title: Carbapenems to Treat Multidrug and Extensively Drug-Resistant Tuberculosis: A Systematic Review.
abstract: BACKGROUND
  Carbapenems (ertapenem, imipenem, meropenem) are used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), even if the published evidence is limited, particularly when it is otherwise difficult to identify the recommended four active drugs to be included in the regimen. No systematic review to date has ever evaluated the efficacy, safety, and tolerability of carbapenems.
  
  
  METHODS
  A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of carbapenem-containing regimens in individuals with pulmonary/extra-pulmonary disease which was bacteriologically confirmed as M/XDR-TB. We used PubMed to identify relevant full-text, English manuscripts up to the 20 December 2015, excluding editorials and reviews.
  
  
  RESULTS
  Seven out of 160 studies satisfied the inclusion criteria: two on ertapenem, one on imipenem, and four on meropenem, all published between 2005 and 2016. Of seven studies, six were retrospective, four were performed in a single center, two enrolled children, two had a control group, and six reported a proportion of XDR-TB cases higher than 20%. Treatment success was higher than 57% in five studies with culture conversion rates between 60% and 94.8%.
  
  
  CONCLUSIONS
  The safety and tolerability is very good, with the proportion of adverse events attributable to carbapenems below 15%.
authors.affiliation: Clinical Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari-Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari 07100, Italy. gsotgiu@uniss.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sotgiu
authors.affiliation: World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, IRCCS (Istituto di Ricovero e Cura a Carattere Sceintifico), Via Roncaccio 16, Tradate 21049, Italy. lia.dambrosio@fsm.it.|Public Health Consulting Group, Lugano 6900, Switzerland. lia.dambrosio@fsm.it.
authors.forename: Lia
authors.initials: L
authors.lastname: D'Ambrosio
authors.affiliation: World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, IRCCS (Istituto di Ricovero e Cura a Carattere Sceintifico), Via Roncaccio 16, Tradate 21049, Italy. rosella.centis@fsm.it.
authors.forename: Rosella
authors.initials: R
authors.lastname: Centis
authors.affiliation: Division of Infection, Royal London Hospital, Barts Health NHS Trust, London E1 2ES, UK. simon.tiberi@bartshealth.nhs.uk.
authors.forename: Simon
authors.initials: S
authors.lastname: Tiberi
authors.affiliation: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Sceintifico) Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy. susanna.esposito@unimi.it.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.affiliation: Clinical Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari-Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari 07100, Italy. simonedore@hotmail.com.
authors.forename: Simone
authors.initials: S
authors.lastname: Dore
authors.affiliation: Pneumology Unit, Fondazione Maugeri, IRCCS (Istituto di Ricovero e Cura a Carattere Sceintifico), Tradate 21049, Italy. antonio.spanevello@fsm.it.|Department of Clinical and Experimental Medicine, University of Insubria, Varese 21100, Italy. antonio.spanevello@fsm.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Spanevello
authors.affiliation: World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, IRCCS (Istituto di Ricovero e Cura a Carattere Sceintifico), Via Roncaccio 16, Tradate 21049, Italy. giovannibattista.migliori@fsm.it.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Migliori
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015780:Carbapenems / Q000009:adverse effects / Q000627:therapeutic use*; D000068456:Clinical Studies as Topic; D000077727:Ertapenem; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D006801:Humans; D015378:Imipenem / Q000009:adverse effects / Q000627:therapeutic use; D000077731:Meropenem; D013845:Thienamycins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D047090:beta-Lactams / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000995:Antitubercular Agents; D015780:Carbapenems; D013845:Thienamycins; D047090:beta-Lactams; D015378:Imipenem; D000077731:Meropenem; D000077727:Ertapenem
keywords: MDR-TB; XDR-TB; carbapenems; effectiveness; ertapenem; imipenem; meropenem; safety; tolerability