ArticleThe Journal of antimicrobial chemotherapy2008
Antimicrobial breakpoints for gram-negative aerobic bacteria based on pharmacokinetic-pharmacodynamic models with Monte Carlo simulation.
Article in The Journal of antimicrobial chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Impact of borderline minimum inhibitory concentration on the outcome of invasive infections caused by Enterobacteriaceae treated with β-lactams: a systematic review and meta-analysis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2015Pooled it
- Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia.European journal of clinical pharmacology · 2015Trial
- Population pharmacokinetics of piperacillin/tazobactam in neonates and young infants.European journal of clinical pharmacology · 2013Trial
- Antimicrobial resistance in veterinary medicine: Mechanisms, regulation and control strategies.Veterinarni medicina · 2026Review
- ASP-COMPLEX: redefining antimicrobial stewardship to improve outcomes in high-risk patients with severe infections.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2026Review
- Modeling of pharmacokinetic/pharmacodynamic parameters in regular intermittent intravenous infusion and translational application of the models in personalized antibiotics dosing.Journal of translational medicine · 2025Article
- Suitability of Piperacillin-Tazobactam for Treating Dogs Infected with Extended-Spectrum β-Lactamase-Producing Enterobacterales: Pharmacokinetic and Pharmacodynamic Analysis.Antibiotics (Basel, Switzerland) · 2025Article
- Model-guided development of pharmacokinetic/pharmacodynamic cut-offs and evaluation of sitafloxacin dosing regimens against target pathogens.Frontiers in pharmacology · 2025Article
- Population Pharmacokinetics and Dose Optimization of Piperacillin in Infants and Children with Pneumonia.Paediatric drugs · 2025Article
- QSAR analysis of five generations of cephalosporins to establish the structural basis of activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus.Molecular diversity · 2024Article
- Biased computation of probability of target attainment for antimicrobial drugs.CPT: pharmacometrics & systems pharmacology · 2023Article
- Article
- Pharmacokinetic/Pharmacodynamic Analysis of Tedizolid Phosphate Compared to Linezolid for the Treatment of Infections Caused by Gram-Positive Bacteria.Antibiotics (Basel, Switzerland) · 2021Article
- The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials.Pharmaceutics · 2021Review
- Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting-Focus on ICU Patients and Gram-Negative Strains.Antibiotics (Basel, Switzerland) · 2020Review
- Therapeutic Effect and Mechanisms of the Novel Monosulfactam 0073.Antimicrobial agents and chemotherapy · 2020Article
- Model-Informed Drug Development, Pharmacokinetic/Pharmacodynamic Cutoff Value Determination, and Antibacterial Efficacy of Benapenem againstAntimicrobial agents and chemotherapy · 2020Article
- Don't Get Wound Up: Revised Fluoroquinolone Breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa.Journal of clinical microbiology · 2019Review
- Dose Selection and Validation for Ceftazidime-Avibactam in Adults with Complicated Intra-abdominal Infections, Complicated Urinary Tract Infections, and Nosocomial Pneumonia.Antimicrobial agents and chemotherapy · 2019Review
- Susceptibility breakpoint for Danofloxacin against swine Escherichia coli.BMC veterinary research · 2019Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
objectivesThis study describes a comprehensive programme designed to develop pharmacokinetic-pharmacodynamic (PK-PD) breakpoints for numerous antimicrobial classes against key gram-negative aerobic bacteria.
methodsA 10,000 subject Monte Carlo simulation was constructed for 13 antimicrobials (21 dosing regimens). Published pharmacokinetic data and protein binding were varied according to log-normal and uniform distributions. MICs were fixed at single values from 0.03 to 64 mg/L. The PK-PD susceptible breakpoint was defined as the MIC at which the probability of target attainment was > or = 90%. PK-PD, CLSI and European Committee on Antimicrobial Susceptibility Testing breakpoints were applied to MICs from the 2005 worldwide Meropenem Yearly Susceptibility Test Information Collection database to evaluate the impact of breakpoint discrepancies.
resultsPK-PD breakpoints were within one dilution of the CLSI and European breakpoints for all antimicrobials tested--with a few exceptions. When discrepancies were noted, the PK-PD breakpoint was lower than the CLSI breakpoint [ceftriaxone (0.5 versus 8 mg/L), ertapenem (0.25 versus 2 mg/L), ciprofloxacin (0.125 versus 1 mg/L) and levofloxacin (0.25-0.5 versus 2 mg/L)] and higher than the European breakpoint [ceftazidime (4-8 versus 1 mg/L), aztreonam (4-8 versus 1 mg/L), although ciprofloxacin was an exception to this pattern (0.125 versus 0.5-1 mg/L)]. For Enterobacteriaceae, breakpoint discrepancies resulted in modest (< or = 10%) differences in the percentages susceptible. In contrast, large (> 15%) discrepancies were noted for Pseudomonas aeruginosa and Acinetobacter baumannii.
conclusionsBreakpoint agreement exists for imipenem, meropenem and the aminoglycosides. In contrast, discrepancies exist for piperacillin/tazobactam, cephalosporins, ertapenem, aztreonam and the fluoroquinolones. These discrepancies are most pronounced for P. aeruginosa and A. baumannii.
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