Mario Tumbarello1,2,3, Francesca Raffaelli1, Maddalena Giannella4, Elisabetta Mantengoli5, Alessandra Mularoni6, Mario Venditti7, Francesco Giuseppe De Rosa8, Loredana Sarmati9, Matteo Bassetti10,11, Gaetano Brindicci12, Marianna Rossi13, Roberto Luzzati14, Paolo Antonio Grossi15, Alberto Corona16, Alessandro Capone17, Marco Falcone18, Cristina Mussini19, Enrico Maria Trecarichi20, Antonio Cascio21, Elena Guffanti22, Alessandro Russo23, Gennaro De Pascale24, Carlo Tascini25, Ivan Gentile26, Angela Raffaella Losito1, Linda Bussini4, Giampaolo Conti27, Giancarlo Ceccarelli7, Silvia Corcione8, Mirko Compagno28, Daniele Roberto Giacobbe10,11, Annalisa Saracino12, Massimo Fantoni1,2, Spinello Antinori29, Maddalena Peghin30, Paolo Bonfanti31,32, Alessandra Oliva7, Andrea De Gasperi22, Giusy Tiseo18, Cristina Rovelli15, Marianna Meschiari33, Nour Shbaklo8, Teresa Spanu1,34, Roberto Cauda1,2, Pierluigi Viale4. 1. Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. 2. Dipartimento di Sicurezza e Bioetica, Università Cattolica del Sacro Cuore, Roma, Italy. 3. Department of Medical Biotechnologies, University of Siena, Siena, Italy. 4. Department of Medical and Surgical Sciences - University of Bologna, Bologna, Italy. 5. SOD Malattie Infettive e Tropicali Azienda Ospedaliero Universitaria Careggi, Firenze, Italy. 6. ISMETT-IRCCS Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy. 7. Dipartimento di Sanità Pubblica e Malattie Infettive, Università Sapienza, Roma, Italy. 8. Deptartment of Medical Sciences, University of Turin, Torino, Italy. 9. Clinical Infectious Diseases, Department of System Medicine, Tor Vergata University, Roma Italy. 10. Infectious Diseases Unit, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy. 11. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy. 12. Operative Unit of Infectious Diseases, Hospital-University Polyclinic of Bari, Italy. 13. UOC Malattie Infettive, Ospedale San Gerardo, Monza. 14. Infectious Diseases Unit, University Hospital of Trieste, Trieste, Italy. 15. Clinica di Malattie Infettive e Tropicali, Università degli Studi dell'Insubria - ASST-Sette Laghi, Varese, Italy. 16. SC Anestesia e Rianimazione, ASST Fatebenefratelli Sacco, Polo Universitario, Milano, Italy. 17. Infezioni Sistemiche ed Immunodepresso, National Institute for Infectious Disease L. Spallanzani, Roma, Italy. 18. Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy. 19. Clinica delle Malattie Infettive, Università di Modena e Reggio Emilia, Modena, Italy. 20. Department of Medical and Surgical Sciences, Infectious and Tropical Disease Unit, Magna Graecia University of Catanzaro, Catanzaro, Italy. 21. Infectious and Tropical Diseases Unit- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties "G. D'Alessandro", University of Palermo, Palermo, Italy. 22. Anestesia Rianimazione 2, ASST GOM Niguarda, Milano, Italy. 23. Internal Medicine Unit, Policlinico Casilino, Rome, Italy. 24. Dipartimento di Scienza dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. 25. Malattie Infettive ad Indirizzo neurologico Ospedale Cotugno, Napoli, Italy. 26. Dipartimento di Medicina Clinica e Chirurgia - Sezione di Malattie Infettive - Università di Napoli "Federico II" - Napoli. 27. Dipartimento Medicina Sperimentale e Clinica Università di Firenze, Firenze, Italy. 28. Clinical Infectious Diseases, Tor Vergata University, Roma Italy. 29. Dipartimento di Scienze Biomediche e Cliniche L. Sacco Università degli Studi di Milano Polo Universitario, Milano, Italy. 30. Clinica Malattie Infettive, Dipartimento di Area Medica Università di Udine e Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy. 31. UOC Malattie Infettive, Ospedale San Gerardo, Monza, Italy. 32. Università Milano Bicocca, Dipartimento di medicina e chirurgia, Milano, Italy. 33. Clinica delle Malattie Infettive, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena, Italy. 34. Dipartimento di Scienze Biotecnologiche di base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy.
Abstract
BACKGROUND: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae (CRE). METHODS: We retrospectively analyzed observational data on the use and outcomes of CAZ-AVI therapy for infections caused by KPC-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens vs. CAZ-AVI monotherapy. RESULTS: The cohort comprised 577 adults with bloodstream infections (BSIs) (n=391) or non-bacteremic infections (nBSIs) involving mainly the urinary tract, lower respiratory tract, intra-abdominal structures. All received treatment with CAZ-AVI alone (n=165) or with one or more other active antimicrobials (n=412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no statistically significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs. 25.0%, P=0.79). In multivariate analysis, mortality was positively associated with the presence at infection onset of septic shock (P=0.002), neutropenia (P <0.001), or an INCREMENT score >8 (P=0.01); with LRTI (P=0.04); and with CAZ-AVI dose adjustment for renal function (P=0.01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P=0.006). All associations remained significant after propensity score adjustment. CONCLUSIONS: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and the potential survival benefits of prolonging CAZ-AVI infusions to 3 hours or more.
BACKGROUND: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae (CRE). METHODS: We retrospectively analyzed observational data on the use and outcomes of CAZ-AVI therapy for infections caused by KPC-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens vs. CAZ-AVI monotherapy. RESULTS: The cohort comprised 577 adults with bloodstream infections (BSIs) (n=391) or non-bacteremic infections (nBSIs) involving mainly the urinary tract, lower respiratory tract, intra-abdominal structures. All received treatment with CAZ-AVI alone (n=165) or with one or more other active antimicrobials (n=412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no statistically significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs. 25.0%, P=0.79). In multivariate analysis, mortality was positively associated with the presence at infection onset of septic shock (P=0.002), neutropenia (P <0.001), or an INCREMENT score >8 (P=0.01); with LRTI (P=0.04); and with CAZ-AVI dose adjustment for renal function (P=0.01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P=0.006). All associations remained significant after propensity score adjustment. CONCLUSIONS:CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and the potential survival benefits of prolonging CAZ-AVI infusions to 3 hours or more.
Authors: Yanqin Huang; Karol Sokolowski; Amisha Rana; Nidhi Singh; Jiping Wang; Ke Chen; Yinzhi Lang; Jieqiang Zhou; Neera Kadiyala; Fiorella Krapp; Egon A Ozer; Alan R Hauser; Jian Li; Jürgen B Bulitta; Zackery P Bulman Journal: Antimicrob Agents Chemother Date: 2021-08-17 Impact factor: 5.191