Vancomycin: We Can't Get There From Here
Background. We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines. Methods. A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12...
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| Published in | Clinical infectious diseases Vol. 52; no. 8; pp. 969 - 974 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford
Oxford University Press
15.04.2011
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Background. We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines. Methods. A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L. Results. At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%. At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered. Conclusions. This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin. |
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| AbstractList | Our findings indicate that vancomycin may not be useful for treating MRSA infections with MICs > 1 mg/L. Aggressive vancomycin dosing, producing an adequate drug exposure, is also associated with a high risk of nephrotoxicity, especially for ICU patients.
(See the article by Kullar et al, on pages 975-981.)
Background. We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines.
Methods. A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L.
Results. At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%. At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered.
Conclusions. This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin. Background. We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines. Methods. A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L. Results. At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%. At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered. Conclusions. This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin. We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines.BACKGROUNDWe sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines.A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L.METHODSA series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L.At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%(.) At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered.RESULTSAt a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%(.) At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered.This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin.CONCLUSIONSThis study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin. We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines. A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L. At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%(.) At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered. This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin. We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines. A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ≥ 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L. At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%. At a MIC of 1 mg/L, ≥3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ≤1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered. This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ≥ 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin. |
| Author | Drusano, George L. Patel, Nimish Lodise, Thomas P. Rodvold, Keith A. Lomaestro, Ben Pai, Manjunath P. |
| Author_xml | – sequence: 1 givenname: Nimish surname: Patel fullname: Patel, Nimish – sequence: 2 givenname: Manjunath P. surname: Pai fullname: Pai, Manjunath P. – sequence: 3 givenname: Keith A. surname: Rodvold fullname: Rodvold, Keith A. – sequence: 4 givenname: Ben surname: Lomaestro fullname: Lomaestro, Ben – sequence: 5 givenname: George L. surname: Drusano fullname: Drusano, George L. – sequence: 6 givenname: Thomas P. surname: Lodise fullname: Lodise, Thomas P. |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24185443$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21460308$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Copyright © 2011 Oxford University Press on behalf of the Infectious Diseases Society of America The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. 2011 2015 INIST-CNRS Copyright University of Chicago, acting through its Press Apr 15, 2011 |
| Copyright_xml | – notice: Copyright © 2011 Oxford University Press on behalf of the Infectious Diseases Society of America – notice: The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. 2011 – notice: 2015 INIST-CNRS – notice: Copyright University of Chicago, acting through its Press Apr 15, 2011 |
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| Keywords | Infection Antibiotic Peptides Glycopeptide Polypeptide Vancomycin Antibacterial agent |
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| References | Kirst (2_6006379) 1998; 42 Jeffres (10_29229316) 2007; 29 (20_38343208) 1998; 26 Moise-Broder (4_18491924) 2004; 43 Hidayat (9_22792540) 2006; 166 West (19_17629764) 2003; 25 Rybak (21_22218561) 2006; 119 (22_35247120) 2009; 53 (1_35402048) 2007; 27 (24_31541219) 2008; 62 Berthoin (26_35673386) 2009; 34 Ingram (11_35579937) 2009; 34 (12_30599618) 2008; 62 (23_30798547) 2008; 52 Drusano (7_18096071) 2004; 2 Rodvold (15_5004741) 1988; 32 Craig (5_17986259) 2003; 17 (25_32053699) 2008; 52 (8_38265150) 2009; 49 Rodvold (17_5272330) 1989; 11 Rybak (3_32992438) 2009; 66 (13_30341427) 2008; 52 (6_38274688) 2006; 42 21880585 - Clin Infect Dis. 2011 Nov;53(9):966-7 21880584 - Clin Infect Dis. 2011 Nov;53(9):965-6 |
