Empiric antibiotics are administered for pneumonia when the causative pathogens are unidentified. Pathogen-directed therapy is impeded by negative culture results and/or culture time lag. This circumstance necessitates a salvage method for pathogen identification, especially when antibiotic therapy has failed. Here, we aimed to preliminarily investigate the HIRA-TAN method in pneumonia with a progressive course despite prior empiric antibiotic therapy. This prospective study was conducted for patients who were referred to Dr. Zainoel Abidin Hospital, Aceh, Indonesia, from December 2016 to January 2017, owing to pneumonia with a progressive course. Sputum or pleural effusion was subjected to culture and the HIRA-TAN assay. The HIRA-TAN identified the candidate causative pathogens based on the difference in the cycle threshold (Ct) between the targeted pathogen and the single-copy human gene. Patients (n=27) were predominantly males (22 patients, 81.5%), with a median age of 62 years. All patients had comorbid disease and were classified as hospital-acquired pneumonia (25 patients, 92.6%) with multilobar infiltrates (22 patients, 81.5%). Bacterial culture identified causative pathogen(s) in some (14 patients, 51.8%), whereas the HIRA-TAN identified pathogen(s) in most (23 patients, 85.2%). The rapid pathogen identification by the HIRA-TAN will provide valuable information in guiding pathogen-directed therapy. The result warrants a larger clinical trial to confirm the clinical efficacy of the HIRA-TAN in patients with progressive pneumonia despite previous antibiotic treatment.