Case Presentation: A 55-year-old man presented with bilateral upper back pain with radiation to the upper chest for the past 1 month. On examination, he had left upper back tenderness. A CT of the chest revealed septic pulmonary emboli. Blood cultures drawn on admission speciated to methicillin-resistant staphylococcus aureus (MRSA). Urine cultures speciated to MRSA as well. Intravenous vancomycin was started.Hospital course was prolonged and was notable for prostatic abscesses (for which he underwent two deroofing procedures by Urology), and persistence of bacteremia despite appropriate vancomycin levels. He was eventually switched to a salvage regimen of daptomycin and ceftaroline. A TTE and subsequent TEE were normal. Prior to planned discharge, he had multiple hypoxic episodes. Upon evaluation, he was asymptomatic. He had a SpO2 of 89% on room air and bibasilar crepitations.Labs revealed an absolute eosinophil count (AEC) of 600 cells/microliter, negative COVID-19 PCR; blood, urine, and sputum cultures were negative. Chest X-Ray revealed diffuse bilateral airspace opacities. CT chest with contrast revealed multiple scattered ground-glass opacities in the bilateral lungs.He was started on Lasix and Meropenem, however, despite adequate diuretic response, his hypoxia worsened requiring 3 L of oxygen. The ID consult team noted the elevated AEC and was concerned for acute eosinophilic pneumonia in the setting of concurrent daptomycin and ceftaroline use. They recommended discontinuing all antibiotics and switching to Vancomycin. He was transferred to the medical ICU due to worsening hypoxia and eventually intubated due to respiratory distress.Bronchoalveolar lavage (BAL) of the right lower lobe was performed. BAL fluid analysis was notable for 10% eosinophils in the BAL fluid. BAL fluid gram stain and cultures were negative. He was empirically treated with intravenous methylprednisolone. Over 48 hours, mechanical ventilation was weaned, and he was extubated. He was switched to oral prednisone.Given rapid improvement with steroids, and in the setting of causative medications, a diagnosis of acute eosinophilic pneumonia was made.

Discussion: Antibiotics such as beta-lactams, imipenem, daptomycin, ceftaroline, have been reported to lead to acute eosinophilic pneumonia. Although peripheral eosinophilia is supportive, it is neither highly sensitive nor specific. The diagnostic criteria [1] include a febrile illness of 4 weeks or less, with acute hypoxemic respiratory failure and diffuse pulmonary opacities, with BAL differential count showing eosinophilia of >25%. Despite having a BAL eosinophil differential of less than 10%, given the high pretest probability in the setting of use of causative medications, and response to treatment, we are confident with our diagnosis of acute eosinophilic pneumonia.The rationale behind using both ceftaroline and daptomycin is due to invitro synergistic activity against MRSA and bolstering innate immune response to infection. It has been associated with reduced odds of clinical failure [2] and faster time to clearance of bacteremia [3].There have been only 2 reported cases of a combination of daptomycin & ceftaroline leading to acute eosinophilic pneumonitis [4][5]. However, individually, both antibiotics have been reported to lead to acute eosinophilic pneumonitis.

Conclusions: Clinicians should be aware of the potential association of acute eosinophilic pneumonia with the use of daptomycin and/or ceftaroline.

IMAGE 1: Chest Radiograph with interval development of diffuse bilateral airspace opacities (left), with chest radiograph on admission (right) for comparison.

IMAGE 2: Computed tomography of chest (with contrast) with multiple scattered ground glass opacities in the bilateral lungs