Antibiotic resistance can lead to increased morbidity, mortality, length of hospital stay, and healthcare expenditures. The study is designed to observe the challenges of antibiotic consumption, related costs, and their resistance pattern in critically ill patients. The study was conducted in ICU from July 2016 to December 2016, at Holy Family Red Crescent Medical College Hospital. The demographic data, antibiotic sensitivity report, the administration of different classes of antibiotics as well as individual drugs and their costs were recorded. In 216 patients, meropenem was the most commonly prescribed antibiotic followed by levofloxacin and ceftriaxone. Meropenem with one or more class of antibiotics had the higher cost (BDT 1,985 and BDT 2,800 per day per patient). Though the cephalosporins are the initial choice as the safest, cheaper antibiotics in developed countries, high rate of resistance was observed in this ICU. The overall sterilization and strict control of nosocomial infections may play a vital role in overcoming the challenges. Use of local antibiogram, narrow-spectrum antibiotics, infectious disease specialist consultation, and restricted authorization to prescribe antibiotics can effectively shift the antibiotic sensitivity and minimize the cost in ICU stay.