Adjunctive therapeutic plasma exchange as rescue therapy in septic shock due to streptococcal infection: a multicentric retrospective cohort study

Abstract Background Septic shock due to streptococcal infection (SRSS) carries a high mortality and is in part driven by toxin-mediated inflammation. Therapeutic plasma exchange (TPE) may modulate the septic host responses by removing injurious mediators while replenishing protective plasma factors, but data specific to SRSS is lacking. We performed a retrospective, multicenter, cohort study of adults with SRSS between 2012–2024. Methods Patients from three tertiary care ECMO centers in Germany and Switzerland were included requiring (i) streptococcal spp. detected in blood or primary focus and (ii) septic shock according to sepsis-3 definition. Adjunctive TPE with fresh frozen plasma at the intensivists` discretion was compared with standard of care (SOC). The primary outcome was 90-day-hospital mortality. Key exploratory outcomes included 24-h kinetics of vasoactive-inotropic score(VIS) and lactate, as well as SRSS-related complications. Results were validated in a 1:1 propensity score–matched (PSM) cohort. Results Of 149 patients, 31 (20.8%) received TPE and 118 (79.2%) SOC. TPE patients were more severely ill at baseline: SOFA 14 (IQR 13.5–15) vs 11 (IQR 8–14) (p<0.001); lactate 6.4 vs 2.8 mmol/L (p<0.001); Vasoactive-Inotropic-Score (VIS) 70.7 vs 23.3 (p<0.001); more frequent invasive ventilation (87% vs 65%), VV-ECMO (36% vs 19%), and renal replacement therapy (96.8% vs 52.5%). Overall, 90-day hospital mortality was 27.5% (TPE 29.0%, SOC 27.1%). Following SOFA-score adjustment, TPE was associated with lower mortality risk (aHR 0.67 [95% CI 0.5–0.9]; p=0.009). This was validated in the PSM cohort, with an aHR for TPE of 0.44 (95% CI 0.3–0.8); p=0.002. Mixed-effects modeling demonstrated a significant VIS reduction only with TPE (fixed effect 24-h change, p=0.027) and improved lactate decrease versus SOC. Conclusion In SRSS, adjunctive TPE was associated with rapid hemodynamic stabilization and improved lactate kinetics. Exploratory adjusted survival analyses support prospective evaluation of TPE in SRSS.