RESUMO
We report an unusual presentation of pulmonary embolism (PE) where a 58-year-old man first developed symptoms of community-acquired pneumonia. Despite antibiotic therapy, he remained unwell with rising inflammatory markers, general malaise and persistent cough. He developed stony dull percussion and absent breath sounds to his left mid to lower zones. Serial chest x-rays showed progression from lobar consolidation to a large loculated left-sided pleural collection. CT chest showed left-sided lung abscess, empyema and bronchopleural fistulation. Incidentally, the scan revealed acute left-sided PE and its distribution corresponded with the location of the left lung abscess and empyema. The sequence of events likely started with PE leading to infarction, cavitation, abscess formation and bronchopleural fistulation. This patient was managed with a 6-month course of rivaroxaban. After completing 2 weeks of intravenous meropenem, he was converted to 4-week course of oral co-amoxiclav and metronidazole and attained full recovery.
Assuntos
Abscesso/diagnóstico por imagem , Antibacterianos/uso terapêutico , Fístula Brônquica/diagnóstico por imagem , Infarto/diagnóstico por imagem , Doenças Pleurais/diagnóstico por imagem , Pneumonia/tratamento farmacológico , Embolia Pulmonar/diagnóstico por imagem , Radiografia Torácica , Abscesso/tratamento farmacológico , Abscesso/patologia , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Fístula Brônquica/tratamento farmacológico , Fístula Brônquica/fisiopatologia , Progressão da Doença , Quimioterapia Combinada , Humanos , Infarto/tratamento farmacológico , Infarto/fisiopatologia , Masculino , Meropeném , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Doenças Pleurais/tratamento farmacológico , Doenças Pleurais/fisiopatologia , Pneumonia/diagnóstico por imagem , Pneumonia/fisiopatologia , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/fisiopatologia , Rivaroxabana/uso terapêutico , Tienamicinas/uso terapêutico , Resultado do TratamentoRESUMO
Endogenous active plasminogen activator inhibitor 1 (PAI-1) was targeted in vivo with monoclonal antibodies (mAbs) that redirect its reaction with proteinases to the substrate branch. mAbs were used as an adjunct to prourokinase (single-chain [sc] urokinase [uPA]) intrapleural fibrinolytic therapy (IPFT) of tetracycline-induced pleural injury in rabbits. Outcomes of scuPA IPFT (0.25 or 0.0625 mg/kg) with 0.5 mg/kg of mouse IgG or mAbs (MA-33H1F7 and MA-8H9D4) were assessed at 24 hours. Pleural fluid (PF) was collected at 0, 10, 20, and 40 minutes and 24 hours after IPFT and analyzed for plasminogen activating (PA), uPA, fibrinolytic activities, levels of total plasmin/plasminogen, α-macroglobulin (αM), mAbs/IgG antigens, free active uPA, and αM/uPA complexes. Anti-PAI-1 mAbs, but not mouse IgG, delivered with an eightfold reduction in the minimal effective dose of scuPA (from 0.5 to 0.0625 mg/kg), improved the outcome of IPFT (P < 0.05). mAbs and IgG were detectable in PFs at 24 hours. Compared with identical doses of scuPA alone or with IgG, treatment with scuPA and anti-PAI-1 mAbs generated higher PF uPA amidolytic and PA activities, faster formation of αM/uPA complexes, and slower uPA inactivation. However, PAI-1 targeting did not significantly affect intrapleural fibrinolytic activity or levels of total plasmin/plasminogen and αM antigens. Targeting PAI-1 did not induce bleeding, and rendered otherwise ineffective doses of scuPA able to improve outcomes in tetracycline-induced pleural injury. PAI-1-neutralizing mAbs improved IPFT by increasing the durability of intrapleural PA activity. These results suggest a novel, well-tolerated IPFT strategy that is tractable for clinical development.