BackgroundBiofilm production has been established as a virulence factor which allows Staphylococcus to adhere and persist in medical devices. The objective was to determine whether therapeutic failure in patients infected with Staphylococcus spp. is linked to biofilm production, the presence of the ica operon, and the bacterial insertion sequence element IS256.MethodsStaphylococcus spp. isolates from patients with device-related infections were collected. Therapeutic failure with proper antimicrobial treatment was registered. Biofilm phenotype was determined by Congo red test agar and Christensen assay. Presence of the ica operon genes A-D and IS256 was detected by PCR. Differences were compared through x2.Results100 isolates from staphylococcal infections episodes were included: 40 sepsis/bacteremia, 32 ependymitis, and 28 peritonitis. 73.77% of CoNS and 79.5% of S. aureus isolates harbored the icaD gene, 29% of all isolates IS256-A+ IS256-D genes, icaA and icaB genes were only found in CoNS (27.8% and 21.3% respectively). Therapeutic failure occurred in 95.4.% of patients with a positive IS256-A+ IS256-D S. epidermidis isolate, RR 5.49 (CI 95% 2.24-13.44 p ≤ 0.0001), and 85.76% in CoNS isolates, RR 2.57 (CI 95% 0.97-6.80, p = 0.05). Although none S. aureus was positive for IS256-A + IS256-D, therapeutic failure was observed in 35.8%.ConclusionsThe presence of icaA/D genes along with the sequence element IS256 was associated with therapeutic failure in most CoNS infections, even though its absence in S. aureus isolates does not ensure therapeutic success.