ArticleAntimicrobial agents and chemotherapy2009
In vivo pharmacodynamic profile of tigecycline against phenotypically diverse Escherichia coli and Klebsiella pneumoniae isolates.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- A chronic Acinetobacter baumannii pneumonia model to study long-term virulence factors, antibiotic treatments, and polymicrobial infections.Nature communications · 2025Article
- Population pharmacokinetics and pulmonary modeling of eravacycline and the determination of microbiological breakpoint and cutoff of PK/PD.Antimicrobial agents and chemotherapy · 2025Article
- Plasma concentration of azithromycin and correlation with clinical outcomes in patients with enteric fever.JAC-antimicrobial resistance · 2025Article
- Clinical Experience with Off-Label Intrathecal Administration of Selected Antibiotics in Adults: An Overview with Pharmacometric Considerations.Antibiotics (Basel, Switzerland) · 2023Review
- Risk Factors and Mortality of Elderly Patients with Hospital-Acquired Pneumonia of Carbapenem-ResistantInfection and drug resistance · 2023Article
- Optimal empiric treatment for KPC-2-producing Klebsiella pneumoniae infections in critically ill patients with normal or decreased renal function using Monte Carlo simulation.BMC infectious diseases · 2021Article
- Efficacy and safety of tigecycline for complicated urinary tract infection: a systematic review.Translational andrology and urology · 2021Article
- Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antibacterial Agents: A Review.Clinical pharmacokinetics · 2020Review
- Pharmacokinetic/Pharmacodynamic Evaluation of a Novel Aminomethylcycline Antibiotic, KBP-7072, in the Neutropenic Murine Pneumonia Model against Staphylococcus aureus and Streptococcus pneumoniae.Antimicrobial agents and chemotherapy · 2019Article
- Treatment outcome of non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae infections: a multicenter study in Taiwan.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2018Article
- Antibacterial effect evaluation of moxalactam against extended-spectrum β-lactamase-producingInfection and drug resistance · 2018Article
- Article
- Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease.Frontiers in microbiology · 2017Article
- Observational
- Piscidin is highly active against carbapenem-resistant Acinetobacter baumannii and NDM-1-producing Klebsiella pneumonia in a systemic Septicaemia infection mouse model.Marine drugs · 2015Article
- Tigecycline displays in vivo bactericidal activity against extended-spectrum-β-lactamase-producing Enterobacteriaceae after 72-hour exposure period.Antimicrobial agents and chemotherapy · 2013Article
- In vitro activity of carbapenems alone and in combination with amikacin against KPC-producing Klebsiella pneumoniae.Journal of clinical medicine research · 2011Article
- In vitro pharmacodynamics of simulated pulmonary exposures of tigecycline alone and in combination against Klebsiella pneumoniae isolates producing a KPC carbapenemase.Antimicrobial agents and chemotherapy · 2011Article
- Article
- Pharmacodynamic profile of tigecycline against methicillin-resistant Staphylococcus aureus in an experimental pneumonia model.Antimicrobial agents and chemotherapy · 2009Article
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3 authors.
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Abstract
Tigecycline is a glycylcycline with activity against Enterobacteriaceae, including multidrug-resistant isolates of Klebsiella pneumoniae and Escherichia coli producing extended-spectrum beta-lactamase (ESBL) and carbapenemases. Herein, we used an in vivo murine thigh model to characterize the pharmacodynamic profile of tigecycline against genotypically and phenotypically diverse K. pneumoniae and E. coli isolates. Doses of 3.125 to 300 mg/kg, divided 1 to 6 times daily, were administered subcutaneously against six (two nonresistant, one carbapenemase, and three ESBL producing) K. pneumoniae strains and five (two nonresistant and three ESBL producing) E. coli strains. The phenotypic profile (reported tigecycline MIC) for all isolates ranged from 0.125 to 2 microg/ml. Mean correlation coefficients of free (f) drug exposures (percentage of the dosing interval that free drug concentration remained above the MIC [fT>MIC], the ratio of the free drug area under the concentration-time curve/MIC [fAUC/MIC], and the ratio of maximum concentration of free drug in serum/MIC) for all 11 isolates were 0.595, 0.969, and 0.897, respectively. The fAUC/MIC was the pharmacodynamic parameter that best described the efficacy of tigecycline against both E. coli and K. pneumoniae. Interestingly, reductions in the number of CFU were noted even though doses achieved an fT>MIC of 0%. With respect to fAUC/MIC in the neutropenic model, the cumulative 80% and 50% effective pharmacodynamic indexes (EI(80) and EI(50)) for all 11 isolates were 8.4 and 4.7, respectively. An experiment in nonneutropenic mice infected with an ESBL-producing E. coli and K. pneumoniae isolate resulted in the lowest tigecycline fAUC/MIC EI(80) and EI(50) values at 1.8 and 1.0 for E. coli and 1.7 and 1.6 for K. pneumoniae. While the phenotypic profile of tigecycline appeared to drive efficacy irrespective of ESBL or carbapenemase production, the presence of a competent immune system markedly reduced this required exposure.
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