Abstract Introduction Tularemia, a rare zoonotic infection caused by Francisella tularensis, is a highly infectious gram-negative coccobacillus. Pulmonary tularemia, though uncommon, can resemble malignancy or chronic infections like tuberculosis, causing diagnostic delay. We report a case presenting as a persistent right lower lobe mass-like consolidation, diagnosed via plasma microbial cell-free DNA sequencing after inconclusive conventional tests. Case Presentation A 77-year-old man with hypertension and hyperlipidemia presented with fever, productive cough, and progressive dyspnea. Chest radiography revealed right lower lobe consolidation, and CT angiography demonstrated a 7.5 cm mass-like opacity with mild right hilar lymphadenopathy and a trace of pleural effusion. The patient received empirical treatment for community-acquired pneumonia with amoxicillin-clavulanate, and was subsequently discharged, showing partial clinical and radiographic resolution on follow-up imaging. One month later, the patient presented again with recurrent fevers, malaise, cough, and dyspnea. Additionally, the patient did report a remote history of exposure to a dead rabbit at his backyard. Repeat CT imaging showed a persistent 6.3 cm right lower lobe mass, prompting pulmonology evaluation and navigational bronchoscopy. Bronchoscopic specimens demonstrated necrotic tissue; however, bacterial, fungal, and mycobacterial cultures, as well as cytologic evaluation from BAL, were nondiagnostic. A comprehensive infectious workup, including blood cultures, was negative. Plasma microbial cell-free DNA sequencing (Karius digital culture) subsequently identified Francisella tularensis, confirming pulmonary tularemia. The patient was treated with ciprofloxacin and doxycycline for 4 weeks, resulting in significant clinical recovery and marked radiologic regression of the mass. Discussion Pulmonary tularemia presenting as a solitary mass-like lesion is extremely rare and can mimic malignancy or chronic infection. Maintaining a broad differential in non-resolving pulmonary consolidations is essential. This case underscores the diagnostic challenge and value of integrating novel molecular tools for improved outcomes in elusive infections. The subacute presentation and imaging findings initially suggested bacterial pneumonia or neoplasm, emphasizing the need to consider atypical pathogens like Francisella tularensis in non-resolving pulmonary consolidations. The organism’s fastidious nature often makes traditional diagnostics, including bronchoscopy and cultures, nondiagnostic. Plasma microbial cell-free DNA sequencing identified the pathogen when standard tests failed, highlighting the growing role of molecular diagnostics in complex infections. Early detection enables targeted therapy, ensuring recovery, and avoiding unnecessary invasive procedures. This abstract is funded by: N/A
Gill et al. (Fri,) studied this question.