Empiric Therapy Regimens
General recommendations and empiric therapeutic regimens for necrotizing fasciitis are outlined below, including treatment based on Gram stain results and treatment for patients allergic to penicillin. [1, 2] Although necrotizing fasciitis is most often associated with bacterial infections, zygomycosis is an uncommon cause. Of 18 such patients with zygomycotic necrotizing fasciitis recently described, 15 were immunocompetent. [3] One must take fungal and bacterial cultures early, even in immunocompetent patients so antifungal therapy can be instituted. [4] However, instituting empiric therapy for fungi is not recommended. In the case of a cobra and other snake bite, identification of the snake and use of a specific antivenin may be pivotal. [5, 6]
One should recall that severe pain is an important clinical symptom separating necrotizing infections from more superficial ones. [7] Tachycardia and elevated levels of creatine kinase, C-reactive protein, and creatinine may also suggest necrotizing fasciitis.
Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA), an emerging phenomenon, must be considered, especially in endemic areas and high-risk situations such as jails and dormitories. Accordingly, specific empiric antibiotic therapy against MRSA is necessary. [8, 9]
Hyperbaric oxygen therapy may also be used, especially if the infection is due to anaerobic organisms, although evidence to support or refute its value is lacking. [10, 11] One can consider combining appropriate intravenous antibiotic therapy with conservative surgery and hyperbaric oxygen and negative-pressure wound therapy in an effort to preserve vital tissues and control the advancing infection. [12] Negative-pressure wound therapy with vacuum-assisted closure should be considered after wound debridement to enhance clinical benefit. [13]
Injection drugs abusers are at heightened risk for skin and soft-tissue infections, including necrotizing fasciitis. Although antimicrobial therapy is important, surgical incision, drainage, and debridement of devitalized tissue are primary measures. [14] There is also a need to reduce the frequency of injection drug use, needle sharing, use of contaminated equipment, and similar risky behaviors.
Additional FDA-approved antibiotics for the treatment of acute bacterial skin and skin structure infections include oritavancin (Orbactiv), dalbavancin (Dalvance), and tedizolid (Sivextro). These agents are active against Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S aureus [MSSA, MRSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus group (includes Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), among others. For complete drug information, including dosing, see the following monographs:
Surgical intervention is the major therapeutic modality in cases of necrotizing fasciitis [15] :
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Most patients with necrotizing fasciitis should return to the operating room 24-36h after the first debridement and then daily thereafter until the surgical team finds no further need for debridement
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Antimicrobial therapy should continue for 48-72h after fever resolves, clinical improvement is evident, and no further surgical debridement is necessary
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A Gram stain and, if suggested a fungal stain, of the exudate demonstrates the presence of pathogens and can provide an early clue to the preferred treatment recommendations [1]
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If history reflects exposure to sewage-contaminated water, gram-negative coverage should be instituted for organisms such Pseudomonas and Aeromonas. [16]
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MRSA is a significant threat in soft-tissue infections, becoming identified more frequently in necrotizing fasciitis. [17]
With urogenital necrotizing fasciitis (Fournier gangrene), prior to surgical resection of necrotic tissues, patients should receive intensive intravenous fluid replacement and parenteral broad-spectrum triple antimicrobial therapy, using a third-generation cephalosporin combined with metronidazole and/ or an aminoglycoside. [18]
Sometimes, classic triple therapy may be replaced with newer groups of antibiotics, such as piperacillin-tazobactam. [18] Clindamycin suppresses toxin production and also may be used.
Use of a special dermal regeneration matrix for coverage of large soft-tissue defects with exposed tendon and/or bone may provide a valuable limb salvage option. [19]
Treatment recommendations based on Gram stain result
Treatment should be guided by local antibiograms. Early initiation of antibiotic therapy may be pivotal. [20] Studies have documented that group A Streptococcus responds better to tedizolid, a second-generation oxazolidinone antibiotic, than to linezolid. A combination of doxycycline plus either ceftriaxone or cefotaxime has been recommended for necrotizing fasciitis due to Vibrio vulnificus. [21]
Gram-positive cocci in chains:
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Penicillin 1-4 million U IV q4h or ampicillin-sulbactam 1.5-3 g IV q6-8h plus
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Clindamycin 600-900 mg IV q8h
Gram-positive rods:
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Clindamycin 600 mg IV q8h or
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Ampicillin-sulbactam 1.5-3 g IV q6h
Gram-negative rods or gram-positive cocci in clusters or mixed: [22]
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Ampicillin-sulbactam 1.5-3 g IV q6-8h plus clindamycin 600-900 mg IV q8h plus ciprofloxacin 400 mg IV q12h or
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Piperacillin-tazobactam 3.375 g IV q6-8h plus clindamycin 600-900 mg IV q8h plus ciprofloxacin 400 mg IV q12h or
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Imipenem-cilastatin 1 g IV q6-8h or
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Meropenem 1 g IV q8h or
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Ertapenem 1 g IV q24h or
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Cefotaxime 2 g IV q6h plus (metronidazole 500 mg IV q6h or clindamycin 600-900 mg IV q8h)
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Since none of the above covers MRSA, in appropriate clinical situations consider vancomycin 1 g IV q12h, daptomycin 6-10 mg/kg IV q24h, [23] or linezolid 600 mg IV q12h
Treatment recommendations for penicillin-allergic patients
See the list below:
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Clindamycin 600 mg IV q8h plus (vancomycin 15 mg/kg IV q12h or linezolid 600 mg PO or IV q12h) plus (aztreonam 1-2 g IV q6-8h or gentamicin 3-5 mg/kg/day IV in 3 divided doses or ciprofloxacin 400 mg IV q12h)
Guidelines
The Infectious Diseases Society of America has updated their guidelines for the diagnosis and management of skin and soft tissue infections. Experimental 16S-rRNA gene analysis with next-generation sequencing and bioinformatics may be utilized to identify the microbiome of necrotizing fasciitis patients when compared to that of routine culture. [24] For the full guidelines, see Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. [25, 26]
In 2018, the World Society of Emergency Surgery (WSES) and the Surgical Infection Society Europe (SIS-E) published recommendations for the management of skin and soft-tissue infections. [27]
Additionally, the University of California San Francisco (UCSF) Medical Center has issued guidelines for the management of suspected skin and soft tissue infections in adults. [28]
