Objective: To investigate the infection of hospital- and community-acquired “erythromycin- induced clindamycin resistant” strains or D-test positives of clinical isolates of Staphylococcus aureus (S. aureus) (with and without methicillin resistance) in a hospital. Methods: Strains of S. aureus isolated from clinical specimens were subjected to D-test and antibiotic profiling. Results: Of the total 278 isolates, 140 (50.35%) were D-test positives and the rest were D-test negatives. Further, of 140 (100%) positives, 87 (62.14%) and 53 (37.85%) strains were from males and females, respectively. Of 140 (100%) positives, 117 (83.57%) were methicillin resistant S. aureus and 23 (16.42%) were methicillin sensitive S. aureus; of 140 strains, 103 (73.57%) strains from persons with and 37 (26.42%) were without related infections; of 140 strains, 91 (65%) and 49 (35%) were from hospital- and community-acquired samples, respectively. In 140 strains, 118 (84.28%) with comorbidities and 22 (15.71%) without comorbidities cases were recorded; similarly, persons with prior antibiotic uses contributed 108 (77.14%) and without 32 (22.85%) positive strains. These binary data of surveillance were analyzed by a univariate analysis. It was evident that the prior antibiotic uses and comorbidities due to other ailments were the determinative factors in D-test positivity, corroborated by low P values, P=0.001 1 and 0.002 4, respectively. All isolates (278) were resistant to 17 antibiotics of nine groups, in varying degrees; the minimum of 28% resistance for vancomycin and the maximum of 97% resistance for gentamicin were recorded. Further, of 278 strains, only 42 (15.1%) strains were resistant constitutively to both antibiotics, erythromycin resistant and clindamycin resistant, while 45 (16.2%) strains were constitutively sensitive to both antibiotics (erythromycin sensitive and clindamycin sensitive). Further, of the rest 191 (68.7%) strains were with erythromycin resistant and clindamycin resistant, of which only 140 (50.35%) strains were D-test positives, while the rest 51 (18.34%) strains were D-test negatives. Conclusions: In view of high prevalence of D-test positive S. aureus strains, and equally high prevalence of multidrug resistant strains both in community and hospital sectors, undertaking of D-test may be routinely conducted for suppurative infections.