Outcomes of Empiric Antibiotic Therapy Based on Hospital Antibiograms in Organ Transplant Recipients with Bacteraemia

• Conditions: Bacteremia; Transplant Recipient

• Registration Number: NCT06874920
• Lead Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Brief Summary

The purpose of this observational study is to examine how using the hospital cumulative antibiogram to guide empirical antibiotic therapy affects outcomes in patients with bloodstream infections who have undergone solid organ transplants. The key question is: does the use of a hospital cumulative antibiogram reduce mortality and improve outcomes in these patients?

Detailed Description

Sepsis is a critical condition responsible for more than 750,000 hospitalisations and 200,000 deaths annually in the US. Severe sepsis remains a leading cause of death worldwide, with in-hospital mortality ranging from 12% to 26% in the US. An early and appropriate antimicrobial therapy in sepsis leads to a decreased progression to septic shock and death. However, physicians are often unaware of microbiological results when confronting sepsis; moreover, adopting a broad spectrum antibiotic therapy can lead to multiple adverse events. Therefore, a good balance between antibiotic efficacy and the consequence of indiscriminate use of broad-spectrum antibiotics is necessary, particularly for immunocompromised individuals at a higher risk of severe sepsis. Different studies have addressed choosing adequate empiric antibiotic in sepsis: multivariable models using readily available epidemiologic factors to predict antimicrobial susceptibility and clinical decision tree to estimate multi-drug resistance (MDR) infections have been developed to help clinicians. Moreover, hospital cumulative antibiograms have been created to identify the most common sensitivity profile for every bacterium.

In this study we will analyse the potential role of hospital cumulative antibiograms in the outcome of solid organ transplant (SOT) recipients with bacteraemia. In particular, the primary objective of the study is to assess the 15-days mortality of SOT recipients with bacteraemia according to the treatment administered referred to overall antimicrobial susceptibility (OAS), while the secondary objectives of the study are to assess the 30-days mortality, the in-hospital mortality, the length of in-hospital, the ICU admission, and the length of Intensive Care Unit (ICU) stay in these patients. Moreover, we will also assess the frequency of empiric therapy change at antibiogram availability, and we will describe the reasons for empiric therapy change.

We will conduct a retrospective single-centre cohort study to investigate the effect of empiric antibiotic treatment according to OAS on outcomes of the target population composed by SOT recipients transplanted in our Centre who were hospitalized at Fondazione IRCCS Ca' Granda Policlinico of Milano from 01/01/2015 to 31/12/2023 and developed monomicrobial bloodstream infection (BSI) due to Acinetobacter baumannii, Enterobacter spp., Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Klebsiella other-than pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Staphylococcus lugdunensis, and Streptococcus spp.

Patients will be divided into two groups according to the overall antimicrobial susceptibility of the empiric antibiotic therapy prescribed based on hospital cumulative antibiograms:

* Patients who have been prescribed an empiric therapy with OAS \< 90%;

* Patients who have been prescribed an empiric therapy with OAS ≥ 90%. Hospital cumulative antibiograms of the years included in the study are already available for the following temporal periods: 2014, 2015, 2016, 2017, 2018, 2019, 2020, 2021, 2022 and 2023. OAS is defined as the ratio of strains of a pathogen which are sensitive to an antibiotic regimen referred to all the strain of this pathogen identified.

Study Timeline

• Study Start: 2024-12-03
• Study First Submitted: 2025-02-06
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-08
• Last Update Submitted: 2025-03-08
• Study First Posted: 2025-03-13
• Last Update Posted: 2025-03-13
• Primary Completion: 2026-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Age ≥ 18 years
• Being SOT
• Monomicrobial bloodstream infection due to Acinetobacter baumannii, Enterobacter spp., Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Klebsiella other-than pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Staphylococcus lugdunensis, and Streptococcus spp.
• Hospitalization in Fondazione IRCCS Cà Granda Policlinico of Milano from 2015 to 2023.

Exclusion Criteria

• Antibiotic therapy administration outside 48h before-after blood culture collection.
• Polymicrobial bloodstream infections.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
15-days mortality	15 days from bloodstream infection

Secondary Outcome Measures

Name	Time	Method
30-days mortality	30 days from bloodstream infection
In-hospital mortality	Up to 24 weeks	From bloodstream infection to hospital discharge
Lenght of hospital stay	Up to 24 weeks	From hospital admission to hospital discharge
ICU admission	Up to 24 weeks	From bloodstream infection to hospital discharge
Lenght of ICU stay	Up to 24 weeks	From ICU admission to ICU discharge
Frequency of empiric therapy change at antibiogram availability	Up to five days	From empiric antibiotic therapy prescription to targeted antibiotic therapy prescription
Reason for empiric antibiotic change	From empiric antibiotic therapy prescription to targeted antibiotic therapy prescription at 5 days	Change from empiric to targeted antibiotic therapy

Trial Locations

Locations (1)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; 🇮🇹 Milano, Italy