Streptokinase in the Management of Empyema: A Randomized Trial
Abstract & Commentary
Robert Muder, MD, Hospital Epidemiologist, Pittsburgh VA Medical Center, Pittsburgh, Section Editor, Hospital Epidemiology, is Associate Editor for Infectious Disease Alert
Synopsis: Although streptokinase is widely used in the management of pleural infection, a large, randomized, controlled trial showed no benefit in terms of mortality, need for surgery, or hospital stay.
Source: Maskell NA, et al. UK Controlled Trial of Intrapleural Streptokinase for Pleural Effusion. N Engl J Med. 2005;352:865-874.
Intrapleural streptokinase is frequently used in the treatment of pleural space infection, despite lack of conclusive evidence of its efficacy. Maskell and colleagues conducted a multicenter, randomized trial of intrapleural streptokinase treatment for pleural infection. Enrolled patients had pleural fluid that was grossly purulent, that was positive for bacteria by culture or gram stain, or had a pH less than 7.2 with clinical evidence of infection. Patients received tube drainage and antimicrobial therapy, as prescribed by the attending physician. Patients were randomized to receive 250,000 IU of streptokinase or placebo twice daily for 6 doses. Primary end points were mortality and need for surgery at 3 months. Secondary end points included death and need for surgical drainage at 12 months, length of hospital stay, residual radiographic abnormality at 3 months, and dynamic lung volumes at 3 months.
Maskell et al enrolled 430 evaluable patients, of whom 208 received streptokinase and 222 received placebo. Follow-up to the primary end points was available for 99% of patients. Treatment and placebo patients were well matched for age, sex, coexisting illness, pleural fluid characteristics, and microbial etiology. There was no difference between the 2 groups in either primary end points, which occurred in 31% of patients receiving streptokinase and 27% of patients receiving placebo (RR, 1.14; 95% CI, 0.85-1.54, P = .43). When analyzed separately for death and need for surgery, there were no differences between the 2 groups. Subgroup analysis failed to reveal any significant differences for subgroups of patients, including those with purulent fluid and those without evidence of loculation. There were no differences between treatment of placebo groups for any of the secondary end points.
Comment by Robert Muder, MD
Use of streptokinase in the treatment of pleural infection is common. It is endorsed by at least 2 published practice guidelines.1,2 However, the efficacy of intrapleural streptokinase has not been verified by adequate clinical trials of sufficient power to detect significant benefit in the clinically important endpoints of mortality and need for surgery. This study is notable for the large number of patients enrolled and for the clinical significance of the end points, namely survival and need for operative intervention. There was no clinically or statistically significant difference between patients receiving streptokinase and those receiving placebo.
Patients who received streptokinase produced high titres of anti-streptokinase antibodies. As Maskell et al point out, this would limit the future use of streptokinase in these patients, should they require it for acute myocardial infarction—a use of streptokinase that has significant clinical benefit. Further, the average wholesale cost of the dose of streptokinase used in this study is approximately $550.
Thus, the routine use of streptokinase for pleural infection does not appear to be warranted. Antimicrobial therapy and tube drainage are adequate treatment for the majority of patients with intrapleural infection.
References
- Davies CWH, et al. BTS Guidelines for the Management of Pleural Infection. Thorax. 2003;58 (Suppl 2):18-28.
- Colice GL, et al. Medical and Surgical Treatment of Parapneumonic Effusions: An Evidence Based Guideline.Chest. 2000;118:1158-1171.
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