Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

Simon Tiberi¹, Marie-Christine Payen², Giovanni Sotgiu³, Lia D'Ambrosio⁴, Valentina Alarcon Guizado⁵, Jan Willem Alffenaar⁶, Marcos Abdo Arbex⁷, Jose A Caminero⁸, Rosella Centis⁹, Saverio De Lorenzo¹⁰, Mina Gaga¹¹, Gina Gualano¹², Aurora Jazmín Roby Arias¹³, Anna Scardigli¹⁴, Alena Skrahina¹⁵, Ivan Solovic¹⁶, Giorgia Sulis¹⁷, Marina Tadolini¹⁸, Onno W Akkerman¹⁹, Edith Alarcon Arrascue²⁰, Alena Aleska²¹, Vera Avchinko¹⁵, Eduardo Henrique Bonini⁷, Félix Antonio Chong Marín¹³, Lorena Collahuazo López¹³, Gerard de Vries²², Simone Dore²³, Heinke Kunst²⁴, Alberto Matteelli¹⁷, Charalampos Moschos¹¹, Fabrizio Palmieri¹², Apostolos Papavasileiou¹¹, Antonio Spanevello²⁵, Dante Vargas Vasquez²⁶, Pietro Viggiani¹⁰, Veronica White²⁷, Alimuddin Zumla²⁸, Giovanni Battista Migliori²⁹

Affiliations

¹ Division of Infection, Barts Healthcare NHS Trust, London, UK These authors contributed equally to this work.
² Division of Infectious Diseases, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium These authors contributed equally to this work.
³ 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.
⁴ 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.
⁵ National Tuberculosis Control Programme, Ministry of Health, Lima, Peru.
⁶ Dept of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁷ University Center of Araraquara, Sao Paulo, Brazil Hospital Nestor Goulart Reis, Sao Paulo State Secretary of Health, Sao Paulo, Brazil.
⁸ 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.
⁹ WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy.
¹⁰ AOVV E. Morelli Hospital, Reference Hospital for MDR and HIV-TB, Sondalo, Italy.
¹¹ MDR-TB Unit, Athens Chest Hospital Sotiria, National Referral Centre for Mycobacteria, Athens, Greece.
¹² Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
¹³ National Tuberculosis Control Programme, Pulmonology Hospital Alfredo J. Valenzuela, Guayaquil, Ecuador.
¹⁴ MDR-TB Unit, Tuberculosis Division, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France.
¹⁵ Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
¹⁶ National Institute for TB, Lung Diseases and Thoracic Surgery, Vysne Hagy, Slovakia.
¹⁷ 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.
¹⁸ Unit of Infectious Diseases, Dept of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
¹⁹ Dept of Pulmonary Diseases and Tuberculosis, TB Center Beatrixoord, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
²⁰ 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.
²¹ Educational Institution "Grodno State Medical University", Grodno, Belarus.
²² KNCV Tuberculosis Foundation, The Hague, The Netherlands.
²³ Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari - Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy.
²⁴ Dept of Respiratory Medicine, Queen Mary University, London, UK.
²⁵ Pneumology Unit, Fondazione Maugeri, IRCCS, Tradate, Italy Dept of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
²⁶ National Hospital Hipólito Unanue, Public Health Institute, Ministry of Health, Lima, Peru.
²⁷ Dept of Respiratory Medicine, Barts Healthcare NHS Trust, London, UK.
²⁸ Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK.
²⁹ WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy giovannibattista.migliori@fsm.it.

PMID: 26965290
DOI: 10.1183/13993003.02146-2015

Free article

Observational Study

Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

Simon Tiberi et al. Eur Respir J. 2016 Apr.

Free article

. 2016 Apr;47(4):1235-43.

doi: 10.1183/13993003.02146-2015. Epub 2016 Mar 10.

Authors

Affiliations

¹ Division of Infection, Barts Healthcare NHS Trust, London, UK These authors contributed equally to this work.
² Division of Infectious Diseases, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium These authors contributed equally to this work.
³ 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.
⁴ 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.
⁵ National Tuberculosis Control Programme, Ministry of Health, Lima, Peru.
⁶ Dept of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁷ University Center of Araraquara, Sao Paulo, Brazil Hospital Nestor Goulart Reis, Sao Paulo State Secretary of Health, Sao Paulo, Brazil.
⁸ 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.
⁹ WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy.
¹⁰ AOVV E. Morelli Hospital, Reference Hospital for MDR and HIV-TB, Sondalo, Italy.
¹¹ MDR-TB Unit, Athens Chest Hospital Sotiria, National Referral Centre for Mycobacteria, Athens, Greece.
¹² Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
¹³ National Tuberculosis Control Programme, Pulmonology Hospital Alfredo J. Valenzuela, Guayaquil, Ecuador.
¹⁴ MDR-TB Unit, Tuberculosis Division, International Union Against Tuberculosis and Lung Disease (The Union), Paris, France.
¹⁵ Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
¹⁶ National Institute for TB, Lung Diseases and Thoracic Surgery, Vysne Hagy, Slovakia.
¹⁷ 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.
¹⁸ Unit of Infectious Diseases, Dept of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
¹⁹ Dept of Pulmonary Diseases and Tuberculosis, TB Center Beatrixoord, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
²⁰ 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.
²¹ Educational Institution "Grodno State Medical University", Grodno, Belarus.
²² KNCV Tuberculosis Foundation, The Hague, The Netherlands.
²³ Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari - Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy.
²⁴ Dept of Respiratory Medicine, Queen Mary University, London, UK.
²⁵ Pneumology Unit, Fondazione Maugeri, IRCCS, Tradate, Italy Dept of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
²⁶ National Hospital Hipólito Unanue, Public Health Institute, Ministry of Health, Lima, Peru.
²⁷ Dept of Respiratory Medicine, Barts Healthcare NHS Trust, London, UK.
²⁸ Division of Infection and Immunity, University College London and NIHR Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK.
²⁹ WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy giovannibattista.migliori@fsm.it.

PMID: 26965290
DOI: 10.1183/13993003.02146-2015

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.

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Renal Fanconi syndrome with meropenem/amoxicillin-clavulanate during treatment of extensively drug-resistant tuberculosis.
Abadie ME, Strich JR, Kim T, Xie YL, Fennelly KP, Olivier KN, Waldman M, Arora K, Holland SM, Chen RY. Abadie ME, et al. Eur Respir J. 2017 Dec 28;50(6):1702023. doi: 10.1183/13993003.02023-2017. Print 2017 Dec. Eur Respir J. 2017. PMID: 29284688 No abstract available.

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Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

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Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

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