Risk of AKI Associated with Vancomycin in Combination with Other Broad-Spectrum Antipseudomonal Antibiotics: Systematic Review and Meta-Analysis
Bibliographic record
Abstract
Background: In hospitalized patients with infections, vancomycin (VAN) is often combined with broad-spectrum antipseudomonal antibiotics (BSAs), but the risk for acute kidney injury (AKI) associated with these combinations has not been comprehensively evaluated in previous meta-analyses. Methods: A systematic search of PubMed/MEDLINE, CENTRAL, EMBASE, and Scopus was conducted to identify studies comparing AKI incidence, severity, and outcomes across VAN-containing combinations from inception to April 15, 2025. Two reviewers independently screened articles for eligibility and discrepancies were resolved by a third reviewer. DerSimonian-Laird random effects meta-analysis was undertaken. Outcomes were stratified by drug combinations and patient populations (ICU vs. non-ICU, pediatric vs. adult). Risk of bias was assessed using Newcastle-Ottawa Scale (NOS) across three criteria: patient selection, comparability and outcomes. All analyses were conducted using RevMan version 5.4. Results: A total of 89 studies, involving 162,192 hospitalized patients were included in the quantitative synthesis, with 62.5% receiving VAN-piperacillin/tazobactam (PTZ), 25.3% VAN-cefepime, 7.4% VAN-carbapenems, 1.6% VAN-other BSAs and 3.2% VAN only. VAN-PTZ was associated with higher risk of AKI compared to all other combinations: OR=2.13, 95% CI 1.77-2.57, I2=70% vs. VAN-carbapenems; OR=1.98, 95% CI 1.74-2.25, I2=78% vs. VAN-cefepime; OR=2.42, 95% CI 1.95-2.99, I2=50% vs. VAN-other BSAs, and also when compared to VAN alone (OR=3.06, 95% CI 2.60-3.60, I2=16%). This effect was consistent across all stages of AKI, age groups (adult and pediatric), and in both ICU and non-ICU populations. In contrast, VAN-PTZ did not differentially affect RRT need or in-hospital mortality when compared to other VAN combinations or VAN alone. Conclusion: VAN-PTZ is a common antibiotic combination to treat infections in hospitalized patients that was associated with a higher risk of AKI. Studies are needed to characterize whether the observed AKI is directly attributable to a nephrotoxic effect of VAN-PTZ and to identify high-risk patient phenotypes suitable for nephroprotective interventions.
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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 | 0.014 | 0.036 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.019 | 0.043 |
| Bibliometrics | 0.009 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| 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".