Letters to the Editor – Brief Case Reports
Ceftazidime-avibactam in urinary tract infections due to carbapenemase-producing Klebsiella in kidney transplantation
Ceftazidima-avibactam en el tratamiento de infecciones urinarias por Klebsiella productora de carbapenemasa en trasplante renal
Fernando Caravaca-Fontán
, Sara Jiménez-Álvaro, Roberto Marcén-Letosa, Ana Fernández-Rodríguez, Carlos Quereda Rodríguez-Navarro
Corresponding author
Servicio de Nefrología, Hospital Universitario Ramón y Cajal, Madrid, Spain
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The recent appearance of carbapenemase-producing enterobacteriaceae has generated a real therapeutic challenge.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">1</span></a> Reported for the first time in the 1990s, in the last year we have witnessed the dissemination of these strains in several Spanish hospitals. This has generated an important epidemiologic problem and a challenging situation in immunosuppressed patients like kidney transplant recipients.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe a case of recurring urinary infections due to <span class="elsevierStyleItalic">Klebsiella pneumoniae</span> carbapenemase (KPC)-producing bacteria in a 78-year-old male who had received a kidney transplant in November 2013. His medical history included chronic kidney disease secondary to membranous glomerulonephritis, for which he had initiated haemodialysis in March 2013. As a postoperative complication, he presented calyceal fistula that was refractory to 2 surgical procedures and was finally repaired by endourologic injection of cyanoacrylate. The first hospitalisation was prolonged for more than 2 months, during which time he had several urinary infections secondary to extended-spectrum beta-lactamase-producing <span class="elsevierStyleItalic">Klebsiella pneumoniae</span>, treated with meropenem. In successive controls, rectal colonisation by KPC was observed. In the following months, he was hospitalised 4 times for urinary infection secondary to KPC, and possible urological causes were ruled out. Different antibiotic regimens were tried, including amikacin and colistin, meropenem at high doses together with tigecycline, as well as colistin and tigecycline. The duration of each of these treatments lasted more than 2 weeks while monitoring the levels of those antibiotics that are more nephrotoxic. The urine cultures became negative, but this was only transitory and the infection recurred weeks after finishing the antibiotic cycle, which led to another hospitalisation. For this reason, we decided to initiate treatment with the recent antibiotic ceftazidime–avibactam (C–A) for 2 weeks at a dose of 1000/250<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h, which achieved the definitive eradication of the urinary infection as well as the KPC carrier state.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Urinary tract infections are an important cause of morbidity, hospitalisations and elevated hospital costs associated with kidney transplantations. The most frequently involved microorganisms are Gram-negative. The dissemination of carbapenem-resistant strains has been associated with higher mortality in transplanted patients.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">2,3</span></a> Prolonged hospitalisation and the previous use of carbapenems have been related with a greater probability of developing these infections. In our patient, the previous endourologic seal of the calyceal fistula with cyanoacrylate made us consider the possible correlation that it may have had with the recurring infections, although there is no evidence in the literature to support this.</p><p id="par0020" class="elsevierStylePara elsevierViewall">This is the first reported case of urinary infection due to KPC in a renal transplant recipient cured with C-A. Avibactam is a non-beta-lactam beta-lactamase inhibitor that, in combination with ceftazidime, has demonstrated a bactericide effect in infections by resistant enterobacteriaceae and those caused by <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">1</span></a> Studies in animal models have demonstrated that C–A is effective in meningitis, septicaemia, pyelonephritis and pneumonia caused by these strains. Currently, it is in phase 3 trial for the treatment of urinary infections and complicated intraabdominal infections in humans.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">4</span></a> In our case, its administration was for compassionate use, and it was shown to be a safe, effective and well tolerated. Clinical trials are necessary to evaluate the efficacy of C–A, although the preliminary results look promising.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Caravaca-Fontán F, Jiménez-Álvaro S, Marcén-Letosa R, Fernández-Rodríguez A, Rodríguez-Navarro CQ. Ceftazidima-avibactam en el tratamiento de infecciones urinarias por <span class="elsevierStyleItalic">Klebsiella</span> productora de carbapenemasa en trasplante renal. Nefrologia. 