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To determine the pathogens associated with surgical site infections (SSIs) and describe patterns of antimicrobial use and resistance in orthopedic and neurosurgical patients in a large university hospital in Vietnam.Prospective cohort study.Cho Ray Hospital, Ho Chi Minh City, Vietnam.All patients who had operations during a 5-week study period.Of 702 surgical patients, 80 (11.4%) developed an SSI. The incidence of SSI among orthopedic patients was 15.2% (48 of 315), and among neurosurgical patients it was 8.3% (32 of 387). Postoperative bacterial cultures of samples from the surgical sites were performed for 55 (68.8%) of the 80 patients with SSI; 68 wound swab specimens and 10 cerebrospinal fluid samples were cultured. Of these 78 cultures, 60 (76.9%) were positive for a pathogen, and 15 (25%) of those 60 cultures yielded multiple pathogens. The 3 most frequently isolated pathogens were Pseudomonas aeruginosa (29.5% of isolates), Staphylococcus aureus (11.5% of isolates), and Escherichia coli (10.3% of isolates). Ninety percent of S. aureus isolates were methicillin resistant, 91% of P. aeruginosa isolates were ceftazidime resistant, and 38% of E. coli isolates were cefotaxime resistant. All but 1 of the 702 patients received antimicrobial therapy after surgery, and the median duration of antimicrobial therapy was 11 days. Commonly used antimicrobials included aminopenicillins and second- and third-generation cephalosporins. Two or more agents were given to 634 (90%) of the patients, and most combination drug regimens (86%) included an aminoglycoside.Our data indicate that the incidence of SSI is high in our study population, that the main pathogens causing SSI are gram-negative bacteria and are often resistant to commonly used antimicrobials, that the use of broad-spectrum antimicrobials after surgery is widespread, and that implementation of interventions aimed at promoting appropriate and evidence-based use of antimicrobials are needed in Vietnam.