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Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae.
Clin Infect Dis. 2019 01 18; 68(3):355-364.CI

Abstract

Background

Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking.

Methods

We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic.

Results

The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P = .005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival.

Conclusions

CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

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    Authors+Show Affiliations

    Tumbarello M
    Institute of Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Università Cattolica del Sacro Cuore, Rome.
    Trecarichi EM
    Institute of Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Università Cattolica del Sacro Cuore, Rome.
    Corona A
    Intensive Care Unit Department of Emergency, Luigi Sacco Hospital-Azienda Socio Sanitaria Territoriale (ASST)-Fatebenefratelli Sacco, University of Milan.
    De Rosa FG
    Department of Medical Sciences, University of Turin.
    Bassetti M
    Infectious Disease Division, Santa Maria Misericordia University Hospital, Udine.
    Mussini C
    Clinica delle Malattie Infettive, Università di Modena e Reggio Emilia.
    Menichetti F
    Infectious Diseases Department, Cisanello Hospital, Pisa.
    Viscoli C
    Infectious Diseases Division, Università di Genova e Ospedale Policlinico San Martino IRCCS per l'oncologia e le neuroscienze, Genoa.
    Campoli C
    Infectious Diseases Unit, Department of Medical and Clinical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum University of Bologna.
    Venditti M
    Dipartimento di Salute Pubblica e Malattie Infettive, Policlinico Umberto I Università 'Sapienza', Rome.
    De Gasperi A
    Anestesia Rianimazione 2-ASST ospedale Niguarda Ca Granda, Milan.
    Mularoni A
    Infectious Diseases Istituto mediterraneo per i trapianti e terapie ad alta specializzazione-IRCCS Palermo.
    Tascini C
    Prima divisione di Malattie Infettive, Ospedale Cotugno, Azienda Ospedaliera dei Colli, Napoli.
    Parruti G
    Unità Operativa Complessa Malattie Infettive, Azienda Unità Sanitaria Locale Pescara.
    Pallotto C
    Infectious Diseases Section, Department of Medicine, University of Perugia.
    Sica S
    Institute of Hematology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Rome.
    Concia E
    Malattie Infettive, Ospedale Universitario di Verona.
    Cultrera R
    Malattie Infettive, Dipartimento di Scienze Mediche, Università degli Studi di Ferrara.
    De Pascale G
    Department of Intensive Care and Anaesthesiology, Fondazione Policlinico Universitario A. Gemelli IRCCS - Università Cattolica del Sacro Cuore, Rome.
    Capone A
    Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani IRCCS Rome.
    Antinori S
    Department of Clinical and Biomedical Sciences "L. Sacco," University of Milan.
    Corcione S
    Department of Medical Sciences, University of Turin.
    Righi E
    Infectious Disease Division, Santa Maria Misericordia University Hospital, Udine.
    Losito AR
    Institute of Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Università Cattolica del Sacro Cuore, Rome.
    Digaetano M
    Clinica delle Malattie Infettive, Università di Modena e Reggio Emilia.
    Amadori F
    Infectious Diseases Department, Cisanello Hospital, Pisa.
    Giacobbe DR
    Infectious Diseases Division, Università di Genova e Ospedale Policlinico San Martino IRCCS per l'oncologia e le neuroscienze, Genoa.
    Ceccarelli G
    Dipartimento di Salute Pubblica e Malattie Infettive, Policlinico Umberto I Università 'Sapienza', Rome.
    Mazza E
    Anestesia Rianimazione 2-ASST ospedale Niguarda Ca Granda, Milan.
    Raffaelli F
    Institute of Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Università Cattolica del Sacro Cuore, Rome.
    Spanu T
    Institute of Microbiology, Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy.
    Cauda R
    Institute of Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Università Cattolica del Sacro Cuore, Rome.
    Viale P
    Infectious Diseases Unit, Department of Medical and Clinical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum University of Bologna.

    MeSH

    AdultAgedAnti-Bacterial AgentsAzabicyclo CompoundsCarbapenem-Resistant EnterobacteriaceaeCeftazidimeDrug CombinationsFemaleHumansItalyKlebsiella InfectionsKlebsiella pneumoniaeMaleMiddle AgedRetrospective StudiesSalvage TherapySurvival AnalysisTreatment Outcomebeta-Lactamase Inhibitors

    Pub Type(s)

    Journal Article
    Observational Study
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    29893802

    Citation

    Tumbarello, Mario, et al. "Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused By Klebsiella Pneumoniae Carbapenemase-producing K. Pneumoniae." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 68, no. 3, 2019, pp. 355-364.
    Tumbarello M, Trecarichi EM, Corona A, et al. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clin Infect Dis. 2019;68(3):355-364.
    Tumbarello, M., Trecarichi, E. M., Corona, A., De Rosa, F. G., Bassetti, M., Mussini, C., Menichetti, F., Viscoli, C., Campoli, C., Venditti, M., De Gasperi, A., Mularoni, A., Tascini, C., Parruti, G., Pallotto, C., Sica, S., Concia, E., Cultrera, R., De Pascale, G., ... Viale, P. (2019). Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 68(3), 355-364. https://doi.org/10.1093/cid/ciy492
    Tumbarello M, et al. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused By Klebsiella Pneumoniae Carbapenemase-producing K. Pneumoniae. Clin Infect Dis. 2019 01 18;68(3):355-364. PubMed PMID: 29893802.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. AU - Tumbarello,Mario, AU - Trecarichi,Enrico Maria, AU - Corona,Alberto, AU - De Rosa,Francesco Giuseppe, AU - Bassetti,Matteo, AU - Mussini,Cristina, AU - Menichetti,Francesco, AU - Viscoli,Claudio, AU - Campoli,Caterina, AU - Venditti,Mario, AU - De Gasperi,Andrea, AU - Mularoni,Alessandra, AU - Tascini,Carlo, AU - Parruti,Giustino, AU - Pallotto,Carlo, AU - Sica,Simona, AU - Concia,Ercole, AU - Cultrera,Rosario, AU - De Pascale,Gennaro, AU - Capone,Alessandro, AU - Antinori,Spinello, AU - Corcione,Silvia, AU - Righi,Elda, AU - Losito,Angela Raffaella, AU - Digaetano,Margherita, AU - Amadori,Francesco, AU - Giacobbe,Daniele Roberto, AU - Ceccarelli,Giancarlo, AU - Mazza,Ernestina, AU - Raffaelli,Francesca, AU - Spanu,Teresa, AU - Cauda,Roberto, AU - Viale,Pierluigi, PY - 2018/03/28/received PY - 2018/06/06/accepted PY - 2018/6/13/pubmed PY - 2018/6/13/medline PY - 2018/6/13/entrez SP - 355 EP - 364 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. VL - 68 IS - 3 N2 - Background: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking. Methods: We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic. Results: The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P = .005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival. Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/29893802/Efficacy_of_Ceftazidime_Avibactam_Salvage_Therapy_in_Patients_With_Infections_Caused_by_Klebsiella_pneumoniae_Carbapenemase_producing_K__pneumoniae_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciy492 DB - PRIME DP - Unbound Medicine ER -