ArticleThe Journal of antimicrobial chemotherapy2021
Optimizing aminoglycoside selection for KPC-producing Klebsiella pneumoniae with the aminoglycoside-modifying enzyme (AME) gene aac(6')-Ib.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Epidemiological Study of the Relationship Between Antimicrobial Resistance Genes and Biofilm-Forming Capacity in Pathogens Causing Chronic Wound Infections.Microorganisms · 2026Article
- Aminoglycosides enhance meropenem/vaborbactam activity against KPC-producingAntimicrobial agents and chemotherapy · 2026Article
- Ceftazidime/avibactam and aztreonam combined with an aminoglycoside combat metallo-β-lactamase-producingAntimicrobial agents and chemotherapy · 2026Article
- Genotypic Resistance Analysis of Bacterial Species Involved in Infectious Keratitis.Diagnostics (Basel, Switzerland) · 2026Article
- Ceftazidime/avibactam alone or in combination with an aminoglycoside for treatment of carbapenem-resistant Enterobacterales infections: A retrospective cohort study.International journal of antimicrobial agents · 2024Article
- Mechanisms of Antibiotic Resistance and Developments in Therapeutic Strategies to CombatInfection and drug resistance · 2024Review
- Long Term Characteristics of Clinical Distribution and Resistance Trends of Carbapenem-Resistant and Extended-Spectrum β-LactamaseInfection and drug resistance · 2023Article
- The role of adjuvants in overcoming antibacterial resistance due to enzymatic drug modification.RSC medicinal chemistry · 2022Review
- Combatting Planktonic and Biofilm Populations of Carbapenem-ResistantAntibiotics (Basel, Switzerland) · 2022Article
- Aminoglycoside-resistance gene signatures are predictive of aminoglycoside MICs for carbapenem-resistant Klebsiella pneumoniae.The Journal of antimicrobial chemotherapy · 2022Article
- Ceftazidime-avibactam based combinations against carbapenemase producingComputational and structural biotechnology journal · 2022Article
- Generating Genotype-Specific Aminoglycoside Combinations with Ceftazidime/Avibactam for KPC-ProducingAntimicrobial agents and chemotherapy · 2021Article
- Genomic Investigation of Carbapenem-ResistantGenes · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesKPC-producing Klebsiella pneumoniae (KPC-Kp) isolates commonly co-harbour the aminoglycoside-modifying enzyme (AME) gene aac(6')-Ib, which encodes an AME that can confer resistance to some of the commercially available aminoglycosides. We sought to determine the influence of AAC(6')-Ib in KPC-Kp on the pharmacodynamic activity of aminoglycosides.
methodsSix KPC-Kp clinical isolates, three with and three without aac(6')-Ib, were analysed. Using these isolates, the bacterial killing of amikacin, gentamicin and tobramycin was assessed in static time-kill experiments. The pharmacodynamic activity of the aminoglycosides was then assessed in a dynamic one-compartment infection model over 72 h using simulated human pharmacokinetics of once-daily dosing with amikacin (15 mg/kg), gentamicin (5 mg/kg) and tobramycin (5 mg/kg).
resultsAt clinically relevant aminoglycoside concentrations in time-kill experiments and the dynamic one-compartment model, gentamicin was more active than amikacin or tobramycin against the isolates harbouring aac(6')-Ib. Amikacin, gentamicin and tobramycin all showed progressively reduced bacterial killing with exposure to repeated doses against most isolates in the dynamic one-compartment model. MIC values were generally not a good predictor of gentamicin pharmacodynamic activity against KPC-Kp, but were more reliable for amikacin and tobramycin.
conclusionsGentamicin may be preferred over amikacin or tobramycin for treatment of KPC-Kp infections. However, gentamicin MICs are not a consistent predictor of its pharmacodynamic activity and unexpected treatment failures are possible.
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