2022
Evaluating spatially adaptive guidelines for the treatment of gonorrhea to reduce the incidence of gonococcal infection and increase the effective lifespan of antibiotics
Yaesoubi R, Cohen T, Hsu K, Gift TL, St. Cyr SB, Salomon JA, Grad YH. Evaluating spatially adaptive guidelines for the treatment of gonorrhea to reduce the incidence of gonococcal infection and increase the effective lifespan of antibiotics. PLOS Computational Biology 2022, 18: e1009842. PMID: 35139073, PMCID: PMC8863219, DOI: 10.1371/journal.pcbi.1009842.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsGonorrheaHomosexuality, MaleHumansIncidenceLongevityMaleNeisseria gonorrhoeaeSexual and Gender MinoritiesConceptsIncidence of gonorrhoeaTreatment guidelinesResistance prevalenceGonorrhea casesTreatment of gonorrheaNational surveillance systemPrevalence of resistanceTransmission dynamic modelGonococcal infectionGonorrhea treatmentMSM populationAntibiotic susceptibilityGonorrheaStandardized guidelinesSurveillance dataPrevalenceIncidenceAntibioticsPotential strategySurveillance systemAbsence of pointsGuidelinesCurrent strategiesEffective lifespanMenvCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding
Tran VN, Shams A, Ascioglu S, Martinecz A, Liang J, Clarelli F, Mostowy R, Cohen T, Abel zur Wiesch P. vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding. BMC Bioinformatics 2022, 23: 22. PMID: 34991453, PMCID: PMC8734216, DOI: 10.1186/s12859-021-04536-3.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsBacteriaComputer SimulationDrug Resistance, BacterialModels, BiologicalConceptsOwn computational model
2020
Drug-target binding quantitatively predicts optimal antibiotic dose levels in quinolones
Clarelli F, Palmer A, Singh B, Storflor M, Lauksund S, Cohen T, Abel S, Wiesch P. Drug-target binding quantitatively predicts optimal antibiotic dose levels in quinolones. PLOS Computational Biology 2020, 16: e1008106. PMID: 32797079, PMCID: PMC7449454, DOI: 10.1371/journal.pcbi.1008106.Peer-Reviewed Original ResearchConceptsDose levelsAntibiotic efficacyDrug-target bindingDose-response relationshipBeta-lactams ampicillinTime-kill curvesDose-response curveNovel resistance mutationsMeasurable biochemical parametersClinical isolatesAntibiotic dose-response curvesAntibiotic actionResistance mutationsBiochemical parametersAdaptive guidelines for the treatment of gonorrhea to increase the effective life span of antibiotics among men who have sex with men in the United States: A mathematical modeling study
Yaesoubi R, Cohen T, Hsu K, Gift TL, Chesson H, Salomon JA, Grad YH. Adaptive guidelines for the treatment of gonorrhea to increase the effective life span of antibiotics among men who have sex with men in the United States: A mathematical modeling study. PLOS Medicine 2020, 17: e1003077. PMID: 32243443, PMCID: PMC7122693, DOI: 10.1371/journal.pmed.1003077.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsGonorrheaHomosexuality, MaleHumansLongevityMaleModels, TheoreticalPractice Guidelines as TopicTreatment OutcomeUnited StatesConceptsFirst-line antibioticsPrevalence of resistanceMSM populationGonorrhea casesPrevalence of gonorrheaTreatment of gonorrheaTransmission of gonorrheaIncidence of gonorrhoeaGonococcal antimicrobial resistanceProportion of casesAlternative surveillance strategiesBurden of gonorrheaEffective surveillance systemTreatment guidelinesGonorrhea treatmentGonorrhoea transmissionClinical effectivenessOverall burdenSurveillance estimatesLife spanGonorrheaDrug susceptibilitySurveillance findingsSurveillance strategiesSurveillance program
2017
Antimicrobial Resistance Risks of Cholera Prophylaxis for United Nations Peacekeepers
Kunkel A, Lewnard JA, Pitzer VE, Cohen T. Antimicrobial Resistance Risks of Cholera Prophylaxis for United Nations Peacekeepers. Antimicrobial Agents And Chemotherapy 2017, 61: 10.1128/aac.00026-17. PMID: 28533237, PMCID: PMC5527623, DOI: 10.1128/aac.00026-17.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsAntibiotic ProphylaxisCholeraDisease OutbreaksDrug Resistance, BacterialHaitiHumansModels, TheoreticalRiskUnited NationsVibrio choleraeConceptsDrug-resistant infectionsAntimicrobial chemoprophylaxisDrug-sensitive infectionsDrug resistance generationCholera importationChemoprophylaxisDrug resistanceImportation eventsInfectionAntibiotic resistanceAntimicrobial resistance risksRiskRelative benefitsResistance generationCholeraPotential resistance risksPotential benefitsResistance riskProphylaxisPrevalenceUsing Chemical Reaction Kinetics to Predict Optimal Antibiotic Treatment Strategies
Wiesch P, Clarelli F, Cohen T. Using Chemical Reaction Kinetics to Predict Optimal Antibiotic Treatment Strategies. PLOS Computational Biology 2017, 13: e1005321. PMID: 28060813, PMCID: PMC5257006, DOI: 10.1371/journal.pcbi.1005321.Peer-Reviewed Original ResearchConceptsOptimal dosingTreatment strategiesOnset of actionAntibiotic treatment strategiesAntibiotic concentrationsOptimal therapyFrequent dosingHigh dosesBacterial infectionsDrug concentrationsDosingBacterial replicationAntibioticsPhysiological fluctuationsAntibiotic effectCellsHIVBacterial growthTherapyCancerInfectionMalariaDoses
2015
