Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia

Nosocomial pneumonia (NP) is associated with considerable morbidity and mortality. Data have shown that inadequate initial antibiotic therapy is a major risk for infection-attributed mortality. The aim of the present study was to measure antibiotic concentration and minimum inhibitory concentration (MIC) in infected hospitalised patients early in therapy, in order to determine whether dose alterations, in those with low drug concentrations, could affect outcomes. Only patients treated with aminoglycosides, fluoroquinolones, and beta-lactams were evaluated. MICs were determined using standard National Committee for Clinical Laboratory Standards procedures. Antibiotics were assayed using validated high-performance liquid chromatographic methods. Pharmacokinetic/pharmacodynamic markers adopted were: aminoglycoside peak/MIC ratio >= 8 mg.L-1; fluoroquinolone peak/MIC >= 10 mg.L-1; beta-lactam peak/MIC >= 4 mg.L-1 and time that plasma levels remain above the MIC >= 70%. 638 patients with NP were included in the study. In 205 patients, both drug concentration and isolate MIC were available, while in other patients, used as controls, one or both parameters were lacking. For clinical outcome, the Acute Physiology and Chronic Health Evaluation 11 score (p<0.0001), the presence of combination therapy (p=0.0014) and whether both MIC and drug concentration (s) were measured (p=0.0002) significantly affected the probability of a good outcome. For microbiological outcome, the MIC for the beta-lactams (<= 2 mg.L-1; p<0.0001) and whether the second drug was a fluoroquinolone or aminoglycoside (fluoroquinolones were better than aminoglycosides; p=0.0177), as well as whether both MIC and drug concentration (s) were measured (p=0.02), affected the probability of eradication. Measurement of drug concentrations and determination of pathogen MIC values with subsequent dose alteration significantly improves the probability of good clinical outcome and pathogen eradication in NP.