Case report
First Series of Patients With XDR and Pre-XDR TB Treated With Regimens That Included Meropenen-clavulanate in Argentina
Primera serie de pacientes con TB-XDR y pre-XDR tratados con esquemas que incluyeron meropenem-clavulanato en Argentina
Domingo Palmero
, Pablo González Montaner, Mónica Cufré, Ana García, Marisa Vescovo, Susana Poggi
Corresponding author
Instituto Prof. Dr. Raúl Vaccarezza, Hospital de Infecciosas Dr. F. J. Muñiz, Buenos Aires, Argentina
Read
11419
Timeswas read the article
2397
Total PDF
9022
Total HTML
Share statistics
array:24 [ "pii" => "S1579212915002773" "issn" => "15792129" "doi" => "10.1016/j.arbr.2015.07.003" "estado" => "S300" "fechaPublicacion" => "2015-10-01" "aid" => "1166" "copyright" => "SEPAR" "copyrightAnyo" => "2014" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2015;51:e49-52" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 4140 "formatos" => array:3 [ "EPUB" => 140 "HTML" => 3233 "PDF" => 767 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0300289615001155" "issn" => "03002896" "doi" => "10.1016/j.arbres.2015.03.012" "estado" => "S300" "fechaPublicacion" => "2015-10-01" "aid" => "1166" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2015;51:e49-52" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 6566 "formatos" => array:3 [ "EPUB" => 110 "HTML" => 5303 "PDF" => 1153 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Nota clínica</span>" "titulo" => "Primera serie de pacientes con TB-XDR y pre-XDR tratados con esquemas que incluyeron meropenem-clavulanato en Argentina" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e49" "paginaFinal" => "e52" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "First series of patients with XDR and pre-XDR TB treated with regimens that included meropenen-clavulanate in Argentina" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Domingo Palmero, Pablo González Montaner, Mónica Cufré, Ana García, Marisa Vescovo, Susana Poggi" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Domingo" "apellidos" => "Palmero" ] 1 => array:2 [ "nombre" => "Pablo" "apellidos" => "González Montaner" ] 2 => array:2 [ "nombre" => "Mónica" "apellidos" => "Cufré" ] 3 => array:2 [ "nombre" => "Ana" "apellidos" => "García" ] 4 => array:2 [ "nombre" => "Marisa" "apellidos" => "Vescovo" ] 5 => array:2 [ "nombre" => "Susana" "apellidos" => "Poggi" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1579212915002773" "doi" => "10.1016/j.arbr.2015.07.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212915002773?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289615001155?idApp=UINPBA00003Z" "url" => "/03002896/0000005100000010/v1_201509302001/S0300289615001155/v1_201509302001/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1579212915001214" "issn" => "15792129" "doi" => "10.1016/j.arbr.2015.04.024" "estado" => "S300" "fechaPublicacion" => "2015-10-01" "aid" => "1000" "copyright" => "SEPAR" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Arch Bronconeumol. 2015;51:520" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2408 "formatos" => array:3 [ "EPUB" => 119 "HTML" => 1828 "PDF" => 461 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Clinical Image</span>" "titulo" => "Transmural Thoracic Lipoma" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "520" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Lipoma torácico transmural" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:6 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1088 "Ancho" => 1659 "Tamanyo" => 111078 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alberto Sierra Solís" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Alberto" "apellidos" => "Sierra Solís" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0300289614002282" "doi" => "10.1016/j.arbres.2014.06.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289614002282?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212915001214?idApp=UINPBA00003Z" "url" => "/15792129/0000005100000010/v1_201509302252/S1579212915001214/v1_201509302252/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S157921291500289X" "issn" => "15792129" "doi" => "10.1016/j.arbr.2015.08.004" "estado" => "S300" "fechaPublicacion" => "2015-10-01" "aid" => "1141000" "copyright" => "SEPAR" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Bronconeumol. 2015;51:515-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2543 "formatos" => array:3 [ "EPUB" => 128 "HTML" => 1900 "PDF" => 515 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>" "titulo" => "Provision of Care by Medical Residents and the Impact on Quality" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "515" "paginaFinal" => "519" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Impacto de la calidad de la atención por parte de los residentes" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Estefanía Llopis Pastor, Estibaliz Pérez Guzmán, Regulo Ávila Martínez, Maria Victoria Villena Garrido, Patricia Sobradillo Ecenarro" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Estefanía" "apellidos" => "Llopis Pastor" ] 1 => array:2 [ "nombre" => "Estibaliz" "apellidos" => "Pérez Guzmán" ] 2 => array:2 [ "nombre" => "Regulo" "apellidos" => "Ávila Martínez" ] 3 => array:2 [ "nombre" => "Maria Victoria" "apellidos" => "Villena Garrido" ] 4 => array:2 [ "nombre" => "Patricia" "apellidos" => "Sobradillo Ecenarro" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0300289615000903" "doi" => "10.1016/j.arbres.2015.01.014" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289615000903?