2023
Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review
Doernberg S, Arias C, Altman D, Babiker A, Boucher H, Creech C, Cosgrove S, Evans S, Fowler V, Fritz S, Hamasaki T, Kelly B, Leal S, Liu C, Lodise T, Miller L, Munita J, Murray B, Pettigrew M, Ruffin F, Scheetz M, Shopsin B, Tran T, Turner N, Williams D, Zaharoff S, Holland T, Patel R, King H, Kinamon T, Dai W, Geres H, Deckard N, Schuler C, Bunn I, Sharma S, Wickward C, Waller J, Wilson H, Mehigan M, Ghazaryan V, Raterman E, Samuel T, Lee M. Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review. Clinical Infectious Diseases 2023, 77: s295-s304. PMID: 37843115, PMCID: PMC10578051, DOI: 10.1093/cid/ciad565.Peer-Reviewed Original ResearchConceptsAntibacterial Resistance Leadership GroupMRSA bloodstream infectionsMethicillin-resistant Staphylococcus aureusBloodstream infectionsClinical trialsPediatric community-acquired pneumoniaInfection researchEnterococcal bloodstream infectionsOptimal vancomycin dosingOptimization of dosingRole of dalbavancinCommunity-acquired pneumoniaShort-course therapyInterventional clinical trialsVancomycin-resistant enterococciVancomycin dosingPositive infectionsNovel agentsLife measuresTreat infectionsClinical practiceNarrative reviewInfectionPositive bacteriaStaphylococcus aureusThe Next Generation: Mentoring and Diversity in the Antibacterial Resistance Leadership Group
Harris A, Souli M, Pettigrew M, Group F. The Next Generation: Mentoring and Diversity in the Antibacterial Resistance Leadership Group. Clinical Infectious Diseases 2023, 77: s331-s335. PMID: 37843116, PMCID: PMC10578050, DOI: 10.1093/cid/ciad532.Peer-Reviewed Original ResearchAdaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2
Murphy T, Kirkham C, D’Mello A, Sethi S, Pettigrew M, Tettelin H. Adaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2. MBio 2023, 14: e00140-23. PMID: 36927061, PMCID: PMC10127715, DOI: 10.1128/mbio.00140-23.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseNontypeable Haemophilus influenzaeObstructive pulmonary diseaseRespiratory epithelial cellsHuman airwaysHaemophilus influenzaeAirway inflammationLung functionMechanisms of persistencePulmonary diseaseEpithelial cellsNovel interventionsChronic lower airway infectionsProgressive lossAirways of adultsLower airway infectionHuman respiratory epithelial cellsCommon debilitating disorderStrains of NTHiNTHi infectionAirway infectionLower airwaysCommon causeSequential isolatesSerial isolates
2022
Impact of antibiotics on off-target infant gut microbiota and resistance genes in cohort studies
Lebeaux RM, Madan JC, Nguyen QP, Coker MO, Dade EF, Moroishi Y, Palys TJ, Ross BD, Pettigrew MM, Morrison HG, Karagas MR, Hoen AG. Impact of antibiotics on off-target infant gut microbiota and resistance genes in cohort studies. Pediatric Research 2022, 92: 1757-1766. PMID: 35568730, PMCID: PMC9659678, DOI: 10.1038/s41390-022-02104-w.Peer-Reviewed Original ResearchConceptsAntibiotic exposureCohort studyDay careDay care attendanceInfant gut microbiotaAntibiotic resistance genesCare attendanceImpact of antibioticsAntibiotic useStool samplesGut microbiotaInfantsGut microbiomeStudy designBacteroides fragilisAntibioticsBackgroundYoung childrenNovel findingsSubsequent exposureExposureFirst yearFurther investigationBaselineResistance genesCareComparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia
