Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection

Hdl Handle:
http://hdl.handle.net/10144/213251
Title:
Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection
Authors:
Bonnet, Maryline; Pardini, Manuela; Meacci, Francesca; Orrù, Germano; Yesilkaya, Hasan; Jarosz, Thierry; Andrew, Peter W.; Barer, Mike; Checchi, Francesco; Rinder, Heinz; Orefici, Graziella; Rüsch-Gerdes, Sabine; Fattorini, Lanfranco; Oggioni, Marco Rinaldo; Melzer, Juliet; Niemann, Stefan; Varaine, Francis
Journal:
PLoS ONE
Abstract:
Introduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals.
Affiliation:
Clinical Research department, Epicentre, Geneva, Switzerland; Dipartimento di Malattie Infettive Parassitarie e Immunomediate, Istituto Superiore di Sanita` , Rome, Italy; Dipartimento di Biologia Molecolare, Universita` di Siena, Siena, Italy; Dipartimento di Scienze Odontostomatologiche, Universita` di Cagliari, Cagliari, Italy; Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom; Essai clinique Evaluation Epidemiologie Statistiques, Paris, France; Sachgebiet Parasitologie Bayerisches, Landesamt fu¨ r Gesundheit und Lebensmittelsicherheit, Oberschleißheim, Germany; National Reference Center for Mycobacteriology, Forschungszentrum Borstel, Borstel, Germany; Medical department, Medecins Sans Frontieres, Paris, France
Publisher:
Public Library of Science
Issue Date:
23-Aug-2011
URI:
http://hdl.handle.net/10144/213251
DOI:
10.1371/journal.pone.0023081
Additional Links:
http://dx.plos.org/10.1371/journal.pone.0023081
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
TB

Full metadata record

DC FieldValue Language
dc.contributor.authorBonnet, Marylineen
dc.contributor.authorPardini, Manuelaen
dc.contributor.authorMeacci, Francescaen
dc.contributor.authorOrrù, Germanoen
dc.contributor.authorYesilkaya, Hasanen
dc.contributor.authorJarosz, Thierryen
dc.contributor.authorAndrew, Peter W.en
dc.contributor.authorBarer, Mikeen
dc.contributor.authorChecchi, Francescoen
dc.contributor.authorRinder, Heinzen
dc.contributor.authorOrefici, Graziellaen
dc.contributor.authorRüsch-Gerdes, Sabineen
dc.contributor.authorFattorini, Lanfrancoen
dc.contributor.authorOggioni, Marco Rinaldoen
dc.contributor.authorMelzer, Julieten
dc.contributor.authorNiemann, Stefanen
dc.contributor.authorVaraine, Francisen
dc.date.accessioned2012-02-28T06:23:29Z-
dc.date.available2012-02-28T06:23:29Z-
dc.date.issued2011-08-23-
dc.identifier.citationPLoS ONE 2011; 6(8):e23081en
dc.identifier.issn1932-6203-
dc.identifier.doi10.1371/journal.pone.0023081-
dc.identifier.urihttp://hdl.handle.net/10144/213251-
dc.description.abstractIntroduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals.en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pone.0023081en
dc.rightsPublished by Public Library of Science, [url]http://www.plosone.org/[/url] Archived on this site by Open Access permissionen
dc.subject.meshTuberculosisen
dc.subject.meshTuberculosis, Multidrug-Resistanten
dc.titleTreatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infectionen
dc.typeArticleen
dc.contributor.departmentClinical Research department, Epicentre, Geneva, Switzerland; Dipartimento di Malattie Infettive Parassitarie e Immunomediate, Istituto Superiore di Sanita` , Rome, Italy; Dipartimento di Biologia Molecolare, Universita` di Siena, Siena, Italy; Dipartimento di Scienze Odontostomatologiche, Universita` di Cagliari, Cagliari, Italy; Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom; Essai clinique Evaluation Epidemiologie Statistiques, Paris, France; Sachgebiet Parasitologie Bayerisches, Landesamt fu¨ r Gesundheit und Lebensmittelsicherheit, Oberschleißheim, Germany; National Reference Center for Mycobacteriology, Forschungszentrum Borstel, Borstel, Germany; Medical department, Medecins Sans Frontieres, Paris, Franceen
dc.identifier.journalPLoS ONEen
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