The genus Fusobacterium comprises numerous Gram-negative, obligate anaerobe species, including F. necrophorum. Pharyngotonsillitis, abscess formation and septicaemia are the most common manifestations of F. necrophorum disease in humans, and it is the causative agent of the rare, but life threatening, Lemierre's disease [1].

In reviews of 2013 and 2014, Brook et al. and Schuetz suggested that, due to the unpredictable nature of their antibiogram, Fusobacterium species are amongst the highly virulent anaerobic pathogens for which individual isolate susceptibility testing should be undertaken [2,3]. Schuetz also documented that resistance was increasing [3]. More recently, Woerther et al. advocated further sequencing-based studies to address resistance determinant analysis amongst anaerobic bacteria, including Fusobacterium spp [4].

There are numerous reports of non-susceptibility to several important classes of antimicrobials in Fusobacterium spp. including: metronidazole, penicillin, clindamycin, moxifloxacin, meropenem and imipenem [[5], [6], [7], [8], [9], [10], [11], [12], [13]]. However, these findings are based on evidence of resistance in a range of Fusobacterium species, often including very few, or an unknown number of F. necrophorum isolates. Brazier and colleagues reported 2% penicillin and 15% erythromycin resistance in UK-derived F. necrophorum strains (n = 100) collected between 1990 and 2000 from a variety of invasive, and non-invasive, clinical infections [14]. Investigators from Denmark reported in 2008 that, in their experience, penicillin resistance was exceptionally rare. They also found reduced activity to erythromycin, as well as imipenem, in a study including 40 Danish isolates collected over a 3-year period from a similar range of clinical infections as the strains in the UK study [15]. Contemporary research shows that non-necrophorum Fusobacterium species are more likely to demonstrate an antimicrobial resistant phenotype than F. necrophorum itself, with 100% of Korean F. necrophorum isolates (n = 21) susceptible to all antibiotics (including: penicillin; imipenem; and metronidazole) [16].

Universally, studies report full F. necrophorum susceptibility to metronidazole, one of the mainstays of treatment, alongside a β-lactam [17]. In 2006, nimD, a gene associated with metronidazole resistance, was detected in a metronidazole resistant Fusobacterium species, only characterised to the genus level, but was not present with the insertion elements IS1168, IS1169 and IS1170 [18]. Other antimicrobial resistance genes (ARGs) detected in fusobacteria (F. nucleatum or genus only) include: blaOXA-85; blaTEM;blacfxA; ermC and ermF; tet(G); tet(L); tet(M); tet(O); tet(Q); and tet(W) [[19], [20], [21], [22], [23]]. In a recent study, analysing publicly available F. necrophorum whole genome data, and five clinical bovine and human isolates, only one strain was shown to harbour known ARGs – msr(D) and tet(T) – encoding potential macrolide and tetracycline resistance [24].

Owing to the paucity of ARG data for F. necrophorum, this study sought to elucidate the presence of ARGs in 385 F. necrophorum control, clinical and study isolates collected at the UK Anaerobe Reference Unit (UKARU) over almost 40 years. The results of whole genome sequencing (WGS) analysis and antimicrobial susceptibility testing (AST) are described and discussed, along with ARG analysis of publicly available F. necrophorum WGS data.