Pettigrew MM, Kwon J, Gent JF, Kong Y, Wade M, Williams DJ, Creech CB, Evans S, Pan Q, Walter EB, Martin JM, Gerber JS, Newland JG, Hofto ME, Staat MA, Fowler VG, Chambers HF, Huskins WC. Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia. MBio 2022, 13: e00195-22. PMID: 35323040, PMCID: PMC9040816, DOI: 10.1128/mbio.00195-22.Peer-Reviewed Original ResearchConceptsCommunity-acquired pneumoniaShort-course strategyBeta-lactam therapyTreatment strategiesAntibiotic useRespiratory microbiomePediatric community-acquired pneumoniaDays of antibioticsShorter antibiotic coursesStandard-strategy groupDays of therapyStandard treatment strategyAntibiotic resistanceAdditional rationaleEffectiveness of interventionsImpact of durationAntibiotic coursesThroat swabsCourse strategyAntibiotic treatmentPediatric pneumoniaCourse treatmentLow prevalencePneumoniaAntibiotic resistance determinantsGastrointestinal Microbiome Disruption and Antibiotic-Associated Diarrhea in Children Receiving Antibiotic Therapy for Community-Acquired Pneumonia
Kwon J, Kong Y, Wade M, Williams DJ, Creech CB, Evans S, Walter EB, Martin JM, Gerber JS, Newland JG, Hofto ME, Staat MA, Chambers HF, Fowler VG, Huskins WC, Pettigrew M. Gastrointestinal Microbiome Disruption and Antibiotic-Associated Diarrhea in Children Receiving Antibiotic Therapy for Community-Acquired Pneumonia. The Journal Of Infectious Diseases 2022, 226: 1109-1119. PMID: 35249113, PMCID: PMC9492313, DOI: 10.1093/infdis/jiac082.Peer-Reviewed Original ResearchConceptsAAD groupAntibiotic-Associated DiarrheaCommunity-Acquired PneumoniaCommon side effectsStudy days 1Days of diarrheaPatient characteristicsAntibiotic therapyNineteen childrenStool samplesSide effectsDay 1Microbiome disruptionMicrobiota profilesGastrointestinal microbiotaMicrobiota characteristicsDiarrheaBacteroides speciesPneumoniaChildrenAntibioticsΒ-lactamsAADBaseline abundanceDysbiosisShort- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children
Williams DJ, Creech CB, Walter EB, Martin JM, Gerber JS, Newland JG, Howard L, Hofto ME, Staat MA, Oler RE, Tuyishimire B, Conrad TM, Lee MS, Ghazaryan V, Pettigrew MM, Fowler VG, Chambers HF, Zaoutis TE, Evans S, Huskins WC, Team A. Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children. JAMA Pediatrics 2022, 176: 253-261. PMID: 35040920, PMCID: PMC8767493, DOI: 10.1001/jamapediatrics.2021.5547.Peer-Reviewed Original ResearchConceptsChildhood community-acquired pneumoniaAntibiotic-associated adverse effectsShort-course strategyClinical responseAdverse effectsDouble-blind placebo-controlled clinical trialPlacebo-controlled clinical trialEnd pointDays of antibioticsEarly clinical improvementInadequate clinical responseOutpatient antibiotic therapyShorter antibiotic durationsSimilar clinical responseCommunity-Acquired PneumoniaPrimary end pointComposite end pointResolution of symptomsAntibiotic treatment strategiesSubset of childrenAntibiotic daysAntibiotic durationClinical improvementAntibiotic therapyInitial treatment
2020
The Lung Microbiome and Pneumonia
Pettigrew MM, Tanner W, Harris AD. The Lung Microbiome and Pneumonia. The Journal Of Infectious Diseases 2020, 223: s241-s245. PMID: 33330898, DOI: 10.1093/infdis/jiaa702.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsDolosigranulum pigrum Cooperation and Competition in Human Nasal Microbiota
