Inadequate treatment of ventilator-associated pneumonia: risk factors and impact on outcomes

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Summary

Initial antibiotic therapy is an important determinant of clinical outcomes in ventilator-associated pneumonia (VAP). Several studies have investigated this issue, with conflicting results. This study investigated risk factors of inadequate empirical antimicrobial therapy and its impact on outcomes for patients with a clinical diagnosis of VAP. The primary outcome was adequacy of antimicrobial therapy. Secondary outcomes were duration of mechanical ventilation, hospital and intensive care unit (ICU) lengths of stay, and mortality due to VAP. Mean age was 62.9 ± 15.2 years, mean APACHE (Acute Physiological Assessment and Chronic Health Evaluation) II score was 20.1 ± 8.1 and mean MODS (Multiple Organ Dysfunction Score) was 3.7 ± 2.5. Sixty-nine (45.7%) of 151 patients with a clinical diagnosis of VAP received inadequate antimicrobial treatment for VAP initially. There were 100 (66.2%) episodes of VAP caused by multidrug-resistant pathogens, of which 56% were inadequately treated, whereas the rate of inadequate antimicrobial therapy for VAP caused by susceptible-drug pathogens was 25.5% (P < 0.001). Multiple logistic regression analysis revealed that the risk of inadequate antimicrobial treatment was more than twice as great for patients with late-onset VAP [odds ratio (OR), 2.93; 95% confidence interval (CI), 1.30–6.64; P = 0.01], and more than three times for patients with VAP caused by multidrug-resistant pathogens (OR, 3.07; 95% CI, 1.29–7.30; P = 0.01) or with polymicrobial VAP (OR, 3.67; 95% CI, 1.21–11.12; P = 0.02). Inadequate antimicrobial treatment was associated with higher mortality for patients with VAP. Two of three independent risk factors for treatment inadequacy were associated with the isolation and identification of micro-organisms.

Introduction

Ventilator-associated pneumonia (VAP) is a common complication in patients requiring mechanical ventilation. Its incidence varies widely depending on the type of population studied and the diagnostic methods and it occurs at rate of 1–3% per day of mechanical ventilation.1, 2, 3, 4, 5, 6, 7, 8 Prolonged intensive care unit (ICU) stay and prolonged mechanical ventilation increase the risk of death.7, 9, 10, 11, 12, 13, 14, 15 Due to the clear association between ventilation and risk of pneumonia, antimicrobial agents are widely prescribed for ventilated patients, and, in more than 50% of the cases, for patients with presumed or diagnosed respiratory tract infections.16 Nevertheless, the use of these drugs in the ICU encourage the increasing incidence of infections caused by multidrug-resistant pathogens and establish a vicious cycle that increases morbidity–mortality rates.17, 18, 19, 20, 21, 22, 23, 24 Using multiple logistic regression, Torres et al. demonstrated that the worsening of respiratory failure, an ultimately or rapidly fatal underlying condition, septic shock and inadequate antibiotic therapy were factors that negatively affected the prognosis of VAP.4 Other authors have also showed that the selection of initial antibiotic therapy is an important determinant of mortality.25, 26, 27, 28, 29, 30

We studied patients with a clinical diagnosis of VAP to identify possible risk factors for inadequate treatment and its subsequent impact on mortality.

Section snippets

Materials and methods

During 40 months, all patients admitted to one of the five medical or surgical intensive care units (70 beds in oncology, respiratory, cardiology, neurology and general ICUs) of Santa Casa Hospital (1700 beds) with a presumed diagnosis of VAP were eligible for this investigation. This study was approved by the Ethics in Human Studies Committee.

A retrospective cohort study design was used. Primary outcome was antimicrobial adequacy. Secondary outcomes were duration of mechanical ventilation,

Results

Sixty-nine (45.7%) of the 151 patients with a clinical diagnosis of VAP received inadequate antimicrobial treatment for VAP initially, with eighty-two (54.3%) patients receiving appropriate antimicrobial agents. Age, sex, immunological status, co-morbidities, prior surgical procedure or MODS were not significantly different between these two groups. Higher APACHE II score was significantly associated with inadequate treatment (P = 0.02). The indications for mechanical ventilation are listed in

Discussion

The presence of unexpected or resistant bacteria may reduce the adequacy of empirical antimicrobial treatment. We identified multidrug-resistant bacteria, polymicrobial VAP and late-onset VAP as independent risk factors for inadequate treatment, which itself was associated with increased in-hospital mortality. Trouillet et al. reported that resistant bacteria caused 57% of episodes of VAP.34 Their results showed that mechanical ventilation for more than seven days, prior antibiotic use and

Acknowledgements

We would like to thank Carlos Luna for critical revision of this paper.

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