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Mount Sinai Hospital Critical Care Research - Current Studies
VAP STUDY
(Ventilator-Associated Pneumonia Study)
A Randomized Trial of Empiric Broad-Spectrum Antibiotics and Invasive Diagnostic Techniques in the setting of Ventilator-Associated Pneumonia
A multicentric CIHR funded study. P.I. Dr. Daren K Heyland
Site Investigator: Dr. Geeta Mehta
Site Co-ordinator: Carlos Martinez
Mount Sinai Hospital has recently joined Kingston General Hospital (Dr. DK Heyland, Principal Investigator, e-mail: dk2@kgh.on.ca) and many other hospitals in Canada and the United States in this multicenter trial supported by the Canadian Institute of Health Research (CIHR).
Ventilator-associated pneumonia (VAP) is associated with a prolonged length of stay in the ICU and may increase risk of death1. Therefore, optimising the management of VAP has the potential for influencing ICU length of stay and mortality in critically ill patients.
To aid in the diagnosis and to identify the infecting organisms, bronchoscopy with the use of bronchoalveolar lavage (BAL) may be more accurate than reliance on standard endotracheal aspirates2. However, recent studies question the accuracy of invasive techniques in patients on antibiotics prior to bronchoscopy3.
‘Late’ VAP (occurring after 4-7 days of mechanical ventilation) is often caused by difficult-to-treat organisms (Pseudomonal species, Acinetobacter, Stenotrophomonas, Methicillin-resistant Staphylococcus aureus). For late-onset VAP, current recommendations support the use of empiric therapy which usually consists of one or two agents, with activity against Gram (-) and Gram (+) organisms4.
Several observational studies have found higher mortality rates in infected patients receiving inadequate empiric antibiotics. The use of two broad-spectrum agents, as recommended in the American Thoracic Society guidelines is not of proven efficacy, and may not be necessary. Therefore the risks and benefits of two empiric broad-spectrum antibiotics need to be evaluated in the context of a randomized clinical trial. The research questions are:
1) In critically ill patients with a clinical suspicion of late-onset VAP, what is the effect of bronchoscopy with bronchoalveolar lavage (BAL) compared to endotracheal aspirates alone on clinical, microbiologic and economic outcomes?
2) In critically ill patients with a clinical suspicion of late-onset VAP, what is the effect of two empiric broad-spectrum antibiotics compared to one broad spectrum antibiotic on clinical, microbiologic and economic outcomes?
This is a multicenter, prospective, randomized trial of 740 critically ill patients with a clinical suspicion of VAP. Eligible subjects: Adults (≥16 years old) with more than 96hrs in the ICU, mechanically ventilated and who develop a clinical suspicion of pneumonia. These criteria must be met within 48 hours preceding eligibility.
The exclusion Criteria are: unsuitable candidate for bronchoscopy as defined by the bronchoscopist. Patients not expected to be in the ICU for more than 24 hours. Known or suspected history of anaphylaxis to penicillins or ciprofloxacin. Women who are pregnant or lactating. Patients already infected or colonized (respiratory tract only) with an organism not sensitive to study drugs. Patients already infected with Pseudomonas species. Already on study drugs. Immunocompromised patients. And previous randomization in this study. Chronic patient (not likely to be discharged from ICU within 3 weeks)
Patients will be randomized to undergo bronchoscopy with BAL or endotracheal aspirates alone (non-quantitative), which will be done within 12 hours of time of randomization. In addition, at time of enrolment, patients will be randomized to receive Meropenem 1g q8h and Ciprofloxacin 400mg q12h or Meropenem alone. Immediately after sampling, physicians will judge the pre-test likelihood that the patient has VAP and all patients will be placed on study antibiotics. When culture results from diagnostic sampling are available 48-72 hours later, clinicians will adjust therapy accordingly. Patients from both groups will be followed prospectively for 28 days or until death or hospital discharge.
The study will evaluate whether the use of two empiric broad-spectrum antibiotics and invasive diagnostic techniques will improve clinical resolution, decrease length of stay and reduce mortality of critically ill patients with a clinical suspicion of late ventilator-associated pneumonia. The diagnostic and therapeutic strategies tested in this study may lead to less morbidity and increased chance of survival in critically ill patients, In addition, by reducing the length of stay and unnecessary use of antibiotics, these strategies will likely contribute to significant costs saving to the health care system.
If you require further information contact me via e-mail at CMartinez@mtsinai.on.ca and I will be happy to help you.
References:
1. Heyland DK, Cook DJ, Griffith L, Keenan S, Brun-Buisson C. The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. Am J Respir Crit Care Med 1999; 159:1249-1256.
2. Cook DJ, Fitzgerald JM, Guyatt GH, Walter S. Evaluation of the protected brush catheter and bronchoalveolar lavage in the diagnosis of nosocomial pneumonia. J Intensive Care Med 1991; 6:196-205.
3. Timsit JF, Misset B, Goldstein FW, Vaury P, Carlet J. Reappraisal of distal diagnostic testing in the diagnosis of ICU-acquired pneumonia. Chest 1995; 108:1632-39.
4. Campbell GD, Niederman MS, Broughton WA, et al. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial strategy, and preventive strategies. A consensus statement. Am J Resp Crit Care Med 1996; 153:1711-1725.