Risk factors for suboptimal target attainment of commonly used ß-lactam antibiotics in older adults: a prospective cohort study.

The Journal of antimicrobial chemotherapy · 2026 · Unclear · Insufficient evidence

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UnclearInsufficient evidencePaper 6634

Study snapshot

PublicationThe Journal of antimicrobial chemotherapy · 2026

Study typecohort

Reported directionUnclear

Evidence ratingInsufficient

Abstract

OBJECTIVES: Age-related pathophysiological changes may impact the pharmacokinetics and pharmacodynamics (PK/PD) of ß-lactam antibiotics, potentially resulting in suboptimal concentrations in older adults. This study evaluated PK/PD target attainment with current intravenous amoxicillin-clavulanate and piperacillin-tazobactam dosing regimens in older adults, identified risk factors for target non-attainment, and assessed the prevalence of toxic concentrations. METHODS: This was a prospective, observational PK study in geriatric inpatients (≥75 years) who were treated intravenously with amoxicillin-clavulanate (1 g/0.2 g q6h as a 30-minute infusion) or piperacillin-tazobactam (4 g/0.5 g q6h as a 3-hour infusion). Trough blood samples were collected in steady-state conditions. Target attainment was evaluated against a 100%fT > MIC target. Risk factors for target non-attainment were identified by multivariable logistic regression analysis. Toxicity thresholds were defined as total Cmin concentrations of 80 mg/L for amoxicillin and 157.2 mg/L for piperacillin. RESULTS: Seventy-four patients (median age (IQR): 87 years (83-90)) were included. The PK/PD target was achieved in 15 of 35 and 33 of 39 patients for amoxicillin-clavulanate and piperacillin-tazobactam, respectively. Multivariable logistic regression analysis revealed an effect of comorbidity burden, assessed by the Cumulative Illness Rating Scale-Geriatric (CIRS-G), and estimated glomerular filtration rate that explained 23.8% of target non-attainment (P < 0.05). Receiver operator characteristic curves identified an eGFR of 67 mL/min/1.73m2 as a threshold associated with an increased risk of target non-attainment. Toxicity thresholds were never exceeded in this study. CONCLUSIONS: Health status and renal function, rather than chronological age, play a significant role in target non-attainment among older adults. Further research is required to delineate predictors for interpatient variability in PK and develop evidence-based dosing strategies. TRIAL REGISTRATION: Registration in ClinicalTrials.govTrial registration number: NCT04436991Registration date: 16/06/2020.

Machine Enhanced Logic

AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typecohort

Effect directionunclear

PopulationGeriatric inpatients (≥75 years) treated intravenously with amoxicillin-clavulanate or piperacillin-tazobactam

Sample size74

ExposureNot supplied

Evidence strengthInsufficientConfidence: 66% · Peer reviewed: yes

Main findings

Among 74 geriatric inpatients (median age 87 years), the 100% fT>MIC PK/PD target was achieved in 15/35 patients receiving amoxicillin-clavulanate and 33/39 receiving piperacillin-tazobactam. Comorbidity burden (CIRS-G) and estimated glomerular filtration rate were associated with target non-attainment (model explained 23.8%; P<0.05), with an eGFR threshold of 67 mL/min/1.73m2 linked to increased risk. Toxicity thresholds were not exceeded.

Outcomes measured

PK/PD target attainment (100% fT>MIC)
Risk factors for PK/PD target non-attainment (multivariable logistic regression)
Prevalence of toxic concentrations (Cmin thresholds for amoxicillin and piperacillin)

View raw extracted JSON

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  "study_type": "cohort",
  "exposure": {
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    "source": null,
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": "Geriatric inpatients (≥75 years) treated intravenously with amoxicillin-clavulanate or piperacillin-tazobactam",
  "sample_size": 74,
  "outcomes": [
    "PK/PD target attainment (100% fT>MIC)",
    "Risk factors for PK/PD target non-attainment (multivariable logistic regression)",
    "Prevalence of toxic concentrations (Cmin thresholds for amoxicillin and piperacillin)"
  ],
  "main_findings": "Among 74 geriatric inpatients (median age 87 years), the 100% fT>MIC PK/PD target was achieved in 15/35 patients receiving amoxicillin-clavulanate and 33/39 receiving piperacillin-tazobactam. Comorbidity burden (CIRS-G) and estimated glomerular filtration rate were associated with target non-attainment (model explained 23.8%; P<0.05), with an eGFR threshold of 67 mL/min/1.73m2 linked to increased risk. Toxicity thresholds were not exceeded.",
  "effect_direction": "unclear",
  "limitations": [],
  "evidence_strength": "insufficient",
  "confidence": 0.66,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "older adults",
    "geriatric inpatients",
    "beta-lactam antibiotics",
    "amoxicillin-clavulanate",
    "piperacillin-tazobactam",
    "pharmacokinetics",
    "pharmacodynamics",
    "target attainment",
    "fT>MIC",
    "renal function",
    "eGFR",
    "CIRS-G",
    "toxicity threshold",
    "prospective observational study"
  ],
  "suggested_hubs": []
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1093/jac/dkag048
PubMed: 41692875

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