{"doi":"10.1093/ofid/ofaf118","title":"Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory <i>Mycobacterium avium</i> Complex Pulmonary Disease","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66–70.40) compared with those with CRP &amp;lt;1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had rrs mutations.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD.</jats:p>\n               </jats:sec>","journal":"Open Forum Infectious Diseases","year":2025,"id":612997,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1578866,"name":"Shiomi Yoshida","orcid":"0000-0002-8197-3829","position":1,"is_corresponding":false},{"id":1578867,"name":"Asami Osugi","orcid":"0000-0002-1354-6040","position":2,"is_corresponding":false},{"id":1066745,"name":"Yuya Tanaka","orcid":"0000-0003-0260-0424","position":3,"is_corresponding":false},{"id":1301050,"name":"Takehiko Kobayashi","orcid":"0000-0002-7990-3741","position":4,"is_corresponding":false},{"id":1578868,"name":"Toshiharu Mitsuhashi","orcid":null,"position":5,"is_corresponding":false},{"id":1578869,"name":"Yohei Kawasaki","orcid":null,"position":6,"is_corresponding":false},{"id":287965,"name":"Satoshi Mitarai","orcid":"0000-0002-2288-077X","position":7,"is_corresponding":false},{"id":1578870,"name":"Kazunari Tsuyuguchi","orcid":"0000-0002-3918-1764","position":8,"is_corresponding":false},{"id":1578865,"name":"Yu Kurahara","orcid":"0000-0002-3606-0975","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory <i>Mycobacterium avium</i> Complex Pulmonary Disease","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Methods</jats:title>\n                  <jats:p>We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66–70.40) compared with those with CRP &amp;lt;1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had rrs mutations.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD.</jats:p>\n               </jats:sec>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40110422","pmcid":"PMC11920506","openalex_id":"https://openalex.org/W4408140397","authors":[],"funders":[],"total_grants":0,"fwci":3.7226,"citation_percentile":0.9289822,"influential_citations":0,"citation_trend":[{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://academic.oup.com/ofid/advance-article-pdf/doi/10.1093/ofid/ofaf118/62206613/ofaf118.pdf","host_type":"journal"},{"url":"https://academic.oup.com/ofid/advance-article-pdf/doi/10.1093/ofid/ofaf118/62206613/ofaf118.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/ofid/article-pdf/12/3/ofaf118/62206613/ofaf118.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/ofid/ofaf118","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40110422","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11920506","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11920506","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11920506?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Mycobacterium research and diagnosis","Tuberculosis Research and Epidemiology","Pneumocystis jirovecii pneumonia detection and treatment"],"mesh_terms":[],"keywords":["Amikacin","Medicine","Refractory (planetary science)","Inhalation","Antibiotics","Mycobacterium avium complex","Microbiology","Internal medicine","Anesthesia","Biology","Amikacin Resistance","Amikacin Liposome Inhalation Suspension","Noncavitary-nodular Bronchiectatic","Rrs Mutation"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"bioproject"},{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T06:02:52.665241Z","pmid":null,"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":[]}