Brugger SD, Eslami SM, Pettigrew MM, Escapa IF, Henke MT, Kong Y, Lemon KP. Dolosigranulum pigrum Cooperation and Competition in Human Nasal Microbiota. MSphere 2020, 5: 10.1128/msphere.00852-20. PMID: 32907957, PMCID: PMC7485692, DOI: 10.1128/msphere.00852-20.Peer-Reviewed Original ResearchConceptsMicrobe-microbe interactionsHuman nasal microbiotaGenomic analysisPhenotypic interactionsBiosynthetic gene clusterSmall genomesNasal microbiotaGene clusterAccessory genomeKey nutrientsNew insightsGenomic capacityBacterial residentsPathogenic speciesNasal microbiota compositionBeneficial bacteriumFunctional assaysDiverse repertoireHuman hostGenomeSpeciesAcid productionMicrobiotaNasal bacteriaBacteria
2019
Non-typeable Haemophilus influenzae isolates from patients with chronic obstructive pulmonary disease contain new phase-variable modA methyltransferase alleles controlling phasevarions
Atack JM, Murphy TF, Pettigrew MM, Seib KL, Jennings MP. Non-typeable Haemophilus influenzae isolates from patients with chronic obstructive pulmonary disease contain new phase-variable modA methyltransferase alleles controlling phasevarions. Scientific Reports 2019, 9: 15963. PMID: 31685916, PMCID: PMC6828955, DOI: 10.1038/s41598-019-52429-6.Peer-Reviewed Original ResearchConceptsNon-typeable Haemophilus influenzaeChronic obstructive pulmonary diseaseObstructive pulmonary diseaseMiddle ear infectionPulmonary diseaseEar infectionsNTHi strainsHaemophilus influenzaeExacerbation of COPDCOPDMiddle earPatientsAllele distributionInfectionInfluenzaeBacterial pathogensDiseaseMultiple allelic variantsAllelic variantsGene expressionAllelesEpigenetic mechanismsLarge panelExacerbationExpressionDiscovery and Contribution of Nontypeable Haemophilus influenzae NTHI1441 to Human Respiratory Epithelial Cell Invasion
Ahearn C, Kirkham C, Chaves L, Kong Y, Pettigrew M, Murphy T. Discovery and Contribution of Nontypeable Haemophilus influenzae NTHI1441 to Human Respiratory Epithelial Cell Invasion. Infection And Immunity 2019, 87: 10.1128/iai.00462-19. PMID: 31427451, PMCID: PMC6803334, DOI: 10.1128/iai.00462-19.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseRespiratory epithelial cellsEnzyme-linked immunosorbent assayEpithelial cellsAirways of adultsObstructive pulmonary diseaseCell invasionHuman respiratory epithelial cellsNontypeable Haemophilus influenzaeCell enzyme-linked immunosorbent assayAlveolar epithelial cellsAcute exacerbationLower airwaysPulmonary diseaseSerum IgGNTHi strainsTherapeutic interventionsHaemophilus influenzaeHuman bronchialSurface-exposed epitopesEpithelial cell invasionIsogenic knockout mutantsNTHiImmunosorbent assayIntracellular survival
2018
Persistence of Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease and Regulation of the Hag/MID Adhesin
Murphy TF, Brauer AL, Pettigrew MM, LaFontaine ER, Tettelin H. Persistence of Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease and Regulation of the Hag/MID Adhesin. The Journal Of Infectious Diseases 2018, 219: 1448-1455. PMID: 30496439, PMCID: PMC6467191, DOI: 10.1093/infdis/jiy680.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseM. catarrhalisPulmonary diseaseMoraxella catarrhalisPersistent strainsDuration of persistenceHuman airwaysCatarrhalisCessation of expressionAirwayMajor pathogenPatientsBacterial pathogensDiseaseVirulence-associated phenotypesAdultsCollected strainsMost strainsExpressionHuman cellsPathogensPathogenesisPersistenceMonthsGastrointestinal Microbiota Disruption and Risk of Colonization With Carbapenem-resistant Pseudomonas aeruginosa in Intensive Care Unit Patients
