Abstract Rationale Pleural infections, such as complicated parapneumonic effusions and empyema, cause significant morbidity and healthcare burden. The MIST2 trial established twice-daily (BID) administration of 10 mg tissue plasminogen activator (tPA) and 5 mg dornase alfa (DNase) as the standard for intrapleural fibrinolytic therapy. However, optimal dosing frequency and total dosing remain unclear. This retrospective study evaluated clinical outcomes of once-daily (QD) versus BID administration of reduced-dose intrapleural fibrinolytics (5 mg tPA/5 mg DNase) in the treatment of pleural infections. Methods We conducted a retrospective cohort study at a single academic center, evaluating adults treated with reduced-dose intrapleural fibrinolytics between April 2019 and August 2024. Patients were grouped by dosing frequency (QD vs BID). The primary outcome was treatment success, defined as survival to discharge without surgery within 30 days. Secondary outcomes included pleural fluid output, length of stay (LOS), mortality, inflammatory markers, radiographic improvement, and adverse events (blood transfusion, recurrence, pain, therapy cessation, or hydropneumothorax). Chi-square tests were used for categorical parameters and Mann-Whitney U tests for continuous variables. Results Fifty-two patients met inclusion criteria (30 QD, 22 BID). Treatment success was comparable (QD 56.7%, BID 63.6%; p = 0.61). Total pleural fluid drained during treatment was higher in the BID group (median 1938 mL vs 1320 mL; p = 0.013). Similarly, fluid drained 24 hours after day 3 (BID 490 mL vs QD 210 mL; p = 0.020) and total drainage since chest tube insertion (BID 2565.5 mL vs QD 1867.5 mL; p = 0.040) were significantly greater in the BID group. Day 1 fever occurred only in the BID group (18.2% vs 0%; p = 0.030). Interestingly, LOS trended higher in the BID group, however, was not statistically significant (median 10.5 vs 7.0 days; p = 0.128). Adverse events, mortality, and radiographic improvement were not significantly different between groups. Conclusion Once-daily reduced-dose intrapleural tPA/DNase achieved comparable treatment success, safety, and key clinical outcomes (including surgery rates, LOS, and mortality) when compared to the standard BID regimen, despite lower drainage volumes. These findings suggest that once-daily dosing may be an effective and practical alternative for managing pleural infections, especially in settings with limited resources or logistical constraints. Further prospective studies are warranted to confirm these results and guide future treatment strategies. This abstract is funded by: None
Javed et al. (Fri,) studied this question.