Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience
Introduction
Pseudomonas aeruginosa is a leading cause of nosocomial infections, which are often severe [1], [2] and difficult to treat because of their increasing resistance to several antibiotics, including carbapenems [3], [4], [5], [6]. There are limited therapeutic options for such infections, and old antibiotics such as colistin, aminoglycosides or fosfomycin are frequently prescribed [7]. Clinical failure [8], the emergence of in vivo resistance [9], superinfection and nephrotoxicity [10], [11] represent the main limitations of currently available drugs, leading to the search of new treatment options.
Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor combination with potent activity against Gram-negative bacteria, particularly against P. aeruginosa for which it is the most active available β-lactam antibiotic [5]. Although C/T has only been approved for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) [12], [13], it has become a suitable and attractive option for the treatment of different infections caused by multidrug-resistant (MDR) or extensively drug-resistant (XDR) P. aeruginosa [14]. In recent years clinical experience with C/T is accumulating and expanding, but only a limited number of cases series have been published [15], [16], [17], [18], [19], [20], [21].
A multicentre nationwide study was performed to report the Italian experience with C/T in the treatment of severe P. aeruginosa infections and to evaluate risk factors associated with clinical failure.
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Study setting and design
A multicentre, retrospective, real-world study of hospitalised patients in 22 public hospitals in Italy who were treated for P. aeruginosa infections between June 2016 and March 2018 (21-month period) was performed. Hospitals were located in 12 Italian regions, namely Friuli Venezia Giulia, Veneto, Lombardia, Emilia Romagna, Liguria, Toscana, Lazio, Abruzzo, Campania, Puglia, Calabria and Sicilia. The Internal Review Board of Medical Area (D.A.M.E) of the co-ordinating centre (Azienda
Results
A total of 101 patients treated with ≥4 days of C/T were evaluated. The clinical characteristics of the patients are shown in Table 1. The median patient age was 67 years (interquartile range 49–74 years) and 66 (65.3%) were male. Almost one-third of the patients (30.7%) showed a chronic renal disease prior to P. aeruginosa infection and, with the exception of seven cases, all patients had at least one serious underlying disease with a mean Charlson comorbidity index of 4.4. At the time of
Discussion
Here we present the largest clinical experience with C/T therapy for the treatment of serious P .aeruginosa infection published so far. We showed that C/T is an effective and safe drug for treating different types of P. aeruginosa infection, including those with off-label indications. Of importance, clinical success was observed in nearly 85% of the patients, notwithstanding the fact that almost 70% of the isolates were MDR or XDR. Importantly, this analysis also indicated that CRRT and sepsis
Acknowledgments
The authors acknowledge as co-authors all of the following CEFTABUSE-IT Study Group members: Matteo Bassetti, Antonio Vena, Nadia Castaldo, Davide Pecori, Elda Righi, Alessia Carnellutti, Filippo Givone, Elena Graziano, Maria Merelli, Barbara Cadeo and Maddalena Peghin (Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy); Annamaria Cattelan, Ludovica Cipriani and Davide Coletto (Unit of Infectious Diseases, Department of Internal Medicine, Azienda
Funding
None.
Competing interests
MB serves on scientific advisory boards for Angelini, AstraZeneca, Bayer, Cubist, Pfizer, Menarini, MSD, Nabriva, Paratek, Roche, Shionogi, Tetraphase, The Medicine Company and Astellas Pharma Inc., and has received funding for travel or speaker honoraria from Algorithm, Angelini, Astellas Pharma Inc., AstraZeneca, Cubist, Pfizer, MSD, Gilead Sciences, Menarini, Novartis, Ranbaxy and Teva; CT has received funds for speaking at symposia organised on behalf of Pfizer, Gilead, Novartis, Merck,
Ethical approval
The Internal Review board of Medical Area (D.A.M.E) of Azienda Ospedaliera Universitaria Integrata di Udine (Udine, Italy) approved this study [18/I.R.B_Bassetti_18], which waived the requirement of informed consent owing to the retrospective design of the study.
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