Skin and Soft Tissue Infections: The New Surgical Infection Society Guidelines

Abstract

Background:

The Surgical Infection Society Guidelines for the treatment of complicated skin and soft tissue infections (SSTIs) were published in October 2009 in Surgical Infections, and an overview of these guidelines was provided at the Thirtieth Annual Meeting of the Society. A summary of this overview is provided.

Methods:

Review of relevant papers related to complicated SSTIs published between 1966 and 2008 with graded recommendations and summations of general epidemiology and recommendations.

Results:

The frequency of SSTI has increased over the past decade, predominately because of an increase in infections caused by community-acquired methicillin-resistant Staphylococcus aureus. Drug resistance is increasing among all pathogens. A total of 61 graded recommendations were made in the complete guidelines, 28 of which are presented here, separated into those for non-necrotizing and necrotizing infections.

Conclusions:

Appropriate antibiotic therapy should be provided in complicated SSTIs. Early diagnosis and treatment of necrotizing infections is paramount, as time to therapy alters morbidity and mortality rates.

The Surgical Infection Society (SIS) Guidelines for the treatment of complicated skin and soft tissue infections (SSTIs) were published in Surgical Infections (Vol. 10, Number 5, 2009) [1]. The guidelines are a product of the Therapeutics and Guidelines Committee of the SIS. The Committee formed an expert panel of members, and individual sub-topics were assigned. The MEDLINE and Cochrane databases and article references were searched for publications between the years 1966 and 2008 pertinent to SSTIs. The search terms were skin or soft tissue infection, necrotizing soft tissue infections (fasciitis, cellulitis, and myositis), skin and skin structure infections, and infections caused by specific pathogens. Evidentiary tables were constructed and recommendations formulated based on a “GRADE” format (Table 1) [2]. Individual sub-topics and recommendations were drafted, combined into a single document by the expert panel and submitted to the Therapeutics and Guidelines Committee for review and revision. The resulting document was evaluated by two independent reviewers appointed by the SIS Executive Council, revisions were made, and the document was reviewed again. The new document was submitted to the full Council for review and final approval. The resulting document was then submitted to Surgical Infections for consideration through the normal peer review process. Final revisions were made and the final guidelines accepted for publication.

Table 1.

Grading of Recommendations

Grade of recommendation/description	Benefit vs. risk and burdens	Methodological quality of supporting evidence	Implications
1A/Strong recommendation, high-quality evidence	Benefits clearly outweigh risk and burdens or vice versa	RCTs without important limitations or overwhelming evidence from observational studies	Strong recommendation; can apply to most patients in most circumstances without reservation
1B/Strong recommendation, moderate-quality evidence	Benefits clearly outweigh risk and burdens or vice versa	RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies	Strong recommendation; can apply to most patients in most circumstances without reservation
1C/Strong recommendation, low-quality or very low-quality evidence	Benefits clearly outweigh risk and burdens or vice versa	Observational studies or case series	Strong recommendation but may change when higher-quality evidence becomes available
2A/Weak recommendation, high-quality evidence	Benefits balanced closely with risks and burden	RCTs without important limitations or overwhelming evidence from observational studies	Weak recommendation; best action may differ depending on circumstances or patients' or societal values
2B/Weak recommendation, moderate-quality evidence	Benefits balanced closely with risks and burden	RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies	Weak recommendation; best action may differ, depending on circumstances or patients' or societal values
2C/Weak recommendation, low-quality or very low-quality evidence	Uncertainty in the estimates of benefits, risks, and burden; benefits, risk, and burden may be balanced closely	Observational studies or case series	Very weak recommendations; other alternatives may be equally reasonable

RCT = randomized controlled trial.

The final SIS Guidelines contain 61 total graded recommendations. However, because of the lack of adequate studies and data, only four level “A” recommendations could be made, whereas 49 level “C” recommendations were made. When considering risk vs. benefit, 52 strong (1) and 9 weak (2) recommendations were made. The guidelines deal exclusively with those SSTIs considered “complicated” under the U.S. Food and Drug Administration (FDA) classification [3]. Most SSTIs, managed by surgeons are complicated. The FDA definition of complicated SSTIs includes those that are deep or necrotizing, usually requiring surgical intervention, including infected ulcers, infected burns, and major abscesses; that occur in patients with specific major co-morbidities; and that necessitate hospitalization. Thus, the definition excludes all superficial skin infections without necrosis and those abscesses that can be treated by incision and drainage alone. The expert panel specifically chose the term “skin and soft tissue infection” rather than the FDA term “skin and skin structure infection,” as necrotizing infections may involve the deep fascia and muscle, tissues not considered part of the skin structure (Fig. 1). For all randomized studies of therapeutic agents in SSTIs, necrotizing infections are specifically excluded. Thus, recommendations are extrapolated from studies of non-necrotizing infections.

FIG. 1.

Focus of Surgical Infection Society skin and soft tissue infection guidelines.

