Antibiotic resistance of bacteria agents (Staphylococcis aureus, Pseudomonas aeruginosa, Escherichia coli andStreptococcus pyogenes) of nosocomial wound infections, were assessed by in vitro susceptibility testing, evaluatingthe possible drug interactions among several antibiotics and the plasmid profile of DNA of isolate. Ninety-sixclinical isolates of (S.aureus, P aeruginosa, E coll and S pyogenes) obtained from two different Hospitals, werecollected. Suceptibility test with 17 antibiotics were performed by the Kirby-Bauer disk diffusion method andMinimal Inhibitory Concentrations [MICs] were determined by macrobroth dilution methodology. There issignificant difference in the resistance between Staphylococcus aureus isolates (43(100%) and Pseudomonasaeruginosa isolates (32(91.4%), [P<0.05]. Resistance to ofloxacin, erythromycin, norfloxacin, tetracyclines andchloramphenicol were more common. Highly resistant isolates were selected for the drug combination.Staphylococcus aureus (C.I) and Pseudomonas aeruginosa (C.I) were used as control isolates. Erythromycin had ahigh MIC50 value against the E coli isolates while it had a moderate effect 47% on all the 1solates. Combination ofciprofloxacin and erythromycin was fully synergistic against one S. pyogenes isolate, while the same combinationresulted in indifferent effect in most of the isolates. Combination therapy could be used to prevent the developmentof resistance and to enhanced antibacterial efficacy. Plasmid bands were seen in all the resistant isolates as revealedthrough agarose gel electrophoresis. The susceptibility test performed in this study suggests that nosocomial woundinfections were caused by organisms that are highly resistance to antibiotics. It is imperative that hygienic conditionsand surveillance initiative be focused in Hospitals in Nigeria to monitor and limit antimicrobial resistance and thespread of these nosocomial organisms, that is a major risk to human health because of its impact on morbidity,mortality and health care costs.