Optimizing outcomes with antimicrobial therapy through pharmacodynamic profiling

Nicolau, David P.

doi:10.1007/s10156-003-0279-x

Cited by 94 publications

(61 citation statements)

References 26 publications

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“…7 Important pharmacokinetic terms include volume of distribution (V d ), not a physiological volume but rather a proportionality constant that relates serum drug concentration to body drug concentrations; clearance, the process of drug elimination (eg, hepatic metabolism, renal fi ltration) from the body over time (eg, volume of fl uid cleared of drug over time); half-life (t 1/2 ), the time it takes the drug serum concentration to decrease by half; maximum concentration (C max ), peak or highest blood concentration after a dose; minimum concentration (C min ), trough or lowest blood concentration just before the next dose; and area under the curve (AUC), total drug presence in the blood and body during a 24-hour period. 6,7 Changes in these pharmacokinetic parameters affect the ability of antibiotics to penetrate infection sites and achieve suffi cient concentrations. Critically ill patients have many pharmacokinetic derangements because of vasodilatation, capillary leak, third spacing, edema, and changes in cardiac, renal, and hepatic body systems 6 (Table 1).…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

“…6,8 The MIC is the lowest concentration necessary to inhibit the growth of 90% of the pathogen population in vitro. [6][7][8] Conversely, the minimum bactericidal concentration is the lowest concentration necessary to irreversibly inhibit 99.9% of bacterial growth, leading to eradication of the inoculum. 9 Antibiotic susceptibility is determined by the relationship between MIC and achievable antibiotic concentration.…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

“…If the MIC is lower than the antibiotic concentration achieved with a safe dose, the pathogen is considered susceptible; an MIC higher than the antibiotic concentration achieved indicates a resistant pathogen. 7 Each antibiotic-pathogen combination has individualized thresholds for determining susceptibility or resistance. The range of concentrations between the MIC and the mutant prevention concentration, or the drug concentration corresponding to the MIC for the least susceptible mutant in a colony, has been called the mutant selection window.…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

“…10 Effective eradication of a pathogen occurs when the dose of antibiotic reaches or maintains optimal concentrations relative to the pathogen MIC. 7 Because proving the drug concentration at the infection site is not typically possible, MIC is used as a surrogate marker for assessing microbiological activity at the site. 8 Antibiotics are classified as having either timedependent or concentration-dependent killing (Table 2, Figure 1).…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

“…Critically ill patients are at risk for unpredictable antibiotic exposure because of previously mentioned physiological derangements. 7 Critical care nurses often administer antibiotics with different frequencies, duration of infusions, and monitoring parameters to improve antibiotic effi cacy.…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

See 4 more Smart Citations

Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis

Fleet

Mueller

2016

Critical Care Nurse

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Sepsis is associated with marked mortality, which may be reduced by prompt initiation of adequate, appropriate doses of antibiotic. Critically ill patients often have physiological changes that reduce blood and tissue concentrations of antibiotic and high rates of multidrug-resistant pathogens, which may affect patients' outcomes. All critical care professionals, including critical care nurses, should understand antibiotic pharmacokinetics and pharmacodynamics to ensure sound antibiotic dosing and administration strategies for optimal microbial killing and patients' outcomes. Effective pathogen eradication occurs when the dose of antibiotic reaches or maintains optimal concentrations relative to the minimum inhibitory concentration for the pathogen. Time-dependent antibiotics, such as β-lactams, can be given as extended or continuous infusions. Concentration-dependent antibiotics such as aminoglycosides are optimized by using high, once-daily dosing strategies with serum concentration monitoring. Vancomycin and fl uoroquinolones are dependent on both time and concentration above the minimum inhibitory concentration. (Critical Care Nurse. 2016;36[2]:22-32) S epsis is a major cause of morbidity and mortality in the United States, affecting more than 650 000 patients per year. The spectrum of sepsis to septic shock is associated with crude mortality rates of 20% to 70%. [1][2][3][4] From the onset of hypotension, the probability of survival is reduced by 12% for each hour of delay before administration of adequate empiric antibiotics. 5Hence, current guidelines advocate early administration of adequate, broad-spectrum, local antibiogram-based antibiotic therapy in appropriate doses to penetrate the suspected site of infection (eg, lungs, cerebral spinal fl uid, intra-abdominal fl uid).1 Physiological changes associated with sepsis can complicate antibiotic dosing, effectiveness, and safety.

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Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%