The most appropriate management is to insert a small-bore pleural drain and begin piperacillin-tazobactam. Complicated parapneumonic effusion and empyema should be suspected in all patients who do not respond to appropriate antibiotic therapy for pneumonia. This patient presented with subacute onset of fever, fatigue, and worsening shortness of breath after antibiotics for pneumonia. Pleural fluid analysis is consistent with a neutrophil-predominant exudate with low pH (<7.2) and negative Gram stain. This defines a complicated parapneumonic effusion that should be drained. If pleural loculations prevent adequate drainage by a single tube, multiple tubes may be needed. Small-bore (10-14 Fr [3.3-4.7 mm]) thoracostomy tubes have been demonstrated to be adequate for most patients with pleural infection and are associated with increased patient comfort.

Large-bore thoracostomy tubes have not demonstrated any advantage over small-bore thoracostomy tubes in the drainage of pleural effusion and are associated with increased patient discomfort.

Some patients with a complicated parapneumonic effusion may respond to appropriate antibiotic therapy alone; however, in most cases simultaneous drainage of the effusion speeds clinical recovery. Empirically selected antibiotics must provide adequate coverage for anaerobic organisms that are common in patients with empyema. Reasonable options include clindamycin, β-lactam plus β-lactamase inhibitors, and carbapenems. Piperacillin-tazobactam is an appropriate antibiotic for this patient, whereas ceftriaxone plus azithromycin and monotherapy with levofloxacin are not appropriate owing to their lack of anaerobic coverage.

Repeating the chest radiograph is not appropriate because this patient requires intervention for his complicated parapneumonic effusion.