Impact of Implementing a Rapid PCR-based Algorithm for Carbapenemase-producing Enterobacterales (CPE) and Infection Control Bundle in a Tertiary Hospital

Official title

Intervention in the CPE Surveillance Algorithm and Isolation Re-evaluation With the Addition of PCR vs. Culture-based Protocol: Real-life Time Differences

Overview

Purpose: Carbapenemase-producing Enterobacterales (CPE) are a growing cause of healthcare-associated infections, linked to high morbidity, mortality, and cost. Current screening methods rely mainly on culture, which can take up to 48 hours and delay infection control actions. This study aims to evaluate the real-life impact of implementing a rapid PCR-based algorithm for CPE detection compared with the standard culture-based protocol, focusing on time differences in isolation and de-isolation decisions in hospitalized patients. Design: A quasi-experimental, before-and-after, retrospective study conducted at Hospital Italiano de Buenos Aires (HIBA). Primary Outcome: Time (in hours) between rectal swab request and change in isolation status (application or removal of isolation label) before and after PCR implementation. Population: Adult patients (≥18 years) admitted between October 2023-April 2024 (pre-intervention) and October 2024-April 2025 (post-intervention), who had contact isolation initiated or discontinued based on CPE surveillance results. Rationale: The introduction of rapid molecular testing could reduce operational delays and unnecessary isolation days, optimizing resource use in a setting with high CPE endemicity.

Detailed description

Background:

Carbapenemase-producing Enterobacterales (CPE) are critical-priority pathogens associated with increased morbidity, mortality, and healthcare costs. Screening and isolation are recommended infection control measures, yet delays inherent to culture-based methods can hinder timely decision-making and overuse limited isolation rooms.

Objective:

To compare the time to initiation and discontinuation of contact isolation-from swab request to result availability and isolation status update-before and after implementing a rapid PCR-based diagnostic protocol for CPE identification.

Design and Setting:

Retrospective, quasi-experimental before-after study at the Hospital Italiano de Buenos Aires, Argentina. The pre-intervention period covers October 1, 2023-April 30, 2024; the post-intervention period covers October 1, 2024-April 30, 2025.

Intervention:

Incorporation of real-time PCR testing (BD MAX™ System) for CPE genes (bla\_KPC, bla\_NDM, bla\_VIM/IMP, bla\_OXA-48-like) into the existing CPE surveillance and isolation reevaluation workflow. The infection control team coordinates sample requests and response actions.

Primary Outcomes:

Time difference (in hours) from surveillance swab request to isolation implementation.

Time difference (in hours) from surveillance swab request to isolation discontinuation.

Secondary Outcomes:

Time differences stratified by weekday versus weekend.

Time differences according to sampling time (08:00-16:00 vs 16:00-08:00).

Time differences according to immunosuppression status.

Time differences in ICU versus general ward settings.

Data Collection:

Four timestamps will be extracted from the electronic health record (EHR): swab request, laboratory check-in, final laboratory result, and change in isolation logo. These will allow computation of operational intervals (request → action), collection delay, processing delay, and action delay.

Statistical Analysis:

Continuous variables will be summarized as medians and interquartile ranges. Median time differences between pre- and post-intervention periods will be compared using mixed-effects linear regression adjusted for immunosuppression, ICU admission, day of the week, and public holidays. Analyses will be conducted using Stata v16.

Ethical Considerations:

The study is retrospective and minimal-risk, involving only secondary use of clinical data. It has been submitted to the CEPI (Comité de Ética de Protocolos de Investigación), Hospital Italiano de Buenos Aires (PRIISA 15728), with waiver of informed consent under CIOMS 2019 Guideline 10.

Expected Impact:

By quantifying real-time process improvements after PCR implementation, this study will provide evidence on diagnostic turnaround times and operational efficiency in infection control practices.

Interventions

• Diagnostic test Rapid PCR-based algorithm for CPE detection
  Implementation of a rapid real-time PCR-based diagnostic algorithm for the detection of carbapenemase-producing Enterobacterales (CPE) integrated into the institutional infection control workflow. The BD MAX™ System detects bla\_KPC, bla\_NDM, bla\_VIM/IMP, and bla\_OXA-48-like genes from rectal swabs. The infection control team manages the process from sample request to result-based isolation decision. The intervention began on November 6, 2024, upon availability of PCR supplies and reagents.

Primary outcome measures

• Time from surveillance swab request to isolation implementation or discontinuation (hours) [Time frame: From the date and time of electronic request for perianal swab collection until the date and time of isolation status update in the EHR, assessed up to 168 hours (7 days).]

