Impact of Direct Antimicrobial Susceptibility Testing on Respiratory Sample of Intensive Care Patient With Suspected VAP

NCT02897466 | Unknown

• 2 other identifiers: P150926AOR15086
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. The international guidelines recommend using broad spectrum antimicrobials especially in patients who received previous antimicrobials, with risk factors of muti-drug resistant (MDR) VAP or after 5 days of mechanical ventilation. Using broad-spectrum antibiotics for 48h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Exposure to imipenem, as short as 1 to 3 days, is associated with a 5-fold increase in the risk of imipenem resistance in the gut microbiota of ICU patients (Armand-Lefevre AAC 2013). Performing AST directly on clinical respiratory samples would hasten the process by at least 24h. The diagnostic performance of a rapid method combining mass spectrometry and direct AST \[DAST\] are previously analyzed, and compared it with the conventional method (mass spectrometry with conventional AST \[CAST\]) and its potential impact was assessed on antimicrobial use in 85 patients (Le DORZE M et al - Clin. Microbiol. Infect. 2015). The results produced by the dast were useable in 85,9% of the cases and the sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1% \[95%CI = 93.3-101\] and 97.4% \[93.7-101\], respectively) and amikacin (88.9% \[81.7-96.1\] and 96.4% \[92.1-100.7\], respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2-91.5) to 100%, and from 86.4 (78.5-94.2) to 100%, respectively. If results had been reported to the clinicians, that DAST would have saved carbapenem prescription in 17 cases (22%) and would have allowed immediate narrow spectrum antimicrobials in 35/85 (41.2%) cases. But, the benefit of DAST was based on a simulation and should be now tested in a randomized fashion. This project is a prospective multicenter study. The hypothesis is that, DAST compared to CAST, would increase the number of adequate antimicrobial therapy within 24 hours in case of late VAP (\> 5 days under mechanical ventilation) with Gram negative bacilli (GNB) in IC patients while sparing carbapenems (imipenem and meropenem). The primary objective is to determine the impact of a strategy using DAST on the rate of day1 adequate therapy without carbapenems in case of late VAP due to GNB.

Conditions

Ventilator-associated Pneumonia

Keywords

ventilator-associated pneumonia; Multidrug-resistant bacteria

Outcome Measures

Primary Outcomes (1)

• The proportion of patients with an adequate antimicrobial therapy without carbapenem (imipenem, meropenem) at Day 1

  The proportion of patients with an adequate antimicrobial therapy without carbapenem (imipenem, meropenem) at Day 1

  2 days

Secondary Outcomes (14)

• The proportion of patients with an adequate antimicrobial therapy at Day1

  2 days

• The number of days alive without carbapenem between day 1 and day 28

  28 days

• The number of days alive without a broad spectrum antibiotic therapy between day 1 and day 28

  28 days

• The proportion of patients with a de-escalation at Day 1 according to previous definition (Weiss et al.)

  2 day

• The proportion of patients with a relapse or a new VAP occured between day 1 and day 28

  28 days

Study Arms (2)

Direct Antimicrobial Susceptibility Testing

EXPERIMENTAL

At day 0: Direct antibiotic susceptibility testing performed directly (DAST) on the respiratory sample At day 1: both results of isolated GNB identification using mass spectrometry and DAST will be given to the physician in charge in order to switch antimicrobial therapy to an antibiotic with a spectrum as narrow as possible with the main objective to avoid whenever possible carbapenems. Conventional antibiotic susceptibility testing (CAST) performed on isolated GNB. At day 2-3: results of CAST will be given to the physician in charge in order to change antimicrobial therapy in case of differences between CAST and DAST (2nd switch to an antibiotic with a spectrum as narrow as possible with the main objective to avoid whenever possible carbapenems)

Other: Direct Antimicrobial Susceptibility Testing

Conventional Antimicrobial Susceptibility Testing

NO INTERVENTION

At day 1 identification of isolated GNB bacilli using mass spectrometry will be given to the physician in charge (usual care in ICU involved) to adapt antibiotic regimen. Conventional antibiotic susceptibility testing (CAST) performed on isolated GNB. At day 2-3: results of CAST will be given to the physician in charge in order to switch antimicrobial therapy to an antibiotic with a spectrum as narrow as possible with the main objective to avoid whenever possible carbapenems.

Interventions

Direct Antimicrobial Susceptibility Testing OTHER

An antibiotic susceptibility testing will be performed directly on respiratory samples with Gram negative bacilli on direct smear examination of intensive care patients suspected of ventilator-associated pneumonia. The result of this test associated with GNB identification using mass spectrometry will be given to the physician in charge of the patient at Day 1, one day earlier than the conventional AST. This rapid method will allow a re-evaluation (adequation and/or de-escalation) of the antibiotic probabilist treatment one day earlier than the conventional method.

Also known as: DAST

Direct Antimicrobial Susceptibility Testing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (18 years or older)
• Need for mechanical ventilation expected for at least 5 days at any time during the ICU stay (including if the intubation was performed before the ICU admission)
• VAP suspected and clinical respiratory samples with GNB at direct smear examination
• At least one condition with a risk factor of multidrug resistant infection:
• Previous use of antimicrobials (at least 2 days in the past 7 days)
• Risk of colonization or infection with MDR or XDR bacteria within 3 months
• Written informed consent has to be obtained from the patients or a surrogate. The patient or his surrogate can withdraw from the study at any time.

You may not qualify if:

• Pregnant or lactating women
• VAP suspected and respiratory samples without GNB at direct smear examination
• VAP that occurred without neither previous antimicrobial exposure in the past 5 days or neither risk of MDR colonization
• Samples send to the lab during night and weekend in center if respiratory samples are not performed during this period
• Active therapeutic limitation
• Known allergy to antibiotics
• Social welfare unavailable

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Bichat Hospital

Paris, 75018, France

RECRUITING

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Interventions

diethylaminosulfur trifluoride

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Laurence ARMAND-LEFEVRE, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurence ARMAND-LEFEVRE, MD

CONTACT

140258500; laurence.armand@aphp.fr

Jean-François TIMSIT, Pr MD

CONTACT

jean-francois.timsit@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 13, 2016
• Study Start: December 11, 2017
• Primary Completion: July 11, 2019
• Study Completion: January 30, 2020
• Last Updated: October 15, 2018

Record last verified: 2018-05

Locations

FR (1)