Impact of early appropriate antimicrobial therapy on survival in Acinetobacter baumannii bloodstream infections

Abstract

The impact of appropriate empirical antimicrobial therapy for Acinetobacter baumannii bacteraemia on patient outcomes has not been clearly established. We assessed predictors of 30-day mortality and the effect of inappropriate empirical antimicrobial treatment on mortality among patients with A. baumannii bacteraemia between July 2005 and June 2008. Initial empirical antimicrobial therapy was considered to be appropriate if the initial antibiotics that were administered within 48 h after the acquisition of a blood culture sample included at least one antibiotic that was active in vitro and when the dosage and route of administration were in accordance with current medical standards. Overall, 103 patients with nosocomial A. baumannii bacteraemia were included in the study. Appropriate empirical therapy was administered to 41.7% of patients within 48 h. The overall mortality rate was 54.4%, with rates of 39.5% and 65% for patients who received appropriate and inappropriate antimicrobial therapy within 48 h, respectively. Thus, a 25.5% reduction in the overall crude mortality rate was associated with adequate early empirical antimicrobial therapy. Multivariate analysis using a Cox regression model showed that significant independent risk factors for mortality were delayed appropriate treatment [hazard ratio (HR) = 2.4, 95% confidence interval (CI) 1.3–4.2; P = 0.004], development of septic shock (HR = 2.6, 95% CI 1.4–4.8; P = 0.004), age > 65 years (HR = 2.1, 95% CI 1.2–3.7; P = 0.007) and mechanical ventilation (HR = 3.3, 95% CI 1.5–7.4; P = 0.003). It is concluded that a delay in receiving appropriate antimicrobial therapy had an adverse influence on clinical outcome in patients with A. baumannii bacteraemia.

Introduction

Acinetobacter baumannii is an important cause of nosocomial infections in many hospitals. It is difficult to control and difficult to treat due to its high resistance in the environment and its ability to develop resistance to antimicrobials. Bacteraemia is the most significant infection caused by A. baumannii, followed by respiratory tract and surgical wound infections [1]. Clinical manifestations of bloodstream infections (BSIs) by this organism range from transient bacteraemia to fulminant disease with high mortality [2]. Acinetobacter baumannii infections frequently develop in critically ill patients who have significant co-morbidities. High levels of resistance to most classes of antibiotics are common in A. baumannii [3], [4]. Multidrug-resistant Acinetobacter infections have an extremely high crude mortality rate and occur most frequently in severely ill patients [5]. The overall mortality rate associated with A. baumannii bacteraemia is reported to be up to 61.6% [6], [7], [8].

In the treatment of serious bacterial infections, initiation of effective antimicrobial therapy is a strong predictor of mortality. In most cases it is necessary to begin treatment before identification of the causative pathogen [9], [10]. Antibiotic resistance is a major clinical problem in treating Acinetobacter infections. Carbapenems have been preferred for use in serious Acinetobacter infections. However, the prevalence of carbapenem-resistant strains has recently been increasing in hospital settings, especially among critically ill patients, and this situation leads to inappropriate empirical antimicrobial therapy, which results in an unfavourable outcome in patients with Acinetobacter bacteraemia [11]. Nevertheless, the relationship between initial appropriate antimicrobial treatment and clinical outcomes is not well established in patients with A. baumannii bacteraemia.

The aim of the present study was to examine predictors of 30-day mortality and the impact of inappropriate empirical antimicrobial treatment on the mortality of patients with A. baumannii bacteraemia. A retrospective analysis of all episodes of nosocomial A. baumannii bacteraemia seen in Ankara Numune Education and Research Hospital (Ankara, Turkey) over a 3-year period was undertaken.