Title
Effect of Aerosolised Colistin in Ventilator Associated Pneumonia
Efficacy and Toxicity of Aerosolised Colistin in Ventilator Associated Pneumonia: A Prospective, Randomized Trial
Phase
Phase 4Lead Sponsor
Tunis UniversityStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
Pneumonia, Ventilator-AssociatedStudy Participants
133the management of Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) gram-negative bacilli (GNB) represent a real therapeutic dilemma in intensive care unit (ICU). Colistin remains an effective agent against MDR GNB. However, because of its side effects, mainly nephrotoxicity, other modalities than the intra venous (IV) route should be tried. Several recent data emphasize the interest of inhaled route. The investigators purpose was to evaluate the effectiveness and systemic toxicity of aerosolized colistin in ventilator associated pneumonia.
prospective, randomized, single-blind study comparing two groups of patients treated with aerosolised (AS) colistin versus colistin intravenously (IV). Included were patients who have mechanical ventilation over 48 hours and that have developed a VAP. A VAP was defined as a CPIS (Clinical Pulmonary Infection Score) >6. Exclusion criteria were septic shock and/or bacteraemia. Included patients were divided into two randomized groups. The 1st received colistin in AS as 4 MU by nebulisation 3 times per 24 h. The 2nd received colistin in IV as a loading dose of 9 MU followed by 4.5MU two times per 24 h. Colistin was given for 14 days or until extubation. Patients were followed for 28 days. Therapeutic efficacy was assessed by a primary outcome: the cure of VAP at day 14 of therapy and defined as resolution of clinical and biological signs of infection that means a CPIS< 6 and bacteriological eradication. Secondary outcomes: duration of mechanical ventilation, ICU stay-length and mortality at day 28. Systemic toxicity was assessed by the occurrence of acute renal failure (ARF) defined as increase of plasma creatinine more than 1.5 times its base value.
colimycin (colistin) powder (1 million units (MU) by flakon) by AS route in addition to imipenem
colimycin (colistin) powder (1 MU by flakon) by intravenous route in addition to imipenem
nebulisation of colimycin (colistin) for 30 minutes 3 times per day during at least 14 days. Nebulisation was made via an ultrasonic vibrating plates nebulizer (Aeroneb Pro® Aerogen Nektar Corporation, Galway, Ireland).
intravenous colimycin (colistin) : 9 MU during 60 minutes followed by 4.5 million units 2 times per day
IV imipenem 1 g three times per day.
IV imipenem 1 g three times per day
the intervention was: AS colistin and "imipenem. the drug administered was colimycin (colistin) powder 1 million units (MU) by a flakon (Sanofi Winthrop Industry) at the dosage of 4 million units (MU) for 30 minutes 3 times per day for at least 14 days in addition to IV imipenem 1 g three times per day. Nebulisation was made via an ultrasonic vibrating plates nebulizer (Aeroneb Pro® Aerogen Nektar Corporation, Galway, Ireland). Inhaled colimycin® requires specific settings of the ventilator to limit turbulence inspiratory flow. The adjustment consisted in a volume controlled mode with a Tidal volume <8 ml / kg, respiratory rate at 12 cycles / min, I / E: 1/1 and an end inspiratory break > 20%.
the intervention was: IV colistin and "imipenem. the intravenous (IV) colistin goup received IV colimycin (colistin) as a loading dose of 9 MU during 60 minutes followed by 4.5 million units 2 times per day in addition to IV imipenem 1 g three times per day.
Inclusion Criteria: Critically ill patients older than 18 years, with mechanical ventilation during more than 48 hours, and who have presented a Ventilator associated Pneumonia (VAP) defined as a CPIS (Clinical Pulmonary Infection Score) of more than six Exclusion Criteria: Age <18 years Pregnancy Septic shock
