Therapeutic failure of monotherapy with either a third-generation cephalosporin or a fluoroquinolone against nontyphoid salmonellae has been observed in clinical practice. Combination therapy with both agents is recommended in the literature for treating life-threatening infections. However, we know of no published case reports that indicate a therapeutic advantage of this combination therapy for nontyphoid salmonellae infections. We describe a 60-year-old man who had breakthrough bacteremia with vertebral osteomyelitis and paravertebral abscess caused by Salmonella enterica serotype Choleraesuis. This was not controlled with sequential monotherapy but was eventually cured with cefotaxime-ciprofloxacin combination therapy. The Etest showed that the strain was susceptible to cefotaxime and ciprofloxacin, but resistant to nalidixic acid. Cefotaxime and ciprofloxacin in combination may be considered as an option for difficult-to-treat salmonellosis.