Staphylococcus saprophyticus is a gram-positive, novobiocinresistant, coagulase-negative staphylococcus species. 1 It is the second most frequent causative microorganism in acute uncomplicated urinary tract infections in young, sexually active women. 2 However, it can present with a variety of complicated genitourinary tract infections which include prostatitis, pyelonephritis, and epididymitis. 3 Staphylococcus saprophyticus bacteremia rarely complicates the involvement of the urinary tract, particularly in immunocompetent hosts. 4 The clinical presentation and diagnosis are usually undistinguished S. saprophyticus bacteremia secondary to pyelonephritis from typical uropathogens. 5 Typically, S. saprophyticus is sensitive to most antimicrobials used to treat UTIs. However, there is rising resistance of S. saprophyticus to empirically and commonly used antibiotics to treat cystitis, hence, rendering the management more challenging. 6 Herein, we report an unusual highly resistant case of S. saprophyticus pyelonephritis leading to bacteremia in an otherwise healthy young female patient who was successfully treated with a course of vancomycin and daptomycin. In addition, we reviewed the literature for similar cases.