Nephrotoxicity Phenotyping and Pharmacokinetic Optimization of Concentration-Dependent Reserve Antibiotics: A Scoping Review for Evidence Synthesis from Global Health Systems
1
Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
Popul. Med. 2026;8(Supplement Supplement 1):A550
ABSTRACT
BACKGROUND:
Concentration-dependent reserve antibiotics achieve variable clinical outcomes with unclear nephrotoxicity mechanisms across diverse healthcare systems. The aim of the study was to map evidence on pharmacokinetic/pharmacodynamic properties, safety, and efficacy of concentration-dependent reserve antibiotics.
METHODS:
A scoping review following Arksey and O'Malley methodology and Joanna Briggs Institute guidelines was conducted to map evidence on concentration-dependent reserve antibiotics. Systematic searches across PubMed, Scopus, and Embase identified eligible studies guided by a Population-Concept-Context framework. Population comprised ICU/non-ICU and critically ill patients with serious infections; concept encompassed PK/PD properties, safety, clinical, and dosing practices; the context included acute-care settings across low, middle and high-income countries. Retrospective and prospective observational cohorts, registry-based analyses, and randomized controlled trials were included. Data extraction utilized standardized forms, followed by narrative synthesis into five evidence summary tables. Study quality was assessed descriptively using the Mixed Methods Appraisal Tool.
RESULTS:
Evidence synthesis encompassed 14 studies (2009–2025) across 9 countries; >2,800 patients (retrospective n=7, prospective n=4, registry n=1, randomized n=2). Predominant pathogens (Acinetobacter, Klebsiella, MRSA) represented >90% MDR/XDR organisms; 20–45% baseline renal impairment. Colistin (Css ≈2 mg/L) and polymyxin B (fAUC/MIC ≈20) showed suboptimal target attainment; daptomycin (AUC/MIC) demonstrated dose-dependent response (86% IE success at ≥8 mg/kg). Clinical cure: colistin 45–55%, polymyxin B 60–75%, daptomycin 80–90%; AKI: polymyxins 40–60% (reversible) versus daptomycin <10%. Breakthrough: Elevated exposure (Css ≥2 mg/L) was not independently nephrotoxic; hemodynamic factors (vasopressors), nutritional status (hypoalbuminemia), and polypharmacy were primary AKI determinants. Best practices: early initiation, high-dose dosing, TDM, loading doses, augmented renal clearance recognition. Gaps: inconsistent PK/PD implementation, limited TDM, sparse LMIC and sub-Saharan evidence.
CONCLUSIONS:
Nephrotoxicity is a multifactorial, modifiable clinical phenotype. Pharmacist-led, PK/PD-informed antimicrobial stewardship with routine therapeutic drug monitoring optimizes dosing and reduces preventable adverse events across resource-diverse healthcare systems.
Concentration-dependent reserve antibiotics achieve variable clinical outcomes with unclear nephrotoxicity mechanisms across diverse healthcare systems. The aim of the study was to map evidence on pharmacokinetic/pharmacodynamic properties, safety, and efficacy of concentration-dependent reserve antibiotics.
METHODS:
A scoping review following Arksey and O'Malley methodology and Joanna Briggs Institute guidelines was conducted to map evidence on concentration-dependent reserve antibiotics. Systematic searches across PubMed, Scopus, and Embase identified eligible studies guided by a Population-Concept-Context framework. Population comprised ICU/non-ICU and critically ill patients with serious infections; concept encompassed PK/PD properties, safety, clinical, and dosing practices; the context included acute-care settings across low, middle and high-income countries. Retrospective and prospective observational cohorts, registry-based analyses, and randomized controlled trials were included. Data extraction utilized standardized forms, followed by narrative synthesis into five evidence summary tables. Study quality was assessed descriptively using the Mixed Methods Appraisal Tool.
RESULTS:
Evidence synthesis encompassed 14 studies (2009–2025) across 9 countries; >2,800 patients (retrospective n=7, prospective n=4, registry n=1, randomized n=2). Predominant pathogens (Acinetobacter, Klebsiella, MRSA) represented >90% MDR/XDR organisms; 20–45% baseline renal impairment. Colistin (Css ≈2 mg/L) and polymyxin B (fAUC/MIC ≈20) showed suboptimal target attainment; daptomycin (AUC/MIC) demonstrated dose-dependent response (86% IE success at ≥8 mg/kg). Clinical cure: colistin 45–55%, polymyxin B 60–75%, daptomycin 80–90%; AKI: polymyxins 40–60% (reversible) versus daptomycin <10%. Breakthrough: Elevated exposure (Css ≥2 mg/L) was not independently nephrotoxic; hemodynamic factors (vasopressors), nutritional status (hypoalbuminemia), and polypharmacy were primary AKI determinants. Best practices: early initiation, high-dose dosing, TDM, loading doses, augmented renal clearance recognition. Gaps: inconsistent PK/PD implementation, limited TDM, sparse LMIC and sub-Saharan evidence.
CONCLUSIONS:
Nephrotoxicity is a multifactorial, modifiable clinical phenotype. Pharmacist-led, PK/PD-informed antimicrobial stewardship with routine therapeutic drug monitoring optimizes dosing and reduces preventable adverse events across resource-diverse healthcare systems.
| eISSN: | 2654-1459 |
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