Effect of Additional Nebulized Amikacin in Ventilator-Associated Pneumonia Caused by Gram Negative Bacteria

Thammasat University60 enrolled

Overview

The purpose of this study is to determine the cure rate from ventilator-associated pneumonia (VAP) caused by Gram negative bacteria when administering add on nebulized amikacin to intravenous antibiotics compared to intravenous antibiotics alone.

After inclusion, the patients are randomized into two groups: nebulized amikacin plus intravenous antibiotic(s) or nebulized placebo plus intravenous antibiotic(s). The dose of nebulized amikacin is 400 mg every 12 hours for 10 days. The patients are followed up on day 3, 7, 10, and 28 for safety and efficacy. The estimate sample size is 84 subjects base on previous study of cure rate in VAP and the authors expected that nebulized amikacin can improve cure rate in VAP subjects for 30% when compared with intravenous antibiotic(s) alone with power of 80% at level of significance 0.05.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Pneumonia, Ventilator-Associated

Interventions

AmikacinDRUG

400 mg, nebulizer, every 12 hours, 10 days

PlaceboDRUG

placebo 4 ml, nebulizer, every 12 hours, 10 days

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age \>/= 18 years * On mechanical ventilator more than 7 days * VAP diagnosis inclusion criteria: 1. new/progressive infiltration of chest radiography 2. 2/3 of the following: 1) fever 2) purulent sputum 3) Wbc \> 12,000 cell/mm3 or \< 4,000 cell/mm3 * Evidence of gram negative bacilli from sputum gram stain or previous sputum culture within 1 week Exclusion Criteria: * History of amikacin allergy * GFR \< 30 mL/min except dialytic patients * Immunocompromised host: HIV CD4 \< 200 cells/mm3, leukemia, lymphoma, received chemotherapy within 3 weeks, Absolute neutrophil count \< 500/mm3 * Severe ARDS (P/F ratio \< 100) * Endobronchial obstruction:endobronchial mass, endobronchial stenosis * Atelectasis * Severe bronchospasm * Lung abscess * Complicated parapneumonic effusion/ Empyema * Chest trauma * Uncontrolled extrapulmonary infection(s) * Received intravenous antibiotic(s) more than 48 hours * Pregnancy/ Lactation

Locations (1)

Thammasat University (Rangsit center)

Pathum Thani, Thailand

Outcomes

Primary Outcomes

cure rate

Cure rate = improvement/ no new infiltration of chest radiography plus 2/3 of the following: 1) No fever within 48 hours after end of the intervention 2) The reduction of secretion 3) The reduction of white blood cell

Time frame: 10 days after end of the intervention

Secondary Outcomes

The reduction of pathogens

quantitative sputum cultures were measured every days for 10 days or no growth of organism.

Time frame: 10 days after end of the intervention

mortality rate

All causes of death during the intervention