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Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment

2016-04-14Journal article Open access
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dc.contributor.authorGjini, Erida
dc.contributor.authorBrito, Patricia H.
dc.date.accessioned2016-04-18T11:56:02Z
dc.date.available2016-04-18T11:56:02Z
dc.date.issued2016-04-14
dc.description.abstractAntimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes.pt_PT
dc.description.sponsorshipInstituto Gulbenkian de Ciência; FCT fellowship: (SFRH/BPD /89907/2012).pt_PT
dc.identifier.citationGjini E, Brito PH (2016) Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment. PLoS Comput Biol 12(4): e1004857. doi:10.1371/journal.pcbi.1004857pt_PT
dc.identifier.doi10.1371/journal.pcbi.1004857pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/580
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relation.publisherversionhttp://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004857pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectImmunitypt_PT
dc.subjectAntibioticspt_PT
dc.subjectDrug therapypt_PT
dc.subjectPathogenspt_PT
dc.subjectImmune responsept_PT
dc.subjectAntimicrobial resistancept_PT
dc.subjectHost-pathogen interactionspt_PT
dc.subjectAntibiotic resistancept_PT
dc.titleIntegrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatmentpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage34pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePLOS Computational Biologypt_PT
oaire.citation.volume12pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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