Derivation and Validation of the Risk Evaluation Score for Pneumonia Involving Resistant Entities (RESPIRE) (RESPIRE)

February 13, 2026 updated by: Peiman Nazerian, Azienda Ospedaliero-Universitaria Careggi

This is a single-center, non-profit observational study with two sequential phases: an initial retrospective phase followed by a prospective phase. Patients were enrolled during two consecutive, non-overlapping periods.

The primary objective of the study is to derive a clinical predictive score for multidrug-resistant (MDR) pathogen-related pneumonia in patients diagnosed with pneumonia presenting to the Emergency Department and/or admitted to the hospital from the community.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study Design and Setting

This is a single-center, non-profit observational study with two sequential phases: an initial retrospective phase and a subsequent prospective phase. Patients were enrolled during two consecutive, non-overlapping periods: from January 1, 2022 to December 31, 2023 (retrospective cohort), and from January 1, 2024 to December 31, 2025 (prospective cohort).

The study was conducted in a hospital setting and is monocentric, carried out at the Emergency Department and the Emergency Sub-Intensive Care Unit of Azienda Ospedaliero Universitaria Careggi, in collaboration with the Units of Microbiology and Virology and Infectious Diseases. Careggi is a large academic hospital that serves as the local hospital for a population of approximately 650,000 inhabitants and acts as a tertiary referral center for about 1,600,000 people.

Retrospective Phase (Derivation Cohort)

During the first observational retrospective phase (2 years), data were collected to establish a retrospective derivation cohort composed of patients with microbiologically confirmed etiological diagnoses of pneumonia. The derivation cohort includes patients who underwent microbiological investigations aimed at identifying the etiological diagnosis of pneumonia within the first 48 hours from admission to Azienda Ospedaliero Universitaria Careggi.

Following an initial screening of microbiological test requests received by the Microbiology and Virology Laboratory-using dedicated software containing microbiological investigations and electronic medical records of patients with pneumonia-patients who underwent diagnostic testing to determine the etiological agent of pneumonia (bacterial, viral, or fungal) on respiratory samples (considered the diagnostic gold standard for etiological assessment) within 48 hours of hospital admission were identified. Subsequently, patients' medical records were reviewed by the investigators to construct the final cohort database.

During the retrospective phase, patients with microbiologically confirmed bacterial, fungal, or viral pneumonia were included in order to create the retrospective cohort. Cases in which no bacterial, fungal, or viral pathogen was identified were excluded. Only patients with positive culture results and available antimicrobial susceptibility testing were selected. Patients with bacterial pneumonia caused by multidrug-resistant (MDR) pathogens identified on culture constituted the study group, whereas patients with bacterial pneumonia caused by non-MDR pathogens constituted the control group. MDR pneumonia was defined as pneumonia caused by bacterial pathogens exhibiting acquired non-susceptibility to at least one agent in three or more antimicrobial categories.

Only patients with a confirmed etiological diagnosis of pneumonia and positive culture results were included, in order to avoid the inclusion of false-negative cases. Negative respiratory culture results (reported in the literature in approximately 40-60% of cases) could have introduced potential selection bias, as culture-negative results do not allow exclusion of pneumonia caused by MDR pathogens.

Prospective Phase (Validation Cohort)

During the second observational prospective phase (2 years), data were collected to establish a prospective cohort of Emergency Department patients, on which the performance of the clinical score derived from the retrospective cohort was evaluated in a purely observational manner.

The validation cohort includes patients diagnosed with pneumonia who underwent microbiological investigations on respiratory samples in the Emergency Department to assess the etiological agent. No additional diagnostic tests were performed beyond routine clinical practice. Only patients with pneumonia who underwent microbiological investigations on respiratory samples at the clinician's discretion were included. After an initial phase, only patients with positive respiratory culture results were included, for the same reasons described above.

The Units of Emergency Medicine and Surgery and Integrated Clinical Assessment and In-Hospital Emergency Pathways were responsible for patient assessment, enrollment, sample collection, and data collection. The Unit of Microbiology and Virology was responsible for identifying microbiological test requests received by the laboratory during the study period and for extracting microbiological data.

Study Objectives

The primary objective of the study is to derive a clinical predictive score for MDR pathogen-related pneumonia in patients diagnosed with pneumonia presenting to the Emergency Department and/or admitted to the hospital from the community.

Secondary objectives are:

  1. validation of the derived clinical score in a prospective patient cohort;
  2. comparison of the performance of the developed score in predicting MDR-related pneumonia with validated scores such as DRIP, Shorr, Park, Shindo, Aliberti, and Schreiber, as well as the ATS/IDSA HCAP criteria;
  3. analysis of positive predictive value (PPV), negative predictive value (NPV), specificity, sensitivity, positive and negative likelihood ratios (LR+ and LR-), and optimal cut-off values;
  4. assessment of score calibration in both the derivation and validation cohorts;
  5. evaluation of clinical impact using decision curve analysis.

Study Type

Observational

Enrollment (Actual)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Florence, Italy
        • Careggi University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

During the initial retrospective observational phase (2 years), data were collected to establish a retrospective derivation cohort composed of patients with microbiologically confirmed etiological diagnoses of pneumonia. The derivation cohort includes patients who underwent microbiological investigations aimed at identifying the etiological cause of pneumonia within the first 48 hours of presentation to Azienda Ospedaliero Universitaria Careggi.

