2024
Durlobactam in combination with β-lactams to combat Mycobacterium abscessus
Shin E, Dousa K, Taracila M, Bethel C, Nantongo M, Nguyen D, Akusobi C, Kurz S, Plummer M, Daley C, Holland S, Rubin E, Bulitta J, Boom W, Kreiswirth B, Bonomo R. Durlobactam in combination with β-lactams to combat Mycobacterium abscessus. Antimicrobial Agents And Chemotherapy 2024, 69: e01174-24. PMID: 39714147, PMCID: PMC11823594, DOI: 10.1128/aac.01174-24.Peer-Reviewed Original ResearchSynergistic effects of sulopenem in combination with cefuroxime or durlobactam against Mycobacterium abscessus
Dousa K, Shin E, Kurz S, Plummer M, Nantongo M, Bethel C, Taracila M, Nguyen D, Kreiswith B, Daley C, Remy K, Holland S, Bonomo R. Synergistic effects of sulopenem in combination with cefuroxime or durlobactam against Mycobacterium abscessus. MBio 2024, 15: e00609-24. PMID: 38742824, PMCID: PMC11237399, DOI: 10.1128/mbio.00609-24.Peer-Reviewed Original ResearchConceptsD,D-carboxypeptidaseMinimum inhibitory concentrationB-lactamPenicillin-binding-proteinCell wall synthesisL,D-transpeptidasesResistance to common antibioticsLowest minimum inhibitory concentrationWall synthesisCystic fibrosisD-carboxypeptidaseMass spectrometry analysisB-lactamaseThioester bondRate of treatment failureCell-based assaysMultiple antibioticsB-lactam ringsCommon antibioticsD-transpeptidasesB-lactamase inhibitorsCysteine residuesTime-kill studiesStructural lung diseaseMultidrug-resistant tuberculosis
2023
Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease
Siegel S, Griffith D, Philley J, Brown-Elliott B, Brunton A, Sullivan P, Fuss C, Strnad L, Wallace R, Winthrop K. Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease. CHEST Journal 2023, 164: 846-859. PMID: 37419144, PMCID: PMC10645596, DOI: 10.1016/j.chest.2023.05.036.Peer-Reviewed Original ResearchConceptsAmikacin liposome inhalation suspensionAmikacin resistanceCulture conversionInhalation suspensionMycobacterium abscessus lung diseasePresence of macrolide resistanceEnd pointsMicrobiological end pointsMonthly sputum culturesSputum culture conversionTreatment-refractory diseaseOpen-label protocolSecondary end pointsOpen-label trialCohort of patientsCavitary diseaseSputum culturePretreatment isolatesM abscessusOpen-labelOral antimicrobialsParenteral antibioticsCompanion therapyMacrolide resistanceMultidrug therapy
2022
Inhibiting Mycobacterium abscessus Cell Wall Synthesis: Using a Novel Diazabicyclooctane β-Lactamase Inhibitor To Augment β-Lactam Action
Dousa K, Nguyen D, Kurz S, Taracila M, Bethel C, Schinabeck W, Kreiswirth B, Brown S, Boom W, Hotchkiss R, Remy K, Jacono F, Daley C, Holland S, Miller A, Bonomo R. Inhibiting Mycobacterium abscessus Cell Wall Synthesis: Using a Novel Diazabicyclooctane β-Lactamase Inhibitor To Augment β-Lactam Action. MBio 2022, 13: e03529-21. PMID: 35073757, PMCID: PMC8787486, DOI: 10.1128/mbio.03529-21.Peer-Reviewed Original ResearchMeSH KeywordsAmoxicillinAnti-Bacterial Agentsbeta-Lactamase Inhibitorsbeta-Lactamasesbeta-LactamsCefuroximeHumansImipenemMicrobial Sensitivity TestsMycobacterium abscessusConceptsD-carboxypeptidaseB-lactamB-lactamaseDisrupt cell wall synthesisStable acyl-enzyme complexesCell wall synthesisAcyl-enzyme complexMichaelis-Menten complexB-lactamase inhibitorsWall synthesisPeptidoglycan synthesisStructural lung diseaseTriple drug combinationIsolates to amoxicillinCell-based assaysMycobacterium abscessusMIC rangeImipenemMichaelis constantAcylation rateInhibitor combinationsDurlobactamMultidrug resistanceTherapeutic regimensCystic fibrosis
2021
“One-Two Punch”: Synergistic ß-Lactam Combinations for Mycobacterium abscessus and Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes
Nguyen D, Dousa K, Kurz S, Brown S, Drusano G, Holland S, Kreiswirth B, Boom W, Daley C, Bonomo R. “One-Two Punch”: Synergistic ß-Lactam Combinations for Mycobacterium abscessus and Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes. Clinical Infectious Diseases 2021, 73: 1532-1536. PMID: 34113990, PMCID: PMC8677594, DOI: 10.1093/cid/ciab535.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsDrug SynergismHumansLactamsMicrobial Sensitivity TestsMycobacterium abscessusMycobacterium Infections, NontuberculousPeptidoglycanConceptsPeptidoglycan synthesis enzymesMinimum inhibitory concentration of clinical isolatesB-lactamCombination of imipenemSynthesis enzymesSynergistic in vitroClinical isolatesMinimum inhibitory concentrationMycobacterium abscessusClinical trialsMycobacterial infectionAbscessusEnzymeCeftarolineImipenem
2020
Insights into the l,d-Transpeptidases and d,d-Carboxypeptidase of Mycobacterium abscessus: Ceftaroline, Imipenem, and Novel Diazabicyclooctane Inhibitors
Dousa K, Kurz S, Taracila M, Bonfield T, Bethel C, Barnes M, Selvaraju S, Abdelhamed A, Kreiswirth B, Boom W, Kasperbauer S, Daley C, Bonomo R. Insights into the l,d-Transpeptidases and d,d-Carboxypeptidase of Mycobacterium abscessus: Ceftaroline, Imipenem, and Novel Diazabicyclooctane Inhibitors. Antimicrobial Agents And Chemotherapy 2020, 64: 10.1128/aac.00098-20. PMID: 32393499, PMCID: PMC7526840, DOI: 10.1128/aac.00098-20.Peer-Reviewed Original ResearchConceptsCeftaroline fosamilB-lactamB-lactamaseNontuberculous mycobacteriaB-lactamase inhibitorsD-carboxypeptidaseB-lactam antibioticsCell wall synthesis proteinsCeftarolineImipenemDiazabicyclooctane inhibitorSteady-state kinetic assaysAvibactamHighest acylation ratesMechanism-based approachGt;100-foldRelebactamSynthesis proteinsD-transpeptidasesKinetic assaysAcylation rateInhibitors
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply