antimicrobial treatment in patients with ventilator-associated tracheobronchitis

Conditions: Mechanical Ventilation Complication; Critical Illness

Summary: antimicrobial treatment could be beneficial in patients with ventilator-associated tracheobronchitis (vat). the hypothesis of this study is that antibiotic treatment for vat (3 or 7 days), compared with no antibiotic treatment, would reduce the incidence of transition from vat to ventilator-associated pneumonia (vap).

the main objective of this randomized controlled multicenter double-blind trial is to assess the efficiency of two durations (3 or 7 days) of antibiotic treatment for vat, compared with no antibiotic treatment, in reducing the incidence of transition from vat to ventilator-associated pneumonia (vap). secondary objectives are to determine the impact of two durations (3 or 7 days) of antibiotic treatment for vat, compared with no antibiotic treatment, on: * duration of mechanical-ventilation free days * duration of antibiotic free days * length of icu stay * mortality at day 28 and day 90 * incidence of icu-acquired colonization related to multidrug resistant (mdr) bacteria * incidence of icu-acquired infection related to mdr bacteria * incidence of ventilator-associated events after informed consent, patients will be randomized (1:1:1) to receive 0 (control group), 3 or 7 days (experimental groups) of antibiotic treatment for vat antibiotic treatment is standardized, based on the time of onset of vat, and presence of risk factors for mdr bacteria: * patients with early-onset vat with no risk factor for mdr bacteria will receive ceftriaxone (2 g iv every 24h). * patients with late-onset vat (after day 4 of mechanical ventilation), or with at least one risk factor for mdr bacteria will receive imipenem (1 g iv every 8h), and ciprofloxacin (400 mg iv every 8h) as empirical treatment. when methicillin-resistant staphylococcus aureus is suspected, linezolid (600 mg iv every 12h) will be added to empirical treatment. patients randomized in control group will receive 7 days of placebo, and those randomized in the first experimental arm (3 days of antibiotics) will receive 4 days of placebo.

Eligibility criteria:
inclusion criteria: * all adult patients hospitalized in the icu with a first episode of vat diagnosed \>48 hours after starting invasive mechanical ventilation are eligible for this study. vat is defined using the following criteria: 1. absence of new infiltrate on chest x ray 2. two of the three following conditions: fever \> 38.5 °c or \ than 12 000 cells per μl or \<than 4000 cells per μl purulent tracheal secretions 3. and positive tracheal aspirate (≥105 cfu/ml) exclusion criteria: * long-term tracheostomy at icu admission * patients who develop vap before vat * patients already receiving antibiotics active against all the microorganisms responsible for vat * severe immunosuppression * pregnancy or breastfeeding * patients \<18 years * patients already included in another study, with potential interaction with the primary objective of the current study * known resistance to imipenem and ciprofloxacin of bacteria responsible for vat * treatment limitation decisions * moribund patients (likely to die within 24 h) * allergy to any of study drugs: hypersensitivity to any carbapenem, severe hypersensitivity (for example anaphylactic reaction or severe cutaneous reaction) to any other antibiotic form beta-lactam group (such as penicillin or cephalosporin), severe hypersensitivity (for example anaphylactic reaction) to any other antibiotic from beta-lactam group (penicillin, monobactam or carbapenem), hypersensitivity to quinolones

Keywords: infectiology biology of infectious agents hygiene pneumology critical care