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157921291500289X?idApp=UINPBA00003Z" "url" => "/15792129/0000005100000010/v1_201509302252/S157921291500289X/v1_201509302252/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "First Series of Patients With XDR and Pre-XDR TB Treated With Regimens That Included Meropenen-clavulanate in Argentina" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e49" "paginaFinal" => "e52" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Domingo Palmero, Pablo González Montaner, Mónica Cufré, Ana García, Marisa Vescovo, Susana Poggi" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Domingo" "apellidos" => "Palmero" "email" => array:1 [ 0 => "djpalmero@intramed.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Pablo" "apellidos" => "González Montaner" ] 2 => array:2 [ "nombre" => "Mónica" "apellidos" => "Cufré" ] 3 => array:2 [ "nombre" => "Ana" "apellidos" => "García" ] 4 => array:2 [ "nombre" => "Marisa" "apellidos" => "Vescovo" ] 5 => array:2 [ "nombre" => "Susana" "apellidos" => "Poggi" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Instituto Prof. Dr. Raúl Vaccarezza, Hospital de Infecciosas Dr. F. J. Muñiz, Buenos Aires, Argentina" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Primera serie de pacientes con TB-XDR y pre-XDR tratados con esquemas que incluyeron meropenem-clavulanato en Argentina" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Extensively drug-resistant tuberculosis (XDR-TB) is caused by <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> strains with resistance to at least isoniazid (H), rifampicin (R), a fluoroquinolone, and a second-line injectable drug (SLI): kanamycin (Km), amikacin (Amk) or capreomycin (Cm). Pre-XDR-TB denotes resistance to H and R, as well as to at least one FQ or one SLI.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> The WHO has estimated the worldwide incidence of MDR-TB (multidrug-resistant TB: resistant to at least H and R) to be 480,000 cases in 2013, of which 9% were XDR-TB.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> In 2013, Argentina's National Reference Laboratory (ANLIS Malbrán) identified 6 cases of XDR-TB and 18 of pre-XDR.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The WHO divides anti-TB drugs into 5 groups: (1) first-line drugs; (2) FQ (ofloxacin, levofloxacin, moxifloxacin); (3) injectables (kanamycin, amikacin, capreomycin, streptomycin); (4) oral bacteriostatic second-line drugs (cycloserine/terizidone, ethionamide/prothionamide, PAS); and (5) anti-TB drugs with limited data on efficacy: clofazimine (Cfz), linezolid (Lzd), amoxicillin/clavulanate (amoxi-clav), carbapenems (imipenem-cilastatin and meropenem) high-dose H, bedaquiline (Bdq) and delamanid (the latter two have been approved for a 6-month course in pre-XDR/XDR-TB). Drugs in groups <span class="elsevierStyleSmallCaps">II</span> to <span class="elsevierStyleSmallCaps">IV</span> (except streptomycin) are considered second-line therapy, while group <span class="elsevierStyleSmallCaps">V</span> drugs are also known as third-line drugs.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Patients with pre-XDR and XDR-TB are usually treated with regimens that include group <span class="elsevierStyleSmallCaps">V</span> drugs, as they are usually resistant to most of the remaining drugs. Treatment given to these patients, therefore, is likely to be less effective. In recent years, studies have shown that meropenem combined with clavulanate (MPC) can have an antimycobacterial and synergic effect.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">4–6</span></a> The aim of this study is to show the efficacy, measured in terms of bacteriologic conversion of sputum, of treatment regimens that include combination meropenem-clavulanate given in the initial stage of pre-XDR and XDR-TB therapy.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Methodology</span><p id="par0020" class="elsevierStylePara elsevierViewall">This is a retrospective study of all patients confined to the drug-resistant TB respiratory isolation unit from 1/1/2012 to 12/31/2013 with a bacteriological diagnosis of pre-XDR and XDR-TB, plus 1 case of adverse reaction/drug interaction. The patients were treated with regimens that included at least 5 group <span class="elsevierStyleSmallCaps">2</span> to <span class="elsevierStyleSmallCaps">5</span> drugs, including MPC, for at least 6 months. In our hospital, we receive patients from Argentina and also immigrants from neighboring countries who have come in search of work. Approximately half of all TB cases diagnosed in Buenos Aires involve recent immigrants from neighboring countries.