Necrotizing Soft-Tissue Infections: An Orthopaedic Emergency

Adam Lee, MD; Addison May, MD, FACS, FCCM; William T. Obremskey, MD, MPH


J Am Acad Orthop Surg. 2019;27(5):e199-e206. 

In This Article

Epidemiology and Risk Factors

NSTIs are a heterogeneous group of rare, limb, and life-threatening processes caused by a variety of bacterial pathogens that may affect patients at any age or health status. An estimated 1,000 cases per year occur with an increasing incidence in the United States.[3] In an analysis of Centers for Disease Control and Prevention data of invasive group A Streptococcus, a common infecting agent in NSTIs, an estimated 10 to 13,000 cases occur each year with a mortality of 29% in cases that involve NSTI.[4] NSTI has a predilection for the aging, infirm population, but all age ranges can be infected. However, up to 40% of patients have no known risk factors.[5,6] Diabetes mellitus is the most prevalent risk factor and is present in up to 71% of infections.[6–11] Intravenous drug abuse is another common predisposing factor in as many as 43% of patients with NSTI.[11] Other associations include smoking, trauma, prior methicillin-resistant Staphylococcus aureus (MRSA) infection, chronic hepatitis C, HIV/AIDS, chronic illness, increasing age, NSAID use, and exposure to persons infected with invasive group A Streptococcus.[6,8,11–14] Using the National Surgical Quality Improvement Program data, a risk calculator found that seven independent variables correlated with mortality including age greater than 60 years, functional status, requiring dialysis, American Society of Anesthesiologists class 4 or higher, emergent surgery, septic shock, and low platelet count.[15]

The infections can be grouped broadly into polymicrobial and monomicrobial subtypes. Polymicrobial NSTIs account for approximately 75% of cases making it the most common presentation.[16,17] These polymicrobial infections are commonly associated with risk factors such as diabetes, peripheral vascular disease, recent surgery, trauma, or immunocompromised hosts. These infections tend to be a combination of aerobic and anaerobic bacteria. A variety of bacterial isolates have been cultured from this type, which tends to arise from a chronic source such as a diabetic foot ulcer.[18] Table 1 lists common organisms cultured in the polymicrobial subtype. The remainder of infections are monomicrobial in nature.

These monomicrobial infections are primarily caused by group A streptococcal infection, other β-hemolytic strep, MRSA, and in the fresh water setting Aeromonas hydrophila. Clostridial species are the most prevalent single organism infecting agents and account for a higher incidence of limb loss and mortality.[16] In cases of saltwater or consumption of oysters/cirrhosis Vibrio vulnificans.[19] These patients presenting with monomicrobial infections may not have the same identifiable risk factors as those described with polymicrobial infections. In the setting of the monomicrobial infection, group A streptococcal infection is likely related to skin injury or hematogenous strep from pharyngeal infection or colonization.

All NSTIs begin with an inoculum of bacteria at the site of infection. Bacteria may be transferred from direct contacts or via skin or nasopharyngeal colonization.[6,14] Wounds ranging from small skin abrasions to large traumatic lacerations may serve as a point of entry. Individuals can be asymptomatic carriers on the skin or mucosal surfaces where transient bacteremia distributes the pathogen to a source of tissue damage to initiate an infection. Cases of NSTI being caused by skin breakdown in a poorly padded splint, external-fixation pin sites, and IV sites are reported.[12,13] Once the infecting agent has gained access into the host, the disease is perpetuated by bacterial virulence factors that facilitate rapid spread and systemic toxicity. Although the exact mechanisms of rapid spread and tissues destruction likely vary between species and are not fully characterized, these factors are theorized to contribute to local tissue progression through tissue ischemia, enzymatic degradation, cell lysis, and a systemic response by the release of toxins into the circulation.[18,20,21] Bacterial inoculation causes the secretion of local cytokines which activates platelets. In the presence of activated white cells, the platelets clump leading to microvascular occlusion. This occlusion in turn disrupts the cutaneous blood supply and lymphatic channels inciting a local hypoxia and cytokine release resulting in cellular dysfunction and death. The local ischemia and subsequent necrosis limits access of antibiotics and humoral response to the affected region and leads to progressive cutaneous nerve damage causing severe pain early in the disease to local anesthesia when nerve endings have died.[21] Invasive group A Streptococcus has a high expression of one such factor called exotoxin that is seen in most strains that produce invasive infections.[20,21] Another common infecting pathogen, MRSA, produces panton-valentine leukocidin, a toxin commonly seen in necrotizing infections that causes muscle necrosis.[8] Toxin production and the host's response to the toxins are potential targets for intervention in patients with these difficult infections.