Table 2 provides an outline of the complete guideline contents. The total document is 32 pages in length and contains 344 references. For this summary, abbreviated recommendations are presented in two categories: Non-necrotizing and necrotizing infections. For non-necrotizing infections, the epidemiology of complicated SSTI and the treatment of non-necrotizing cellulitis and complicated abscesses are discussed. For necrotizing infections, epidemiology, diagnosis, and treatment are discussed with a focus on rapidly progressing necrotizing SSTIs.

Table 2.

Guideline Contents

Methods

Definitions of skin and soft tissue infections

Epidemiology of skin and soft tissue infections

• Necrotizing infections

• Nosocomial and chronic infections

• Bite and water-associated infections

• Community-acquired methicillin-resistant Staphylococcus aureus infections

Treatment of skin and soft tissue infections

• Non-necrotizing cellulitis

º Antibiotic therapy

º Therapy of bite wounds

• Complicated abscesses

• Necrotizing skin and soft tissue infections

º Diagnosis

º Therapeutic approach

º Surgical therapy

º Antibiotic therapy

• Rapidly progressive soft tissue infections

º Rationale for use of protein synthesis-inhibiting agents

º Staphylococcal toxic shock syndrome

º Community-acquired methicillin-resistant S. aureus

º Group A streptococcal infections

º Clostridial infections

º Vibrio infections

• Diabetic food infections

º Microbiology

º Choice of antibiotic regimen

º Topical agents

º Osteomyelitis

º Surgical interventions

Adjunctive therapies

• Extracorporeal plasma treatment

• Hyperbaric oxygen

• Intravenous immunoglobulin

The epidemiology of complicated SSTIs has changed somewhat in the last decade. As shown in Figure 2, the frequency of SSTI has increased significantly since the late 1990s, predominately because of an increase in infections caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA) [4]. Staphylococcus aureus remains the most common pathogen isolated from complicated SSTIs. Table 3 provides the rank order of bacterial pathogens isolated from SSTI [5]. These data come from the SENTRY Program, which includes 5,800 consecutive patients admitted to hospitals in Canada and 32 states in the U.S. and includes both community- and hospital-acquired infections. In these data, S. aureus accounts for greater than 40% of all isolates, with Pseudomonas aeruginosa being the second most common isolate at 11%. Over the period from 1998 to 2004, the number of SSTI pathogens resistant to at least one antibiotic increased for S. aureus, Enterococcus spp., P. aeruginosa, Escherichia coli, and Klebsiella spp., with nearly 50% of the S. aureus isolates now being resistant to methicillin [5]. The epidemiology of surgical site infections (SSIs) is slightly different, with an even greater shift toward gram-positive pathogens (S. aureus, coagulase-negative staphylococci, and Enterococcus spp.—greater than 50% of isolates) [6]. In this population of patients, MRSA isolates now equal or exceed methicillin-sensitive strains of Staphylococcus. Graded treatment recommendations for complicated, non-necrotizing SSTIs are presented in Table 4.

FIG. 2.

Increasing frequency of skin and soft tissue infections. Reprinted with permission from Pallin DJ, Egan DJ, Pelletier AJ, et al. Increased U.S. emergency department visits for skin and soft tissue infections, and changes in antibiotic choices, during the emergence of community-associated methicillin-resistant Staphylococcus aureus. Ann Emerg Med 2008;51:291–298.

Table 3.

Rank Order of Bacterial Pathogens Producing Skin and Soft Tissue Infections in North America, 1998–2004

Rank	Pathogen	No. of isolates (% of total)
1	Staphylococcus aureus	2,602 (44.6)
2	Pseudomonas aeruginosa	648 (11.1)
3	Enterococcus spp.	542 (9.3)
4	Escherichia coli	422 (7.2)
5	Enterobacter spp.	282 (4.8)
6	Klebsiella spp.	248 (4.2)
7	β-hemolytic Streptococcus	237 (4.1)
8	Proteus mirabilis	166 (2.8)
9	Coagulase-negative Staphylococcus	161 (2.8)
10	Serratia spp.	125 (2.1)

Table 4.

Graded Recommendations for Complication, Non-Necrotizing Skin and Soft Tissue Infections

Non-necrotizing cellulitis: Erysipelas and cellulitis	Complicated abscesses
For moderate to severe infections, parenteral penicillin agent of choice (1C)	Simple abscesses may respond to incision and drainage alone (2B)
Treatment failures may occur if β-lactam agents are used alone in severe cases (1C)	More complex abscesses and those with substantial cellulitis require adjuvant antibiotic therapy (1C)
Protein synthesis-inhibitory agents alone or in combination with cell wall-active agents; e.g., clindamycin or a macrolide, should be given in severe cases (1B/C)	Inadequate response to therapy should prompt evaluation of the adequacy of drainage (1C)
Increasing macrolide resistance among streptococci introduces concern about the value of these drugs (1C)	Empiric antibiotic therapy should be directed toward the most likely pathogens (1B)
Other regimens that may be considered are antistaphylococcal penicillins, cefazolin, and ceftriaxone (2B/C)	Agents covering community-acquired MRSA should be considered in most settings (1B)
	Treatment of suspected polymicrobial infections should include coverage of enteric gram-negative and anaerobic pathogens (1B)

MRSA = methicillin-resistant Staphylococcus aureus.