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The hospital laboratory performed susceptibility testing for H, R, etambutol (E) and streptomycin (S) using quick fluorometric and solid media proportions methods. The ANLIS Malbrán performed susceptibility testing for ofloxacin (Ofx), cycloserine (Cs), ethionamide (Eto), PAS, kanamycin, amikacin and capreomycin using the solid media proportions method; for Cfz, Ldz and moxifloxacin [Mfx] using MIC determination in liquid medium; and for pyrazinamidase (Z) using the pyrazinamidase test.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Indication for MPC was determined empirically. Therapeutic regimens were designed on the basis of previous treatment received and the results of susceptibility testing, when available. Patients gave a sputum sample for culture each month. Favorable evolution was defined as bacteriologic conversion (negative results from two consecutive monthly cultures) when first negative result occurred before month 6 of treatment.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The results were published following approval by the Independent Ethics Committee of the Instituto Vaccarezza (authorization No. 30/15) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the drugs and doses given.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">A total of 10 patients (5 women) were enrolled in the study, with an average age of 37.5 years. Five had previously received multiple treatment, and 5 had received no treatment.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Radiologically, all showed bilateral involvement with cavitation. Nine cases were diagnosed as pre-XDR or XDR-TB, and 1 received a complicated therapy regimen due to serious adverse reactions and drug interactions (a liver transplant recipient who contracted TB).</p><p id="par0055" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the characteristics and evolution of the 10 patients receiving therapy regimens including MPC. Briefly, 8 patients showed sputum conversion by the end of the follow-up period. These patients continued with a second, 18-month phase of treatment during which only MPC was discontinued. Two patients died during follow-up, 1 due to worsening of TB due to treatment failure, and the other due to respiratory failure secondary to pulmonary destruction, despite good bacterial response. At the date of publication, not all patients have completed their treatment. By way of preliminary data, of the 8 patients that continued to the end of the initial follow-up phase (receiving MPC), 1 died due to hepatic failure not associated with TB (liver transplant recipient), treatment failed in 1 case, with bacteriological reversion after conversion to negative. Of the remaining 6 patients, 3 completed the treatment after meeting WHO “cured” outcome criteria,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> and 3 continue receiving treatment, with bacteriological conversion at the time of publication.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">Drug-resistance in TB is a major therapeutic challenge. Standard MDR-TB treatment guidelines have been drawn up, consisting of 2 core drugs, 1 FQ and 1 SLI, combined with 2 oral bacteriostatic agents and pyrazinamide.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,3</span></a> In the case of pre-XDR and XDR-TB, treatment consists of the best possible combination of drugs based on susceptibility testing, history of previous treatment regimens, and drug availability. Two important new drugs, bedaquiline and/or delamanid,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> are currently not available in Argentina in the context of disease management programs.</p><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">M. tuberculosis</span> is resistant to beta-lactam antibiotics because it produces an extended-spectrum beta-lactamase (BlaC), which is irreversibly inhibited by clavulanate. Since meropenem is more resistant to BlaC than other beta-lactams, the combination of this drug with clavulanate could be highly bactericidal for both susceptible and resistant strains, including non-replicating strains.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In this patient series we used regimens that included MPC in the initial 6-month phase in hospitalized patients. We observed no adverse reactions associated with MPC. However, the length of time needed to administer the drug is an inconvenience, and 2 patients required implantation of a port device. Eight of our 10 study patients responded well to this initial phase of treatment with Lzd-Mfx-MPC as core drugs.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In conclusion, MPC, however inconvenient due to the route of administration, combined with other group <span class="elsevierStyleSmallCaps">V</span> drugs could be effective as a first-stage treatment strategy for pre-XDR and XDR TB.