Abstract This paper describes the wound microbiology and outcome of using systemic antibiotic prophylaxis (SAP) in mass burn casualties (MBC). The charts of 31 patients (mean age: 21 years, mean burn area: 42% of the total body surface area) injured in a dust explosion were reviewed for 1 month after the burn. Polymicrobial and rare pathogen wound infections (Acinetobacter junii, Aeromonas sobri, et al) were common in MBC due to sterility breech. Following the use of SAP for 2 to 14 days after admission, there was a reduction in wound infection rate from 45% at week 1 postburn to 10% at week 4. In addition, no blood stream infection occurred in the first week after the burns. Multidrug-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Candida albicans were the top three wound pathogens cultured. Multidrug-resistant microorganism infections were found in 39% of the patients, and the odds ratios for the these infections in burn patients with more than ≥40% total body surface area and in patients receiving two or more classes of antibiotics were 41.7 (95% confidence interval [CI] = 2.1–810.7, P = .01) and 9.9 (95% CI= 1.0–92.7, P = .04), respectively. Although SAP did not prevent wound or blood stream infections, no mortality occurred in our patients. A randomized controlled study is needed to investigate the impact of SAP on burn mortality in MBC.