Clostridioides difficile, a spore forming bacterium, is a leading cause of nosocomial infections. C. difficile infections cause severe diarrhoea, inflammation, and enlargement of the colon. Spores are crucial mediators of C. difficile infection initiation, dissemination, and re-infection. Our team has identified that cephamycins can inhibit sporulation by targeting the key sporulation-specific penicillin binding protein CdSpoVD. SpoVD proteins are highly conserved among spore forming bacterium and play an essential role in synthesis and remodelling of peptidoglycan during sporulation. However, recent research has shown that acquisition of a sporulation specific protein, CdSpoCR, can block the ability of cephamycins to inhibit sporulation. To understand how CdSpoCR facilitates resistance to the cephamycins, we produced the protein recombinantly and assessed the affinity of a panel of clinical compounds. Our data show that many available beta-lactam antibiotics are unable to bind CdSpoCR or bind with low affinity. Here we present the structure of CdSpoCR and discuss the arrangement of the protein active site and active site interactions with a beta-lactam antibiotic. This is the first time a link between antimicrobial resistance and the sporulation process have been observed, have profound impacts in both health care and animal production environments.