Clindamycin Improves Outcomes in Necrotizing Fasciitis due to Group A Streptococcus.

Clindamycin Improves Outcomes in Necrotizing Fasciitis due to Group A Streptococcus.

Watkins Richard R

Hospital Medicine Alert

2017

2017-05

Despite aggressive surgical and medical therapy (i.e., debridement and potent intravenous antibiotics), necrotizing fasciitis (NF) remains a devastating infection with a mortality rate of 15-36%. Recent Infectious Diseases Society of America (IDSA) guidelines recommend using clindamycin in the treatment of NF, although strong scientific evidence is lacking. Therefore, Andreoni and colleagues aimed to determine whether clindamycin improves outcomes in NF by modulating virulence factors of clindamycin-susceptible and clindamycinresistant strains of invasive Group A Streptococcus (GAS) in vitro and using a mouse model. The investigators injected either a clindamycinsusceptible or a clindamycin-resistant GAS clinical isolate into the flanks of mice, and then treated them with either low-dose clindamycin, high-dose clindamycin, or saline. The mice were sacrificed on day 3 post-inoculation, and the size of the resulting skin lesions and their bacterial counts were measured. Also, biopsy material from a patient with NF of the arm who underwent multiple debridements (on days 0, 2, and 4) was prepared in the same fashion as the mouse tissue. This patient was treated with intravenous ceftriaxone 2 g daily and clindamycin 900 mg qid. Treatment with clindamycin in the mice that were infected with clindamycin-susceptible strains significantly reduced skin lesion sizes, but the bacterial burden was the same compared to the untreated animals. Interestingly, the animals infected with clindamycin-resistant strains who received clindamycin also had smaller skin lesions but reduced bacterial counts. When mice were injected with a clindamycin dose lower than the MIC of the infecting strain, the severity of the clinical manifestations was similar or slightly less compared to the untreated ones. In both the clindamycin-susceptible and clindamycin-resistant groups, GAS virulence factors DNase and SLO were inhibited by clindamycin. However, the in vitro model showed sub-inhibitory clindamycin concentrations caused upregulation of GAS virulence factors in both the clindamycin-susceptible and clindamycin-resistant GAS isolates. In the debrided tissue from the patient with NF, clindamycin concentration in the necrotic tissue was 10 times higher than the MIC of the infecting GAS strain. The bacterial load in the necrotic tissue was 106 CFU/g compared to 103 in the apparently adjacent healthy tissue. DNase activity was greater in the tissue with the higher bacterial counts and, by the second debridement (day 2), was undetectable.

Debridement; Treatment Outcomes; Streptococcus; Clindamycin – Therapeutic Use; Fasciitis; Necrotizing – Drug Therapy; Necrotizing – Therapy

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