title: Efficacy and safety of meropenem-clavulanate added to linezolid-containing regimens in the treatment of MDR-/XDR-TB.
abstract: Clinical experience on meropenem-clavulanate to treat tuberculosis (TB) is anecdotal (according to case reports on 10 patients). The aim of our case-control study was to evaluate the contribution of meropenem-clavulanate when added to linezolid-containing regimens in terms of efficacy and safety/tolerability in treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases after 3 months of second-line treatment. 37 cases with MDR-/XDR-TB were prescribed meropenem-clavulanate (3 g daily dose) in addition to a linezolid-containing regimen (dosage range 300-1200 mg·day(-1)), designed according to international guidelines, which was prescribed to 61 controls. The clinical severity of cases was worse than that of controls (drug susceptibility profile, proportion of sputum-smear positive and of re-treatment cases). The group of cases yielded a higher proportion of sputum-smear converters (28 (87.5%) out of 32 versus nine (56.3%) out of 16; p=0.02) and culture converters (31 (83.8%) out of 37 versus 15 (62.5%) out of 24; p=0.06). Excluding XDR-TB patients (11 (11.2%) out of 98), cases scored a significantly higher proportion of culture converters than controls (p=0.03). One case had to withdraw from meropenem-clavulanate due to increased transaminase levels. The results of our study provide: 1) preliminary evidence on effectiveness and safety/tolerability of meropenem-clavulanate; 2) reference to design further trials; and 3) a guide to clinicians for its rationale use within salvage/compassionate regimens.
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.forename: Jan Wilem
authors.initials: JW
authors.lastname: Alffenaar
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sotgiu
authors.forename: Rosella
authors.initials: R
authors.lastname: Centis
authors.forename: Lia
authors.initials: L
authors.lastname: D'Ambrosio
authors.forename: Simon
authors.initials: S
authors.lastname: Tiberi
authors.forename: Mathieu S
authors.initials: MS
authors.lastname: Bolhuis
authors.forename: Richard
authors.initials: R
authors.lastname: van Altena
authors.forename: Piero
authors.initials: P
authors.lastname: Viggiani
authors.forename: Andrea
authors.initials: A
authors.lastname: Piana
authors.forename: Antonio
authors.initials: A
authors.lastname: Spanevello
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Migliori
mesh_terms: D000081:Acetamides / Q000008:administration & dosage*; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage*; D016022:Case-Control Studies; D019818:Clavulanic Acid / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage*; D013845:Thienamycins / Q000008:administration & dosage*; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000081:Acetamides; D000995:Antitubercular Agents; D023303:Oxazolidinones; D013845:Thienamycins; D019818:Clavulanic Acid; D000077731:Meropenem; D000069349:Linezolid