A serious problem confronting clinical laboratories and hospital formulary practices is the delayed availability of approved, commercially prepared susceptibility test reagents for newer antimicrobials. A current example is gatifloxacin, a new 8-methoxy fluoroquinolone with expanded potency against many Gram-positive pathogens. This study addresses the use of "surrogate marker" fluoroquinolones to predict susceptibility for gatifloxacin. Reference broth microdilution MIC results for 29,632 strains isolated in United States medical centers (SENTRY Antimicrobial Surveillance Program, 1997-99) were used: staphylococci (9,940 strains), enterococci (2,570), Streptococcus pneumoniae (3,784), Enterobacteriaceae (10,670) and Pseudomonas aeruginosa (2,668). Gatifloxacin interpretation categories were compared to those of ciprofloxacin and levofloxacin by regression statistics and error rate bounding analyses. For the Enterobacteriaceae, the absolute categorical agreement was 97.9 to 98.7% (false-susceptible or very-major error [VME], 0.03%-0.1%) for comparisons of both ciprofloxacin and levofloxacin with gatifloxacin. P. aeruginosa testing was more problematic (higher minor error rates), but acceptable at 0.6% to 1.1% VME and a 85.7% to 89.9% overall agreement. Ciprofloxacin results used to predict gatifloxacin in Gram-positive species was almost without VME (0.0%-0.2%) because gatifloxacin was significantly superior against these species, especially for S. pneumoniae, where gatifloxacin (MIC(90,) 0.5 microg/ml) was fourfold more potent than levofloxacin (MIC(90,) 2 microg/ml). The preferred gatifloxacin predictor drug was ciprofloxacin for all species except S. pneumoniae and P. aeruginosa, where levofloxacin results had a slightly greater predictive value. Susceptibility testing results for selected currently available fluoroquinolones can be used to predict susceptibility to gatifloxacin with high confidence. Many Gram-positive cocci, however, will be categorized as false-resistant by this interim method since gatifloxacin has a 11% to 34% wider spectrum of activity compared to ciprofloxacin when testing staphylococci and enterococci. Clinical laboratories can reliably use these suggested "surrogate markers" until reliable tests for gatifloxacin become available.