This patient should undergo thoracentesis to determine why he is not improving with treatment. Nonresponsive pneumonia is defined as an inadequate clinical response despite appropriate antimicrobial therapy. In most patients with ventilator-associated pneumonia (VAP), effective antimicrobial treatment usually results in defervescence and reduction in leukocyte count within 72 hours of beginning therapy, with improvement of oxygenation and decreased secretions, if hypoxia and excessive secretions were present. In patients who do not respond to appropriate antimicrobial treatment after 72 hours or who do not continue improving or worsen after an initial therapeutic response, it is imperative to search for another explanation for the patient's clinical findings (such as an infectious complication, another site of infection, or an alternate diagnosis). The possibility of a parapneumonic process should always be considered in the differential diagnosis of nonresponsive pneumonia. A new, or increasing, pleural effusion could represent a parapneumonic effusion, empyema, or a lung abscess. Thoracentesis and pleural fluid examination should be performed because the results could significantly alter management.

Suprainfections can occur, including suprainfection with gram-negative organisms, but the finding of only gram-positive cocci on Gram stain does not support this as a cause of nonresponse. Thus, broadening antimicrobial therapy to cover gram-negative organisms is not warranted.

With a new fever and no change in respiratory symptoms or oxygenation requirements, drug fever resulting from nafcillin therapy might be considered, especially if the chest radiograph was unchanged or showed improvement. Antimicrobial agents, particularly β-lactam agents, can cause drug fever but usually do not cause the level of leukocytosis seen in this patient. Because treatment for methicillin-sensitive Staphylococcus aureus VAP should continue for at least 7 days, the antibiotic should be changed to a different class if drug fever is suspected but not stopped altogether.

Evaluation of infectious complications or extrapulmonary sources of infection should occur before considering a bronchoscopy and bronchoalveolar lavage (BAL). BAL may be considered when there is a suspicion of antibiotic-resistant organisms not isolated from sputum culture.