2025
P-1503. Dual β-Lactam Approach for Treatment of Mycobacterium abscessus Infections in Adults – Results in 19 Patients
Kalyatanda G, Dousa K, Lyons H, Mardourian M, Rhodes J, Iakovidis A, El-Helou G, Wilson B, Daley C, Holland S, Kreiswirth B, Nguyen D, Shin E, Kurz S, Johnson J, Bonomo R. P-1503. Dual β-Lactam Approach for Treatment of Mycobacterium abscessus Infections in Adults – Results in 19 Patients. Open Forum Infectious Diseases 2025, 12: ofae631.1672. PMCID: PMC11778049, DOI: 10.1093/ofid/ofae631.1672.Peer-Reviewed Original ResearchSubspecies abscessusB-lactamAssociated with high cure ratesIn vitro susceptibility resultsMulti-drug regimensCurrent treatment regimensSolid organ transplantationHigh cure ratesTime to initiationOptimize treatment outcomesMab infectionSynergy testClinical cureImmunocompromised patientsPulmonary infectionDiscontinued treatmentTreatment regimensCase reportClinical outcomesCure rateImmunocompromised individualsAutoimmune diseasesTreatment successEarly treatmentCulture conversionP-788. Exploring β-Lactam Interactions with DacB1: Unraveling Optimal Therapies for Combating Drug-Resistant Mycobacterium tuberculosis
Nantongo M, Nguyen D, Shin E, Bethel C, Taracila M, Dousa K, Kurz S, Nguyen L, Kreiswirth B, Boom W, Bonomo R. P-788. Exploring β-Lactam Interactions with DacB1: Unraveling Optimal Therapies for Combating Drug-Resistant Mycobacterium tuberculosis. Open Forum Infectious Diseases 2025, 12: ofae631.982. PMCID: PMC11778675, DOI: 10.1093/ofid/ofae631.982.Peer-Reviewed Original ResearchMinimum inhibitory concentrationAcyl-enzyme adductOxyanion holeB-lactamB-lactamasePeptidoglycan synthesis pathwayCarbonyl groupHydrophobic interactionsElectrospray ionization mass spectrometryAcyl-enzyme formationB-lactam antibioticsMichaelis-Menten complexC1‐methyl groupProtein motifsPeptidoglycan biosynthesisDrug-resistant Mycobacterium tuberculosisIonization mass spectrometryPeptidoglycan synthesisD-carboxypeptidaseAnalysis of meropenemB-lactamase inhibitorsClinical isolatesBroth microdilutionClinically achievable concentrationsSynthesis pathway
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 tuberculosisDurlobactam, a Diazabicyclooctane β‑Lactamase Inhibitor, Inhibits BlaC and Peptidoglycan Transpeptidases of Mycobacterium tuberculosis
Nantongo M, Nguyen D, Bethel C, Taracila M, Li Q, Dousa K, Shin E, Kurz S, Nguyen L, Kreiswirth B, Boom W, Plummer M, Bonomo R. Durlobactam, a Diazabicyclooctane β‑Lactamase Inhibitor, Inhibits BlaC and Peptidoglycan Transpeptidases of Mycobacterium tuberculosis. ACS Infectious Diseases 2024, 10: 1767-1779. PMID: 38619138, DOI: 10.1021/acsinfecdis.4c00119.Peer-Reviewed Original ResearchConceptsESI-MSElectrospray ionization mass spectrometryIonization mass spectrometryB-lactamase inhibitorsAcyl-enzyme complexMycobacterial cell wall synthesisMolecular dockingMass spectrometryActive siteInhibit BlaCPeptidoglycan transpeptidaseDiazabicyclooctaneSynthesisAntibiotic susceptibility testingCell wall synthesisInhibition kineticsDrug targetsB-lactamaseDurlobactamSusceptibility testingComplexDockingSpectrometryWall synthesisPeptidoglycan synthesis
