Risk Factors and Outcomes of Endocarditis Due to Non-HACEK Gram-Negative Bacilli: Data from the Prospective Multicenter Italian Endocarditis Study Cohort

Abstract

The objective of this study was to investigate predisposing factors and outcomes of infective endocarditis (IE) caused by non-HACEK Gram-negative bacilli (GNB) in a contemporary multicenter cohort. Patients with IE due to GNB, prospectively observed in 26 Italian centers from 2004 to 2011, were analyzed. Using a case-control design, each case was compared to three age- and sex-matched controls with IE due to other etiologies. Logistic regression was performed to identify risk factors for IE due to GNB. Factors associated with early and late mortality were assessed by Cox regression analysis. The study group comprised 58 patients with IE due to GNB. We found that was the most common pathogen, followed by and The genitourinary tract as a source of infection (odds ratio [OR], 13.59; 95% confidence interval [CI], 4.63 to 39.93; < 0.001), immunosuppression (OR, 5.16; 95% CI, 1.60 to 16.24; = 0.006), and the presence of a cardiac implantable electronic device (CIED) (OR, 3.57; 95% CI, 1.55 to 8.20; = 0.003) were factors independently associated with IE due to GNB. In-hospital mortality was 13.8%, and mortality rose to 30.6% at 1 year. A multidrug-resistant (MDR) etiology was associated with in-hospital mortality (hazard ratio [HR], 21.849; 95% CI, 2.672 to 178.683; = 0.004) and 1-year mortality (HR, 4.408; 95% CI, 1.581 to 12.287; = 0.005). We conclude that the presence of a genitourinary focus, immunosuppressive therapy, and an indwelling CIED are factors associated with IE due to GNB. MDR etiology is the major determinant of in-hospital and long-term mortality.

Epidemiology and outcomes of non-HACEK infective endocarditis in the southeast United States

“…Additionally, over half of the cohort were re-hospitalized, and roughly one-third of patients died after 12 months from index infection. These outcome data are consistent with previous reports of non-HACEK GN IE [1,2,12]. In our cohort, patients who received definitive fluoroquinolone-based combination therapy and who presented with septic shock were significantly more likely to succumb to poor outcomes within 90-days post index infection compared to those who did not.…”

“…colonization or infection with GN organisms. These exposures have been identified in previously published reports, highlighting the complexity of this infection [1,2,[16][17][18][19]. Non-HACEK GN organisms, except for Salmonella spp., have limited ability to form biofilms and have low affinity to endocardial epithelium, accounting for the limited number of reported endocarditis cases due to these pathogens.…”

“…To our knowledge, this is the largest published cohort describing patient outcomes of non-HACEK GN IE from a single center, and even fewer reports have described outcomes in the United States population. Infective endocarditis from non-HACEK GN organisms has been primarily reported in PWID for many decades, with only a few reports of healthcare-associated cases [1,2,8,[12][13][14][15]. In our cohort, the majority of patients reported active or a history of injection drug use, which likely represents their main risk factor for IE.…”

“…Non-HACEK Gram-negative (GN) infective endocarditis (IE) is a relatively rare condition associated with significant morbidity and mortality [1,2]. While Gram-positive bacteria are typically the predominant causative organisms associated with IE, the increasing prevalence of invasive infections due to non-HACEK (i.e., organisms other than Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella spp.)…”

“…People who inject drugs (PWID) are traditionally thought to be at higher risk for non-HACEK GN IE [6][7][8], and many subsequently do not receive cardiac valve surgery due to the risk of recidivism [9]. Additionally, the collateral damage and toxicities observed with long-term use of the fluoroquinolone and aminoglycoside antibiotic classes that are recommended for use as combination therapies are concerning, and data supporting the use of combination therapy over monotherapy are conflicting [1,2].…”