, minor wound is unknown, tetanus–diphtheria (TD) toxoids should be administered.94,95 Both TD toxoids and tetanus immune globulin should be administered to patients who have never been immunized.90,96
Because the rabies virus can be transmitted via saliva, rabies may be a potential complication of a bite. When the symptoms of rabies develop after a bite, the prognosis for survival is poor. Roughly 3% of rabies cases documented in animals were in dogs (the most frequent vectors are skunks, raccoons, and bats).97,98 In the United States, recommendations for postexposure prophylaxis after a dog bite depend on the health of the dog. If the animal is healthy and able to be observed for a 10-day period, active prophylaxis is only required if the dog develops signs of rabies.85,87,97 If the dog is known or suspected to be rabid, postexposure procedures should be initiated; current treatment guidelines should be consulted for appropriate management recommendations.97,98 Outside of the United States, locally applicable guidelines such as those from the World Health Organization should be consulted.99
Evaluation of Therapeutic Outcomes
Evaluation of treatment for either animal or human bites should follow the same general guidelines. Bite victims treated on an outpatient basis with oral antimicrobials should be followed up within 24 hours by either phone or office visit.16 Hospitalization or change to IV therapy should be considered if the infection has progressed. For hospitalized patients with no improvement in signs and symptoms following 24 hours of appropriate therapy, surgical debridement may be needed. Physical therapy may be needed to improve complications such as residual joint stiffness and loss of function, particularly after human bites involving clenched-fist injuries.
PERSONALIZED PHARMACOTHERAPY
Desired treatment outcomes for the various types of SSTIs described in this chapter are achieved through close monitoring and frequent patient assessment, including judicious evaluation of antimicrobial therapies. SSTIs are challenging in that cultures are often not performed due to the unavailability of easily obtained culturable specimens and the low yield of common culturing techniques. Empiric antibiotic selection based on most likely pathogens is an effective strategy in less severe infections such as erysipelas, impetigo, and furuncles. However, treatment of more severe infections such as cellulitis, DFI, and necrotizing fasciitis should be individualized based on properly obtained culture specimens and documented pathogens and susceptibilities whenever possible. Aggressive antimicrobial use must be balanced against unnecessary administration of drugs that may lead to increased antimicrobial resistance, adverse effects, and cost. Proper evaluation of an individual patient’s severity of infection and risk of complications allows for selection of appropriate antimicrobials for treatment of infection and selection of appropriate treatment settings (e.g., inpatient vs. outpatient), both of which may allow for the most cost-effective therapy.
ABBREVIATIONS
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