What are the empiric antibiotics for necrotizing fasciitis?

From the Guidelines

Empiric antibiotic therapy for necrotizing fasciitis should include broad-spectrum coverage targeting both aerobic and anaerobic organisms, particularly group A Streptococcus and mixed flora including anaerobes, with a recommended regimen of piperacillin-tazobactam or a carbapenem, plus vancomycin or linezolid for MRSA coverage, and clindamycin to inhibit toxin production, as recommended by the 2018 WSES/SIS-E consensus conference 1. The choice of empiric antibiotics is crucial in the management of necrotizing fasciitis, as delays in appropriate treatment can significantly increase mortality.

• The initial empirical antibiotic regimen should comprise broad-spectrum drugs including anti-MRSA and anti-Gram-negative coverage, as recommended by the 2018 WSES/SIS-E consensus conference 1.
• Vancomycin treatment should be avoided in patients with renal impairment and when MRSA isolate shows a MIC for vancomycin ≥ 1.5 mg/mL, and alternative anti-MRSA agents such as daptomycin or linezolid should be considered 1.
• The choice of anti-Gram-negative treatment should be based on local prevalence of ESBL-producing Enterobacateriaceae and multidrug-resistant organisms (MDROs) non-fermenters, as recommended by the 2018 WSES/SIS-E consensus conference 1.
• De-escalation of antibiotic therapy should be based on clinical improvement, cultured pathogens, and results of rapid diagnostic tests where available, as recommended by the 2018 WSES/SIS-E consensus conference 1. Surgical debridement remains the cornerstone of treatment and should not be delayed while waiting for antibiotics to take effect.
• The antibiotic regimen should be adjusted based on culture results, typically continuing for 48-72 hours after the patient is clinically stable with no further need for surgical debridement, usually resulting in a 10-14 day total course, as suggested by the practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America 1. Clindamycin is particularly important in the regimen because it suppresses bacterial toxin production even when bacteria are no longer replicating, potentially reducing the severity of systemic inflammatory response and tissue destruction.
• Prompt surgical consultation is recommended for patients with aggressive infections associated with signs of systemic toxicity or suspicion of necrotizing fasciitis or gas gangrene, as recommended by the practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America 1.

From the FDA Drug Label

The study evaluated meropenem at doses of 500 mg administered intravenously every 8 hours and imipenem-cilastatin at doses of 500 mg administered intravenously every 8 hours. The clinical efficacy rates by pathogen are provided in Table 8 The values represent the number of patients clinically cured/number of clinically evaluable patients at the post-treatment follow-up visit, with the percent cure in parentheses (Fully Evaluable analysis set)

Empiric Antibiotics for Necrotizing Fasciitis:

• Meropenem is used for the treatment of complicated skin and skin structure infections, which may include necrotizing fasciitis.
• The clinical efficacy rates for meropenem in the treatment of complicated skin and skin structure infections are provided in the drug label.
• However, the drug label does not explicitly state the use of meropenem as an empiric antibiotic for necrotizing fasciitis.
• Based on the information provided, meropenem may be considered as an option for the treatment of complicated skin and skin structure infections, but the decision to use it as an empiric antibiotic for necrotizing fasciitis should be made with caution and considering the specific clinical scenario 2.
• The choice of empiric antibiotics should be guided by the suspected or confirmed causative pathogens and local antimicrobial resistance patterns.
• It is essential to note that necrotizing fasciitis is a severe and potentially life-threatening condition that requires prompt and aggressive treatment, including surgical intervention and antimicrobial therapy.

From the Research

Empiric Antibiotics for Necrotizing Fasciitis

• The treatment of necrotizing fasciitis requires a multifaceted approach, including surgical source control, life support, clinical monitoring, and antimicrobial therapy 3.
• Broad-spectrum coverage is advisable for polymicrobial infections, with acceptable monotherapy regimens including piperacillin-tazobactam or a carbapenem 3.
• Alternative therapies include ceftolozane-tazobactam, ceftazidime-avibactam in association with an antianaerobic agent, and new cephalosporins active against methicillin-resistant Staphylococcus aureus (MRSA) such as ceftaroline and ceftobiprole 3.
• Linezolid provides MRSA coverage and toxin inhibition, and its use as empiric treatment for necrotizing soft tissue infections has been associated with a shorter duration of MRSA-active therapy and lower incidence of new-onset acute kidney injury 4.

Specific Antibiotic Regimens

• Empiric linezolid use for necrotizing soft tissue infections has been shown to be effective and safe, with a shorter average duration of MRSA-active therapy compared to vancomycin/clindamycin 4.
• Aminopenicillin ± sulbactam in combination with clindamycin and/or metronidazole is recommended as initial calculated antibiotic treatment for necrotizing fasciitis 5.
• Antibiotics such as clindamycin, trimethoprim-sulfamethoxazole, and rifampin have been shown to be effective against community-associated MRSA isolates 6.

Considerations for MRSA-Directed Therapy

• MRSA has emerged as a significant causative agent of monomicrobial necrotizing fasciitis, particularly in endemic areas 6, 7.
• MRSA-directed antibiotic therapy should be considered when treating patients suspected of having necrotizing fasciitis in areas where community-associated MRSA infection is endemic 6, 7.