BMJ  2006;332:552 (4 March), doi:10.1136/bmj.332.7540.552

Letter

Intrapleural streptokinase for pleural infection

EDITOR—In their editorial on intrapleural streptokinase for pleural infection Bouros and Light raise several points about the results of the MIST1 trial.^{1 2}

They say that a treatment effect may have been overlooked since MIST1 enrolled a representative population of patients with pleural infection, including those with late "organised" disease. The analysis in the primary publication describing our trial result shows that this is not true.² In the online data repository, a subgroup analysis in 208 patients with a presentation history of less than 14 days (a sample about five times larger than any previous trial) in whom late stage disease is unlikely showed there was no treatment effect.

Data showing that streptokinase is unlikely to have had a therapeutic effect in the subgroup of patients with early loculated empyema is also presented in the online data repository.² No evidence of any treatment benefit was found in 318 patients with unequivocally loculated pleural fluid on chest radiography.

Our patients were not unrepresentatively old. The mean age of patients in the MIST1 trial was 60, which is in the range reported previously.^3-5

The prevalence of comorbidity in MIST1 does not imply a particularly frail population. Many of the comorbid diseases are minor (such as gastro-oesophageal reflux). A high prevalence of such symptoms is related to the care taken to describe the population accurately.

Both large and small chest tubes were used at the doctor's discretion. Which tube size was used did not predict outcome (unpublished data). An adequately powered, randomised trial is required to assess whether image guided chest tube insertion leads to better outcomes.

Patients were referred for surgery using the same criteria as outlined in the previous small (31 patients) trial.⁵

The overall result of MIST1 showed no evidence of a benefit from intrapleural streptokinase. If there are benefits in one substantial subgroup, there must be commensurate disadvantages in other subgroups to produce the overall trial result. Thus streptokinase should not be used for empyema for any subset of patients without well executed randomised trials defining patients who will benefit.

Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB nickmaskell{at}doctors.org.uk

MRC Clinical Trials Unit, London NW1 2DA

Oxford Centre for Respiratory Medicine, Oxford Radcliffe Hospital, Oxford OX3 7LJ

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Competing interests: None declared.

References

1. Bouros D, Antoniou K, Light RW. Intrapleural streptokinase for pleural infection. BMJ 2006;332: 133-4.[Free Full Text]
2. Maskell NA, Davies CW, Nunn AJ, Hedley EL, Gleeson FV, Miller R, et al. UK controlled trial of intrapleural streptokinase for pleural infection. N Eng J Med 2005;352: 865-74.[Abstract/Free Full Text]
3. Davies RJ, Triall ZC, Gleeson FV. Randomised controlled trial of intrapleural streptokinase in community acquired pleural infection. Thorax 1997:52: 416-21.[Abstract]
4. Diacon AH, Theron J, Schuurmans MM, Van de Wal BW, Bolliger CT. Intrapleural streptokinase for empyema and complicated parapneumonic effusions. Am J Resp Crit Care Med 2004;70: 49-53.
5. Bouros D, Schiza, Tzanakis N, Chalkiadakis G, Drositis J, Siafakas N. Intrapleural urokinase versus normal saline in the treatment of complicated parapneumonic effusions and empyema. Am J Resp Crit Care Med 1999;159: 37-42.[Abstract/Free Full Text]

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Relevant Article

Intrapleural streptokinase for pleural infection

Demosthenes Bouros, Katerina M Antoniou, and Richard W Light
BMJ 2006 332: 133-134. [Extract] [Full Text] [PDF]