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres560397" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec576640" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres560398" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec576641" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methodology" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-12-16" "fechaAceptado" => "2015-03-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec576640" "palabras" => array:5 [ 0 => "Tuberculosis" 1 => "XDR-TB" 2 => "Carbapenems" 3 => "Meropenem" 4 => "Clavulanate" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec576641" "palabras" => array:5 [ 0 => "Tuberculosis" 1 => "TB-XDR" 2 => "Carbapenems" 3 => "Meropenem" 4 => "Clavulanato" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">XDR (extensively drug-resistant) and pre-XDR tuberculosis (TB) seriously compromise prognosis and treatment possibilities, and inevitably require the use of group <span class="elsevierStyleSmallCaps">V</span> drugs (World Health Organization). The progress of all patients with XDR and pre-XDR TB seen in a specialized unit during 2012 and 2013 and treated with regimens that included at least 6 months of meropenem-clavulanate (MPC), capreomycin, moxifloxacin, linezolid, clofazimine, high-dose isoniazid, PAS, and bedaquiline in 1 case, were retrospectively analyzed. Ten patients were treated, 9 with an extensive pattern of resistance to at least 6 drugs, and 1 because of adverse reactions and drug interactions leading to a similar situation. Eight of the 10 patients treated achieved bacteriological sputum conversion (2 consecutive negative monthly cultures) over a period of 2–7 months, while 2 died. No adverse reactions attributable to prolonged administration of MPC were observed.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La tuberculosis extensamente resistente (TB-XDR) y pre-XDR comprometen seriamente el pronóstico de la enfermedad, y su tratamiento requiere inevitablemente el uso de fármacos del grupo <span class="elsevierStyleSmallCaps">V</span> (Organización Mundial de la Salud [OMS]). Se analizó retrospectivamente la evolución de todos los pacientes con TB pre-XDR y XDR asistidos en un servicio especializado durante 2012 y 2013, medicados con regímenes que incluyeron por lo menos 6 meses de meropenem-clavulanato (MPC), capreomicina, moxifloxacina, linezolid, clofazimina, isoniacida en alta dosis, PAS y en un caso bedaquilina. Fueron tratados 10 pacientes, 9 de ellos con un extenso patrón de resistencia a un mínimo de 6 fármacos y uno por reacciones adversas e interacciones medicamentosas que generaron una situación análoga. Ocho de los 10 pacientes tratados, hicieron la conversión bacteriológica del esputo (2 cultivos mensuales consecutivos negativos) en un lapso de 2 a 7 meses, en tanto que 2 fallecieron. No se observaron reacciones adversas atribuibles a la administración prolongada del MPC.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as: Palmero D, González Montaner P, Cufré M, García A, Vescovo M, Poggi S. Primera serie de pacientes con TB-XDR y pre-XDR tratados con esquemas que incluyeron meropenem-clavulanato en Argentina. Arch Bronconeumol. 2015;51:e49–e52.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">IM: intramuscular; IV: intravenous; Mfx: moxifloxacin; QTc: corrected QT interval; PAS: para-aminosalicylic acid.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dose and Administration \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Most Common Adverse Effects \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Amikacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15<span class="elsevierStyleHsp" style=""></span>mg/kg/d, IM or IV, diluted \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Oto- and nephrotoxicity, electrolyte disorders \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Amoxicillin-clavulanate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxicillin 500<span class="elsevierStyleHsp" style=""></span>mg-clavulanate 125<span class="elsevierStyleHsp" style=""></span>mg, oral q8<span class="elsevierStyleHsp" style=""></span>h. Used because clavulanate formulations were not available on the market. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Digestive, hepatic, hyper-sensitivity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bedaquiline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400<span class="elsevierStyleHsp" style=""></span>mg/d for 2 weeks, then 200<span class="elsevierStyleHsp" style=""></span>mg three times weekly for 22 weeks, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">QTc prolongation, hepatitis, cannot be co-administered with Mfx. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Capreomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15<span class="elsevierStyleHsp" style=""></span>mg/kg/d, IM or IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Oto- and nephrotoxicity, electrolyte disorders \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Clofazimine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100<span class="elsevierStyleHsp" style=""></span>mg/d, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Skin pigmentation, abdominal colic \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cycloserine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15<span class="elsevierStyleHsp" style=""></span>mg/kg/d in 3 doses, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Convulsions, behavioral disorders, depression \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Etambutol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100<span