Antimicrobial susceptibility data from United States medical centers participating in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance program were analyzed. These results indicate that ciprofloxacin resistance in commonly encountered nosocomial pathogens has reached a level where fluoroquinolones may no longer provide assured empiric monotherapy for serious infections nor provide a spectrum as a co-drug equivalent to aminoglycosides. Local susceptibility testing data must be assessed before fluoroquinolone empiric therapy can be used with confidence.