Journal Information
Vol. 35. Issue. 4.July - August 2015
Pages 347-420
Vol. 35. Issue. 4.July - August 2015
Pages 347-420
Letters to the Editor – Brief Case Reports
DOI: 10.1016/j.nefroe.2015.10.002
Open Access
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
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Fernando Caravaca-Fontán
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fcaravacaf@gmail.com

Corresponding author.
, Sara Jiménez-Álvaro, Roberto Marcén-Letosa, Ana Fernández-Rodríguez, Carlos Quereda Rodríguez-Navarro
Servicio de Nefrología, Hospital Universitario Ramón y Cajal, Madrid, Spain
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Dear Editor:

Enterobacteriaceae are an important cause of infections, especially in immunocompromised patients. The recent appearance of carbapenemase-producing enterobacteriaceae has generated a real therapeutic challenge.1 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.

We describe a case of recurring urinary infections due to Klebsiella pneumoniae 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 Klebsiella pneumoniae, 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 1000/250mg every 12h, which achieved the definitive eradication of the urinary infection as well as the KPC carrier state.

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.2,3 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.

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 Pseudomonas aeruginosa.1 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.4 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.

Conflict of interest

The authors have no conflicts of interest to declare.

References
[1]
M.J. Satlin, S.G. Jenkins, T.J. Walsh.
The global challenge of carbapenem-resistant Enterobacteriaceae in transplant recipients and patients with hematologic malignancies.
Clin Infect Dis, 58 (2014), pp. 1274-1283
[2]
F. Perez, D. van Duin.
Carbapenem-resistant Enterobacteriaceae: a menace to our most vulnerable patients.
Cleve Clin J Med, 80 (2013), pp. 225-233
[3]
J.S. Kalpoe, E. Sonnenberg, S.H. Factor, J. del Río Martín, T. Schiano, G. Patel, et al.
Mortality associated with carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients.
Liver Transpl, 18 (2012), pp. 468-474
[4]
P. Lagacé-Wiens, A. Walkty, J.A. Karlowsky.
Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections.
Core Evid, 9 (2014), pp. 13-25

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 Klebsiella productora de carbapenemasa en trasplante renal. Nefrologia. 2015;35:412–413.

Copyright © 2015. Sociedad Española de Nefrología
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