Impact of the duration of antibiotics on clinical events in patients with Pseudomonas aeruginosa ventilator-associated pneumonia: study protocol for a randomized controlled study

Adrien Bouglé, Arnaud Foucrier, Hervé Dupont, Philippe Montravers, Alexandre Ouattara, Pierre Kalfon, Pierre Squara, Tabassome Simon, Julien Amour, iDIAPASON study group, Adrien Bouglé, Arnaud Foucrier, Hervé Dupont, Philippe Montravers, Alexandre Ouattara, Pierre Kalfon, Pierre Squara, Tabassome Simon, Julien Amour, iDIAPASON study group

Abstract

Background: Ventilator-associated pneumonia (VAP) accounts for 25% of infections in intensive care units. Compared to a long duration (LD) of antibiotic therapy, a short duration (SD) has a comparable clinical efficacy with less antibiotic use and less multidrug-resistant (MDR) pathogen emergence, with the exception of documented VAP of non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA). These results have led the American Thoracic Society to recommend SD therapy for VAP, except for PA-VAP. Thus the beneficial effect of SD therapy in PA-VAP is still a matter of debate. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) versus prolonged antibiotic therapy (15 days) in PA-VAP.

Methods/design: The impact of the duration of antibiotics on clinical events in patients with Pseudomonas aeruginosa ventilator-associated pneumonia (iDIAPASON) trial is a randomized, open-labeled non-inferiority controlled trial, conducted in 34 French intensive care units (ICUs), comparing two groups of patients with PA-VAP according to the duration (8 days or 15 days) of effective antibiotic therapy against PA. The primary outcome is a composite endpoint combining day 90 mortality and PA-VAP recurrence rate during hospitalization in the ICU. Furthermore, durations of mechanical ventilation and hospitalization, as well as number and types of extrapulmonary infections or acquisition of MDR pathogens during the hospitalization in the ICU will be recorded. Recurrence with predefined criteria (clinical suspicion of VAP associated with a positive quantitative culture of a respiratory sample) will be evaluated by two independent experts.

Discussion: Demonstrating that an SD (8 days) versus LD (15 days) therapy strategy in PA-VAP treatment is safe and not associated with an increased mortality or recurrence rate could lead to a change in practices and guidelines in the management of antibiotic therapy of this frequent ICU complication. This strategy could lead to decreased antibiotic exposure during hospitalization in the ICU and in turn reduce the acquisition and the spread of MDR pathogens.

Trial registration: ClinicalTrials.gov: NCT02634411 . Registered on 19 November 2015.

Keywords: Antibiotic; Antibiotic resistance; Bacterial infection; Bacterial pneumonia; Intensive care; Nosocomial infections; Pseudomonas aeruginosa; Respiratory tract infection; Ventilator-associated pneumonia.

Figures

Fig. 1
Fig. 1
Conduct of the study. Study protocol flowchart. SAPS 2: Simplified acute physiology score II; SOFA: Sequential organ failure assessment; CPIS: clinical pulmonary infection score
Fig. 2
Fig. 2
Template of recommended content for the schedule of enrollment, interventions, and assessment. SAPS 2: simplified acute physiology score (SAPS II); SOFA: sequential organ failure assessment (SOFA) score; CPIS: clinical pulmonary infection score

