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Infective endocarditis (IE) caused by non-HACEK gram-negative bacilli (GNB) is poorly characterised and may be emerging as a consequence of medical progress. We performed an observational retrospective case-control study. Cases were non-HACEK GNB IE, definite or possible (modified Duke criteria), diagnosed in adults between 2007 and 2020 in six French referral hospitals. Two controls were included for each case (IE due to other bacteria, matched by sites and diagnosis date). Non-HACEK GNB were identified in 2.4% (77/3230) of all IE during the study period, with a mean age of 69.2 ± 14.6 years, and a large male predominance (53/77, 69%). Primary pathogens were  Escherichia coli  ( n  = 33),  Klebsiella  sp. ( n  = 12) and  Serratia marcescens  ( n  = 9), including eight (10%) multidrug-resistant GNB. Compared to controls ( n  = 154: 43%  Streptococcus  sp., 41%  Staphylococcus  sp. and 12%  Enterococcus  sp.), non-HACEK GNB IE were independently associated with intravenous drug use (IVDU, 8% vs. 2%,  p  = .003), active neoplasia (15% vs. 6%,  p  = .009), haemodialysis (9% vs. 3%,  p  = .007) and healthcare-associated IE (36% vs. 18%,  p  = .002). Urinary tract was the main source of infection ( n  = 25, 33%) and recent invasive procedures were reported in 29% of cases. Non-HACEK GNB IE were at lower risk of embolism (31% vs. 47%,  p  = .002). One-year mortality was high ( n  = 28, 36%). Comorbidities, particularly malignant hemopathy and cirrhosis, were associated with increased risk of death. Non-HACEK GNB are rarely responsible for IE, mostly as healthcare-associated IE in patients with complex comorbidities (end-stage renal disease, neoplasia), or in IVDUs.

Non-HACEK gram-negative bacilli endocarditis: a multicentre retrospective case-control study