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Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia
F Scaglione1, S Esposito, S Leone
1Department of Pharmacology, Chemotherapy and Toxicology, Faculty of Medicine, University of Milan, Milan, Italy. francesco.scaglione@unimi.it
Abstract:
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 >or=8 mg L(-1); fluoroquinolone peak/MIC >or=10 mg L(-1); beta-lactam peak/MIC >or=4 mg L(-1) and time that plasma levels remain above the MIC >or=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 beta-lactams (
Insights
Optimizing antibiotic dosing by measuring drug levels and pathogen susceptibility (minimum inhibitory concentration) significantly improves clinical outcomes and pathogen eradication in hospital-acquired pneumonia (HAP). This approach enhances treatment effectiveness for critically ill patients.
Area of Science:
- Infectious Diseases
- Clinical Pharmacy
- Pharmacokinetics/Pharmacodynamics
Background:
- Nosocomial pneumonia (NP) is a significant cause of morbidity and mortality in hospitalized patients.
- Inadequate initial antibiotic therapy is a primary risk factor for infection-attributed mortality in NP.
- Optimizing antibiotic therapy requires understanding drug concentrations and pathogen susceptibility.
Purpose of the Study:
- To measure antibiotic concentrations and minimum inhibitory concentrations (MICs) in NP patients early in therapy.
- To determine if dose adjustments based on these measurements can improve clinical and microbiological outcomes.
- To evaluate the impact of pharmacokinetic/pharmacodynamic (PK/PD) marker achievement on treatment success.
Main Methods:
- Study included 638 hospitalized patients with NP, focusing on those treated with aminoglycosides, fluoroquinolones, and beta-lactams.
- Antibiotic concentrations were measured using high-performance liquid chromatography (HPLC).
- MICs were determined using standard laboratory procedures. PK/PD targets included specific peak/MIC ratios and time above MIC.
Main Results:
- Measuring both drug concentration and MIC, and subsequent dose alteration, significantly improved the probability of good clinical outcomes.
- Factors influencing clinical outcome included APACHE II score, combination therapy, and measurement of drug concentration/MIC.
- Microbiological outcomes, specifically pathogen eradication, were positively affected by lower beta-lactam MICs and the use of fluoroquinolones over aminoglycosides.
Conclusions:
- Measurement of antibiotic concentrations and pathogen MICs, coupled with dose adjustments, is crucial for optimizing NP treatment.
- This individualized approach significantly enhances the likelihood of successful clinical outcomes and pathogen eradication.
- The findings support the routine implementation of therapeutic drug monitoring and susceptibility testing in NP management.
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