Pettigrew MM, Gent JF, Kong Y, Halpin AL, Pineles L, Harris AD, Johnson JK. Gastrointestinal Microbiota Disruption and Risk of Colonization With Carbapenem-resistant Pseudomonas aeruginosa in Intensive Care Unit Patients. Clinical Infectious Diseases 2018, 69: 604-613. PMID: 30383203, PMCID: PMC6669284, DOI: 10.1093/cid/ciy936.Peer-Reviewed Original ResearchConceptsCarbapenem-resistant Pseudomonas aeruginosaIntensive care unit patientsCare unit patientsPiperacillin-tazobactamUnit patientsICU patientsMarker of riskMaryland Medical CenterRisk of colonizationRibosomal RNA gene sequencingRNA gene sequencingAdmission swabCRPA infectionPseudomonas aeruginosaICU admissionPatient characteristicsMicrobiota disruptionMedical CenterGastrointestinal tractAdditional swabsAntimicrobial exposureLower riskEvaluated associationsPatientsProtective roleChanges in IgA Protease Expression Are Conferred by Changes in Genomes during Persistent Infection by Nontypeable Haemophilus influenzae in Chronic Obstructive Pulmonary Disease
Gallo MC, Kirkham C, Eng S, Bebawee RS, Kong Y, Pettigrew MM, Tettelin H, Murphy TF. Changes in IgA Protease Expression Are Conferred by Changes in Genomes during Persistent Infection by Nontypeable Haemophilus influenzae in Chronic Obstructive Pulmonary Disease. Infection And Immunity 2018, 86: 10.1128/iai.00313-18. PMID: 29760213, PMCID: PMC6056860, DOI: 10.1128/iai.00313-18.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseasePersistent infectionPulmonary diseaseIgA proteaseProtease expressionNontypeable Haemophilus influenzaeAcute exacerbationLower airwaysRespiratory tractNTHi strainsHaemophilus influenzaeInfectionNTHiNatural infectionHuman pathobiontAltered expressionPatientsDiseasePersistent strainsExpressionCritical roleExacerbationAirwayInitial acquisitionHaemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease
Pettigrew MM, Ahearn CP, Gent JF, Kong Y, Gallo MC, Munro JB, D’Mello A, Sethi S, Tettelin H, Murphy TF. Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e3256-e3265. PMID: 29555745, PMCID: PMC5889651, DOI: 10.1073/pnas.1719654115.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseCandidate vaccine antigensHuman airwaysPulmonary diseaseVaccine antigensRespiratory tract pathogensHuman respiratory tractProspective studyTract pathogensNTHi isolatesRespiratory tractAnimal modelsVaccine developmentHuman infectionsAirwayNTHiSurface moleculesAmino acid sequence changesWhole-genome sequencingAntigenBacterial pathogensDiseaseSubset of strainsVirulence functionsAzithromycin Pharmacodynamics against Persistent Haemophilus influenzae in Chronic Obstructive Pulmonary Disease
Tsuji BT, Fisher J, Boadi-Yeboah R, Holden PN, Sethi S, Pettigrew MM, Murphy TF. Azithromycin Pharmacodynamics against Persistent Haemophilus influenzae in Chronic Obstructive Pulmonary Disease. Antimicrobial Agents And Chemotherapy 2018, 62: 10.1128/aac.01995-17. PMID: 29180527, PMCID: PMC5786777, DOI: 10.1128/aac.01995-17.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary disease patientsObstructive pulmonary disease patientsChronic obstructive pulmonary diseaseHollow-fiber infection modelStrains of NTHiPulmonary disease patientsObstructive pulmonary diseasePulmonary diseaseConcentration-dependent activityDisease patientsPharmacodynamic profilePharmacodynamic responseSame patientHaemophilus influenzaeInfection modelPatientsAzithromycinPersistent strainsDaysAirwayNTHiPharmacodynamicsInfluenzaeDiseaseHaemophilus
2017
Risk Factors and Outcomes Associated with Multidrug-Resistant Acinetobacter baumannii upon Intensive Care Unit Admission