Secondary outcome measures (3)

• Sample collection delay (hours) [Time frame: From the date and time of electronic request for perianal swab collection until laboratory check-in of the sample, assessed up to 72 hours.]
• Laboratory processing delay (hours) [Time frame: From the date and time of laboratory check-in until the date and time of final laboratory result, assessed up to 96 hours.]
• Action delay after laboratory result (hours) [Time frame: From the date and time of final laboratory result until the date and time of isolation status update in the EHR, assessed up to 72 hours.]

Eligibility criteria

Inclusion criteria

• Adult patients aged ≥18 years
• Patients screened for carbapenemase-producing Enterobacterales (CPE) carriage by perianal swab within the first 5 days of hospital admission
• Patients newly identified as CPE-colonized, leading to initiation of contact isolation
• Patients found to be decolonized, leading to discontinuation of contact isolation
• Patients with indication for active surveillance at hospital admission:

• Transfer from another healthcare facility
• Hospitalization in another healthcare center within the previous month
• Patients undergoing active surveillance during hospitalization:

• First surveillance swab in high-risk neutropenic patients (HAR flag)
• First surveillance swab in immunosuppressed units, such as hematopoietic stem-cell transplant wards
• Patients evaluated for discontinuation of contact precautions who meet all of the following:

• Prior CPE-positive surveillance sample
• At least 3 months since the last positive result and last hospitalization
• No systemic antibiotic exposure during that period

Exclusion criteria

• Lost samples
• Insufficient samples
• Invalid laboratory test results requiring repeat sampling

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Diagnostic

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• van Duin D, Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence. 2017 May 19;8(4):460-469. doi: 10.1080/21505594.2016.1222343. Epub 2016 Aug 11. PMID 27593176
• Orena BS, Liporace MF, Teri A, Girelli D, Salari F, Mutti M, Giordano G, Alteri C, Gentiloni Silverj F, Matinato C, Callegaro A, Cariani L. Active Surveillance of Patients Colonized with CRE: A Single-Center Study Based on a Combined Molecular/Culture Protocol. Antibiotics (Basel). 2024 Nov 6;13(11):1053. doi: 10.3390/antibiotics13111053. PMID 39596746
• Lim C, Ashley EA, Hamers RL, Turner P, Kesteman T, Akech S, Corso A, Mayxay M, Okeke IN, Limmathurotsakul D, van Doorn HR. Surveillance strategies using routine microbiology for antimicrobial resistance in low- and middle-income countries. Clin Microbiol Infect. 2021 Oct;27(10):1391-1399. doi: 10.1016/j.cmi.2021.05.037. Epub 2021 Jun 7. PMID 34111583
• Knight GM, Dyakova E, Mookerjee S, Davies F, Brannigan ET, Otter JA, Holmes AH. Fast and expensive (PCR) or cheap and slow (culture)? A mathematical modelling study to explore screening for carbapenem resistance in UK hospitals. BMC Med. 2018 Aug 16;16(1):141. doi: 10.1186/s12916-018-1117-4. PMID 30111322
• A C, N C, A S, A P, E Y, F G, M C. Validation of a rapid molecular detection test for gram-negative multidrug-resistant bacteria in rectal swabs upon admission of patients to the intensive care unit. Diagn Microbiol Infect Dis. 2024 Jun;109(2):116250. doi: 10.1016/j.diagmicrobio.2024.116250. Epub 2024 Mar 8. PMID 38479092
• Fasciana T, Antonelli A, Bianco G, Lombardo D, Codda G, Roscetto E, Perez M, Lipari D, Arrigo I, Galia E, Tricoli MR, Calvo M, Niccolai C, Morecchiato F, Errico G, Stefani S, Cavallo R, Marchese A, Catania MR, Ambretti S, Rossolini GM, Pantosti A, Palamara AT, Sabbatucci M, Serra N, Giammanco A. [The CCM Project "Phenotypic and molecular screening methodologies for the detection of coloniza-tions PMID 39679488
• Lydeamore MJ, Wu D, Donker T, Gorrie C, Higgs CK, Easton M, Hennessy D, Geard N, Howden BP, Cooper BS, Wilson A, Peleg AY, Stewardson AJ. Changes in isolation guidelines for CPE patients results in only mild reduction in required hospital beds. Infect Dis Health. 2025 May;30(2):128-131. doi: 10.1016/j.idh.2024.10.004. Epub 2024 Nov 24. PMID 39586760
• Jimenez A, Fennie K, Munoz-Price LS, Ibrahimou B, Pekovic V, Abbo LM, Martinez O, Rosello G, Sposato K, Doi Y, Trepka MJ. Duration of carbapenemase-producing Enterobacteriales carriage among ICU patients in Miami, FL: A retrospective cohort study. Am J Infect Control. 2021 Oct;49(10):1281-1286. doi: 10.1016/j.ajic.2021.06.006. Epub 2021 Jun 17. PMID 34146625

Identifiers

NCT: NCT07397416 · CEPI No. 7443 PRIISA 15728

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