2023
Eradicating Pulmonary Mycobacterium abscessus: The Promise of Dual β-Lactam Therapy
Alahmdi B, Dousa K, Kurz S, Kaufman A, Bonomo R, Taimur S. Eradicating Pulmonary Mycobacterium abscessus: The Promise of Dual β-Lactam Therapy. Open Forum Infectious Diseases 2023, 10: ofad312. PMID: 37383246, PMCID: PMC10296056, DOI: 10.1093/ofid/ofad312.Peer-Reviewed Original Research
2022
1432. Exploring Cell Wall Targets to Overcome Mycobacterium tuberculosis (Mtb): Ceftriaxone (CRO) Inhibits LdtMt2, a Major Peptidoglycan (PG) Synthase
Nguyen D, Redmond S, Dousa K, Bethel C, Taracila M, Li Q, Kurz S, Pavelka M, Papp-Wallace K, Holland S, Kreiswirth B, Boom H, Bonomo R. 1432. Exploring Cell Wall Targets to Overcome Mycobacterium tuberculosis (Mtb): Ceftriaxone (CRO) Inhibits LdtMt2, a Major Peptidoglycan (PG) Synthase. Open Forum Infectious Diseases 2022, 9: ofac492.1261. PMCID: PMC9752925, DOI: 10.1093/ofid/ofac492.1261.Peer-Reviewed Original ResearchDrug-resistant tuberculosisB-lactamaseMTB isolatesDifficult-to-treat infectionsB-lactamase inhibitorsFractional inhibitory concentration indexMultidrug-resistant mycobacteriaIn vitro susceptibilityCystic Fibrosis FoundationBroth microdilution methodPG synthasesElectrospray ionization-mass spectrometryCeftriaxone MICsDR-TBSusceptibility testingImipenemMeropenemTB guidelinesCeftriaxoneB-lactamTreatment strategiesClinical studiesLowered MICClavulanateMicrodilution methodInhibiting 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 ResearchConceptsD-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
1390. Durlobactam, a Diazabicyclooctane (DBO) β-lactamase Inhibitor (BLI), Inhibits BlaC and Peptidoglycan (PG) Transpeptidases of Mycobacterium tuberculosis (Mtb): A Novel Approach to Therapeutics for Tuberculosis (TB)?
Nguyen D, Bethel C, Taracilla M, Li Q, Dousa K, Kurz S, Nguyen L, Kreiswirth B, Boom W, Bonomo R. 1390. Durlobactam, a Diazabicyclooctane (DBO) β-lactamase Inhibitor (BLI), Inhibits BlaC and Peptidoglycan (PG) Transpeptidases of Mycobacterium tuberculosis (Mtb): A Novel Approach to Therapeutics for Tuberculosis (TB)? Open Forum Infectious Diseases 2021, 8: 780-780. PMCID: PMC8643912, DOI: 10.1093/ofid/ofab466.1582.Peer-Reviewed Original ResearchB-lactamMultidrug-resistant TBTreatment of TBNovel therapiesMtb H37RvAvibactamRelebactamCarbapenemsClavulanateMicrodilution methodAcyl-enzyme complexTherapeutic potentialDurlobactamMeropenemMICDual actionTranspeptidasePre-incubationDiazabicyclooctaneMtbAmoxicillinPeriod of pre-incubationTuberculosis“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 ResearchConceptsPeptidoglycan synthesis enzymesMinimum inhibitory concentration of clinical isolatesB-lactamCombination of imipenemSynthesis enzymesSynergistic in vitroClinical isolatesMinimum inhibitory concentrationMycobacterium abscessusClinical trialsMycobacterial infectionAbscessusEnzymeCeftarolineImipenem