class="elsevierStyleHsp" style=""></span>mg/d, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Optic neuritis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Ethionamide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15<span class="elsevierStyleHsp" style=""></span>mg/kg/d in 3 doses, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metallic taste, toxic hepatitis, hypothyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">High dose isoniazid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10<span class="elsevierStyleHsp" style=""></span>mg/kg/d, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Toxic hepatitis, polyneuritis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Levofloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">700<span class="elsevierStyleHsp" style=""></span>mg/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tendinitis, toxic hepatitis, neurotoxicity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Linezolid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">600<span class="elsevierStyleHsp" style=""></span>mg/d, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyneuritis, mononeuritis, optic neuritis, bone marrow depression \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Meropenem \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>g IV diluted q8<span class="elsevierStyleHsp" style=""></span>h until sputum culture is negative, then 1<span class="elsevierStyleHsp" style=""></span>g q8<span class="elsevierStyleHsp" style=""></span>h, IV diluted \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Inflammation of injection site, digestive, hypokalemia, convulsions, hepatotoxicity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Moxifloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400<span class="elsevierStyleHsp" style=""></span>mg/d, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tendinitis, toxic hepatitis, neurotoxicity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PAS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15<span class="elsevierStyleHsp" style=""></span>mg/kg/d in 3 doses, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Digestive, hypothyroidism, hepatotoxicity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pyrazinamide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25<span class="elsevierStyleHsp" style=""></span>mg/kg/d, oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Toxic hepatitis, hyperuricemia \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab906615.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Drugs and Dosage Used in 10 Patients Receiving Treatment Regimens that Included Meropenem/Amoxicillin-clavulanate.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">AMK: amikacin; Amoxi-clav: amoxicillin-clavulanate; AR: adverse reactions; Bdq: bedaquiline; Cm: capreomycin; CKF: chronic kidney failure; Clf: clofazimine; Cs: cycloserine; DBT: diabetes; E: etambutol; Eto: ethionamide; FQ: fluoroquinolones; H<span class="elsevierStyleSup">hd</span>: high dose isoniazid (600<span class="elsevierStyleHsp" style=""></span>mg/d); IDU: illegal drug user; Km: kanamycin; Lfx: levofloxacin; Lzd: linezolid; MRP: meropenem; Mfx: moxifloxacin; Ofx: ofloxacin; PAS: para-aminosalicylic acid; R: rifampicin; S: streptomycin; SLI: second line injectables; Z: pyrazinamide.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nationality \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Previous Treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Category \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Culture \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Resistances<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ARs to Anti-TB Drugs \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Evolution at 6 Months<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Comorbidities \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Uruguay \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pre-XDR (SLI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C (−) at month 4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, H, R, E, Z, Km, Cm, Amk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, Mfx, Cs, Eto, PAS, Lzd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Argentina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pre-XDR (FQ) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C (−) at month 4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, H, R, E, Z, Km, Cm, AMK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Polyneuritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, AMK, Mfx, Eto, Lzd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Argentina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">XDR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">D (+)C (+) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, H, R, E, Z, Km, Cm, Ofx, Lfx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, Mfx, Cs, Eto, PAS, Lzd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Treatment failure Died \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CKFIDU \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Peru \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">XDR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C (−) at month 4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, H, R, E, Z, Km, Cs, PAS, Ofx, Lzd, Clf \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, Mfx, H<span class="elsevierStyleSup">hd</span>, Eto, Lzd, CFZ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Argentina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No (nurse) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pre-XDR (SLI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C (−) at month 6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, H, R, E, Z, Km, AMK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Digestive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, Mfx, Cs, Eto, PAS, Lzd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">DBT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Argentina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pre-XDR (SLI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C (−) at month 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, H, R, E, Z, Km, AMK \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, Mfx, Cs, Eto, PAS, Lzd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Argentina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RA, R-tacrolimus interaction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C (−) at month 5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">H, E, PAS, Cs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hepatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, AMK, Mfx, Lzd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CKFDBT Liver transplant \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Argentina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">XDR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C (−) at month 6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, H, R, E, Z, Km, Cs, PAS, Ofx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Digestive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, Mfx, Cm, PAS, Lzd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Peru \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pre-XDR (FQ) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C (−) at month 4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, H, R, E, Z, Ofx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, AMK, Mfx, Cs, Eto, Lzd \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Favorable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Argentina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">XDR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C (−) at month 4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">S, H, R, E, Z, Km, Cm, Ofx, Mfx, Cs, Eto \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">DigestiveHematologic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amoxi-clav, MRP, Cm, BDQ, PAS, Lfx \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Died<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AnorexianerviosaDiarrhea due to <span class="elsevierStyleItalic">C. difficile</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab906614.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Ethionamide susceptibility testing frequently returned un-interpretable results. Resistance to group <span class="elsevierStyleSmallCaps">IV</span> and <span class="elsevierStyleSmallCaps">V</span> drugs was considered approximate due to poor consistency across results.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Favorable evolution: bacteriological conversion (2 consecutive negative monthly sputum cultures), the first occurring before the end of the 6-month treatment period.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Patient died in hospital due to respiratory failure, despite bacteriological conversion.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the 10 Patients Receiving Treatment Regimens That Included Meropenem/Amoxicillin-clavulanate.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization (WHO). Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. WHO/HTM/TB/2014.11" ] ] ] 1 => array:3 [ "identificador" => "bib0040" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "WHO. Global Tuberculosis Report 2014. WHO/HTM/TB/2014.08" ] ] ] 2 => array:3 [ "identificador" => "bib0045" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Documento de consenso sobre diagnóstico, tratamiento y prevención de la tuberculosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. González Martín" 1 => "J.M. García García" 2 => "L. Anibarro" 3 => "R. Vidal" 4 => "J. Esteban" 5 => "R. Blanquer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.arbres.2010.02.010" "Revista" => array:6 [ "tituloSerie" => "Arch Bronconeumol" "fecha" => "2010" "volumen" => "46" "paginaInicial" => "255" "paginaFinal" => "274" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20444533" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0050" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical use of the meropenem-clavulanate combination for extensively drug-resistant tuberculosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.C. Payen" 1 => "S. de Wit" 2 => "C. Martín" 3 => "R. Sergysels" 4 => "I. Muylle" 5 => "Y. van Laethem" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5588/ijtld.11.0414" "Revista" => array:6 [ "tituloSerie" => "Int J Tuberc Lung Dis" "fecha" => "2012" "volumen" => "16" "paginaInicial" => "558" "paginaFinal" => "560" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22325421" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0055" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of meropenem/clavulanate added to linezolid containing regimens in the treatment of M/XDR-TB" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. De Lorenzo" 1 => "J.W. Alffenaar" 2 => "G. Sotgiu" 3 => "R. Centis" 4 => "L. D’Ambrosio" 5 => "S. Tiberi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00124312" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2013" "volumen" => "41" "paginaInicial" => "1386" "paginaFinal" => "1392" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22997218" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0060" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is there a place for β-lactams in the treatment of multidrug-resistant/extensively drug-resistant tuberculosis? Synergy between meropenem and amoxicillin/clavulanate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "X. Gonzalo" 1 => "F. Drobniewski" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jac/dks395" "Revista" => array:6 [ "tituloSerie" => "J Antimicrob Chemother" "fecha" => "2013" "volumen" => "68" "paginaInicial" => "366" "paginaFinal" => "369" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23070734" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000005100000010/v1_201509302252/S1579212915002773/v1_201509302252/en/main.assets" "Apartado" => array:4 [ "identificador" => "9347" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Case reports" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/15792129/0000005100000010/v1_201509302252/S1579212915002773/v1_201509302252/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212915002773?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 3 | 14 |
| 2024 October | 69 | 22 | 91 |
| 2024 September | 80 | 24 | 104 |
| 2024 August | 98 | 47 | 145 |
| 2024 July | 72 | 20 | 92 |
| 2024 June | 98 | 32 | 130 |
| 2024 May | 93 | 29 | 122 |
| 2024 April | 62 | 37 | 99 |
| 2024 March | 74 | 17 | 91 |
| 2024 February | 30 | 23 | 53 |
| 2023 March | 24 | 3 | 27 |
| 2023 February | 98 | 26 | 124 |
| 2023 January | 78 | 30 | 108 |
| 2022 December | 89 | 37 | 126 |
| 2022 November | 112 | 29 | 141 |
| 2022 October | 119 | 41 | 160 |
| 2022 September | 136 | 25 | 161 |
| 2022 August | 165 | 49 | 214 |
| 2022 July | 121 | 41 | 162 |
| 2022 June | 115 | 34 | 149 |
| 2022 May | 149 | 49 | 198 |
| 2022 April | 140 | 35 | 175 |
| 2022 March | 161 | 69 | 230 |
| 2022 February | 179 | 42 | 221 |
| 2022 January | 147 | 52 | 199 |
| 2021 December | 125 | 51 | 176 |
| 2021 November | 116 | 55 | 171 |
| 2021 October | 96 | 49 | 145 |
| 2021 September | 93 | 54 | 147 |
| 2021 August | 110 | 43 | 153 |
| 2021 July | 105 | 25 | 130 |
| 2021 June | 140 | 39 | 179 |
| 2021 May | 132 | 42 | 174 |
| 2021 April | 235 | 97 | 332 |
| 2021 March | 223 | 45 | 268 |
| 2021 February | 168 | 28 | 196 |
| 2021 January | 177 | 24 | 201 |
| 2020 December | 119 | 29 | 148 |
| 2020 November | 118 | 17 | 135 |
| 2020 October | 119 | 15 | 134 |
| 2020 September | 112 | 27 | 139 |
| 2020 August | 116 | 20 | 136 |
| 2020 July | 108 | 34 | 142 |
| 2020 June | 125 | 27 | 152 |
| 2020 May | 172 | 11 | 183 |
| 2020 April | 259 | 31 | 290 |
| 2020 March | 233 | 40 | 273 |
| 2020 February | 247 | 28 | 275 |
| 2020 January | 197 | 28 | 225 |
| 2019 December | 140 | 29 | 169 |
| 2019 November | 139 | 29 | 168 |
| 2019 October | 110 | 19 | 129 |
| 2019 September | 103 | 23 | 126 |
| 2019 August | 77 | 17 | 94 |
| 2019 July | 83 | 23 | 106 |
| 2019 June | 119 | 14 | 133 |
| 2019 May | 143 | 17 | 160 |
| 2019 April | 180 | 43 | 223 |
| 2019 March | 128 | 29 | 157 |
| 2019 February | 111 | 19 | 130 |
| 2019 January | 114 | 16 | 130 |
| 2018 December | 108 | 24 | 132 |
| 2018 November | 104 | 26 | 130 |
| 2018 October | 99 | 37 | 136 |
| 2018 September | 48 | 15 | 63 |
| 2018 May | 34 | 1 | 35 |
| 2018 April | 50 | 7 | 57 |
| 2018 March | 59 | 8 | 67 |
| 2018 February | 31 | 13 | 44 |
| 2018 January | 46 | 12 | 58 |
| 2017 December | 40 | 9 | 49 |
| 2017 November | 35 | 10 | 45 |
| 2017 October | 32 | 9 | 41 |
| 2017 September | 24 | 13 | 37 |
| 2017 August | 32 | 16 | 48 |
| 2017 July | 36 | 12 | 48 |
| 2017 June | 53 | 22 | 75 |
| 2017 May | 66 | 21 | 87 |
| 2017 April | 56 | 16 | 72 |
| 2017 March | 57 | 11 | 68 |
| 2017 February | 39 | 13 | 52 |
| 2017 January | 26 | 10 | 36 |
| 2016 December | 39 | 15 | 54 |
| 2016 November | 62 | 13 | 75 |
| 2016 October | 53 | 20 | 73 |
| 2016 September | 77 | 27 | 104 |
| 2016 August | 60 | 21 | 81 |
| 2016 July | 39 | 15 | 54 |
| 2016 May | 0 | 8 | 8 |
| 2016 April | 0 | 1 | 1 |
| 2016 March | 2 | 0 | 2 |
| 2016 February | 1 | 3 | 4 |
| 2016 January | 0 | 14 | 14 |
| 2015 October | 2 | 2 | 4 |
Show all