2015;35:412–413.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0025" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The global challenge of carbapenem-resistant <span class="elsevierStyleItalic">Enterobacteriaceae</span> in transplant recipients and patients with hematologic malignancies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.J. Satlin" 1 => "S.G. Jenkins" 2 => "T.J. Walsh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/cid/ciu052" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2014" "volumen" => "58" "paginaInicial" => "1274" "paginaFinal" => "1283" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24463280" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0030" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Carbapenem-resistant <span class="elsevierStyleItalic">Enterobacteriaceae</span>: a menace to our most vulnerable patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F. Perez" 1 => "D. van Duin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3949/ccjm.80a.12182" "Revista" => array:6 [ "tituloSerie" => "Cleve Clin J Med" "fecha" => "2013" "volumen" => "80" "paginaInicial" => "225" "paginaFinal" => "233" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23547093" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0035" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mortality associated with carbapenem-resistant <span class="elsevierStyleItalic">Klebsiella pneumoniae</span> infections in liver transplant recipients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.S. Kalpoe" 1 => "E. Sonnenberg" 2 => "S.H. Factor" 3 => "J. del Río Martín" 4 => "T. Schiano" 5 => "G. Patel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/lt.23374" "Revista" => array:6 [ "tituloSerie" => "Liver Transpl" "fecha" => "2012" "volumen" => "18" "paginaInicial" => "468" "paginaFinal" => "474" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22467548" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0040" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Lagacé-Wiens" 1 => "A. Walkty" 2 => "J.A. Karlowsky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/CE.S40698" "Revista" => array:6 [ "tituloSerie" => "Core Evid" "fecha" => "2014" "volumen" => "9" "paginaInicial" => "13" "paginaFinal" => "25" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24493994" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003500000004/v1_201511210014/S2013251415000784/v1_201511210014/en/main.assets" "Apartado" => array:4 [ "identificador" => "42662" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor - Brief comments on case reports" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003500000004/v1_201511210014/S2013251415000784/v1_201511210014/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251415000784?idApp=UINPBA000064" ]
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| 2021 February | 51 | 21 | 72 |
| 2021 January | 43 | 15 | 58 |
| 2020 December | 42 | 14 | 56 |
| 2020 November | 38 | 14 | 52 |
| 2020 October | 32 | 16 | 48 |
| 2020 September | 41 | 11 | 52 |
| 2020 August | 48 | 12 | 60 |
| 2020 July | 41 | 17 | 58 |
| 2020 June | 52 | 15 | 67 |
| 2020 May | 74 | 7 | 81 |
| 2020 April | 85 | 20 | 105 |
| 2020 March | 43 | 21 | 64 |
| 2020 February | 55 | 22 | 77 |
| 2020 January | 59 | 22 | 81 |
| 2019 December | 74 | 22 | 96 |
| 2019 November | 79 | 24 | 103 |
| 2019 October | 32 | 17 | 49 |
| 2019 September | 79 | 43 | 122 |
| 2019 August | 32 | 14 | 46 |
| 2019 July | 73 | 38 | 111 |
| 2019 June | 40 | 23 | 63 |
| 2019 May | 44 | 31 | 75 |
| 2019 April | 94 | 38 | 132 |
| 2019 March | 55 | 22 | 77 |
| 2019 February | 18 | 18 | 36 |
| 2019 January | 33 | 23 | 56 |
| 2018 December | 94 | 41 | 135 |
| 2018 November | 148 | 19 | 167 |
| 2018 October | 118 | 26 | 144 |
| 2018 September | 81 | 21 | 102 |
| 2018 August | 59 | 22 | 81 |
| 2018 July | 48 | 17 | 65 |
| 2018 June | 51 | 15 | 66 |
| 2018 May | 51 | 9 | 60 |
| 2018 April | 52 | 16 | 68 |
| 2018 March | 44 | 11 | 55 |
| 2018 February | 46 | 5 | 51 |
| 2018 January | 37 | 8 | 45 |
| 2017 December | 46 | 7 | 53 |
| 2017 November | 34 | 13 | 47 |
| 2017 October | 34 | 11 | 45 |
| 2017 September | 34 | 10 | 44 |
| 2017 August | 36 | 8 | 44 |
| 2017 July | 38 | 23 | 61 |
| 2017 June | 43 | 20 | 63 |
| 2017 May | 49 | 19 | 68 |
| 2017 April | 23 | 18 | 41 |
| 2017 March | 24 | 18 | 42 |
| 2017 February | 36 | 5 | 41 |
| 2017 January | 27 | 10 | 37 |
| 2016 December | 39 | 16 | 55 |
| 2016 November | 49 | 25 | 74 |
| 2016 October | 72 | 25 | 97 |
| 2016 September | 101 | 22 | 123 |
| 2016 August | 135 | 7 | 142 |
| 2016 July | 133 | 10 | 143 |
| 2016 June | 101 | 0 | 101 |
| 2016 May | 116 | 0 | 116 |
| 2016 April | 75 | 0 | 75 |
| 2016 March | 85 | 0 | 85 |
| 2016 February | 92 | 0 | 92 |
| 2016 January | 74 | 0 | 74 |
| 2015 December | 98 | 0 | 98 |
| 2015 November | 62 | 0 | 62 |
Show all