2020
1572. Combination Cefuroxime and Sulopenem is active in vitro against Mycobacterium abscessus
Dousa K, Nguyen D, Kurz S, Taracila M, Bethel C, Bonomo R. 1572. Combination Cefuroxime and Sulopenem is active in vitro against Mycobacterium abscessus. Open Forum Infectious Diseases 2020, 7: s785-s785. PMCID: PMC7778327, DOI: 10.1093/ofid/ofaa439.1752.Peer-Reviewed Original ResearchQualified Infectious Disease ProductFood and Drug AdministrationMab infectionClinical isolatesColony-forming unitsCell wall synthesis proteinsMycobacterium abscessusB-lactamOral step-down therapyNontuberculous mycobacteriaStep-down therapyUS Food and Drug AdministrationB-lactam antibioticsVisible bacterial growthMiddlebrook 7H9 brothCharacterized isolatesMIC distributionSynthesis proteinsClinical strainsOral formulationMAB isolatesClinical trialsActivity in vitroDrug AdministrationBacterial growth1642. A Novel β-lactamase Inhibitor (Durlobactam, DUR) and β-Lactams Enhance Susceptibility Against Multidrug-Resistant (MDR) Mycobacterium abscessus (Mab)
Dousa K, Kurz S, Bethel C, Miller A, Bonomo R. 1642. A Novel β-lactamase Inhibitor (Durlobactam, DUR) and β-Lactams Enhance Susceptibility Against Multidrug-Resistant (MDR) Mycobacterium abscessus (Mab). Open Forum Infectious Diseases 2020, 7: s810-s811. PMCID: PMC7777676, DOI: 10.1093/ofid/ofaa439.1822.Peer-Reviewed Original ResearchMinimum inhibitory concentrationB-lactamAmbler class AB-lactamase inhibitorsStructural lung diseaseB-lactam antibioticsImprove treatment outcomesTargeting multiple stepsMiddlebrook 7H9 brothVisible bacterial growthB-lactamaseDurlobactamBlaMabClinical isolatesColony-forming unitsMechanism of actionLung infectionCell wall structureRestore susceptibilityClinical strainsHydrolyzed penicillinsNontuberculous mycobacteriaLung diseaseMAB isolatesTreatment outcomesDrug-Resistant Tuberculosis A Glance at Progress and Global Challenges
Dousa K, Kurz S, Bark C, Bonomo R, Furin J. Drug-Resistant Tuberculosis A Glance at Progress and Global Challenges. Infectious Disease Clinics Of North America 2020, 34: 863-886. PMID: 33011048, DOI: 10.1016/j.idc.2020.06.001.Peer-Reviewed Original ResearchConceptsSecond-line medicationsMultidrug-resistant Mycobacterium tuberculosisDrug susceptibility predictionOral formulationMultinational trialDrug resistancePublic health threatEconomic burdenDiagnostic techniquesTuberculosisAdequate clinical resourcesClinical resourcesHealth threatLaboratory servicesSummary for Clinicians: 2020 Clinical Practice Guideline Summary for the Treatment of Nontuberculous Mycobacterial Pulmonary Disease.
