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Molecular methods allow for a rapid identification of the main causative agents of pneumonia along with the most frequent resistance genes. Prolonged broad-spectrum antibiotic therapy without microbiological evidence of infection drives antimicrobial resistance. We evaluated if the result provided by the molecular method is helpful for antimicrobial de-escalation. All respiratory samples collected and directly processed via Real-Time PCR from patients with suspected pneumonia, of whom clinical data were available, were included in this study. In 82 patients out of a total of 174 (47.1%), antimicrobial therapy was modified after the molecular test, and in 28/82 (34.1%), antimicrobial de-escalation was carried out. Among the 92 patients in whom therapy was not modified, 33 (35.9%) were did not receive any antimicrobial therapy before the molecular test and no antibiotics were prescribed after the test. Therefore, in 61 (28 + 33) out of the 174 (35%) patients, unnecessary antimicrobials were discontinued or avoided. The syndromic panel used at our institution can be of help in better choosing when empiric antibiotic de-escalation therapy could be feasible.