Cephalothin Sodium

Antimicrobial-resistant thermophilic Campylobacter species (TCS) pose tremendous public health problems because they are zoonotic, difficult to treat and usually harboured by food-producing animals (FPAs). This study ascertained the phenotypic antimicrobial resistance (AMR) in 56 phenotypically identified TCS from slaughtered cattle, poultry, and humans in Enugu State, Nigeria. The presence of selected AMR and virulence genes harboured by the animal and human isolates were also detected and compared in 36 PCR-confirmed Campylobacter species. All the 56 TCS were multidrug-resistant as none were susceptible to ampicillin, penicillin-G, amoxicillin-clavulanic acid, cephalothin and metronidazole. The isolates were 92.9 %, 62.5 %, 92.9 %, 42.9 %, 26.8 %, 25 %, 28.6 %, 53.7 %, 30.1 %, 32.1 % and 55.4 % resistant to ceftriaxone, nalidixic acid, cefotaxime, enrofloxacin, ciprofloxacin, streptomycin, gentamycin, erythromycin, azithromycin, chloramphenicol and tetracycline, respectively. The top four most effective classes of antimicrobials were aminoglycosides > macrolides > amphenicol > fluoroquinolones. The AMR genes detected and the percentage of the isolates that harboured them were: aadE-1 (33.3 %), aphA-3-1 (36.1 %), tetO (44.4%), Bla_oxa-61 (61.1 %) and the multidrug efflux pump, cmeB (86.1%). Virulence genes detected and the corresponding percentage of TCS that harboured them were: cdtB (61.1 %), flaA (47.2 %), ciaB (38.9 %), and pldA (38.9 %). The cmeB was significantly detected in animal isolates (p = 0.018, OR = 5.1, CI = 0.7-6.6) while Bla_OXA-61 predominated in human isolates (p = 0.019, OR = 6.2). Likewise, ciaB virulence gene was mostly detected (p = 0.019, OR = 6.4, CI = 1.3-25) in animal isolates. The findings underscore the roles of FPAs in the zoonotic dissemination of Campylobacter-associated AMR and virulence genes in the study area. This warrants the adoption of One Health control strategies to limit spread of the multidrug-resistant zoonotic Campylobacter species.

The spread of antimalarial drug resistance is a substantial challenge in achieving global malaria elimination. Consequently, the identification of novel therapeutic candidates is a global health priority. Malaria parasite necessitates hemoglobin degradation for its survival, which is mediated by Falcipain 2 (FP2), a promising antimalarial target. In particular, FP2 is a key enzyme in the erythrocytic stage of the parasite's life cycle. Here, we report the screening of approved drugs listed in DrugBank using a computational pipeline that includes drug-likeness, toxicity assessments, oral toxicity evaluation, oral bioavailability, docking analysis, maximum common substructure (MCS) and molecular dynamics (MD) Simulations analysis to identify capable FP2 inhibitors, which are hence potential antiplasmodial agents. A total of 45 drugs were identified, which have positive drug-likeness, no toxic features and good bioavailability. Among these, six drugs showed good binding affinity towards FP2 compared to E64, an epoxide known to inhibit FP2. Notably, two of them, Cefalotin and Cefoxitin, shared the highest MCS with E64, which suggests that they possess similar biological activity as E64. In an investigation using MD for 100 ns, Cefalotin and Cefoxitin showed adequate protein compactness as well as satisfactory complex stability. Overall, these computational approach findings can be applied for designing and developing specific inhibitors or new antimalarial agents for the treatment of malaria infections.Communicated by Ramaswamy H. Sarma.