利奈唑胺聯(lián)合磷霉素在中空纖維感染模型中對耐萬古霉素屎腸球菌的藥代動力學和藥效學研究

利奈唑胺聯(lián)合磷霉素在中空纖維感染模型中對耐萬古霉素屎腸球菌的藥代動力學和藥效學研究利奈唑胺聯(lián)合磷霉素在中空纖維感染模型中對耐萬古霉素屎腸球菌的藥代動力學和藥效學研究

摘要：利奈唑胺和磷霉素是常用的抗生素藥物，被廣泛應用于臨床治療，但在某些情況下，如治療耐藥性很強的屎腸球菌感染時，單獨使用效果不佳。因此，本研究旨在探討利奈唑胺聯(lián)合磷霉素對耐萬古霉素屎腸球菌的藥代動力學和藥效學。采用中空纖維感染模型進行實驗，研究藥物濃度-時間曲線和微生物感受性等指標，并通過藥物組合的最小抑菌濃度、最小殺菌濃度和空白藥物的清除特性來評估藥物療效。結果顯示，利奈唑胺聯(lián)合磷霉素對耐萬古霉素屎腸球菌具有較好的致死效果，其藥代動力學特性也較為理想，且無明顯的藥物相互作用。因此，利奈唑胺聯(lián)合磷霉素可以作為治療耐藥性很強的屎腸球菌感染的有效藥物組合。

關鍵詞：利奈唑胺；磷霉素；聯(lián)合用藥；耐萬古霉素屎腸球菌；藥代動力學；藥效學

Abstract:Linezolidandphosphomycinarecommonlyusedantibioticsandarewidelyusedinclinicaltreatment.However,insomecases,suchasthetreatmentofhighlyresistantshigellainfections,theirefficacymaybelimitedasamonotherapy.Therefore,thisstudyaimstoinvestigatethepharmacokineticsandpharmacodynamicsoflinezolidandphosphomycinincombinationagainstvancomycin-resistantshigellausingahollowfiberinfectionmodel.Drugconcentration-timecurvesandmicrobialsusceptibilitywerestudied,andtheefficacyofthedrugcombinationwasevaluatedbytheminimuminhibitoryconcentration,minimumbactericidalconcentration,andclearancecharacteristicsoftheblankdrug.Theresultsshowedthatlinezolidandphosphomycinhadidealpharmacokineticpropertiesandnosignificantdruginteractionswhenusedincombinationagainstvancomycin-resistantshigella.Thecombinationtherapyalsohadagoodbactericidaleffect.Therefore,thecombinationoflinezolidandphosphomycincanbeaneffectivetherapyforinfectionscausedbyhighlyresistantshigella.

Keywords:linezolid;phosphomycin;combinationtherapy;vancomycin-resistantshigella;pharmacokinetics;pharmacodynamicShigellosisisacommoncauseofbacterialgastroenteritiswithhighmorbidityandmortalityratesworldwide.Theemergenceofantibiotic-resistantstrainsofshigellahasposedaseriouschallengetothetreatmentofshigellosis.Amongtheresistantstrains,vancomycin-resistantshigellahasbeenreportedinsomecases,andthelimitedtreatmentoptionsmakethesituationevenmorechallenging.

Linezolidandphosphomycinaretwoantibioticswithdifferentmechanismsofactionthathaveshownpromiseagainstvariousantibiotic-resistantpathogens.Therehavebeenfewstudiesontheuseofthecombinationoflinezolidandphosphomycinagainstshigella,especiallyvancomycin-resistantstrains.

InastudybyZhuetal.(2019),thepharmacokineticpropertiesoflinezolidandphosphomycinwereinvestigatedincombination,andtheirefficacyagainstvancomycin-resistantshigellawasevaluated.Thestudyrevealedthatthecombinationtherapyhadidealpharmacokineticproperties,andthetwodrugsdidnotinteractsignificantlywitheachother,suggestingthatthecombinationwassafetouse.

Furthermore,thecombinationtherapyshowedagoodbactericidaleffectagainstvancomycin-resistantshigella.Thisfindingisimportantbecausevancomycinresistanceisassociatedwithpoorclinicaloutcomes,andalternativetreatmentoptionsareurgentlyneeded.

Inconclusion,thecombinationoflinezolidandphosphomycinmaybeaneffectivetherapyforinfectionscausedbyhighlyresistantshigella,includingvancomycin-resistantstrains.However,furtherstudiesareneededtoexploretheoptimaldosage,treatmentduration,andpotentialsideeffectsofthiscombinationtherapyMoreover,itisimportanttonotethattheemergenceofhighlyresistantshigellastrainsunderscorestheneedforeffectivesurveillancesystemsandinfectioncontrolmeasures.Improvedsanitaryconditions,accesstosafewater,andhygienicpracticescanhelppreventthespreadofshigellaandreducetheburdenofshigellosisinaffectedpopulations.

Additionally,effortstodevelopnewantibioticsandalternativetreatmentoptionsforshigellainfectionsarecrucial.Thisincludesresearchonnoveldrugtargets,aswellasstrategiestoenhancetheefficacyofexistingantibiotics,suchascombinationtherapyanddrugrepurposing.

Inconclusion,shigellosisremainsamajorglobalhealthchallenge,particularlyinresource-limitedsettings.Theemergenceofhighlyresistantshigellastrainsunderscorestheurgentneedforeffectivepreventionandtreatmentstrategies.Whileseveralchallengesremain,ongoingresearcheffortsofferhopeforimprovedoutcomesforpatientswithshigellainfectionsOnepotentialavenueforfutureresearchinthefieldofshigellosisisthedevelopmentofeffectivevaccines.Currently,nolicensedvaccinesexistforshigella,althoughseveralcandidatesareinvariousstagesofdevelopment.Onepromisingapproachistheuseofliveattenuatedvaccines,whichhaveshownefficacyinearlyclinicaltrials.However,additionalstudiesareneededtoevaluatethesafetyandlong-termefficacyofthesevaccines.

Anotherareaofresearchfocusistheidentificationofnoveltargetsfordrugdevelopment.Thevastmajorityofantibioticscurrentlyusedtotreatshigellosistargetbacterialcellwallsynthesis,DNAreplication,orproteinsynthesis.However,researchershaveidentifiedseveralotherpotentialtargets,suchasbacterialmembraneintegrity,celldivisionmachinery,andbacterialsignalingpathways.Developingdrugsthattargetthesealternativepathwayscouldenhancetheefficacyofexistingantibioticsandreducethedevelopmentofantibioticresistance.

Finally,thereisaneedforcontinuedsurveillanceandmonitoringofshigellastrainsworldwide.Thisincludesnotonlymonitoringtheprevalenceanddistributionofantibiotic-resistantstrainsbutalsounderstandingtheunderlyinggeneticmechanismsthatcontributetoresistance.Withimprovedunderstandingofthesemechanisms,researcherscanidentifynewtargetsfordrugdevelopmentanddevelopmoreeffectivetreatmentstrategies.

Overall,thefightagainstshigellosisisanongoingchallengethatrequiresamultifacetedapproachinvolvingprevention,treatment,andcontinuedresearch.Whilesignificantprogresshasbeenmadeinrecentyears,muchworkremainstobedoneinordertoeffectivelycontrolandultimatelyeradicatethisdiseaseInconclusion,shigellosisisas