Case Report
Bedaquiline and Delamanid: Salvage Therapy in Mycobacterium avium Infection With Treatment Failure
Helena Albendín-Iglesiasa,b,
, José Antonio Camineroc,d, Carlos Galera Peñarandaa,b
Corresponding author
a Unity of HIV-STI, University Hospital of Virgen de la Arrixaca, Murcia, Spain
b Instituto Murciano de la Investigación Biosanitaria (IMIB), Murcia, Spain
c Unidad de Tuberculosis y Micobacteriosis, Servicio de Neumología, Hospital General Universitario de Gran Canaria “Dr. Negrín”, Las Palmas de G.C., Spain
d Director de Actividades Científicas, ALOSA TB ACADEMY, Spain
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It compresses and displaces the superior vena cava without infiltration (white arrow). Medially it contacts the aortic arch. Subsequently compresses and obliterates the tracheal lumen without signs of infiltration. There are areas of increased density compatible with intracystic hemorrhage (black arrow). (D) VATS: Mediastinal lesion of cystic appearance. The dark content (hematoserosus) is observed in its interior due to the thinness of its wall in some areas (black arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Sergio Cerrato Delgado, Mireia Rusca Giménez, Dionisio Espinosa Jimenez" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Sergio" "apellidos" => "Cerrato Delgado" ] 1 => array:2 [ "nombre" => "Mireia" "apellidos" => "Rusca Giménez" ] 2 => array:2 [ "nombre" => "Dionisio" "apellidos" => "Espinosa Jimenez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289623000194?idApp=UINPBA00003Z" "url" => "/03002896/0000005900000005/v2_202307310834/S0300289623000194/v2_202307310834/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S030028962300011X" "issn" => "03002896" "doi" => "10.1016/j.arbres.2023.01.006" "estado" => "S300" "fechaPublicacion" => "2023-05-01" "aid" => "3248" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2023;59:326-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case Report</span>" "titulo" => "Mediastinal Lymphangioma With an Atypical Location in an Adult Patient" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "326" "paginaFinal" => "327" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2561 "Ancho" => 2007 "Tamanyo" => 416408 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a–c) (original images) – Whole-body CT – (a) coronal, contrast-enhanced (b) axial, unenhanced: prevertebral heterogeneous low-density (4 HU – fluid content) mass involving the thoracic aorta, from D6 to L1 (through diaphragm); (c) axial, contrast-enhanced: discrete heterogeneous density of retroperitoneal fat and central low attenuation areas in the left kidney; (d–e) (original mages) Chest-abdomen MRI – (d) MRI (sagittal): multiseptated serpiginous lesion in the posterior mediastinum/prevertebral (white arrow), forming a structure that molds to vascular structures (10.5<span class="elsevierStyleHsp" style=""></span>cm in the craniocaudal diameter). (e) MRI (axial): left perirenal lesion molding to the renal hilum (white arrow), hyperintense on T2-weighted sequences, with multiloculated areas (equally hyperintense on T2).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rita Queiroz-Rodrigues, Pedro Cruz, Ana Catarina Silva" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Rita" "apellidos" => "Queiroz-Rodrigues" ] 1 => array:2 [ "nombre" => "Pedro" "apellidos" => "Cruz" ] 2 => array:2 [ "nombre" => "Ana Catarina" "apellidos" => "Silva" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S030028962300011X?idApp=UINPBA00003Z" "url" => "/03002896/0000005900000005/v2_202307310834/S030028962300011X/v2_202307310834/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case Report</span>" "titulo" => "Bedaquiline and Delamanid: Salvage Therapy in <span class="elsevierStyleItalic">Mycobacterium avium</span> Infection With Treatment Failure" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "328" "paginaFinal" => "329" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Helena Albendín-Iglesias, José Antonio Caminero, Carlos Galera Peñaranda" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Helena" "apellidos" => "Albendín-Iglesias" "email" => array:1 [ 0 => "helena_ai@hotmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "José Antonio" "apellidos" => "Caminero" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 2 => array:3 [ "nombre" => "Carlos" "apellidos" => "Galera Peñaranda" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Unity of HIV-STI, University Hospital of Virgen de la Arrixaca, Murcia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto Murciano de la Investigación Biosanitaria (IMIB), Murcia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Tuberculosis y Micobacteriosis, Servicio de Neumología, Hospital General Universitario de Gran Canaria “Dr. Negrín”, Las Palmas de G.C., Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Director de Actividades Científicas, ALOSA TB ACADEMY, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2942 "Ancho" => 3341 "Tamanyo" => 325462 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution of hemoglobin and C-reactive protein. Time plot of the therapies received. Hb: Hemoglobin, RCP: reactive protein C, TDF: Tenofovir disoproxil fumarate, TAF: tenofovir alafenamide, FTC: emtricitabine, EFV: efavirenz, DTG: dolutegravir, BIC: bictegravir, TD: twicely day.