References

    1. Fujitani S, Sun H-Y, Yu VL, Weingarten JA. Pneumonia due to Pseudomonas aeruginosa: part I: epidemiology, clinical diagnosis, and source. Chest. 2011;139:909–19. doi: 10.1378/chest.10-0166.
    1. Gaynes R, Edwards JR, National Nosocomial Infections Surveillance System Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005;41:848–54. doi: 10.1086/432803.
    1. Neuhauser MM, Weinstein RA, Rydman R, et al. Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA. 2003;289:885–8. doi: 10.1001/jama.289.7.885.
    1. Crouch Brewer S, Wunderink RG, Jones CB, Leeper KV. Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest. 1996;109:1019–29. doi: 10.1378/chest.109.4.1019.
    1. Trouillet J-L, Vuagnat A, Combes A, et al. Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms. Clin Infect Dis. 2002;34:1047–54. doi: 10.1086/339488.
    1. Garnacho-Montero J, Sa-Borges M, Solé-Violán J, et al. Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: an observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med. 2007;35:1888–95. doi: 10.1097/01.CCM.0000275389.31974.22.
    1. Planquette B, Timsit J-F, Misset BY, et al. Pseudomonas aeruginosa ventilator-associated pneumonia. Predictive factors of treatment failure. Am J Respir Crit Care Med. 2013;188:69–76. doi: 10.1164/rccm.201210-1897OC.
    1. Rello J, Mariscal D, March F, et al. Recurrent Pseudomonas aeruginosa pneumonia in ventilated patients: relapse or reinfection? Am J Respir Crit Care Med. 1998;157:912–6. doi: 10.1164/ajrccm.157.3.9703014.
    1. Chastre J, Wolff M, Fagon J-Y, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290:2588–98. doi: 10.1001/jama.290.19.2588.
    1. Borg MA. Bed occupancy and overcrowding as determinant factors in the incidence of MRSA infections within general ward settings. J Hosp Infect. 2003;54:316–8. doi: 10.1016/S0195-6701(03)00153-1.
    1. American Thoracic Society, Infectious Diseases Society of America Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388–416. doi: 10.1164/rccm.200405-644ST.
    1. Micek ST, Ward S, Fraser VJ, Kollef MH. A randomized controlled trial of an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia. Chest. 2004;125:1791–9. doi: 10.1378/chest.125.5.1791.
    1. Kollef MH, Kollef KE. Antibiotic utilization and outcomes for patients with clinically suspected ventilator-associated pneumonia and negative quantitative BAL culture results. Chest. 2005;128:2706–13. doi: 10.1378/chest.128.4.2706.
    1. Stolz D, Smyrnios N, Eggimann P, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J. 2009;34:1364–75. doi: 10.1183/09031936.00053209.
    1. Fekih Hassen M, Ayed S, Ben Sik Ali H, et al. Durée de l’antibiothérapie lors du traitement des pneumopathies acquises sous ventilation mécanique : comparaison entre sept jours et dix jours. Étude pilote. Ann Fr Anesth Reanim. 2009;28:16–23. doi: 10.1016/j.annfar.2008.10.021.
    1. Capellier G, Mockly H, Charpentier C, et al. Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment. PLoS One. 2012;7:e41290. doi: 10.1371/journal.pone.0041290.
    1. Kollef MH, Chastre J, Clavel M, et al. A randomized trial of 7-day doripenem versus10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care. 2012;16:R218. doi: 10.1186/cc11862.
    1. Pugh R, Grant C, Cooke RP, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2011; CD007577. doi: 10.1002/14651858.CD007577.pub2.
    1. Dimopoulos G, Poulakou G, Pneumatikos IA, et al. Short- vs long-duration antibiotic regimens for ventilator-associated pneumonia. Chest. 2013;144:1759. doi: 10.1378/chest.13-0076.
    1. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63:e61–111. doi: 10.1093/cid/ciw353.
    1. Dunnett CW, Gent M. Significance testing to establish equivalence between treatments, with special reference to data in the form of 2X2 tables. Biometrics. 1977;33:593–602. doi: 10.2307/2529457.
    1. Combes A, Luyt C-E, Fagon J-Y, et al. Early predictors for infection recurrence and death in patients with ventilator-associated pneumonia. Crit Care Med. 2007;35:146–54. doi: 10.1097/01.CCM.0000249826.81273.E4.
    1. Siempos II, Athanassa Z, Falagas ME. Frequency and predictors of ventilator-associated pneumonia recurrence: a meta-analysis. Shock. 2008;30:487–95. doi: 10.1097/SHK.0b013e31816f1f7c.
    1. Tumbarello M, De Pascale G, Trecarichi EM, et al. Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients. Intensive Care Med. 2013;39:682–92. doi: 10.1007/s00134-013-2828-9.

Source: PubMed

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