title: Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.
abstract: No large study to date has ever evaluated the effectiveness, safety and tolerability of imipenem/clavulanate versus meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to compare the therapeutic contribution of imipenem/clavulanate versus meropenem/clavulanate added to background regimens to treat MDR- and XDR-TB cases.84 patients treated with imipenem/clavulanate-containing regimens showed a similar median number of antibiotic resistances (8 versus 8) but more fluoroquinolone resistance (79.0% versus 48.9%, p<0.0001) and higher XDR-TB prevalence (67.9% versus 49.0%, p=0.01) in comparison with 96 patients exposed to meropenem/clavulanate-containing regimens. Patients were treated with imipenem/clavulanate- and meropenem/clavulanate-containing regimens for a median (interquartile range) of 187 (60-428) versus 85 (49-156) days, respectively.Statistically significant differences were observed on sputum smear and culture conversion rates (79.7% versus 94.8%, p=0.02 and 71.9% versus 94.8%, p<0.0001, respectively) and on success rates (59.7% versus 77.5%, p=0.03). Adverse events to imipenem/clavulanate and meropenem/clavulanate were reported in 5.4% and 6.5% of cases only.Our study suggests that meropenem/clavulanate is more effective than imipenem/clavulanate in treating MDR/XDR-TB patients.
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: 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: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy These authors contributed equally to this work.
authors.forename: Rosella
authors.initials: R
authors.lastname: Centis
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: International Union against Tuberculosis and Lung Disease (The Union), Lima, Peru MDR-TB Unit, Tuberculosis Division, International Union against Tuberculosis and Lung Disease (The Union), Paris, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Alarcon Arrascue
authors.affiliation: University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Alffenaar
authors.affiliation: MDR-TB Unit, Tuberculosis Division, International Union against Tuberculosis and Lung Disease (The Union), Paris, France Pneumology Dept, Hospital General de Gran Canaria "Dr. Negrin", Las Palmas de Gran Canaria, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Caminero
authors.affiliation: MDR-TB Unit, Athens Chest Hospital Sotira, 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: 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, Catholic University Ruzomberok, Ruzomberok, 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: National Tuberculosis Control Programme, Ministry of Health, Lima, Peru.
authors.forename: Valentina
authors.initials: V
authors.lastname: Alarcon Guizado
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: 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: University of Groningen, University Medical Center Groningen, Dept of Pulmonary Diseases and Tuberculosis; TB Center Beatrixoord, Groningen, The Netherlands.
authors.forename: Onno W
authors.initials: OW
authors.lastname: Akkerman
authors.affiliation: Educational Institution "Grodno State Medical University", Grodno, Belarus.
authors.forename: Alena
authors.initials: A
authors.lastname: Aleksa
authors.affiliation: Educational Institution "Grodno State Medical University", Grodno, Belarus.
authors.forename: Janina
authors.initials: J
authors.lastname: Artsukevich
authors.affiliation: Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
authors.forename: Vera
authors.initials: V
authors.lastname: Auchynka
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 Sotira, 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 Sotira, National Referral Centre for Mycobacteria, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papavasileiou
authors.affiliation: Division of Infectious Diseases, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium.
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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Piana
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*; D015331:Cohort Studies; D057186:Comparative Effectiveness Research; D024881:Drug Resistance, Bacterial; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage*; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D013183:Sputum / Q000378:metabolism; D013845:Thienamycins / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D013845:Thienamycins; D019818:Clavulanic Acid; D015378:Imipenem; D000077731:Meropenem