Expanded Diagnostic Strategy in Older Adults Hospitalized With Community-Acquired Acute Respiratory Infection (NeuBluMul)

Participants receive an expanded diagnostic strategy in addition to conventional diagnostic assessment. The strategy includes multiplex respiratory PCR, bedside lung ultrasound, and serial procalcitonin measurements. Results are integrated into a predefined diagnostic and therapeutic algorithm to support decisions regarding antibiotic initiation, continuation, modification, de-escalation, and discontinuation.

A protocolized diagnostic strategy combining multiplex respiratory PCR using the BIOFIRE Pneumonia Panel plus, bedside lung ultrasound using the BLUE protocol, and serial procalcitonin measurements. Diagnostic results are integrated into a predefined algorithm to support decisions regarding antibiotic initiation, continuation, modification, de-escalation, and discontinuation.

Participants receive conventional diagnostic assessment and antimicrobial management according to usual clinical practice. Etiological diagnostic tests may be performed at the discretion of the treating physician.

Conventional diagnostic assessment and antimicrobial management according to usual clinical practice. Etiological diagnostic tests are performed at the discretion of the treating physician.

Total antibiotic exposure, calculated as the sum of days of therapy for all antibiotics received for the index acute respiratory infection, including antibiotic therapy administered during hospitalization and antibiotic therapy prescribed at hospital discharge. Each antibiotic received on a given calendar day contributes one day of therapy; therefore, days of concomitant antibiotic therapy are counted separately for each antibiotic.

Total exposure to high-impact antibiotics, calculated as the sum of days of therapy for all high-impact antibiotics received for the index acute respiratory infection. High-impact antibiotics are predefined as levofloxacin, moxifloxacin, piperacillin-tazobactam, ceftaroline, ceftobiprole, cefiderocol, cefepime, ceftazidime-avibactam, ceftolozane-tazobactam, carbapenems, vancomycin, and linezolid. Each antibiotic received on a given calendar day contributes one day of therapy; concomitant antibiotics are counted separately.

Proportion of participants in whom antibiotic therapy is de-escalated during the index hospitalization or after discharge. Antibiotic de-escalation is defined as switching from a high-impact antibiotic to a low-impact antibiotic or discontinuing antibiotic therapy, according to the predefined classification in the study protocol.

Proportion of participants requiring escalation to high-impact antibiotic therapy for the index acute respiratory infection. Antibiotic escalation is defined as the need to change to an antibiotic classified as high-impact according to the predefined classification in the study protocol.

Proportion of participants in whom at least one pathogen is detected by the multiplex pneumonia panel PCR performed on a respiratory sample.

Time in hours from hospital admission to the availability of the microbiological result establishing the microbiological diagnosis.

Proportion of participants in whom at least one multidrug-resistant microorganism is detected in any microbiological sample. Multidrug-resistant microorganisms are defined as methicillin-resistant Staphylococcus aureus (MRSA); Enterobacterales producing extended-spectrum beta-lactamases (ESBL), AmpC beta-lactamases, or carbapenemases; Pseudomonas aeruginosa resistant to at least one antibiotic in each of the following classes: penicillins, cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides; carbapenem-resistant Acinetobacter baumannii; and Stenotrophomonas maltophilia.

Proportion of participants who develop at least one complication related to the index acute respiratory infection, including empyema, sepsis, lung abscess, acute respiratory distress syndrome, multiorgan failure, or venous thromboembolism.

Total number of days from hospital admission to hospital discharge.

Proportion of participants requiring admission to the intensive care unit (ICU) during the index hospitalization.

Total number of days spent in the intensive care unit (ICU) during the index hospitalization among participants requiring ICU admission.

Proportion of participants who die from any cause during the index hospitalization.

Proportion of participants who die from any cause within 30 days after hospital discharge.

Proportion of participants who develop a new episode of respiratory infection requiring a new course of antibiotic therapy during the index hospitalization or within 30 days after hospital discharge.

Proportion of participants requiring hospital readmission for any cause within 30 days after hospital discharge.

Proportion of participants who experience at least one adverse event considered related to antibiotic therapy, including phlebitis and Clostridioides difficile infection.

