Tom Schaberg

Antibiotic treatment and factors influencing short and long term outcomes of acute exacerbations of chronic bronchitis

Background: The MOSAIC study compared moxifloxacin with three standard antibiotic regimens in patients with Anthonisen type 1 acute exacerbations of chronic bronchitis (AECB). Further exploratory analyses were performed to identify prognostic factors of short and long term clinical outcomes and their value for clinical research. Methods: Outpatients aged ⩾45 years were screened between AECB episodes, randomised to treatment upon presenting with an AECB, assessed 7–10 days after study treatment, and followed monthly until a new AECB or for up to 9 months. Logistic regression assessed the predictive factors for clinical cure (return to pre-AECB status) and clinical success (cure or improvement), and a stepwise Cox regression model time to a composite event (failure of study treatment, new AECB, or further antibiotic treatment for AECB). Results: In multivariate analyses, clinical cure was positively influenced by treatment with moxifloxacin (odds ratio (OR) 1.49; 95% CI 1.08 to 2.04) while cardiopulmonary disease (OR 0.59; 95% CI 0.38 to 0.90), forced expiratory volume in 1 second (FEV1) <50% predicted (OR 0.48; 95% CI 0.35 to 0.67), and ⩾4 AECBs in the previous year (OR 0.68; 95% CI 0.48 to 0.97) predicted a poorer outcome. For clinical success, treatment with moxifloxacin had a positive influence (OR 1.57; 95% CI 1.03 to 2.41) while cardiopulmonary disease (OR 0.41; 95% CI 0.25 to 0.68) and use of acute bronchodilators (OR 0.50; 95% CI 0.30 to 0.84) predicted a poorer outcome. The occurrence of the composite event was influenced by antibiotic treatment (hazard ratio (HR) 0.82; 95% CI 0.68 to 0.98), age ⩾65 years (HR 1.22; 95% CI 1.01 to 1.47), FEV1<50% predicted (HR 1.27; 95% CI 1.05 to 1.53), ⩾4 AECBs in previous year (HR 1.63; 95% CI 1.34 to 1.99), and acute bronchodilator use (HR 1.48; 95% CI 1.17 to 1.87). For the composite event the beneficial effect of moxifloxacin was primarily seen in patients aged ⩾65 years. Conclusion: Despite selection of a homogeneous population of patients with chronic bronchitis, between group differences relating to antibiotic treatment could still be confounded by factors related to medical history, severity of disease, and use of concomitant medications. The design of future clinical trials should take these factors into account.

Phenotypically Activated γδ T Lymphocytes in the Peripheral Blood of Patients with Tuberculosis

Surface molecules with the potential relevance for resistance against Mycobacterium tuberculosis were investigated. The expression of lymphocyte function antigen-1, very late antigen (VLA)-4, l-selectin, intercellular adhesion molecule (ICAM)-1, major histocompatibility complex class II, Fas, and CD40 on alphabeta T cells, gammadelta T cells, NK cells, and monocytes of healthy donors and patients with tuberculosis were analyzed. A high activation status of gammadelta T cells and increased levels of soluble ICAM-1 in plasma of patients with tuberculosis versus healthy individuals was detected. Tuberculosis patients with and without an underlying systemic disease could be segregated by differential expression of VLA-4 and ICAM-1 on gammadelta T cells and on monocytes. The composition of peripheral blood mononuclear cells varied slightly, whereas the proportion of monocytes decreased significantly in patients with tuberculosis, compared with healthy controls. The activation phenotype of peripheral gammadelta T cells in patients with tuberculosis emphasizes the role of these T cells in controlling the inflammatory process during tuberculosis and perhaps other microbial infections.

NOSOCOMIAL PNEUMONIA IN THE CRITICAL CARE UNIT

Nosocomial pneumonia poses a major threat to the recovery of patients receiving mechanical ventilation. In addition, nosocomial pneumonia is often difficult to diagnose. This article examines the extent of the threat and some of the difficulties facing the critical care physician when diagnosing nosocomial pneumonia.

Evidence for a platelet-activating factor receptor on human alveolar macrophages.

In this report we demonstrate evidence which strongly suggests that human alveolar macrophages possess receptor for the platelet activating factor (PAF). We investigated the effects of PAF by measuring (a) the intracellular free calcium concentration [Ca2+]i, using the fura-2 method in single isolated cells and (b) the production of superoxide anion. PAF increased [Ca2+]i in a dose-dependent manner (EC50 = 1 x 10(-8) M), whereas lyso-PAF had no effect. The initial increase of [Ca2+]i was followed by a slow decrease to a sustained elevation of [Ca2+]i significantly above basal values. While the initial rise in [Ca2+]i was only slightly reduced in Ca(2+)-free medium (1 mM EGTA), the sustained phase was totally abolished. The sustained calcium increase was also blocked after preincubation of AM with the calcium-channel blocker nitrendipine. PAF increased the production of superoxide anion (O2-) by human alveolar macrophages in a dose- dependent manner. The effects of PAF on [Ca2+]i and (O2-) could be blocked by the PAF-specific antagonist WEB 2086 dose dependently, indicating a receptor-mediated event.

Phenotypically activated gammadelta T lymphocytes in the peripheral blood of patients with tuberculosis.

Surface molecules with the potential relevance for resistance against Mycobacterium tuberculosis were investigated. The expression of lymphocyte function antigen-1, very late antigen (VLA)-4, l-selectin, intercellular adhesion molecule (ICAM)-1, major histocompatibility complex class II, Fas, and CD40 on alphabeta T cells, gammadelta T cells, NK cells, and monocytes of healthy donors and patients with tuberculosis were analyzed. A high activation status of gammadelta T cells and increased levels of soluble ICAM-1 in plasma of patients with tuberculosis versus healthy individuals was detected. Tuberculosis patients with and without an underlying systemic disease could be segregated by differential expression of VLA-4 and ICAM-1 on gammadelta T cells and on monocytes. The composition of peripheral blood mononuclear cells varied slightly, whereas the proportion of monocytes decreased significantly in patients with tuberculosis, compared with healthy controls. The activation phenotype of peripheral gammadelta T cells in patients with tuberculosis emphasizes the role of these T cells in controlling the inflammatory process during tuberculosis and perhaps other microbial infections.