Necrotizing fasciitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Other Imaging Findings | Other Diagnostic Studies

Treatment

Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Future or Investigational Therapies

Case Studies

Case#1

Overview

Necrotizing fasciitis or fasciitis necroticans, commonly known as “flesh-eating bacteria,” is a rare infection of the deeper layers of skin and subcutaneous tissues, easily spreading across the fascial plane within the subcutaneous tissue. Many types of bacteria can cause necrotizing fasciitis (eg. Group A streptococcus, Vibrio vulnificus, Clostridium perfringens, Bacteroides fragilis), of which Group A streptococcus (also known as Streptococcus pyogenes) is the most common cause.

Causes

• Drugs
  • Panitumumab

Symptoms

The infection begins locally, at a site of trauma, which may be severe (such as the result of surgery), minor, or even non-apparent. The affected skin is classically, at first, very painful without any grossly visible change. With progression of the disease, tissue becomes swollen, often within hours. Diarrhea and vomiting are common symptoms as well. Inflammation does not show signs right away if the bacteria is deep within the tissue. If it is not deep, signs of inflammation such as redness and swollen or hot skin show very quickly. Skin color may progress to violet and blisters may form, with subsequent necrosis (death) of the subcutaneous tissues. Patients with necrotizing fasciitis typically have a fever and appear very ill. More severe cases progress within hours, and the mortality rate is high, about 30%. Even with medical assistance, antibiotics take a great deal of time to react to the bacteria, allowing the infection to progress to a more serious state.

Pathophysiology

“Flesh-eating bacteria” is a misnomer, as the bacteria do not actually eat the tissue. They cause the destruction of skin and muscle by releasing toxins (virulence factors). These include streptococcal pyogenic exotoxins and other virulence factors. S. pyogenes produces an exotoxin known as a superantigen. This toxin is capable of activating T-cells non-specifically. This causes the over-production of cytokines that over-stimulate macrophages. The macrophages cause the actual tissue damage by releasing oxygen free radicals that are normally intended to destroy bacteria but are capable of damaging nearly any macromolecule they contact in the body.

Treatment

The diagnosis is confirmed by either blood cultures or aspiration of pus from tissue, but early medical treatment is crucial and often presumptive; thus, antibiotics should be started as soon as this condition is suspected. Initial treatment often includes a combination of intravenous antibiotics including penicillin, vancomycin and clindamycin. If necrotizing fasciitis is suspected, surgical exploration is always necessary, often resulting in aggressive debridement (removal of infected tissue). As in other maladies characterized by massive wounds or tissue destruction, hyperbaric oxygen treatment can be a valuable adjunctive therapy, but is not widely available. Amputation of the affected organ(s) may be necessary. Repeat explorations usually need to be done to remove additional necrotic tissue. Typically, this leaves a large open wound which often requires skin grafting. The associated systemic inflammatory response is usually profound, and most patients will require monitoring in an intensive care unit.

Antimicrobial regimen

• Necrotizing fasciitis

• 1. Mixed infections

• 1.1 Adults

• Preferred regimen (1): Piperacillin-tazobactam 3.37 g IV q6–8h AND Vancomycin 30 mg/kg/day IV q12h
• Note: In case of severe pencillin allergy, use clindamycin or metronidazole with an aminoglycoside or fluoroquinolone
• Preferred regimen (2): Imipenem-cilastatin 1 g IV q6–8h
• Preferred regimen (3): Meropenem 1 g IV q8h
• Preferred regimen (4): Ertapenem 1 g IV q24h
• Preferred regimen (5): Cefotaxime 2 g IV q6h AND Metronidazole 500 mg IV q6h
• Preferred regimen (6): Cefotaxime 2 g IV q6h AND Clindamycin 600–900 mg IV q8h

• 1.2 Pediatrics

• Preferred regimen (1): Piperacillin-tazobactam 60–75 mg/kg/dose of the Piperacillin component IV q6h AND Vancomycin 10–13 mg/kg/dose IV q8h
• Note: Severe pencillin allergy, use clindamycin or metronidazole with an aminoglycoside or fluoroquinolone)
• Preferred regimen (2): Meropenem 20 mg/kg/dose IV q8h
• Preferred regimen (3): Ertapenem 15 mg/kg/dose IV q12h for children 3 months-12 years
• Preferred regimen (4): Cefotaxime 50 mg/kg/dose IV q6h AND Metronidazole 7.5 mg/kg/dose IV q6h
• Preferred regimen (5): Cefotaxime 50 mg/kg/dose IV q6h AND Clindamycin 10–13 mg/kg/dose IV q8h

