IntroductionClostridium difficile(C. difficile) is one of the major causes of diarrhea transmitted by the fecal-oral route.C. difficiletype BI/NAP1/027 is responsible for the most severeC. difficileinfection (CDI). It is a major cause of antibiotic-associated diarrhea followed byClostridium perfringens,Staphylococcus aureus,andKlebsiella oxytoca.Historically, clindamycin, cephalosporins, penicillins, and fluoroquinolones were related to CDI. We conducted this study to evaluate the antibiotics associated with CDI in recent times.MethodsWe conducted a retrospective, single-center study over a period of eight years. A total of 58 patients were enrolled in the study. Patients with diarrhea and positiveC. difficiletoxin in stool were evaluated for antibiotics given, age, presence of malignancy, previous hospital stay for more than three days in the last three months, and any comorbidities.ResultsAmong patients who developed CDI, prior antibiotics for at least four days duration were given in 93% (54/58) of patients. The most common antibiotics associated withC. difficileinfection were piperacillin/tazobactam in 77.60% (45/58), meropenem in 27.60% (16/58), vancomycin in 20.70% (12/58), ciprofloxacin in 17.20% (10/58), ceftriaxone in 16% (9/58), and levofloxacin in 14% (8/58) of patients, respectively. Seven percent (7%) of patients with CDI did not receive any prior antibiotics. Solid organ malignancy was present in 67.20% and hematological malignancy in 27.60% of CDI patients. Ninety-eight percent (98%, 57/58) of patients treated with proton pump inhibitors, 93% of patients with a previous hospital stay for more than three days, 24% of patients with neutropenia, 20.1% of patients aged more than 65 years, 14% of patients with diabetes mellitus, and 12% of patients with chronic kidney disease also developedC. difficileinfection.ConclusionThe antibiotics associated withC. difficileinfection are piperacillin/tazobactam, meropenem, vancomycin, ciprofloxacin, ceftriaxone, and levofloxacin. Other risk factors for CDI are proton pump inhibitor use, prior hospital admission, solid organ malignancy, neutropenia, diabetes mellitus (DM), and chronic kidney disease (CKD).