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Beta-lactam antibiotic concentrations in critically ill patients with standard and adjusted dosages: A prospective observational study

Areskog Lejbman, Ilja LU ; Torisson, Gustav LU orcid ; Resman, Fredrik LU and Sjövall, Fredrik LU orcid (2024) In Acta Anaesthesiologica Scandinavica
Abstract
Introduction
Antibiotic concentration target attainment is known to be poor in critically ill patients. Dose adjustment is recommended in patients with altered clearance, obesity and those with bacterial species with intermediate susceptibility. The aim of this study was to investigate the variation of antibiotic concentration in critically ill patients with standard or adjusted dosing regimens.

Methods
The concentration of three beta-lactam antibiotics used in the intensive care unit (ICU) setting, cefotaxime, piperacillin/tazobactam, and meropenem, was measured in patients with confirmed or suspected infection. Mid-dose and trough values were collected during a single dosing interval. The pharmacokinetic endpoints were a... (More)
Introduction
Antibiotic concentration target attainment is known to be poor in critically ill patients. Dose adjustment is recommended in patients with altered clearance, obesity and those with bacterial species with intermediate susceptibility. The aim of this study was to investigate the variation of antibiotic concentration in critically ill patients with standard or adjusted dosing regimens.

Methods
The concentration of three beta-lactam antibiotics used in the intensive care unit (ICU) setting, cefotaxime, piperacillin/tazobactam, and meropenem, was measured in patients with confirmed or suspected infection. Mid-dose and trough values were collected during a single dosing interval. The pharmacokinetic endpoints were a free antibiotic concentration that, during the whole dosing interval, was above MIC (100% ƒT > MIC, primary endpoint) or above four times MIC (100% ƒT > 4MIC, secondary endpoint). Non-species related MIC breakpoints were used (1 mg/L for cefotaxime, 8 mg/L for piperacillin/tazobactam, and 2 mg/L for meropenem).

Results
We included 102 patients (38 cefotaxime, 30 piperacillin/tazobactam, and 34 meropenem) at a single ICU, with a median age of 66 years. In total, 73% were males, 40% were obese (BMI ≥30) and the median SAPS 3 score was 63 points. Of all patients, 78 patients (76%) reached the primary endpoint (100%ƒT > MIC), with 74% for cefotaxime, 67% for piperacillin/tazobactam and 88% for meropenem. Target attainment for 100% ƒT > 4MIC was achieved in 40 (39%) patients, overall, with 34% for cefotaxime, 30% for piperacillin/tazobactam and 53% for meropenem. In patients with standard dose 71% attained 100%ƒT > MIC and 37% for 100%ƒT > 4MIC. All patients with reduced dose attained 100%ƒT > MIC and 27% attained 100% ƒT > 4MIC. In patients with increased dose 79% attained 100%ƒT > MIC and 48% 100%ƒT > 4MIC respectively.

Conclusions
Beta-lactam antibiotics concentration vary widely in critically ill patients. The current standard dosing regimens employed during the study were not sufficient to reach 100% ƒT > MIC in approximately a quarter of the patients. In patients where dose adjustment was performed, the group with increased dose also had low target attainment, as opposed to patients with dose reduction, who all reached target. This suggests the need for further individualization of dosing where therapeutic drug monitoring can be an alternative to further increase target attainment. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Acta Anaesthesiologica Scandinavica
publisher
Wiley-Blackwell
external identifiers
  • pmid:38407447
  • scopus:85186574593
ISSN
0001-5172
DOI
10.1111/aas.14382
language
English
LU publication?
yes
id
fc0807d5-6348-4ae9-8469-bd276b63a9fb
date added to LUP
2024-02-26 20:31:51
date last changed
2024-03-21 15:16:50
@article{fc0807d5-6348-4ae9-8469-bd276b63a9fb,
  abstract     = {{Introduction<br/>Antibiotic concentration target attainment is known to be poor in critically ill patients. Dose adjustment is recommended in patients with altered clearance, obesity and those with bacterial species with intermediate susceptibility. The aim of this study was to investigate the variation of antibiotic concentration in critically ill patients with standard or adjusted dosing regimens.<br/><br/>Methods<br/>The concentration of three beta-lactam antibiotics used in the intensive care unit (ICU) setting, cefotaxime, piperacillin/tazobactam, and meropenem, was measured in patients with confirmed or suspected infection. Mid-dose and trough values were collected during a single dosing interval. The pharmacokinetic endpoints were a free antibiotic concentration that, during the whole dosing interval, was above MIC (100% ƒT &gt; MIC, primary endpoint) or above four times MIC (100% ƒT &gt; 4MIC, secondary endpoint). Non-species related MIC breakpoints were used (1 mg/L for cefotaxime, 8 mg/L for piperacillin/tazobactam, and 2 mg/L for meropenem).<br/><br/>Results<br/>We included 102 patients (38 cefotaxime, 30 piperacillin/tazobactam, and 34 meropenem) at a single ICU, with a median age of 66 years. In total, 73% were males, 40% were obese (BMI ≥30) and the median SAPS 3 score was 63 points. Of all patients, 78 patients (76%) reached the primary endpoint (100%ƒT &gt; MIC), with 74% for cefotaxime, 67% for piperacillin/tazobactam and 88% for meropenem. Target attainment for 100% ƒT &gt; 4MIC was achieved in 40 (39%) patients, overall, with 34% for cefotaxime, 30% for piperacillin/tazobactam and 53% for meropenem. In patients with standard dose 71% attained 100%ƒT &gt; MIC and 37% for 100%ƒT &gt; 4MIC. All patients with reduced dose attained 100%ƒT &gt; MIC and 27% attained 100% ƒT &gt; 4MIC. In patients with increased dose 79% attained 100%ƒT &gt; MIC and 48% 100%ƒT &gt; 4MIC respectively.<br/><br/>Conclusions<br/>Beta-lactam antibiotics concentration vary widely in critically ill patients. The current standard dosing regimens employed during the study were not sufficient to reach 100% ƒT &gt; MIC in approximately a quarter of the patients. In patients where dose adjustment was performed, the group with increased dose also had low target attainment, as opposed to patients with dose reduction, who all reached target. This suggests the need for further individualization of dosing where therapeutic drug monitoring can be an alternative to further increase target attainment.}},
  author       = {{Areskog Lejbman, Ilja and Torisson, Gustav and Resman, Fredrik and Sjövall, Fredrik}},
  issn         = {{0001-5172}},
  language     = {{eng}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Acta Anaesthesiologica Scandinavica}},
  title        = {{Beta-lactam antibiotic concentrations in critically ill patients with standard and adjusted dosages: A prospective observational study}},
  url          = {{http://dx.doi.org/10.1111/aas.14382}},
  doi          = {{10.1111/aas.14382}},
  year         = {{2024}},
}