Biapenem

Clostridium difficile (C. difficile) stands as a primary cause of health-care-associated colitis in adults; however, extraintestinal manifestations of C. difficile, particularly bacteremia, are exceptionally rare. In this report, we document a case of an elderly male with multiple comorbidities who presented with an acute onset of fever. Diagnostic testing revealed the presence of concurrent bacteremia involving C. difficile and Klebsiella pneumonia. The multilocus sequence typing analysis identified this C. difficile strain as ST81. After receiving a combination treatment of vancomycin and biapenem, the patient successfully recovered and was subsequently discharged. This case report elucidates the clinical presentation and treatment strategies for C. difficile ST81 bacteremia, underscoring the critical need for heightened monitoring of extraintestinal infections in high-risk patients.

Antimicrobial resistance has been an increasingly serious threat to global public health. The contribution of non-antibiotic pharmaceuticals to the development of antibiotic resistance has been overlooked. Our study found that the anti-inflammatory drug phenylbutazone could protect P. aeruginosa against antibiotic mediated killing by binding to the efflux pump regulator MexR. In this study, antibiotic activity against P. aeruginosa alone or in combination with phenylbutazone was evaluated in vitro and in vivo. Resazurin accumulation assay, transcriptomic sequencing, and PISA assay were conducted to explore the underlying mechanism for the reduced antibiotic susceptibility caused by phenylbutazone. Then EMSA, ITC, molecular dynamic simulations, and amino acid substitutions were used to investigate the interactions between phenylbutazone and MexR. We found that phenylbutazone could reduce the susceptibility of P. aeruginosa to multiple antibiotics, including parts of β-lactams, fluoroquinolones, tetracyclines, and macrolides. Phenylbutazone could directly bind to MexR, then promote MexR dissociating from the mexA-mexR intergenic region and de-repress the expression of MexAB-OprM efflux pump. The overexpressed MexAB-OprM pump resulted in the reduced antibiotic susceptibility. And the His41 and Arg21 residues of MexR were involved in the phenylbutazone-MexR interaction. We hope this study would imply the potential risk of antibiotic resistance caused by non-antibiotic pharmaceuticals.