{"doi":"10.1093/jacamr/dlaf068","title":"Pharmacodynamics of aztreonam/ceftazidime/avibactam and polymyxin B versus New Delhi MBL-producing Acinetobacter baumannii","abstract":"Abstract Background Acinetobacter baumannii has become an increasingly urgent public health concern among global health agencies due to high rates of carbapenem resistance. Carbapenem-resistant A. baumannii (CRAB) that express both oxacillinases and MBLs is especially problematic due to resistance to all β-lactams. Methods Two clinical A. baumannii isolates, AR-0033 and AR-0083, harbouring blaNDM-1 (for both isolates MICaztreonam >64 mg/L, MICceftazidime/avibactam >128/4 mg/L, MICpolymyxin B = 1 mg/L, MICcefiderocol ≥16 mg/L) were treated with mono- or combination therapies of aztreonam/ceftazidime/avibactam and polymyxin B (PMB) in static time–kill studies over 24 h. Replicate time–kills were analysed by integrating the area under the cfu/mL-versus-time curve using the linear-trapezoidal method and normalizing to the growth control to produce the log-ratio area (LRA). The LRA was mathematically modelled as a function of aztreonam concentrations using a Hill-type function to identify the IC50 values for aztreonam. Results Treatment with aztreonam/ceftazidime/avibactam achieved <2 log10 cfu/mL reduction by 24 h for all concentrations in both isolates. Monotherapies of PMB at 0.75, 1.5, 3.0 and 6.0 mg/L displayed maximum killing by 6 h against AR-0033. Monte Carlo simulations of human pharmacokinetics of aztreonam showed that package insert dosing resulted in a average free steady-state concentration above the target aztreonam IC50 values for AR-0033 ≥96% of time when in combination with ceftazidime/avibactam and PMB. Conclusions This study supports the potential utility of low-dose PMB therapy in combination with β-lactams to combat NDM-producing CRAB.","journal":"JAC-Antimicrobial Resistance","year":2025,"id":539371,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1426892,"name":"Anant P. Shah","orcid":null,"position":1,"is_corresponding":false},{"id":1069717,"name":"Brian M. Ho","orcid":"0000-0003-1533-6263","position":2,"is_corresponding":false},{"id":1426893,"name":"Navaldeep Singh","orcid":null,"position":3,"is_corresponding":false},{"id":1070229,"name":"Harriet de Souza","orcid":null,"position":4,"is_corresponding":false},{"id":350707,"name":"Nicholas M. Smith","orcid":"0000-0002-0212-2787","position":5,"is_corresponding":false},{"id":1426891,"name":"Jacob T. Dumbleton","orcid":null,"position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-19T02:52:30.048313Z","pmid":"40322085","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":[]}