Abstract and Introduction

Abstract

Acinetobacter baumannii is a nosocomial pathogen associated with severe illness and death. Glucocorticoid aerosol is a common inhalation therapy in patients receiving invasive mechanical ventilation. We conducted a prospective cohort study to analyze the association between glucocorticoid aerosol therapy and A. baumannii isolation from ventilator patients in China. Of 497 enrolled patients, 262 (52.7%) received glucocorticoid aerosol, and A. baumannii was isolated from 159 (32.0%). Glucocorticoid aerosol therapy was an independent risk factor for A. baumannii isolation (hazard ratio 1.5, 95% CI 1.02–2.28; p = 0.038). Patients receiving glucocorticoid aerosol had a higher cumulative hazard for A. baumannii isolation and analysis showed that glucocorticoid aerosol therapy increased A. baumannii isolation in most subpopulations. Glucocorticoid aerosol was not a direct risk factor for 30-day mortality, but A. baumannii isolation was independently associated with 30-day mortality in ventilator patients. Physicians should consider potential A. baumannii infection when prescribing glucocorticoid aerosol therapy.

Introduction

Acinetobacter baumannii, a gram-negative coccobacillus, is a major nosocomial pathogen worldwide. A. baumannii is particularly challenging in intensive care units (ICUs). According to the Extended Prevalence of Infection in Intensive Care study, aimed at providing information on the prevalence of infection in ICUs worldwide, Acinetobacter spp. constituted 8.8% of all culture-positive ICU infections in 2007^[1], which increased to 11.4% in 2017^[2]. However, infection rates differed markedly, ranging from 1.0% in North America to 25.6% in Asia and the Middle East and 22.9% in eastern Europe^[2]. Patients on invasive mechanical ventilation are particularly vulnerable to A. baumannii infection and colonization due to airway barrier destruction and bacterial virulence factors such as motility, epithelial adherence, and biofilm formation that enable A. baumannii colonization in the airways^[3,4]. A. baumannii in patient airways is associated with longer hospitalization, higher medical expenses, and increased mortality rates^[5–7]. Identifying risk factors for A. baumannii infection is crucial for implementing preventive measures and decreasing overall illness and death.

Aerosol inhalation is widely used in patients requiring mechanical ventilation. Glucocorticoids are frequently administered during aerosol therapy, especially in China^[8–10]. Compared with systemic application, aerosol therapy has several advantages, including targeted delivery to the lungs, faster response, and fewer systemic side effects^[11,12]. However, the aerosols and droplets generated during aerosol inhalation can become sources of respiratory pathogens^[13], and inhaled glucocorticoids might suppress pulmonary immunity^[14], which could increase the opportunity for nosocomial acquisition. Inhaled corticosteroids are associated with an increased risk for pneumonia in patients with chronic obstructive pulmonary disease (COPD)^[15]. However, the effects of glucocorticoid aerosol inhalation on nosocomial infection risk has not been clearly elucidated.

Glucocorticoid aerosol therapy is mainly indicated for patients with asthma, COPD^[16], acute respiratory distress syndrome (ARDS)^[17], and some pathophysiological conditions, such as airway hyperresponsiveness^[18], hyperinflammation, and mucosal edema^[19]. In the past decade, use of glucocorticoid aerosol therapy has increased in hospitals in China; on average, >40% of patients on mechanical ventilation receive this therapy^[9]. In addition, a market analysis determined that aerosolized glucocorticoid sales in China were almost 3-fold higher in 2018 than in 2012^[20].

Although epidemiology has demonstrated a slow increase in A. baumannii infection globally over the past decade^[1,2], the increase in A. baumannii incidence in China appears to have outpaced increases in other regions worldwide^[21–23]. According to the China Antimicrobial Surveillance Network (CHINET), a national surveillance of the trends of bacterial strains isolated from the major hospitals in China, the number of Acinetobacter spp. strains increased by 2.7-fold in 2018 compared with 2012^[23,24]. Previously, we reported a marked increase in the incidence of A. baumannii–related bloodstream infections and incidence of pneumonia-related A. baumannii infections in ICUs in China that were 3.2-fold higher during 2017–2018 than during 2011–2012^[25]. A. baumannii was the most frequent bacterial isolate in ventilator-associated pneumonia in China, and rates were 35.7%–52.7%^[26,27]. Furthermore, the incidence of the drug-resistant phenotype of A. baumannii is high. According to CHINET reports, carbapenem-resistant A. baumannii strains increased from 31% in 2005 to 66.7% in 2014^[28], then to ≈80% in 2018^[29]. We previously reported that carbapenem resistance rates in ICUs in China increased from 25% during 2011–2012 to 95.7% during 2017–2018^[25]. A multicenter study of ICUs in China reported that multidrug-resistant (MDR) A. baumannii was detected in 40% of all cases^[30].

We hypothesized that increased use of glucocorticoid aerosol therapy might contribute to increased A. baumannii incidence. Therefore, we performed a prospective cohort study of critically ill patients receiving invasive mechanical ventilation in China to determine whether use of aerosolized glucocorticoid increased the risk for A. baumannii isolation.