Cefotetan Disodium

A notch is defined as the frequency point at which hearing loss is greater than 15 dB when compared to one octave above and below. C3 dip or 1 kHz notch is rarely seen and not much information is known about the clinical profile of such condition. The aim of this case report is to highlight the audiological profile of a case with 1kHz notch and discuss the possible causes for the same. Case A (16 yrs) was referred with a complaint of hearing loss and speech understanding difficulty specially at school. The teen had taken multiple medications for several health related issues like malaria, appendicitis and the understanding difficulty was evident during this period. Detailed audiological evaluation revealed a significant C3 dip in the right ear and normal hearing sensitivity in the left ear. Evidences from literature suggests strong correlation between drugs like Cefotetan, cefotaime, piperacillin, ampicillin (appendicitis treatment) and chloroquine (malaria) and hearing loss. Hence, we concluded that the possible cause of 1khz is ototoxic medication.

With the aim of discovering small molecule inhibitors of the sporulation process in Clostridioides difficile, we prepared a series of C-7 α-(4-substituted-1H-1,2,3-triazol-1-yl)acetamide analogues of cefotetan, a known inhibitor of the C. difficile sporulation-specific protein target CdSpoVD. These analogues were evaluated using both in vitro binding assays with CdSpoVD and antisporulation assays against C. difficile. Further design concepts were aided utilizing the predicted docking scores (DS) using both AlphaFold (AF) models, and a crystal structure of the CdSpoVD protein (PDB 7RCZ). Despite being 1 order of magnitude more potent as a sporulation inhibitor than cefotetan, in vivo studies on compound 6a in a murine-model of C. difficile infection demonstrated comparable spore shedding capabilities as cefotetan. Importantly, compound 6a had no concerning broad spectrum antibacterial activities, toxicity, or hemolytic activity and thus has potential for further drug development.