Blanco N, Harris AD, Rock C, Johnson JK, Pineles L, Bonomo RA, Srinivasan A, Pettigrew MM, Thom KA. Risk Factors and Outcomes Associated with Multidrug-Resistant Acinetobacter baumannii upon Intensive Care Unit Admission. Antimicrobial Agents And Chemotherapy 2017, 62: 10.1128/aac.01631-17. PMID: 29133567, PMCID: PMC5740370, DOI: 10.1128/aac.01631-17.Peer-Reviewed Original ResearchConceptsMedical intensive care unitSurgical intensive care unitIntensive care unitICU admissionRisk factorsCare unitIntensive care unit admissionBroad-spectrum antibiotic useMultidrug-resistant Acinetobacter baumanniiPositive clinical cultureCare unit admissionRetrospective cohort analysisAssociated risk factorsEmpirical antibiotic selectionInfection control practicesPrevalence of MDRMaryland Medical CenterPerirectal surveillance culturesImportant nosocomial pathogenUnit admissionAdult patientsICU typePrevious admissionsCurrent hospitalizationActive surveillanceImmunoglobulin A Protease Variants Facilitate Intracellular Survival in Epithelial Cells By Nontypeable Haemophilus influenzae That Persist in the Human Respiratory Tract in Chronic Obstructive Pulmonary Disease
Murphy TF, Kirkham C, Gallo MC, Yang Y, Wilding GE, Pettigrew MM. Immunoglobulin A Protease Variants Facilitate Intracellular Survival in Epithelial Cells By Nontypeable Haemophilus influenzae That Persist in the Human Respiratory Tract in Chronic Obstructive Pulmonary Disease. The Journal Of Infectious Diseases 2017, 216: 1295-1303. PMID: 28968876, PMCID: PMC5853902, DOI: 10.1093/infdis/jix471.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseNontypeable Haemophilus influenzaeObstructive pulmonary diseaseExpression of IgARespiratory epithelial cellsLysosomal-associated membrane protein 1Pulmonary diseaseEpithelial cellsIntracellular survivalHaemophilus influenzaeHuman respiratory epithelial cellsPathogenesis of infectionHuman respiratory tractIgA proteasePassage of strainsMembrane protein 1Host cellsProtease expressionNTHi infectionNTHi isolatesRespiratory tractHost epithelial cellsIgAIntracellular persistenceReduced survivalPanel 4: Report of the Microbiology Panel
Barenkamp SJ, Chonmaitree T, Hakansson AP, Heikkinen T, King S, Nokso‐Koivisto J, Novotny LA, Patel JA, Pettigrew M, Swords WE. Panel 4: Report of the Microbiology Panel. Otolaryngology 2017, 156: s51-s62. PMID: 28372529, PMCID: PMC5490388, DOI: 10.1177/0194599816639028.Peer-Reviewed Original ResearchConceptsOtitis mediaUpper respiratory tract infectionRespiratory tract infectionsAcute otitis mediaOtitis media casesRespiratory syncytial virusFuture treatment optionsTract infectionsBacterial coinfectionBacterial virulence determinantsBasic laboratory studiesSyncytial virusTreatment optionsAntibiotic treatmentEpidemiology of diseaseAnimal modelsPanel membersClinical practicePubMed databaseNational HarborVirulence determinantsChildrenInitial reviewBacteriologyDraft reviewsPanel 6: Vaccines
Pettigrew MM, Alderson MR, Bakaletz LO, Barenkamp SJ, Hakansson AP, Mason KM, Nokso‐Koivisto J, Patel J, Pelton SI, Murphy TF. Panel 6: Vaccines. Otolaryngology 2017, 156: s76-s87. PMID: 28372533, PMCID: PMC5505493, DOI: 10.1177/0194599816632178.Peer-Reviewed Original ResearchConceptsPneumococcal otitis mediaOtitis mediaVaccine antigensVaccine developmentH influenzaePneumococcal serotypesHaemophilus influenzae protein DSignificant health care burdenAdditional pneumococcal serotypesCorrelates of protectionHealth care burdenRecurrent otitis mediaEffectiveness of vaccinesTympanostomy tube insertionProtein-based vaccinesCandidate vaccine antigensOM pathogensOM visitsPCV effectivenessPneumococcal vaccineRespiratory virusesVaccine protectionTube insertionMoraxella catarrhalisCare burden