UMEM Educational Pearls

Empiric antimicrobial treatment for necrotizing soft tissue infections (NSTIs) should include coverage of a wide range of pathogens including Staphylococcus spp, Streptococcus spp, anaerobic bacteria and gram negative bacteria. Treatment should also include an agent that suppresses toxin production by group A Streptococcus (GAS), with the Infectious Diseases Society of America (IDSA) guidelines recommending clindamycin plus penicillin for treatment of GAS causing necrotizing fasciitis and toxic shock syndrome. A typical empiric NSTI regimen would be vancomycin plus clindamycin plus piperacillin-tazobactam. 

Linezolid is an appealing alternative to clindamycin and vancomycin, as it has anti-toxin effects via inhibition of exotoxin expression, potent in vitro activity against Streptococcus spp, activity against methicillin-resistant Staphylococcus aureus (MRSA), and potential for less adverse effects than clindamycin plus vancomycin. Several recent studies have looked at using linezolid in lieu of clindamycin plus vancomycin when treating NSTIs.

Published Studies:

Dorazio and colleagues published a retrospective single center study compared 62 matched pairs of patients who received linezolid vs. clindamycin plus vancomycin as part of their NSTI treatment.

• Primary outcome was mortality at 30 days and secondary outcomes were the rates of C. difficile infection and rates of acute kidney injury (AKI). 
• No statistically significant difference in any primary or secondary outcomes noted, although there was a trend towards more AKI with clindamycin plus vancomycin versus linezolid 
  • AKI rates: 9.68% in the clindamycin + vancomycin group vs 1.61% in the linezolid group; HR 6 [95% CI .73-276]

Heil and colleagues published a retrospective single center cohort study examined patients who received either linezolid (n = 29) or clindamycin (n = 26) for treatment invasive soft tissue infection or necrotizing fasciitis with GAS isolated from blood and/or tissue.

• There was no difference in any primary or secondary outcomes, which included inpatient mortality, duration of vasopressor requirement, hospital length of stay, rates adverse drug events and change in Sequential Organ Failure Assessment score from baseline through 72 hours of hospitalization.

Lehman and colleagues published a retrospective single center study compared patients who received linezolid (n = 21) versus clindamycin plus vancomycin (n = 28) in addition to gram-negative and anaerobic coverage for empiric treatment of NSTIs.

• The primary outcome of duration of MRSA-active therapy was 2.9 days in the linezolid group versus 3.9 days in the vancomycin group (p = 0.04)
• The only secondary outcome that reached statistical significance was new-onset AKI, with a rate of 38.1% in the vancomycin plus clindamycin group versus 0% in the linezolid group (0%)

Bottom Line:

When added to an agent with good gram negative and anaerobic coverage (i.e. piperacillin-tazobactam), linezolid may be a more viable option for coverage of MRSA and GAS toxin production during empiric NSTI treatment when compared to clindamycin plus vancomycin. This is largely due to a more favorable side effect profile.

References

1. Stevens, Dennis L et al. “Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 59,2 (2014): e10-52. 
2. Dorazio, Joshua et al. “Clindamycin Plus Vancomycin Versus Linezolid for Treatment of Necrotizing Soft Tissue Infection.” Open forum infectious diseases vol. 10,6 ofad258. 11 May. 2023
3. Heil, Emily L et al. “Comparison of Adjuvant Clindamycin vs Linezolid for Severe Invasive Group A Streptococcus Skin and Soft Tissue Infections.” Open forum infectious diseases vol. 10,12 ofad588. 24 Nov. 2023
4. Lehman, Alexandra et al. “Impact of Empiric Linezolid for Necrotizing Soft Tissue Infections on Duration of Methicillin-Resistant _Staphylococcus aureus_-Active Therapy.” Surgical infections vol. 23,3 (2022): 313-317.