Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital
ABSTRACTINTRODUCTION: Monte Carlo simulations have been used for selecting optimal antibiotic regimens for treatment of bacterial infections. The aim of this study was to assess the pharmacokinetic and pharmacodynamic target attainment of intravenous β-lactam regimens commonly used to treat bloodstr...
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| Format: | Article |
| Language: | English |
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Sociedade Brasileira de Medicina Tropical (SBMT)
2015-10-01
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| Series: | Revista da Sociedade Brasileira de Medicina Tropical |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822015000500539&lng=en&tlng=en |
| _version_ | 1811244657165729792 |
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| author | Guilherme Henrique Furtado Leandro Cardinal Rodrigo Spineli Macedo Juliana Oliveira Silva Eduardo Alexandrino Medeiros Joseph Levente Kuti David Paul Nicolau |
| author_facet | Guilherme Henrique Furtado Leandro Cardinal Rodrigo Spineli Macedo Juliana Oliveira Silva Eduardo Alexandrino Medeiros Joseph Levente Kuti David Paul Nicolau |
| author_sort | Guilherme Henrique Furtado |
| collection | DOAJ |
| description | ABSTRACTINTRODUCTION: Monte Carlo simulations have been used for selecting optimal antibiotic regimens for treatment of bacterial infections. The aim of this study was to assess the pharmacokinetic and pharmacodynamic target attainment of intravenous β-lactam regimens commonly used to treat bloodstream infections (BSIs) caused by Gram-negative rod-shaped organisms in a Brazilian teaching hospital.METHODS: In total, 5,000 patients were included in the Monte Carlo simulations of distinct antimicrobial regimens to estimate the likelihood of achieving free drug concentrations above the minimum inhibitory concentration (MIC; fT > MIC) for the requisite periods to clear distinct target organisms. Microbiological data were obtained from blood culture isolates harvested in our hospital from 2008 to 2010.RESULTS: In total, 614 bacterial isolates, including Escherichia coli, Enterobacterspp., Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, were analyzed Piperacillin/tazobactam failed to achieve a cumulative fraction of response (CFR) > 90% for any of the isolates. While standard dosing (short infusion) of β-lactams achieved target attainment for BSIs caused by E. coliand Enterobacterspp., pharmacodynamic target attainment against K. pneumoniaeisolates was only achieved with ceftazidime and meropenem (prolonged infusion). Lastly, only prolonged infusion of high-dose meropenem approached an ideal CFR against P. aeruginosa; however, no antimicrobial regimen achieved an ideal CFR against A. baumannii.CONCLUSIONS:These data reinforce the use of prolonged infusions of high-dose β-lactam antimicrobials as a reasonable strategy for the treatment of BSIs caused by multidrug resistant Gram-negative bacteria in Brazil. |
| first_indexed | 2024-04-12T14:29:00Z |
| format | Article |
| id | doaj.art-b62421cbaa9640fba3da7019e20232c6 |
| institution | Directory Open Access Journal |
| issn | 1678-9849 |
| language | English |
| last_indexed | 2024-04-12T14:29:00Z |
| publishDate | 2015-10-01 |
| publisher | Sociedade Brasileira de Medicina Tropical (SBMT) |
| record_format | Article |
| series | Revista da Sociedade Brasileira de Medicina Tropical |
| spelling | doaj.art-b62421cbaa9640fba3da7019e20232c62022-12-22T03:29:21ZengSociedade Brasileira de Medicina Tropical (SBMT)Revista da Sociedade Brasileira de Medicina Tropical1678-98492015-10-0148553954510.1590/0037-8682-0122-2015S0037-86822015000500539Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospitalGuilherme Henrique FurtadoLeandro CardinalRodrigo Spineli MacedoJuliana Oliveira SilvaEduardo Alexandrino MedeirosJoseph Levente KutiDavid Paul NicolauABSTRACTINTRODUCTION: Monte Carlo simulations have been used for selecting optimal antibiotic regimens for treatment of bacterial infections. The aim of this study was to assess the pharmacokinetic and pharmacodynamic target attainment of intravenous β-lactam regimens commonly used to treat bloodstream infections (BSIs) caused by Gram-negative rod-shaped organisms in a Brazilian teaching hospital.METHODS: In total, 5,000 patients were included in the Monte Carlo simulations of distinct antimicrobial regimens to estimate the likelihood of achieving free drug concentrations above the minimum inhibitory concentration (MIC; fT > MIC) for the requisite periods to clear distinct target organisms. Microbiological data were obtained from blood culture isolates harvested in our hospital from 2008 to 2010.RESULTS: In total, 614 bacterial isolates, including Escherichia coli, Enterobacterspp., Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, were analyzed Piperacillin/tazobactam failed to achieve a cumulative fraction of response (CFR) > 90% for any of the isolates. While standard dosing (short infusion) of β-lactams achieved target attainment for BSIs caused by E. coliand Enterobacterspp., pharmacodynamic target attainment against K. pneumoniaeisolates was only achieved with ceftazidime and meropenem (prolonged infusion). Lastly, only prolonged infusion of high-dose meropenem approached an ideal CFR against P. aeruginosa; however, no antimicrobial regimen achieved an ideal CFR against A. baumannii.CONCLUSIONS:These data reinforce the use of prolonged infusions of high-dose β-lactam antimicrobials as a reasonable strategy for the treatment of BSIs caused by multidrug resistant Gram-negative bacteria in Brazil.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822015000500539&lng=en&tlng=enMonte Carlo simulationPharmacodynamicsGram-negative bacteriaBloodstream infections |
| spellingShingle | Guilherme Henrique Furtado Leandro Cardinal Rodrigo Spineli Macedo Juliana Oliveira Silva Eduardo Alexandrino Medeiros Joseph Levente Kuti David Paul Nicolau Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital Revista da Sociedade Brasileira de Medicina Tropical Monte Carlo simulation Pharmacodynamics Gram-negative bacteria Bloodstream infections |
| title | Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital |
| title_full | Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital |
| title_fullStr | Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital |
| title_full_unstemmed | Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital |
| title_short | Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital |
| title_sort | pharmacokinetic pharmacodynamic target attainment of intravenous β lactam regimens against gram negative bacteria isolated in a brazilian teaching hospital |
| topic | Monte Carlo simulation Pharmacodynamics Gram-negative bacteria Bloodstream infections |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822015000500539&lng=en&tlng=en |
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