{"doi":"10.1093/jac/dkaa480","title":"Optimizing aminoglycoside selection for KPC-producing <i>Klebsiella pneumoniae</i> with the aminoglycoside-modifying enzyme (AME) gene <i>aac(6’)-Ib</i>","abstract":"OBJECTIVES: KPC-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. METHODS: Six 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). RESULTS: At 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. CONCLUSIONS: Gentamicin 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.","journal":"Journal of Antimicrobial Chemotherapy","year":2020,"id":71352,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":377034,"name":"Amisha P. Rana","orcid":"0000-0001-8441-9084","position":1,"is_corresponding":false},{"id":377035,"name":"Fiorella Krapp","orcid":"0000-0002-8404-2827","position":2,"is_corresponding":false},{"id":377036,"name":"Shitalben Patel","orcid":"0000-0003-3710-0497","position":3,"is_corresponding":false},{"id":377037,"name":"Yanqin Huang","orcid":"0000-0003-2316-6727","position":4,"is_corresponding":false},{"id":283133,"name":"Egon A. Ozer","orcid":"0000-0002-7131-3691","position":5,"is_corresponding":false},{"id":274090,"name":"Alan R. Hauser","orcid":"0000-0003-4596-7939","position":6,"is_corresponding":false},{"id":377038,"name":"Zackery P. Bulman","orcid":"0000-0002-5396-911X","position":7,"is_corresponding":false},{"id":377033,"name":"David A. Butler","orcid":"0000-0003-0528-771X","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T21:43:57.004133Z","pmid":"33326561","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}