Predictors of Mortality for Methicillin-Resistant Staphylococcus aureus Health-Care–Associated Pneumonia

Jeffres, Meghan N.; Isakow, Warren; Doherty, Joshua A.; McKinnon, Peggy S.; Ritchie, David J.; Micek, Scott T.; Kollef, Marin H.

doi:10.1378/chest.130.4.947

Cited by 205 publications

(161 citation statements)

References 42 publications

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“…9 Others also failed to demonstrate the benefits of recently recommended higher serum vancomycin trough concentrations >15 mg/l in achieving better clinical outcomes. 10,11,17 The current findings may justify the vancomycin trough concentration between 10 and 15 mg/l as an effective and safe target for MRSA infection in critically ill patients. However, this observation has not been interpreted in the presence of MICs, and caution must be exercised before applying this finding to other study populations.…”

Section: Discussionmentioning

confidence: 73%

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients

et al. 2012

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Section: Discussionmentioning

confidence: 73%

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients

et al. 2012

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“…On the basis of the results of this study and the frequency with which lung infections occur in critically ill patients, it has been advocated that achieving this pharmacokinetic-pharmacodynamic target of AUC 0-24 /MIC ratio of Ն400 should optimize clinical benefit (6). Although AUC 0-24 is not routinely monitored in clinical practice, Jeffres et al (14) have shown that trough concentrations from intermittent dosing are correlated with AUC and thus are regarded as an appropriate surrogate measure for the AUC 0-24 and as the most practical method to monitor vancomycin dosing (26,28). Some studies have successfully described use of a nomogram to guide continuousinfusion dosing (24).…”

Section: Discussionmentioning

confidence: 98%

Vancomycin Dosing in Critically Ill Patients: Robust Methods for Improved Continuous-Infusion Regimens

Roberts

Taccone

Udy

et al. 2011

Antimicrob Agents Chemother

201

177

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Despite the development of novel antibiotics active against Gram-positive bacteria, vancomycin generally remains the first treatment, although rapidly achieving concentrations associated with maximal efficacy provides an unresolved challenge. The objective of this study was to conduct a population pharmacokinetic analysis of vancomycin in a large population of critically ill patients. This was a retrospective data collection of 206 adult septic critically ill patients who were administered vancomycin as a loading dose followed by continuous infusion. The concentration-versus-time data for vancomycin in serum was analyzed by a nonlinear mixed-effects modeling approach using NONMEM. Monte Carlo simulations were performed using the final covariate model. We found that the best population pharmacokinetic model consisted of a one-compartment linear model with combined proportional and additive residual unknown variability. The volume of distribution of vancomycin (1.5 liters/kg) was described by total body weight and clearance (4.6 liters/h) by 24-hour urinary creatinine clearance (CrCl), normalized to body surface area. Simulation data showed that a 35-mg/kg loading dose was necessary to rapidly achieve vancomycin concentrations of 20 mg/liter. Daily vancomycin requirements were dependent on CrCl, such that a patient with a CrCl of 100 ml/min/1.73 m 2 would require at least 35 mg/kg per day by continuous infusion to maintain target concentrations. In conclusion, we have found that higher-than-recommended loading and daily doses of vancomycin seem to be necessary to rapidly achieve therapeutic serum concentrations in these patients.

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“…Prior to the present study, Jeffres et al sought to evaluate the use of targeted trough concentrations of 15 to 20 mg/liter in patients with MRSA pneumonia (17). Additional calculations were also performed to approximate the vancomycin AUCs, and no differences between survivors and nonsurvivors were observed.…”

Section: Discussionmentioning

confidence: 99%

Vancomycin AUC ₂₄ /MIC Ratio in Patients with Complicated Bacteremia and Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus and Its Association with Attributable Mortality during Hospitalization

Brown

Forrest

2012

Antimicrob Agents Chemother

104

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Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated bacteremia (CB) and infective endocarditis (IE).The gold standard treatment for these infections is vancomycin. A vancomycin area under the concentration-time curve from 0 to 24 h (AUC 24 )/MIC ratio of >400 has been suggested as a target to achieve clinical effectiveness, and yet to date no study has quantitatively investigated the AUC 24 /MIC ratio and its association with attributable mortality (AM). We performed a review of patients treated for MRSA CB and IE from 1 July 2006 to 30 June 2008. AM was defined as deaths where CB or IE was documented as the main cause or was mentioned as the main diagnosis. Classification and regression tree analysis (CART) was used to identify the AUC 24 /MIC ratio associated with AM. Mann-Whitney and Fisher exact tests were used for univariate analysis, and logistic regression was used for multivariate modeling. The MICs were determined by Etest, and the AUC 24 was determined using a maximum a posteriori probability-Bayesian estimator. A total of 32 CB and 18 IE patients were enrolled. The overall crude mortality and AM were 24 and 16%, respectively. The CART-derived partition for the AUC 24 /MIC ratio and AM was <211. Patients with an AUC 24 /MIC ratio of <211 had a >4-fold increase in AM than patients who received vancomycin doses that achieved an AUC 24 /MIC ratio of >211 (38 and 8%, respectively; P ‫؍‬ 0.02). In bivariate analysis the APACHE-II score and an AUC 24 /MIC ratio of <211 were significantly associated with AM. In the multivariate model, the APACHE-II score (odds ratio, 1.24; P ‫؍‬ 0.04) and a vancomycin AUC/MIC ratio of <211 (odds ratio, 10.4; P ‫؍‬ 0.01) were independent predictors of AM. In our analysis, independent predictors of AM were the APACHE-II score and an AUC 24 /MIC ratio of <211. We believe further investigations are warranted.

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Predictors of Mortality for Methicillin-Resistant Staphylococcus aureus Health-Care–Associated Pneumonia

Cited by 205 publications

References 42 publications

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients

Vancomycin Dosing in Critically Ill Patients: Robust Methods for Improved Continuous-Infusion Regimens

Vancomycin AUC ₂₄ /MIC Ratio in Patients with Complicated Bacteremia and Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus and Its Association with Attributable Mortality during Hospitalization

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Predictors of Mortality for Methicillin-Resistant Staphylococcus aureus Health-Care–Associated Pneumonia

Cited by 205 publications

References 42 publications

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients

The relationship between trough concentration of vancomycin and effect on methicillin-resistant Staphylococcus aureus in critically ill patients

Vancomycin Dosing in Critically Ill Patients: Robust Methods for Improved Continuous-Infusion Regimens

Vancomycin AUC 24 /MIC Ratio in Patients with Complicated Bacteremia and Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus and Its Association with Attributable Mortality during Hospitalization

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Vancomycin AUC ₂₄ /MIC Ratio in Patients with Complicated Bacteremia and Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus and Its Association with Attributable Mortality during Hospitalization