Total direct healthcare costs associated with antimicrobial therapy and the diagnostic procedures included in the expanded diagnostic strategy. Costs will include antimicrobial therapy, serial procalcitonin measurements, bedside lung ultrasound, and multiplex pneumonia panel PCR testing.

The association between the presence or absence of a pneumonia-compatible lung ultrasound BLUE profile (ultrasound profile present/absent) and microbiological diagnostic category (bacterial, viral, mixed bacterial-viral, or no microbiological diagnosis) will be measured using Cramér's V coefficient. Lung ultrasound will be performed according to the BLUE protocol, and microbiological categories will be determined using tests performed during the index hospitalization. Cramér's V will be calculated from a 2 × 4 contingency table, yielding a single unitless numerical value ranging from 0 (no association) to 1 (maximum association). Participants with insufficient microbiological data will be excluded. Diagnostic category distributions according to ultrasound findings will also be reported descriptively.

The association between the presence or absence of posterolateral alveolar and/or pleural syndrome (PLAPS) on lung ultrasound (PLAPS present/absent) and microbiological diagnostic category (bacterial, viral, mixed bacterial-viral, or no microbiological diagnosis) will be measured using Cramér's V coefficient. Lung ultrasound will be performed according to the BLUE protocol, and microbiological categories will be determined using tests performed during the index hospitalization. Cramér's V will be calculated from a 2 × 4 contingency table, yielding a single unitless numerical value ranging from 0 (no association) to 1 (maximum association). Participants with insufficient microbiological data will be excluded. Diagnostic category distributions according to ultrasound findings will also be reported descriptively.

The association between the presence or absence of a B' lung ultrasound profile (B' profile present/absent) and microbiological diagnostic category (bacterial, viral, mixed bacterial-viral, or no microbiological diagnosis) will be measured using Cramér's V coefficient. Lung ultrasound will be performed according to the BLUE protocol, and microbiological categories will be determined using tests performed during the index hospitalization. Cramér's V will be calculated from a 2 × 4 contingency table, yielding a single unitless numerical value ranging from 0 (no association) to 1 (maximum association). Participants with insufficient microbiological data will be excluded. Diagnostic category distributions according to ultrasound findings will also be reported descriptively.

The association between the presence or absence of an A/B lung ultrasound profile (A/B profile present/absent) and microbiological diagnostic category (bacterial, viral, mixed bacterial-viral, or no microbiological diagnosis) will be measured using Cramér's V coefficient. Lung ultrasound will be performed according to the BLUE protocol, and microbiological categories will be determined using tests performed during the index hospitalization. Cramér's V will be calculated from a 2 × 4 contingency table, yielding a single unitless numerical value ranging from 0 (no association) to 1 (maximum association). Participants with insufficient microbiological data will be excluded. Diagnostic category distributions according to ultrasound findings will also be reported descriptively.

The association between the presence or absence of a C lung ultrasound profile (C profile present/absent) and microbiological diagnostic category (bacterial, viral, mixed bacterial-viral, or no microbiological diagnosis) will be measured using Cramér's V coefficient. Lung ultrasound will be performed according to the BLUE protocol, and microbiological categories will be determined using tests performed during the index hospitalization. Cramér's V will be calculated from a 2 × 4 contingency table, yielding a single unitless numerical value ranging from 0 (no association) to 1 (maximum association). Participants with insufficient microbiological data will be excluded. Diagnostic category distributions according to ultrasound findings will also be reported descriptively.

The association between the presence or absence of pleural effusion on lung ultrasound (pleural effusion present/absent) and microbiological diagnostic category (bacterial, viral, mixed bacterial-viral, or no microbiological diagnosis) will be measured using Cramér's V coefficient. Lung ultrasound will be performed according to the BLUE protocol, and microbiological categories will be determined using tests performed during the index hospitalization. Cramér's V will be calculated from a 2 × 4 contingency table, yielding a single unitless numerical value ranging from 0 (no association) to 1 (maximum association). Participants with insufficient microbiological data will be excluded. Diagnostic category distributions according to ultrasound findings will also be reported descriptively.