Kurz S, Zha B, Herman D, Holt M, Daley C, Ruminjo J, Thomson C. Summary for Clinicians: 2020 Clinical Practice Guideline Summary for the Treatment of Nontuberculous Mycobacterial Pulmonary Disease. Annals Of The American Thoracic Society 2020, 17: 1033-1039. PMID: 32870060, DOI: 10.1513/annalsats.202003-222cme.Peer-Reviewed Original ResearchInsights 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 rateInhibitorsTime to Expand the Picture of Mycobacterial Lipids: Spotlight on Nontuberculous Mycobacteria
Kurz S, Rivas-Santiago B. Time to Expand the Picture of Mycobacterial Lipids: Spotlight on Nontuberculous Mycobacteria. American Journal Of Respiratory Cell And Molecular Biology 2020, 62: 275-276. PMID: 31580721, PMCID: PMC7055696, DOI: 10.1165/rcmb.2019-0324ed.Peer-Reviewed Original Research
2019
1385. Mechanism-Based, In Vitro Inhibition of Mycobacterium abscessus: Assessing β-Lactam Therapy
Dousa K, Kurz S, Bethel C, Barnes M, Taracilla M, Selvaraju S, Jacobs M, Kreiswirth B, Kasperbauer S, Daley C, Bonomo R. 1385. Mechanism-Based, In Vitro Inhibition of Mycobacterium abscessus: Assessing β-Lactam Therapy. Open Forum Infectious Diseases 2019, 6: s503-s503. PMCID: PMC6809419, DOI: 10.1093/ofid/ofz360.1249.Peer-Reviewed Original ResearchB-lactamaseColony-forming unitsIn vitro susceptibility testingB-lactamase inhibitorsTherapeutically achievable concentrationsMab infectionRescue regimenMiddlebrook 7H9 brothVisible bacterial growthSusceptibility testingClinical isolatesImipenemBlaMabTreated patientsRelebactamAvibactamNontuberculous mycobacteriaB-lactamM. abscessusMAB isolatesTest agentsIn vitro inhibitionMAb complexesMAbMICThe effect of respiratory viral assay panel on antibiotic prescription patterns at discharge in adults admitted with mild to moderate acute exacerbation of COPD: a retrospective before- after study
Tickoo M, Ruthazer R, Bardia A, Doron S, Andujar-Vazquez GM, Gardiner BJ, Snydman DR, Kurz SG. The effect of respiratory viral assay panel on antibiotic prescription patterns at discharge in adults admitted with mild to moderate acute exacerbation of COPD: a retrospective before- after study. BMC Pulmonary Medicine 2019, 19: 118. PMID: 31262278, PMCID: PMC6604457, DOI: 10.1186/s12890-019-0872-0.Peer-Reviewed Original ResearchConceptsRespiratory viral panelChronic obstructive pulmonary diseaseObstructive pulmonary diseaseAntibiotic prescriptionsAcute exacerbationPulmonary diseaseViral panelAntibiotic prescription patternsPositive smoking statusAntibiotic prescription ratesProportion of patientsObstructive sleep apneaTertiary medical centerStudy of patientsUse of antibioticsAECOPD patientsConclusionsIn patientsPrescription patternsPrescription ratesPrimary outcomeSingle centerSleep apneaSmoking statusMean ageResultsA total
2018
786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?
Dousa K, Kreiswirth B, Kurz S, Bonomo R. 786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection? Open Forum Infectious Diseases 2018, 5: s281-s281. PMCID: PMC6254396, DOI: 10.1093/ofid/ofy210.793.Peer-Reviewed Original ResearchB-lactamB-lactamase inhibitorsMycobacterium abscessus infectionB-lactam antibioticsBenefits of combinationB-lactamaseCeftarolineHydrolyzed penicillinsMycobacterium abscessusAvibactamDiazabicyclooctane inhibitorBlaMabMycobacterial infectionMicrodilution methodClinical modelDiazabicyclooctaneInhibitorsInfectionMICInhibited growthNovel combinationCarbapenemsPotential combinationRelebactamMIC90
2017
Drug Resistance Assays for Mycobacterium tuberculosis
Kurz S, Salfinger M. Drug Resistance Assays for Mycobacterium tuberculosis. 2017, 1359-1365. DOI: 10.1007/978-3-319-47266-9_33.Peer-Reviewed Original ResearchDetection of drug resistanceEpidemic of drug-resistant tuberculosisAgar proportion methodAntimicrobial susceptibility testingDrug-resistant tuberculosisDrug resistance assaysDetection of patientsDrug-resistant Mycobacterium tuberculosis strainsMycobacterium tuberculosis strainsMinimal inhibitory concentrationPharmacodynamic correlationsSusceptibility testingDrug resistanceLiquid medium systemsEffective treatmentTuberculosis strainsScreening testProportion methodGenotyping methodsResistance assaysBacteriological methodsInhibitory concentrationMycobacterium tuberculosisTuberculosisPatients
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