Background: Increasing antibiotic resistance, usually from irrational pharmacotherapy, poses a grave challenge to clinicians in managing multidrug-resistance infections. Aim and objective: To focus attention on the rising incidence of pandrug-resistant infections, related issues and concerns, and their containment. Materials and methods: The short communication is prompted by the recently reported in vitro sensitivity of gram-negative bacteria to a combination of ceftriaxone + sulbactam + EDTA. Appropriate observations from literature are cited to complement the outcome of the said study. Results: Pandrug resistance (PDR) is defined as a non-susceptibility of the bacteria to all antimicrobial agents in all antimicrobial categories. This is not true that it is restricted to only gram-negative bacteria. Staphylococcal aureus, a gram-positive bacteria, may too develop such resistance. The in vitro sensitivity observations do not necessarily get reflected in actual clinical effectiveness and efficacy. Therapy is a herculean task. Judicious use of antibiotics and strict infection control measures, preferably as a part of an antibiotic stewardship program, are mandatory to reduce the prevalence of PDR, nay the drug resistance as such. Conclusion: Pandrug resistance, meaning resistance to all classes of antibiotics, can develop not only in the case of gram-negative bacteria but also gram-positive bacteria, like S. aureus. It is best prevented rather than treated. Clinical significance: Implementation of the antibiotic stewardship program, mainly comprising rational antibiotic therapy, has the potentials to go a long way in safeguarding against PDR, nay antibiotic resistance as such.