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

¹ Universit� degli Studi di Milano, Dip. Di Farmacologia, Milano, and ² Dept of Infectious Diseases, Second University of Naples, Naples, Italy. ³ Ordway Research Institute, Albany, NY, USA.

CORRESPONDENCE: F. Scaglione, Dept of Pharmacology, Chemotherapy and Toxicology, Faculty of Medicine, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy. E-mail: francesco.scaglione{at}unimi.it

Keywords: Nosocomial pneumonia, optimising antibiotic therapy, pharmacokinetic/pharmacodynamic indices

Received: October 1, 2008
Accepted January 21, 2009

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 β-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; β-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 II 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 β-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.