Dataset Information

Nebulized Bacteriophage in a Patient With Refractory Mycobacterium abscessus Lung Disease.

ABSTRACT: An elderly man with refractory Mycobacterium abscessus lung disease previously developed anti-phage neutralizing antibodies while receiving intravenous phage therapy. Subsequent phage nebulization resulted in transient weight gain, decreased C-reactive protein, and reduced Mycobacterium burden. Weak sputum neutralization may have limited the outcomes, but phage resistance was not a contributing factor.

SUBMITTER: Dedrick RM

PROVIDER: S-EPMC9251665 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Nebulized Bacteriophage in a Patient With Refractory Mycobacterium abscessus Lung Disease.

Dedrick Rebekah M RM Freeman Krista G KG Nguyen Jan A JA Bahadirli-Talbott Asli A Cardin Mitchell E ME Cristinziano Madison M Smith Bailey E BE Jeong Soowan S Ignatius Elisa H EH Lin Cheng Ting CT Cohen Keira A KA Hatfull Graham F GF

Open forum infectious diseases 20220412 7

An elderly man with refractory Mycobacterium abscessus lung disease previously developed anti-phage neutralizing antibodies while receiving intravenous phage therapy. Subsequent phage nebulization resulted in transient weight gain, decreased C-reactive protein, and reduced Mycobacterium burden. Weak sputum neutralization may have limited the outcomes, but phage resistance was not a contributing factor. ...[more]

PMID: 35794944

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Project description:BackgroundMycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance.Research questionDoes treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease?Study design and methodsIn an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance.ResultsOf 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%).InterpretationIn a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy.Trial registryClinicalTrials.gov; No.: NCT03038178; URL: www.Clinicaltrialsgov.

Dataset Information

Nebulized Bacteriophage in a Patient With Refractory Mycobacterium abscessus Lung Disease.

Publications

Nebulized Bacteriophage in a Patient With Refractory <i>Mycobacterium abscessus</i> Lung Disease.

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