During the second prospective observational phase (2 years), data were collected to establish a prospective cohort of Emergency Department patients, in which the performance of the clinical score derived from the retrospective cohort was evaluated in a purely observational manner.

Description

Inclusion Criteria:

All patients:

  • aged ≥18 years
  • who underwent respiratory sample collection within 48 hours of hospital admission and had subsequent positive culture results oleading to a confirmed etiological diagnosis of community-acquired pneumonia (CAP)
  • Pneumonia was clinically defined by the presence of two or more clinical signs or symptoms (body temperature <36.0°C or >38.0°C; respiratory rate >20 breaths/min; oxygen saturation on room air <90%; arterial partial pressure of oxygen <60 mmHg; cough; sputum production; white blood cell count <4,000/μL or >10,000/μL; bandemia >10%), in addition to radiographic evidence of a new parenchymal opacity or cavitation.
  • Only patients with positive respiratory culture results were included in the analysis.

During the prospective phase, only patients whose microbiological samples were collected in the Emergency Department were enrolled.

Exclusion Criteria:

  • informed consent was not provided
  • age was <18 years or >90 years
  • pregnant
  • pneumonia occurred after more than 48 hours from hospital admission (hospital-acquired pneumonia).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
MDR Pneumonia Group (Derivation Cohort)
Patients with microbiologically confirmed bacterial pneumonia caused by multidrug-resistant (MDR) pathogens, identified on respiratory culture and antimicrobial susceptibility testing, enrolled during the retrospective phase. MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories.
Other: RESPIRE score
RESPIRE is a clinical risk prediction score developed to estimate the probability of pneumonia caused by multidrug-resistant (MDR) pathogens. In this observational study, the RESPIR-E score is derived and validated using routinely collected clinical and microbiological data. The score is not applied to guide clinical decision-making and does not influence diagnostic or therapeutic management. It is evaluated solely for observational and research purposes.
Non-MDR Pneumonia Group (Derivation Cohort)
Patients with microbiologically confirmed bacterial pneumonia caused by non-multidrug-resistant pathogens, identified on respiratory culture with available antimicrobial susceptibility testing, enrolled during the retrospective phase. This group served as the comparison cohort for score derivation.
Other: RESPIRE score
RESPIRE is a clinical risk prediction score developed to estimate the probability of pneumonia caused by multidrug-resistant (MDR) pathogens. In this observational study, the RESPIR-E score is derived and validated using routinely collected clinical and microbiological data. The score is not applied to guide clinical decision-making and does not influence diagnostic or therapeutic management. It is evaluated solely for observational and research purposes.
Pneumonia Validation Cohort (Prospective)
Consecutive patients presenting to the Emergency Department with a diagnosis of pneumonia who underwent microbiological investigations on respiratory samples during the prospective phase (January 1, 2024-December 31, 2025). This cohort was used to prospectively validate the clinical predictive score derived from the retrospective cohort in a purely observational manner.
Other: RESPIRE score
RESPIRE is a clinical risk prediction score developed to estimate the probability of pneumonia caused by multidrug-resistant (MDR) pathogens. In this observational study, the RESPIR-E score is derived and validated using routinely collected clinical and microbiological data. The score is not applied to guide clinical decision-making and does not influence diagnostic or therapeutic management. It is evaluated solely for observational and research purposes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical score (RESPIRE) derivation
Time Frame: Within 48 hours from Emergency Department presentation / hospital admission.
The primary objective of the study is to derive a clinical predictive score for MDR pathogen-related pneumonia in patients diagnosed with pneumonia presenting to the Emergency Department and/or admitted to the hospital from the community.
Within 48 hours from Emergency Department presentation / hospital admission.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
validation of the derived clinical score in a prospective patient cohort;
Time Frame: Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.
validation of the derived clinical score in a prospective patient cohort;
Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.
comparison of the performance of the developed score in predicting MDR-related pneumonia with validated scores
Time Frame: Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.
comparison of the performance of the developed score in predicting MDR-related pneumonia with validated scores such as DRIP, Shorr, Park, Shindo, Aliberti, and Schreiber, as well as the ATS/IDSA HCAP criteria (Measure: Area under the curve,sensibility, specificity, PPV, NPV, +LR, -LR)
Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.
PPV, NPV, specificity, sensitivity, LR+, LR-, Youden
Time Frame: Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.
analysis of positive predictive value (PPV), negative predictive value (NPV), specificity, sensitivity, positive and negative likelihood ratios (LR+ and LR-), and optimal cut-off values;
Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.
Calibration
Time Frame: Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.
assessment of score calibration in both the derivation and validation cohorts;
Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.
Clinical utiliy
Time Frame: Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.
evaluation of clinical impact using decision curve analysis (eg. treatment variation %)
Within 48 hours of the index Emergency Department presentation or hospital admission for pneumonia.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliero-Universitaria Careggi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2022

Primary Completion (Actual)

February 1, 2026

Study Completion (Actual)

February 8, 2026

Study Registration Dates

First Submitted

February 8, 2026

First Submitted That Met QC Criteria

February 13, 2026

First Posted (Actual)

February 23, 2026

Study Record Updates

Last Update Posted (Actual)

February 23, 2026

Last Update Submitted That Met QC Criteria

February 13, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CEAVC 29707

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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