{"doi":"10.1093/ofid/ofaf745","title":"An Observational Cohort Study of Targeted Antibiotic Treatments of Cystic Fibrosis Exacerbations","abstract":"Abstract Background Cystic fibrosis (CF) pulmonary exacerbations shorten survival. Treatment guidelines omit minimal inhibitory concentration (MIC)–based antibiotic dose selection. We tested whether MIC-guided intravenous antibiotic strategies prolong time between exacerbations. Methods We retrospectively studied randomly chosen intravenous antibiotic–treated pulmonary exacerbations from 2015 to 2018, followed through 2021. Using pre-admission sputum culture–derived MICs to select dosing targets, we estimated measured:target ratios for β-lactam steady-state and aminoglycoside area under the curve pharmacokinetics. We used Kaplan-Meier and Cox proportional hazards methods to test whether measured:target ratios were associated with time to next exacerbation. We evaluated serial laboratory measurements with linear mixed-effects models for adverse events. We tested model sensitivities to concurrent treatments and severe acute respiratory syndrome coronavirus 2 pandemic–related events. Results Compared with measured:target ratios ≤1, β-lactam ratios >1 were associated with a median of 19 more (from 204 to 223) exacerbation-free days (91 exacerbations; hazard ratio [HR], 0.60; 95% CI, 0.37–0.99; P = .045); aminoglycoside ratios >1 were associated with a median of 83 more (from 153 to 236) exacerbation-free days (65 exacerbations; HR, 0.54; 95% CI, 0.31–0.93; P = .026); both antibiotic ratios >1 simultaneously were associated with a median of 210 more (from 185 to 396) exacerbation-free days (60 exacerbations; HR, 0.33; 95% CI, 0.15–0.71; P = .004). No toxic antibiotic levels and few adverse laboratory or clinical events occurred. Models were insensitive to other treatments and pandemic events. Conclusions MIC-guided antibiotic dosing prolongs time between pulmonary exacerbations with few adverse events. Reduced exacerbation frequency predicts better survival and may improve quality of life for people with CF.","journal":"Open Forum Infectious Diseases","year":2025,"id":587742,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7983,"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":726644,"name":"Kristyn A. Packer","orcid":null,"position":1,"is_corresponding":false},{"id":528473,"name":"Luis G. Vargas Buonfiglio","orcid":"0000-0001-8252-0859","position":2,"is_corresponding":false},{"id":1342252,"name":"Zubin Bhakta","orcid":null,"position":3,"is_corresponding":false},{"id":452162,"name":"Andrew Ulrich","orcid":null,"position":4,"is_corresponding":false},{"id":382955,"name":"Rhonda D. Szczesniak","orcid":"0000-0003-0705-715X","position":5,"is_corresponding":false},{"id":1143617,"name":"Mark A. Fisher","orcid":"0000-0002-7138-7025","position":6,"is_corresponding":false},{"id":1503861,"name":"Warren E. Regelmann","orcid":null,"position":7,"is_corresponding":false},{"id":1503862,"name":"David C Young","orcid":null,"position":8,"is_corresponding":false},{"id":397913,"name":"Theodore G. Liou","orcid":"0000-0003-0121-4847","position":9,"is_corresponding":false},{"id":1342253,"name":"H. R. D. Jacobs","orcid":null,"position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:59:39.958043Z","pmid":"41550698","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":[]}