title: Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration.
abstract: In an examination of the relationships among plasma aminoglycoside concentrations, the minimal inhibitory concentration (MIC) for the infecting organism, and therapeutic outcome, data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin, tobramycin, and amikacin. Clinical response to therapy occurred in 188 (80%) patients. Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response (P less than .00001 and P less than .0001, respectively). A graded dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response. By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response. These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy.
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D005839:Gentamicins / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011897:Random Allocation; D014031:Tobramycin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D005839:Gentamicins; D000583:Amikacin; D014031:Tobramycin