Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

Simon Tiberi¹, Giovanni Sotgiu², Lia D'Ambrosio³, Rosella Centis⁴, Marcos Abdo Arbex⁵, Edith Alarcon Arrascue⁶, Jan Willem Alffenaar⁷, Jose A Caminero⁸, Mina Gaga⁹, Gina Gualano¹⁰, Alena Skrahina¹¹, Ivan Solovic¹², Giorgia Sulis¹³, Marina Tadolini¹⁴, Valentina Alarcon Guizado¹⁵, Saverio De Lorenzo¹⁶, Aurora Jazmín Roby Arias¹⁷, Anna Scardigli¹⁸, Onno W Akkerman¹⁹, Alena Aleksa²⁰, Janina Artsukevich²⁰, Vera Auchynka¹¹, Eduardo Henrique Bonini⁵, Félix Antonio Chong Marín¹⁷, Lorena Collahuazo López¹⁷, Gerard de Vries²¹, Simone Dore²², Heinke Kunst²³, Alberto Matteelli¹³, Charalampos Moschos⁹, Fabrizio Palmieri¹⁰, Apostolos Papavasileiou⁹, Marie-Christine Payen²⁴, Andrea Piana²², Antonio Spanevello²⁵, Dante Vargas Vasquez²⁶, Pietro Viggiani¹⁶, 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 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.
³ 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.
⁴ WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy These authors contributed equally to this work.
⁵ University Center of Araraquara, Sao Paulo, Brazil Hospital Nestor Goulart Reis, Sao Paulo State Secretary of Health, Sao Paulo, Brazil.
⁶ 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.
⁷ University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
⁸ 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.
⁹ MDR-TB Unit, Athens Chest Hospital Sotira, National Referral Centre for Mycobacteria, Athens, Greece.
¹⁰ Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
¹¹ Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
¹² National Institute for TB, Lung Diseases and Thoracic Surgery, Vysne Hagy, Catholic University Ruzomberok, Ruzomberok, Slovakia.
¹³ 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.
¹⁴ Unit of Infectious Diseases, Dept of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
¹⁵ National Tuberculosis Control Programme, Ministry of Health, Lima, Peru.
¹⁶ AOVV E. Morelli Hospital, Reference Hospital for MDR and HIV-TB, Sondalo, Italy.
¹⁷ National Tuberculosis Control Programme, Pulmonology Hospital Alfredo J. Valenzuela, Guayaquil, Ecuador.
¹⁸ MDR-TB Unit, Tuberculosis Division, International Union against Tuberculosis and Lung Disease (The Union), Paris, France.
¹⁹ University of Groningen, University Medical Center Groningen, Dept of Pulmonary Diseases and Tuberculosis; TB Center Beatrixoord, Groningen, The Netherlands.
²⁰ Educational Institution "Grodno State Medical University", Grodno, Belarus.
²¹ KNCV Tuberculosis Foundation, The Hague, The Netherlands.
²² Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari - Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy.
²³ Dept of Respiratory Medicine, Queen Mary University, London, UK.
²⁴ Division of Infectious Diseases, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium.
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: 27076583
DOI: 10.1183/13993003.00214-2016

Free article

Observational Study

Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

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

Free article

. 2016 Jun;47(6):1758-66.

doi: 10.1183/13993003.00214-2016. Epub 2016 Apr 13.

Authors

Affiliations

¹ Division of Infection, Barts Healthcare NHS Trust, London, UK These authors contributed equally to this work.
² 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.
³ 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.
⁴ WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Tradate, Italy These authors contributed equally to this work.
⁵ University Center of Araraquara, Sao Paulo, Brazil Hospital Nestor Goulart Reis, Sao Paulo State Secretary of Health, Sao Paulo, Brazil.
⁶ 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.
⁷ University of Groningen, University Medical Center Groningen, Dept of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
⁸ 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.
⁹ MDR-TB Unit, Athens Chest Hospital Sotira, National Referral Centre for Mycobacteria, Athens, Greece.
¹⁰ Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
¹¹ Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus.
¹² National Institute for TB, Lung Diseases and Thoracic Surgery, Vysne Hagy, Catholic University Ruzomberok, Ruzomberok, Slovakia.
¹³ 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.
¹⁴ Unit of Infectious Diseases, Dept of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
¹⁵ National Tuberculosis Control Programme, Ministry of Health, Lima, Peru.
¹⁶ AOVV E. Morelli Hospital, Reference Hospital for MDR and HIV-TB, Sondalo, Italy.
¹⁷ National Tuberculosis Control Programme, Pulmonology Hospital Alfredo J. Valenzuela, Guayaquil, Ecuador.
¹⁸ MDR-TB Unit, Tuberculosis Division, International Union against Tuberculosis and Lung Disease (The Union), Paris, France.
¹⁹ University of Groningen, University Medical Center Groningen, Dept of Pulmonary Diseases and Tuberculosis; TB Center Beatrixoord, Groningen, The Netherlands.
²⁰ Educational Institution "Grodno State Medical University", Grodno, Belarus.
²¹ KNCV Tuberculosis Foundation, The Hague, The Netherlands.
²² Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari - Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy.
²³ Dept of Respiratory Medicine, Queen Mary University, London, UK.
²⁴ Division of Infectious Diseases, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium.
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: 27076583
DOI: 10.1183/13993003.00214-2016

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.

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Comment in

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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Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

Affiliations

Comparison of effectiveness and safety of imipenem/clavulanate- versus meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

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Abstract

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