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Mycobacterium avium</span> management still remains a challenge today, given the ease with which antimicrobial resistance and adverse effects of combination therapy occur.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> Bedaquiline and delamanid have been shown to be very effective in the treatment of drug-resistant tuberculosis.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> Both drugs have very good in vitro activity against most nontuberculous mycobacteria (NTM).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Moreover, several articles have already shown bedaquiline to be effective in their presentation.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">4,5</span></a> However, no experience with delamanid in the treatment of NTM has been published.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 46-year-old male diagnosed with stage C3 HIV infection in June 2020. He started antiretroviral treatment (ART) and six months later was admitted to our hospital due to abdominal pain. (CD4: 54<span class="elsevierStyleHsp" style=""></span>cells/mm<span class="elsevierStyleSup">3</span>, HIV viral load: undetectable). Computed tomography showed an abdominal mass formed by multiple mesenteric and retroperitoneal lymphadenopathies. Biopsy of the adenopathies showed growth of <span class="elsevierStyleItalic">M. avium</span>, and no mutations associated with resistance to clarithromycin, amikacin or rifampicin were detected. Treatment was started with rifampicin, azithromycin, and ethambutol.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In April 2021 he was admitted again because of abdominal pain. Gastroscopy was performed and showed duodenal mucosa with biopsy reported as granulomatous inflammation, possibly due to MNT. Considering the possibility of treatment failure, it was decided to boost the treatment by adding amikacin (three weeks) and levofloxacin. In view of his good clinical evolution, he was discharged from hospital in July 2021 on azithromycin, levofloxacin, and ethambutol, withdrawing rifampicin due to interactions with the ART (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">He was readmitted for abdominal pain and weight loss in October 2021 and required treatment with morphine for pain control; blood tests showed C-reactive protein 7.4<span class="elsevierStyleHsp" style=""></span>mg/dL and hemoglobin 9.5<span class="elsevierStyleHsp" style=""></span>g/dL. Abdominal computed tomography showed an increase in the mesenteric lymph node mass with partial necrosis. Blood cultures drawn in May, July, and October 2021 showed <span class="elsevierStyleItalic">M. avium</span> growth. The patient claimed to have taken all the medication, so it was accepted that he presented a therapeutic failure to the schemes used, and a resistance study was performed and reported: clarithromycin MIC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>g/ml (sensitive), moxifloxacin MIC 8<span class="elsevierStyleHsp" style=""></span>g/ml (resistant), and linezolid<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>32<span class="elsevierStyleHsp" style=""></span>g/ml (resistant). Mutations associated with resistance to clarithromycin, amikacin, and rifampicin were still not detected. Compassionate use of bedaquiline and delamanid was requested, as well as an extended sensitivity study to these drugs in order to build a new rescue therapeutic regimen. While waiting for pharmacy approval, he started treatment with seven drugs: azithromycin, amikacin, meropenem, linezolid, rifampicin, moxifloxacin and cycloserine. After confirming susceptibility to delamanid (MIC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.5<span class="elsevierStyleHsp" style=""></span>mg/dL) and bedaquiline (MIC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.06<span class="elsevierStyleHsp" style=""></span>mg/dL), a new therapeutic treatment was prescribed in January 2022 with azithromycin, cycloserine, bedaquiline (400<span class="elsevierStyleHsp" style=""></span>mg/day for two weeks followed by 200<span class="elsevierStyleHsp" style=""></span>mg three times a week), delamanid (100<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h), and meropenem. After one month of treatment the patient presented a decrease in pain, reduction of inflammatory parameters, disappearance of anemia, negativization of blood cultures, and improvement in nutritional status. He was discharged at the end of February 2022 with azithromycin, cycloserine, bedaquiline, and delamanid; the treatment that he maintains at present (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). He has required weekly ECG monitoring without presenting QT interval lengthening.