In this episode of Hospital Medicine Unplugged, we take on pleural empyema in the hospital—recognize fast, drain early, cover smart, escalate on time—because delays and resistant bugs kill. We set the stage: hospital-acquired empyema hits harder than community-acquired (~47% vs ~17% mortality), driven by MRSA and Pseudomonas/Gram-negatives, poly-microbial mixes, and sicker hosts. Translation: broader empiric antibiotics, earlier drainage, lower threshold for surgery. Diagnosis you can’t miss: persistent fever, pleuritic pain, failure to improve on pneumonia therapy, and a new/large effusion. Ultrasound first (bedside, maps loculations, guides the tap), contrast CT to define split pleura/loculation or abscess, then diagnostic thoracentesis. Call it complicated when pus or pleural pH <7.20 (often with low glucose, high LDH)—that’s a drain now moment. Empiric antibiotics—match the source:• Community-acquired: ceftriaxone (or similar) + anaerobic coverage (e.g., metronidazole) or ampicillin/sulbactam.• Hospital-acquired/post-procedural: vancomycin + anti-Pseudomonal β-lactam (piperacillin–tazobactam or cefepime). Keep anaerobe coverage.• Avoid aminoglycosides in the pleural space; no intrapleural antibiotics. De-escalate to cultures but don’t drop anaerobes unless ruled out. Drainage—the make-or-break:• Small-bore, US-guided chest tube early for pus, low pH, large/loculated effusions.• If output stalls or loculations persist, go to intrapleural enzyme therapy (IET): tPA + DNase—combo beats monotherapy and cuts OR need.• Escalate to VATS for failure of medical therapy, thick peel, trapped lung, or advanced (organizing) stage. Early VATS shortens LOS and complications; thoracotomy for the rare, refractory cases or when VATS isn’t feasible. Risk tools & triage: RAPID score (Renal, Age, Purulence, Infection source, Dietary/albumin) spotlights patients who need aggressive upfront therapy and early surgical consult. Layer in SOFA/qSOFA if septic. What delays look like—and how to avoid them: atypical elders, sedation blunting exam, “treating pneumonia harder” without tapping the chest, and weekend/after-hours imaging gaps. Counterpunch with a protocol that auto-triggers US → thoracentesis → tube if pH <7.2/pus and pre-authorizes IET/VATS when drainage is inadequate. Supportive care that moves the needle:• Nutrition (hypoalbuminemia worsens outcomes), glucose control, DVT prophylaxis, analgesia that preserves ventilation.• Daily output + imaging reassessment; tube position checks and flush protocols.• ID + Pulm + Thoracic Surgery at the table from day one. Micro pearls: hospital bugs = MRSA, Pseudomonas, Enterobacterales, Enterococcus, anaerobes; community bugs = Streptococci (incl. anginosus group), S. aureus, anaerobes. Inoculate pleural fluid into blood culture bottles to boost yield; polymicrobial = think aspiration/anaerobes. We close with the Empyema Bundle:(1) Flag high-risk (HAP, malignancy, postop, diabetes, renal disease, high RAPID).(2) US at bedside → diagnostic tap on any moderate/large or complex effusion.(3) Empiric antibiotics matched to source (MRSA/Pseudomonas in HAP) + keep anaerobes.(4) Early small-bore tube for pus/pH <7.2/large locules.(5) tPA + DNase if drainage stalls within 24–48 h.(6) Early VATS for non-responders or organizing stage—don’t wait for day 5–7 failure.(7) Daily goal checks (fever, WBC/CRP, output, aeration) and culture-driven de-escalation.(8) Nutrition/DVT/oral care & lung expansion to speed recovery and cut readmits. Bottom line: source-control early, cover the right bugs, and escalate decisively. That’s how you beat hospital-acquired empyema—and keep lungs expanding, not organizing.