Evolving antimicrobial resistance in a patient receiving palliative OPAT for a vascular graft infection: a case report

Prosthetic vascular graft infection is devastating and frequently fatal. Cure requires removal of the graft and reperfusion by placement of a new graft. However, no evidence based guidelines exist for management where removal of the graft is not possible. We describe a patient who lived in a state of chronic infection suppression through outpatient parenteral antimicrobial therapy (OPAT) over a period of 32 months, and outline the challenges experienced and strategies used to suppress infection in the face of escalating antimicrobial resistance. To date there have been very few reports of OPAT used in the palliative context and this case illustrates the microbiological issues that can arise and the importance of the full OPAT multi-disciplinary team in managing these issues and optimising the patient's quality and length of life

Clostridioides difficile canonical L,D-transpeptidases catalyze a novel type of peptidoglycan cross-links and are not required for beta-lactam resistance

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea worldwide with significant morbidity and mortality. This organism is naturally resistant to several beta-lactam antibiotics that inhibit the polymerization of peptidoglycan, an essential component of the bacteria cell envelope. Previous work has revealed that C. difficile peptidoglycan has an unusual composition. It mostly contains 3-3 cross-links, catalyzed by enzymes called L,D-transpeptidases (Ldts) that are poorly inhibited by beta-lactams. It was therefore hypothesized that peptidoglycan polymerization by these enzymes could underpin antibiotic resistance. Here, we investigated the catalytic activity of the three canonical Ldts encoded by C. difficile (LdtCd1, LdtCd2, and LdtCd3) in vitro and explored their contribution to growth and antibiotic resistance. We show that two of these enzymes catalyze the formation of novel types of peptidoglycan cross-links using meso-diaminopimelic acid both as a donor and an acceptor, also observed in peptidoglycan sacculi. We demonstrate that the simultaneous deletion of these three genes only has a minor impact on both peptidoglycan structure and resistance to beta-lactams. This unexpected result therefore implies that the formation of 3-3 peptidoglycan cross-links in C. difficile is catalyzed by as yet unidentified noncanonical Ldt enzymes