Methods: We conducted a retrospective evaluation to compare outcomes in MICU patients with severe sepsis and septic shock who received MER for ≥72h administered as EI 1 g over 3 h Q8H with a total daily dose (TDD) 3g (1/2015-1/2017) vs SI 500 mg over 30 min Q6H with TDD 2 g (1/2012-1/2014). ICU mortality and clinical response (CR) were evaluated as endpoints. CR was defined by improvement in signs and symptoms of infection.
Results: Of 667 patients who received MER, 148 were included (EI n=52, SI n=96). Age, weight, comorbidities (malignancy 31 vs 33%, P=0.8; chronic liver disease [CLD] 15 vs 23%, P=0.4), severity of illness (median mAPACHE II 18 vs 19, P=0.6; SOFA 5 vs 6, P=0.5) and vasopressors’ use (75 vs 79%, P=0.5) were comparable between EI and SI groups. Serum creatinine (SCr) was lower in EI group (median 1.1 vs 1.4 SI, P=0.05). Gram-negative (GN) pathogens (MIC≤0.25 mg/mL, 94%) were identified in 44% of patients in EI vs 38% in SI group, P=0.5. MER TDD was higher in EI group (3 vs 1.5g SI, P<0.01) with no difference in use of combination therapy (64 vs 46%, P=0.06). ICU mortality (median time to death 9 days) was lower (19 vs 37%, P=0.047) and CR was higher (83 vs 46%, P=0.038) in EI vs SI group. Total pressor days on MER were shorter (2 vs 3 days, P<0.01) and white blood cell normalization rate was higher (87% vs 51%, P<0.01) in EI vs SI group, whereas there was no difference in days of mechanical ventilation, duration of MER therapy and ICU stay. After adjusting for SCr, severity of illness scores, combination therapy and SI group in a multivariate model, CLD (OR 3.3, 95% CI 1.36-7.77, P=0.008) and lower MER TDD (OR 1.8, 95% CI 1.09-2.98, P=0.02) were independent predictors of ICU mortality.
Conclusion: In this cohort of MICU patients with severe sepsis or septic shock and low MIC of GN pathogens, there was improved mortality and CR in MER EI group. Our finding of potential benefit of higher MER TDD in these patients warrants further exploration in a prospective study.
D. Altshuler, None
J. Papadopoulos, None
V. Pham, None
Y. Dubrovskaya, None