Alphanumerics in parenthesis refer to grading (see Table 1).

Necrotizing SSTIs are discussed separately for several reasons. These infections are greater in severity and may involve a different spectrum of pathogens than non-necrotizing infections. Because of the severity and rapidity of progression, establishing an accurate diagnosis and instituting timely appropriate antibiotic therapy and surgical debridement is of much greater importance. Unfortunately, no randomized or large, well-designed non-randomized studies exist to help establish therapy of necrotizing SSTIs. The overall mortality rate for necrotizing SSTI remains significant (∼24% overall), ranging from 9%–73% in 67 studies published between 1980 and 2008 [7]. Because of the severity and specific pathogenicity, these infections frequently involve deeper layers of tissue, including the deep dermis, subcutaneous fat, fascia, and muscle.

Necrotizing infections may be divided into two categories: Those caused by a mixture of pathogens and those involving a single more virulent pathogen that have rapidly progressive courses. Necrotizing SSTIs caused by mixed pathogens are more common and typically arise from an inciting source that may have been indolent, including peri-rectal infections, colonic pathology, intravenous drug use, trauma, chronic diabetic ulceration, and SSIs. Such mixed infections involve an average of four organisms and typically spread along the fascia and fascial planes where the blood supply is tenuous [8]. In contrast, infections that are rapidly progressive involve pathogens that are more virulent, typically producing exotoxins that contribute significantly to the pathogenesis of the infection. These infections are characterized by rapid clinical deterioration and fast spread through tissues. Fortunately, such infections are rare, as they have a high mortality rate. Both gram-positive and gram-negative pathogens may cause infections of this nature, the most common being Group A Streptococcus, Clostridium spp., community-acquired MRSA, Vibrio spp., Aeromonas hydrophilia, and Pasteurella spp.

Table 5 includes the graded recommendations for the diagnosis and treatment of necrotizing SSTI. Delays in diagnosis contribute to delays in appropriate antibiotic and surgical therapy, leading to greater morbidity and a higher mortality rate. There are several signs and clinical findings that are fairly specific for necrotizing infection, but most occur late in the course of disease and are not highly sensitive. Thus, a high index of suspicion is mandatory, and in the presence of specific findings, exploration is warranted.

Table 5.

Graded Recommendations for the Diagnosis and Treatment of Necrotizing Skin and Soft Tissue Infections

Diagnosis
• Delays in diagnosis increase both the morbidity and the mortality rate (1C)
• The presence of gas on soft tissue imaging is specific for necrotizing infections and more sensitive than physical examination (1C)
• Computed tomography and magnetic resonance imaging improve the detection of soft tissue gas (1B)
• Radiographic findings of tissue fluid and edema are neither sensitive nor specific for necrotizing infection (1C)
• Clinical features strongly suggestive of necrotizing infection (1C)	Laboratory values predictive of the presence of necrotizing infection (1C)
1. pain disproportionate to the findings on physical examination	1. white blood cell count >14 × 10⁹/L
2. tense edema	2. serum sodium concentration <135 mmol/L
3. bullae	3. blood urea nitrogen concentration >15 mg/dL
4. skin ecchymosis/necrosis
5. cutaneous anesthesia
6. systemic toxicity
7. progression despite antibiotic therapy
Treatment
• Early appropriate antibiotic coverage of inciting pathogens (1C)
• Timely surgical debridement improves outcome (1C)
• Adequate surgical debridement of involved tissue improves outcome (1C)
• Frequent re-evaluation or return to the operating room within 24 h should be undertaken to ensure adequacy of debridement and lack of progression (1C)
Antibiotic therapy
• Empiric antibiotic therapy should be directed toward the likely pathogens (1C)
• Likely pathogens differ depending on the clinical setting, inciting pathophysiology, and previous exposure to antibiotics (1C)
• Frequently polymicrobial and may involve anaerobic and anaerobic gram-positive and gram-negative pathogens (1C)
• Assuming that relevant pathogens are covered appropriately, several single-agent regimens probably are effective, including imipenem-cilastatin, meropenem, ertapenem, piperacillin-tazobactam, ticarcillin-clavulanic acid, and tigecycline (2C)
• Numerous combinations of agents probably are equally effective in the treatment of NSTIs provided appropriate coverage of relevant pathogens is ensured (2C)
• Increasing resistance of gram-negative bacilli to ampicillin/sulbactam raises concern about the use of this agent unless local sensitivities are known (1C)
• For rapidly progressive infections, combination therapy with cell wall-active agent and protein synthesis-inhibiting agents should be used:
– Group A streptococci, Clostridium spp., community-acquired MRSA or toxic shock syndrome: Clindamycin, linezolid, or erythromycin (1C)
– Vibrio spp., Aeromonas hydrophilia, or Pasteurella spp: Tetracycline, minocycline (1C)

MRSA = methicillin-resistant Staphylococcus aureus.

See Table 1 for definitions of alphanumeric grades (in parenthesis).

Footnotes

Author Disclosure Statement

No conflicting financial interests exist.

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