| References_xml | – volume: 43 start-page: 925 issn: 0312-5963 issue: 13 year: 2004 ident: 4_18491924 publication-title: Clinical pharmacokinetics doi: 10.2165/00003088-200443130-00005 – volume: 2 start-page: 289 issn: 1740-1526 issue: 4 year: 2004 ident: 7_18096071 publication-title: Nature reviews. Microbiology doi: 10.1038/nrmicro862 – volume: 62 start-page: 168 issn: 0305-7453 issue: 1 year: 2008 ident: 12_30599618 publication-title: Journal of Antimicrobial Chemotherapy doi: 10.1093/jac/dkn080 – volume: 17 start-page: 479 issn: 0891-5520 issue: 3 year: 2003 ident: 5_17986259 publication-title: Infectious disease clinics of North America doi: 10.1016/S0891-5520(03)00065-5 – volume: 42 start-page: S35 issn: 1058-4838 issue: Supplement_1 year: 2006 ident: 6_38274688 publication-title: Clinical Infectious Diseases doi: 10.1086/491712 – volume: 119 start-page: S37 issn: 0002-9343 issue: 6 Suppl 1 year: 2006 ident: 21_22218561 publication-title: The American journal of medicine doi: 10.1016/j.amjmed.2006.04.001 – volume: 53 start-page: 3894 issn: 0066-4804 issue: 9 year: 2009 ident: 22_35247120 publication-title: Antimicrobial Agents and Chemotherapy doi: 10.1128/AAC.01585-08 – volume: 34 start-page: 555 issn: 0924-8579 issue: 6 year: 2009 ident: 26_35673386 publication-title: International journal of antimicrobial agents doi: 10.1016/j.ijantimicag.2009.08.005 – volume: 52 start-page: 1330 issn: 0066-4804 issue: 4 year: 2008 ident: 13_30341427 publication-title: Antimicrobial Agents and Chemotherapy doi: 10.1128/AAC.01602-07 – volume: 26 start-page: 1 issn: 1058-4838 issue: 1 year: 1998 ident: 20_38343208 publication-title: Clinical Infectious Diseases doi: 10.1086/516284 – volume: 52 start-page: 2156 issn: 0066-4804 issue: 6 year: 2008 ident: 23_30798547 publication-title: Antimicrobial Agents and Chemotherapy doi: 10.1128/AAC.01046-07 – volume: 52 start-page: 4528 issn: 0066-4804 issue: 12 year: 2008 ident: 25_32053699 publication-title: Antimicrobial Agents and Chemotherapy doi: 10.1128/AAC.00904-08 – volume: 25 start-page: 485 issn: 0149-2918 issue: 2 year: 2003 ident: 19_17629764 publication-title: Clinical therapeutics doi: 10.1016/S0149-2918(03)80091-7 – volume: 42 start-page: 1303 issn: 0066-4804 issue: 5 year: 1998 ident: 2_6006379 publication-title: Antimicrobial Agents and Chemotherapy doi: 10.1128/AAC.42.5.1303 – volume: 49 start-page: 507 issn: 1058-4838 issue: 4 year: 2009 ident: 8_38265150 publication-title: Clinical Infectious Diseases doi: 10.1086/600884 – volume: 27 start-page: 1001 issn: 1875-9114 year: 2007 ident: 1_35402048 doi: 10.1592/phco.27.7.1001 – volume: 32 start-page: 848 issn: 0066-4804 issue: 6 year: 1988 ident: 15_5004741 publication-title: Antimicrobial Agents and Chemotherapy doi: 10.1128/AAC.32.6.848 – volume: 34 start-page: 570 issn: 0924-8579 issue: 6 year: 2009 ident: 11_35579937 publication-title: International journal of antimicrobial agents doi: 10.1016/j.ijantimicag.2009.07.011 – volume: 166 start-page: 2138 issn: 0003-9926 issue: 19 year: 2006 ident: 9_22792540 publication-title: Archives of Internal Medicine doi: 10.1001/archinte.166.19.2138 – volume: 29 start-page: 1107 issn: 0149-2918 issue: 6 year: 2007 ident: 10_29229316 publication-title: Clinical therapeutics doi: 10.1016/j.clinthera.2007.06.014 – volume: 11 start-page: 269 issn: 0163-4356 issue: 3 year: 1989 ident: 17_5272330 publication-title: Therapeutic drug monitoring doi: 10.1097/00007691-198905000-00009 – volume: 66 start-page: 82 issn: 1079-2082 issue: 1 year: 2009 ident: 3_32992438 publication-title: American Journal of Health-System Pharmacy doi: 10.2146/ajhp080434 – volume: 62 start-page: 1065 issn: 0305-7453 issue: 5 year: 2008 ident: 24_31541219 publication-title: Journal of Antimicrobial Chemotherapy doi: 10.1093/jac/dkn288 – reference: 21880585 - Clin Infect Dis. 2011 Nov;53(9):966-7 – reference: 21880584 - Clin Infect Dis. 2011 Nov;53(9):965-6 |
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| Snippet | Background. We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent... Our findings indicate that vancomycin may not be useful for treating MRSA infections with MICs > 1 mg/L. Aggressive vancomycin dosing, producing an adequate... We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin... |
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| SubjectTerms | Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - adverse effects Anti-Bacterial Agents - pharmacokinetics Anti-Bacterial Agents - pharmacology Antibacterial agents Antibiotics Antibiotics. Antiinfectious agents. Antiparasitic agents ARTICLES AND COMMENTARIES Biological and medical sciences Dosage Dose response relationship Effectiveness studies Humans Infections Infectious diseases Kidneys Medical sciences Methicillin-Resistant Staphylococcus aureus - drug effects Microbial Sensitivity Tests Monte Carlo methods Nephrotoxicity Pharmacology Pharmacology. Drug treatments Population estimates Ratios Regression analysis Serum - chemistry Simulation Staphylococcal Infections - drug therapy Staphylococcal Infections - microbiology Staphylococcus aureus Staphylococcus infections Toxicity Vancomycin - administration & dosage Vancomycin - adverse effects Vancomycin - pharmacokinetics Vancomycin - pharmacology |
| Title | Vancomycin: We Can't Get There From Here |
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