Antimicrobial pharmacokinetics and dosing in critically ill adults receiving prolonged intermittent renal replacement therapy: A systematic review
Bibliographic record
Abstract
Prolonged intermittent renal replacement therapy (PIRRT) is gaining popularity as a renal replacement modality in intensive care units, but there is a relative lack of guidance regarding antimicrobial clearance and dosing when compared with other modalities. The objectives of this systematic review were to: (1) identify and describe the pharmacokinetics (PK) of relevant antimicrobials used in critically ill adults receiving PIRRT, (2) evaluate the quality of evidence supporting these data, and (3) propose dosing recommendations based on the synthesis of these data. A search strategy for multiple databases was designed and executed to identify relevant published evidence describing the PK of antimicrobials used in critically ill adults receiving PIRRT. Quality assessment, evaluation of reporting, and relevant data extraction were conducted in duplicate. Synthesis of PK/pharmacodynamic (PD) outcomes, dosing recommendations from study authors, and physicochemical properties of included antibiotics were assessed by investigators in addition to the quality of evidence to develop dosing recommendations. Thirty-nine studies enrolling 452 patients met criteria for inclusion and provided PK and/or PD data for 20 antimicrobials in critically ill adults receiving PIRRT. Nineteen studies describe both PK and PD outcomes. Vancomycin (12 studies, 171 patients), meropenem (7 studies, 84 patients), and piperacillin/tazobactam (5 studies, 56 patients) were the most frequent antimicrobials encountered. The quality of evidence was deemed strong for 7/20 antimicrobials, and strong dosing recommendations were determined for 9/20 antimicrobials. This systematic review updates and addresses issues of quality in previous systematic reviews on this topic. Despite an overall low quality of evidence, strong recommendations were able to be made for almost half of the identified antimicrobials. Knowledge gaps persist for many antimicrobials, and higher quality studies (i.e., population PK studies with assessment of PD target attainment) are needed to address these gaps.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.039 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.008 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".