Classic reaction kinetics can explain complex patterns of antibiotic action
Abel Zur Wiesch P, Abel S, Gkotzis S, Ocampo P, Engelstädter J, Hinkley T, Magnus C, Waldor MK, Udekwu K, Cohen T. Classic reaction kinetics can explain complex patterns of antibiotic action. Science Translational Medicine 2015, 7: 287ra73. PMID: 25972005, PMCID: PMC4554720, DOI: 10.1126/scitranslmed.aaa8760.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsEscherichia coliKineticsMicrobial Sensitivity TestsVibrio choleraeConceptsOptimal dosing strategiesAntibiotic treatment strategiesTime-kill curvesAntibiotic effectGrowth suppressionCell formationChemotherapeutic regimensClinical trialsDosing strategiesTreatment strategiesTuberculosis therapyPersister cell formationDrug effectsBacterial infectionsVariety of antibioticsOrigin and Proliferation of Multiple-Drug Resistance in Bacterial Pathogens
Chang HH, Cohen T, Grad YH, Hanage WP, O'Brien TF, Lipsitch M. Origin and Proliferation of Multiple-Drug Resistance in Bacterial Pathogens. Microbiology And Molecular Biology Reviews 2015, 79: 101-116. PMID: 25652543, PMCID: PMC4402963, DOI: 10.1128/mmbr.00039-14.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsBacteriaBacterial InfectionsDrug Resistance, Multiple, BacterialHost-Pathogen InteractionsHumansConceptsMDR infectionsPublic health threatMultiple drug resistanceHigh prevalenceMore effective interventionsDifferent underlying mechanismsMultidrug resistanceEffective interventionsHealth threatUnderlying mechanismInfectionBacterial pathogensMDRCommon mechanismDifferent pathogensProliferationPathogensPrevalenceHypothetical mechanismHow competition governs whether moderate or aggressive treatment minimizes antibiotic resistance
Colijn C, Cohen T. How competition governs whether moderate or aggressive treatment minimizes antibiotic resistance. ELife 2015, 4: e10559. PMID: 26393685, PMCID: PMC4641510, DOI: 10.7554/elife.10559.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsBacteriaBacterial InfectionsDrug Resistance, BacterialModels, Theoretical
2011
Bayesian methods for fitting mixture models that characterize branching tree processes: An application to development of resistant TB strains
Izu A, Cohen T, Mitnick C, Murray M, De Gruttola V. Bayesian methods for fitting mixture models that characterize branching tree processes: An application to development of resistant TB strains. Statistics In Medicine 2011, 30: 2708-2720. PMID: 21717491, PMCID: PMC3219798, DOI: 10.1002/sim.4287.Peer-Reviewed Original ResearchConceptsCharacterization of uncertaintyBayesian approachBayesian methodsBranching tree modelStatistical methodsMixture modelBranching treeNatural wayPrior informationDrug resistance-conferring mutationsSuch cross-sectional dataDrug-resistant TBResistant TB strainsCombination of antibioticsDrug resistance mutationsMeasurement errorResistance-conferring mutationsTB strainsSingle patientTreatment policyPatientsMultiple drugsDiagnostic specimensCross-sectional dataGenetic mutationsModels to understand the population-level impact of mixed strain M. tuberculosis infections
Sergeev R, Colijn C, Cohen T. Models to understand the population-level impact of mixed strain M. tuberculosis infections. Journal Of Theoretical Biology 2011, 280: 88-100. PMID: 21514304, PMCID: PMC3111980, DOI: 10.1016/j.jtbi.2011.04.011.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Bacterial AgentsDrug Resistance, BacterialHumansModels, TheoreticalMutationMycobacterium tuberculosisSpecies SpecificityTuberculosisConceptsDrug-resistant strainsMixed strain infectionsStrain infectionDrug-sensitive tuberculosisDrug-resistant tuberculosisM. tuberculosis infectionLower basic reproductive numberDrug-resistant infectionsTuberculosis patientsTuberculosis infectionTreatment successDrug-resistant bacteriaFuture burdenLong-term effectsStrain-specific differencesDrug resistanceInfectionPopulation-level impactTuberculosisM. tuberculosisMixed infectionsMycobacterium tuberculosisBasic reproductive numberCo-infected hostsSmall subpopulation
2010
Prolonged deferral of antiretroviral therapy in the SAPIT trial: Did we need a clinical trial to tell us that this would increase mortality?
Boulle A, Clayden P, Cohen K, Cohen T, Conradie F, Dong K, Geffen N, Grimwood A, Hurtado R, Kenyon C, Lawn S, Maartens G, Meintjes G, Mendelson M, Murray M, Rangaka M, Sanne I, Spencer D, Taljaard J, Variava E, Venter WD, Wilson D. Prolonged deferral of antiretroviral therapy in the SAPIT trial: Did we need a clinical trial to tell us that this would increase mortality? South African Medical Journal 2010, 100: 566,568,570-571. PMID: 20822639, DOI: 10.7196/samj.4434.Peer-Reviewed Original Research
2008
Seasonality of Antibiotic-Resistant Streptococcus pneumoniae That Causes Acute Otitis Media: A Clue for an Antibiotic-Restriction Policy?
Dagan R, Barkai G, Givon-Lavi N, Sharf AZ, Vardy D, Cohen T, Lipsitch M, Greenberg D. Seasonality of Antibiotic-Resistant Streptococcus pneumoniae That Causes Acute Otitis Media: A Clue for an Antibiotic-Restriction Policy? The Journal Of Infectious Diseases 2008, 197: 1094-1102. PMID: 18419528, PMCID: PMC2652754, DOI: 10.1086/528995.Peer-Reviewed Original Research