title: Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.
abstract: No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p<0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6-9)versus 5 (4-6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49-156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment).The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR- and XDR-TB cases.
authors.affiliation: Division of Infection, Barts Healthcare NHS Trust, London, UK These authors contributed equally to this work.
authors.forename: Simon
authors.initials: S
authors.lastname: Tiberi
authors.affiliation: Division of Infectious Diseases, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium These authors contributed equally to this work.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Payen
authors.affiliation: Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari - Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy These authors contributed equally to this work.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sotgiu
authors.affiliation: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy Public Health Consulting Group, Lugano, Switzerland These authors contributed equally to this work.
authors.forename: Lia
authors.initials: L
authors.lastname: D'Ambrosio
authors.affiliation: National Tuberculosis Control Programme, Ministry of Health, Lima, Peru.
authors.forename: Valentina
authors.initials: V
authors.lastname: Alarcon Guizado
authors.affiliation: Dept of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Alffenaar
authors.affiliation: University Center of Araraquara, Sao Paulo, Brazil Hospital Nestor Goulart Reis, Sao Paulo State Secretary of Health, Sao Paulo, Brazil.
authors.forename: Marcos
authors.initials: M
authors.lastname: Abdo Arbex
authors.affiliation: Pneumology Dept, Hospital General de Gran Canaria "Dr. Negrin", Las Palmas de Gran Canaria, Spain MDR-TB Unit, Tuberculosis Division, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Caminero
authors.affiliation: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Centis
authors.affiliation: AOVV E. Morelli Hospital, Reference Hospital for MDR and HIV-TB, Sondalo, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: De Lorenzo
authors.affiliation: MDR-TB Unit, Athens Chest Hospital Sotiria, National Referral Centre for Mycobacteria, Athens, Greece.
authors.forename: Mina
authors.initials: M
authors.lastname: Gaga
authors.affiliation: Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: Gualano
authors.affiliation: National Tuberculosis Control Programme, Pulmonology Hospital Alfredo J. Valenzuela, Guayaquil, Ecuador.
authors.forename: Aurora Jazmín
authors.initials: AJ
authors.lastname: Roby Arias
authors.affiliation: MDR-TB Unit, Tuberculosis Division, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Scardigli
authors.affiliation: Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
authors.forename: Alena
authors.initials: A
authors.lastname: Skrahina
authors.affiliation: National Institute for TB, Lung Diseases and Thoracic Surgery, Vysne Hagy, Slovakia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Solovic
authors.affiliation: University Dept of Infectious and Tropical Diseases, WHO Collaborating Centre for TB/HIV Co-infection and for TB Elimination - University of Brescia and Brescia Spedali Civili General Hospital, Brescia, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Sulis
authors.affiliation: Unit of Infectious Diseases, Dept of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Tadolini
authors.affiliation: Dept of Pulmonary Diseases and Tuberculosis, TB Center Beatrixoord, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Onno W
authors.initials: OW
authors.lastname: Akkerman
authors.affiliation: MDR-TB Unit, Tuberculosis Division, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France International Union Against Tuberculosis and Lung Disease (The Union), Lima, Peru.
authors.forename: Edith
authors.initials: E
authors.lastname: Alarcon Arrascue
authors.affiliation: Educational Institution "Grodno State Medical University", Grodno, Belarus.
authors.forename: Alena
authors.initials: A
authors.lastname: Aleska
authors.affiliation: Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
authors.forename: Vera
authors.initials: V
authors.lastname: Avchinko
authors.affiliation: University Center of Araraquara, Sao Paulo, Brazil Hospital Nestor Goulart Reis, Sao Paulo State Secretary of Health, Sao Paulo, Brazil.
authors.forename: Eduardo Henrique
authors.initials: EH
authors.lastname: Bonini
authors.affiliation: National Tuberculosis Control Programme, Pulmonology Hospital Alfredo J. Valenzuela, Guayaquil, Ecuador.
authors.forename: Félix Antonio
authors.initials: FA
authors.lastname: Chong Marín
authors.affiliation: National Tuberculosis Control Programme, Pulmonology Hospital Alfredo J. Valenzuela, Guayaquil, Ecuador.
authors.forename: Lorena
authors.initials: L
authors.lastname: Collahuazo López
authors.affiliation: KNCV Tuberculosis Foundation, The Hague, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: de Vries
authors.affiliation: Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari - Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Dore
authors.affiliation: Dept of Respiratory Medicine, Queen Mary University, London, UK.
authors.forename: Heinke
authors.initials: H
authors.lastname: Kunst
authors.affiliation: University Dept of Infectious and Tropical Diseases, WHO Collaborating Centre for TB/HIV Co-infection and for TB Elimination - University of Brescia and Brescia Spedali Civili General Hospital, Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Matteelli
authors.affiliation: MDR-TB Unit, Athens Chest Hospital Sotiria, National Referral Centre for Mycobacteria, Athens, Greece.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Moschos
authors.affiliation: Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Palmieri
authors.affiliation: MDR-TB Unit, Athens Chest Hospital Sotiria, National Referral Centre for Mycobacteria, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papavasileiou
authors.affiliation: Pneumology Unit, Fondazione Maugeri, IRCCS, Tradate, Italy Dept of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Spanevello
authors.affiliation: National Hospital Hipólito Unanue, Public Health Institute, Ministry of Health, Lima, Peru.
authors.forename: Dante
authors.initials: D
authors.lastname: Vargas Vasquez
authors.affiliation: AOVV E. Morelli Hospital, Reference Hospital for MDR and HIV-TB, Sondalo, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Viggiani
authors.affiliation: Dept of Respiratory Medicine, Barts Healthcare NHS Trust, London, UK.
authors.forename: Veronica
authors.initials: V
authors.lastname: White
authors.affiliation: Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK.
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.affiliation: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy giovannibattista.migliori@fsm.it.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Migliori
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage*; D019818:Clavulanic Acid / Q000008:administration & dosage*; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D012189:Retrospective Studies; D013845:Thienamycins / Q000008:administration & dosage*; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D013845:Thienamycins; D019818:Clavulanic Acid; D000077731:Meropenem