Abstract: Background: Infective endocarditis (IE) due to non-HACEK bacilli (Haemophilus species, Actinobacillus, Car diobacterium, Eikenella, or Kingella) is uncommon and poorly described. The objectives of this study were to describe non-HACEK Gram-Negative Bacilli (GNB) IE cases and compare characteristic of IE produced by Enterobacterales and non-fermenting (NF) GNB. Methods: From January 2008 to December 2018, 3910 consecutive patients with definitive IE diagnosis, defined with Modified Duke criteria, either clinical or pathological criteria (e.g. demonstration of non-HACEK GNB in valve culture)were prospectively included. Results: A total of 104 IE cases were caused by non-HACEK GNB (2.6%). Compared to IE due to other micro organisms (excluding HACEK GNB), patients with non-HACEK GNB IE presented with higher age (71 years [IQR 62?78] vs 68 years [IQR: 57?77]; p = 0.026), higher proportion of women (52% vs 31.5%, p < 0.001), higher Charlson Index (5 [IQR: 4?8] vs 4 [IQR 3?7], p = 0.003) and higher in-hospital mortality (36.5% vs 27.1%, p = 0.034). Enterobacterales cases were more frequently associated with genitourinary focus (32.8% vs 5.0%, p = 0.001). NFGNB endocarditis more frequently affected right valves (20.0% vs. 6.3%, p = 0.033), had more common healthcare-related acquisition (67.5% vs. 43.7%, p = 0.030) and venous catheter as focus (40.0% vs. 17.2%, p = 0.019). In the multivariant model, factors related with hospital mortality were: age (OR 1.05, 95%CI 1.00?1.09, p = 0.042), prosthetic valve (OR 2.31, 95%CI 0.90?5.88, p = 0.080), and not performing surgery when indicated (OR 3.60, 95%CI 1.17?11.05, p = 0.025).Patients treated with quinolone combination had lower mortality (OR 0.29; 95%CI 0.09?0.96; p = 0.043). Conclusion: Non-HACEK GNB IE is a rare infection characterized by affecting elderly patients with high co morbidity, nosocomial acquisition and unfavorable outcome. Age, prosthetic valve and not performing surgery when indicated are associated with mortality.

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