Intravenous Immunoglobulin G Therapy in Streptococcal Toxic Shock Syndrome: A European Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P=.02) and 3 (P=.04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P=.03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.

Group A streptococcal toxic shock syndrome associated with pelvic peritonitis following diagnostic hysteroscopy in a healthy woman: a case report and review

“…Case-control studies on the use of immunoglobulin preparations in streptococcal TSS show a reduction in mortality from 67% to 34% [1,2,11]. Despite the absence of randomised controlled trials, most experts advocate the use of immunoglobulins in severely shocked patients-preferably early in the disease course [1,2,12].…”

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

“…Six papers were secondarily extracted via peer review of abstracts 98, 102, 103, 104, 105, 106. The all‐cause mortality rate in the IVIG group was significantly lower than that of the control group ( n  = 6, risk ratio: 0.7 [95% CI: 0.56–0.95]) and the ICU mortality rate was also significantly lower ( n  = 1, risk ratio: 0.71 [95% CI: 0.60–0.84]).…”

Therapeutic targets in necrotizing soft tissue infections

“…This resulted in 40% of patients in the placebo arm (vs 16% in the interventional arm) receiving IVIG before inclusion, thereby reducing the contrast between both arms and potentially blunting any beneficial effect related to IVIG. Third, the dose of IVIG administered (25 g daily for 3 days) was lower than in previous studies (for instance, 1 g/kg of body weight on day 1 and 0.5 g/kg on days 2 and 3 in the study by Darenberg et al [15]), and was thus possibly suboptimal. Nevertheless, in spite of these limitations, the study by Madsen et al [16] provides valuable data and represents a big step forward in an evidence-based approach of NSTIs.…”

“…In this setting, the efficacy of intravenous immunoglobulins (IVIG) remains debated [10]. Several observational studies have indeed reported conflicting results [11][12][13][14] and one small randomized controlled trial [15] was prematurely terminated because of slow patient recruitment after including 21 patients (10 in the IVIG group and 11 in the placebo group). This study demonstrated a significant reduction in the SOFA score at days 2 and 3 in patients of the IVIG group as compared to others, as well as a significant increase in plasma neutralizing activity against superantigens.…”