Role of Pharmacokinetics and Pharmacodynamics: Does the Dose Matter?

MacGowan, Alasdair

doi:10.1086/321855

Cited by 20 publications

(7 citation statements)

References 15 publications

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“…The general view is that t.MIC is the major PK/PD index that determines the in vivo efficacy of b-lactams, including penicillins, cephalosporins, monobactams and carbapenems, while, conversely, the Cmax/ MIC and AUC24h/MIC ratios are the important PK/PD indices that correlate with the efficacy of aminoglycosides and fluoroquinolones [6,7,16,17].…”

Section: Discussionmentioning

confidence: 99%

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

Scaglione¹,

Esposito²,

Leone³

et al. 2009

Eur Respir J

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Nosocomial pneumonia (NP) is associated with considerable morbidity and mortality. Data have shown that inadequate initial antibiotic therapy is a major risk for infectionattributed 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 b-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 o8 mg?L that plasma levels remain above the MIC o70%. 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 (p50.0014) and whether both MIC and drug concentration(s) were measured (p50.0002) significantly affected the probability of a good outcome. For microbiological outcome, the MIC for the b-lactams (f2 mg?L -1 ; p,0.0001) and whether the second drug was a fluoroquinolone or aminoglycoside (fluoroquinolones were better than aminoglycosides; p50.0177), as well as whether both MIC and drug concentration(s) were measured (p50.02), 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.

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Section: Discussionmentioning

confidence: 99%

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

Scaglione¹,

Esposito²,

Leone³

et al. 2009

Eur Respir J

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“…The efficiency of killing for concentrationdependent agents is correlated with the peak serum concentration and MIC for the organism. The ratio of peak concentration to MIC for such agents is usually predictive of bacterial eradication [36][37][38].…”

mentioning

confidence: 99%

The Importance of Bactericidal Drugs: Future Directions in Infectious Disease

Finberg

Moellering

Tally

et al. 2004

Clinical Infectious Diseases

184

114

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The bulk of the evidence supports the concept that, in treating endocarditis and meningitis, it is important to use antibacterial agents with in vitro bactericidal activity. This conclusion is based on both human and animal data. The data to support bactericidal drugs' superiority to bacteriostatic drugs do not exist for most other clinical situations, and animal models do not support this concept in some situations. Clinicians should be aware that drugs that are bacteriostatic for one organism may in fact be bactericidal for another organism or another strain of the same organism.

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“…For some drugs, the pharmacological effect is dependent on the C max . For example, aminoglycosides, which are widely used antibiotics, needs to achieve a C max that is at least eight -to 10 -fold higher than the minimum inhibitory concentration ( MIC ) to obtain a clinical response ≥ 90% [14,15] . The unit of C max is concentration unit (e.g., nanogram per milliliter [ng/mL]).…”

Section: Maximum Plasma Concentration ( C Max ) and Time Of Maximum Cmentioning

confidence: 99%