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In our patient, bedaquiline and delamanid were administered on a compassionate use basis due to the ineffectiveness of other drugs commonly used in the treatment of <span class="elsevierStyleItalic">M. avium.</span> Both drugs allowed a scheme to be established that has proved to be highly effective, with no evidence of resistance or cardiological toxicity to date. Our experience supports the use of bedaquiline and delamanid in salvage treatments in patients with disseminated <span class="elsevierStyleItalic">M. avium</span> for whom there is no other therapeutic alternative.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0030" class="elsevierStylePara elsevierViewall">There is no funding related to this article.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interests</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interests" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2942 "Ancho" => 3341 "Tamanyo" => 325462 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution of hemoglobin and C-reactive protein. Time plot of the therapies received. Hb: Hemoglobin, RCP: reactive protein C, TDF: Tenofovir disoproxil fumarate, TAF: tenofovir alafenamide, FTC: emtricitabine, EFV: efavirenz, DTG: dolutegravir, BIC: bictegravir, TD: twicely day.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antimycobacterial strategies to evade antimicrobial resistance in the nontuberculous mycobacteria" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B.C. Millar" 1 => "J.E. Moore" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/ijmy.ijmy_153_18" "Revista" => array:6 [ "tituloSerie" => "Int J Mycobacteriol" "fecha" => "2019" "volumen" => "8" "paginaInicial" => "7" "paginaFinal" => "21" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30860173" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "WHO consolidated guidelines on tuberculosis. Module 4: treatment – drug-resistant tuberculosis treatment, 2022 update" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2022" "editorial" => "World Health Organization" "editorialLocalizacion" => "Geneva" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In vitro activity of bedaquiline and delamanid against nontuberculous mycobacteria, including macrolide-resistant clinical isolates" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.H. Kim" 1 => "B.W. Jhun" 2 => "S.M. Moon" 3 => "S.Y. Kim" 4 => "K. Jeon" 5 => "O.J. Kwon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.00665-19" "Revista" => array:6 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2019" "volumen" => "63" "paginaInicial" => "e00665" "paginaFinal" => "e00719" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31182533" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Preliminary results of bedaquiline as salvage therapy for patients with nontuberculous mycobacterial lung disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.V. Philley" 1 => "R.J. Wallace" 2 => "J.L. Benwill" 3 => "V. Taskar" 4 => "B.A. Brown-Elliott" 5 => "F. Thakkar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.14-2764" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2015" "volumen" => "148" "paginaInicial" => "499" "paginaFinal" => "506" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25675393" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bedaquiline as treatment for disseminated nontuberculous mycobacteria infection in 2 patients co-infected with HIV" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Gil" 1 => "N. Sweeney" 2 => "V. Barrett" 3 => "S. Morris-Jones" 4 => "R.F. Miller" 5 => "V.J. Johnston" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3201/eid2703.202359" "Revista" => array:6 [ "tituloSerie" => "Emerg Infect Dis" "fecha" => "2021" "volumen" => "27" "paginaInicial" => "944" "paginaFinal" => "948" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33622490" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/03002896/0000005900000005/v2_202307310834/S0300289623000418/v2_202307310834/en/main.assets" "Apartado" => array:4 [ "identificador" => "93865" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case reports" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03002896/0000005900000005/v2_202307310834/S0300289623000418/v2_202307310834/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289623000418?idApp=UINPBA00003Z" ]
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