• 2. Streptococcus infection

• 2.1 Adults

• Preferred regimen: Penicillin 2–4 MU IV q4–6h AND Clindamycin 600–900 mg IV q8h
• Note: In case of severe pencillin allergy, use vancomycin, linezolid, quinupristin/dalfopristin, daptomycin

• 2.2 Pediatric

• Preferred regimen: Penicillin 0.06–0.1 MU/kg/dose IV q6h AND Clindamycin 10–13 mg/kg/dose IV q8h
• Note: In case of severe pencillin allergy, use vancomycin, linezolid, quinupristin/dalfopristin, daptomycin

• 3. Staphylococcus aureus

• 3.1 Adults

• Preferred regimen (1): Nafcillin 1–2 g IV q4h
• Note: In case of severe pencillin allergy, use vancomycin, linezolid, quinupristin/dalfopristin, daptomycin
• Preferred regimen (2): Oxacillin 1–2 g IV q4h
• Preferred regimen (3): Cefazolin 1 g IV q8h
• Preferred regimen (4): Vancomycin 30 mg/kg/day IV q12h
• Preferred regimen (5): Clindamycin 600–900 mg IV q8h

• Pediatrics

• Preferred regimen (1): Nafcillin 50 mg/kg/dose IV q6h
• Note: In case of severe pencillin allergy, use vancomycin, linezolid, quinupristin/dalfopristin, daptomycin
• Preferred regimen (2): Oxacillin 50 mg/kg/dose IV q6h
• Preferred regimen (3): Cefazolin 33 mg/kg/dose IV q8h
• Preferred regimen (4): Vancomycin 15 mg/kg/dose IV q6h
• Preferred regimen (5): Clindamycin 10–13 mg/kg/dose IV q8h (bacteriostatic; potential cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in MRSA)

• 4. Clostridium species

• 4.1 Adults

• Preferred regimen: Clindamycin 600–900 mg IV q8h AND Penicillin 2–4 MU IV q4–6h

• 4.2 Pediatrics

• Preferred regimen: Clindamycin 10–13 mg/kg/dose IV q8h AND Penicillin 0.06-0.1 MU/kg/dose IV q6h

• 5. Aeromonas hydrophila

• 5.1 Adults

• Preferred regimen (1): Doxycycline 100 mg IV q12h AND ciprofloxacin 500 mg IV q12h

• Preferred regimen (2): Doxycycline 100 mg IV q12h AND ceftriaxone 1 to 2 g IV q24h

• 5.2 Pediatrics

• Not recommended for children but may need to use in life-threatening situations

• 6. Vibrio vulnificus

• 6.1 Adults

• Preferred regimen (1): Doxycycline 100 mg IV q12h AND ceftriaxone 1 g IV qid
• Preferred regimen (2): Doxycycline 100 mg IV q12h AND cefotaxime 2 g IV tid

• 6.2 Pediatrics

• Not recommended for children but may need to use in life-threatening situation

Prognosis

This disease is one of the fastest-spreading infections known, as it spreads easily across the fascial plane within the subcutaneous tissue. For this reason, it is popularly called the “flesh-eating disease,” and, although rare, it became well-known to the public in the 1990s. Even with today's modern medicine, the prognosis can be bleak, with a mortality rate of approximately 25% and severe disfigurement common in survivors.

Other bacterial strains

In February 2004, a rarer but even more serious form of the disease has been observed in increasing frequency, with several cases found specifically in California. In these cases, the bacterium causing it was a strain of Staphylococcus aureus (i.e. Staphylococcus, not Streptococcus as stated above) which is resistant against methicillin, the antibiotic usually used for treatment (see Methicillin-resistant Staphylococcus aureus for details).

“Super Strep” appeared in Ohio and Texas in 1992 and 1993 and was contracted by approximately 140 people. It took under 12 hours to incapacitate most and caused 3 days of very high fevers. The death rate in 1993 was reported to be 10%, with a majority of the victims having mild to severe brain damage.

See also

• Mucormycosis, a rare fungal infection which can present like necrotizing fasciitis
• Toxic shock syndrome

References

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