Evaluation of antimicrobial usage vs. susceptibility relationships typically involves single agents. However, susceptibility profiles may be affected by multiple drugs. From 1992 through 1996, we studied relationships between drug usage and the susceptibility (only susceptibility rates of ≥70%) ofAcinetobacter anitratus (baumannii), Enterobacter aerogenes, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis,andSerratia marcescensto 22 agents. Linear regression was used to assess usage of each agent vs. susceptibility to it and to all agents. Only relationships with a coefficient of determination of ≥0.5 and a negative slope were evaluated and classified as increasing drug use and decreasing susceptibility (↑D, ↓%S) or decreasing drug use and increasing susceptibility (↓D, ↑%S). The mean numbers (range) of drugs associated with a change in susceptibility were 1.7 (0-14) and 0.6 (0-7), respectively, for ↑D, ↓%S and ↓D, ↑%S relationships. Multiple antimicrobials are associated with susceptibility to other drugs; thus, surveillance of these relationships should not be limited to single drugs.