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

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

Interventions

OTHER

Direct Antimicrobial Susceptibility Testing

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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Laurence ARMAND-LEFEVRE, MD · Assistance Publique - Hôpitaux de Paris

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-12-11

Primary Completion

2019-07-11

Completion

2020-01-30

Countries

• France

Study Locations