An anaerobic environment limits the microbicidal capacity of polymorphonuclear neutrophils (PMNs). To augment PMN killing under these conditions, the characteristics and mechanisms of clindamycin uptake by human PMNs were studied. The peak intracellular concentration of clindamycin was approximately 40 times greater than the extracellular concentration. Clindamycin uptake was rapid, saturable, and temperature-dependent. Intracellular accumulation of the drug was inhibited in acid pH, and agents that collapsed the transmembrane pH gradients also inhibited uptake. Isolated PMN lysosomes also accumulated clindamycin against a large concentration gradient, and uptake was reduced by collapsing the translysosomal membrane pH gradient. The intracellular drug was fully bioactive. These studies demonstrate that clindamycin is rapidly accumulated by PMNs, that drug uptake is related to a pH gradient, and that clindamycin appears to be lysosomotropic.

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The National Heart, Lung, and Blood Institute, along with the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases, convened a panel to develop recommendations for treatment, prevention, and research for respiratory failure from severe acute respiratory syndrome (SARS) and other newly emerging infections. The clinical and pathological features of acute lung injury (ALI) from SARS appear indistinguishable from ALI from other causes. The mainstay of treatments for ALI remains supportive. Patients with ALI from SARS who require mechanical ventilation should receive a lung protective, low tidal volume strategy. Adjuvant treatments recommended include prevention of venous thromboembolism, stress ulcer prophylaxis, and semirecumbent positioning during ventilation. Based on previous experience in Canada, infection control resources and protocols were recommended. Leadership structure, communication, training, and morale are an essential aspect of SARS management. A multicenter, placebo-controlled trial of corticosteroids for late SARS is justified because of widespread clinical use and uncertainties about relative risks and benefits. Studies of combined pathophysiologic endpoints were recommended, with mortality as a secondary endpoint. The group recommended preparation for studies, including protocols, ethical considerations, Web-based registries, and data entry systems.