Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study.

OBJECTIVE: Intravenous immunoglobulin as an adjunctive treatment in sepsis was regarded as promising by a Cochrane meta-analysis of smaller trials. In this phase III multicenter trial, we assessed whether intravenous immunoglobulin G (ivIgG) reduced 28-day mortality and improved morbidity in patients with score-defined severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Twenty-three medical and surgical intensive care units in university centers and large teaching hospitals. PATIENTS: Patients (n = 653) with score-defined sepsis (sepsis score 12-27) and score-defined sepsis-induced severity of disease (Acute Physiology and Chronic Health Evaluation II score 20-35). INTERVENTIONS: Patients were assigned to receive either placebo or ivIgG (day 0, 0.6 g/kg body weight; day 1, 0.3 g/kg body weight). MEASUREMENTS AND MAIN RESULTS: The prospectively defined primary end point was death from any cause after 28 days. Prospectively defined secondary end points were 7-day all-cause mortality, short-term change in morbidity, and pulmonary function at day 4. Six hundred fifty-three patients from 23 active centers formed the intention-to-treat group, 624 patients the per-protocol group (placebo group, n = 303; ivIgG group, n = 321). The 28-day mortality rate was 37.3% in the placebo group and 39.3% in the ivIgG group and thus not significantly different (p = .6695). Seven-day mortality was not reduced, and 4-day pulmonary function was not improved. Drug-related adverse events were rare in both groups. Exploratory findings revealed a 3-day shortening of mechanical ventilation in the surviving patients and no effect of ivIgG on plasma levels of interleukin-6 and tumor necrosis factor receptors I and II. CONCLUSIONS: In patients with score-defined severe sepsis, ivIgG with a total dose of 0.9 g/kg body weight does not reduce mortality.

[Nephrology-part 3: Urinary tract infections]. / Nephrologie-Teil 3Harnwegsinfektionen.

Urinary tract infections are one of the most common bacterial infectious diseases in humans. Depending on the localization and the effectiveness of pathogenetic factors, various clinical pictures (lower urinary tract infection, pyelonephritis, asymptomatic bacteriuria) have to be differentiated. There are virulence factors of microorganisms on the one hand and defense mechanisms on the other, which influence the manifestation and the course of disease. The process of bacterial attachment to the epithelial cells of the boundary layer, the internalization and invasion of bacteria could be important for acute and chronic disease. Disturbances of local defense mechanisms, such as increased urinary glucose concentration in diabetes or variations of Tamm-Horsfall protein and defensin levels, may influence the course of infection. On the basis of microbiological and laboratory findings as well as the results of clinical and ultrasound procedures, the decision on the therapeutic strategy should be made. There are different treatment recommendations for acute uncomplicated and complicated cases as well as for chronic diseases. Future investigations should focus on effective therapeutic options for special immunocompromised patients in relation to the microbiological aspects and defense mechanisms of the host.