Ana Motos1,2,3,4, Gianluigi Li Bassi1,2,3,5, Francesco Pagliara1,6,7, Laia Fernandez-Barat1,2,3,4, Hua Yang1, Eli Aguilera Xiol1,2,3, Tarek Senussi1,6,7, Francesco A Idone1,8,9, Chiara Travierso1,10,11,12, Chiara Chiurazzi1,13, Rosanel Amaro1,2,3,4, Minlan Yang1,4, Joaquim Bobi1,2, Montserrat Rigol1,2, David P Nicolau14, Gerard Frigola15, Roberto Cabrera1,2,3, Jose Ramirez15, Paolo Pelosi6,7, Francesco Blasi11,12, Massimo Antonelli8,9, Antonio Artigas16, Jordi Vila17, Marin Kollef18, Antoni Torres19,2,3,4. 1. Division of Animal Experimentation, Department of Pulmonary and Critical Care Medicine, Hospital Clínic, Barcelona, Spain. 2. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 3. Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CIBERES), Barcelona, Spain. 4. University of Barcelona, Barcelona, Spain. 5. Critical Care Research Group, The Prince Charles Hospital, Chermside, Australia. 6. Department of Surgical Sciences and Integrated Diagnostics (DISC), IRCCS AOU San Martino IST, Genoa, Italy. 7. San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy. 8. Department of Anesthesiology, Intensive Care, and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 9. Università Cattolica del Sacro Cuore, Rome, Italy. 10. Division of Pneumology, ASST Rhodense "Guido Salvini" Hospital, Garbagnate Milanese, Italy. 11. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy. 12. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 13. Istituto Humanitas, Milan, Italy. 14. Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA. 15. Department of Pathology, Hospital Clinic, Barcelona, Spain. 16. Autonomous University of Barcelona, Department of Intensive Care Medecine, CIBER Enfermedades Respiratorias, Corporacion Sanitaria Universitaria Parc Tauli, Sabadell, Spain. 17. Microbiology Department, Hospital Clínic, CRESIB ISglobal, Barcelona, Spain. 18. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. 19. Division of Animal Experimentation, Department of Pulmonary and Critical Care Medicine, Hospital Clínic, Barcelona, Spain atorres@clinic.cat.
Abstract
The rising frequency of multidrug-resistant and extensively drug-resistant (MDR/XDR) pathogens is making more frequent the inappropriate empirical antimicrobial therapy (IEAT) in nosocomial pneumonia, which is associated with increased mortality. We aim to determine the short-term benefits of appropriate empirical antimicrobial treatment (AEAT) with ceftolozane/tazobactam (C/T) compared with IEAT with piperacillin/tazobactam (TZP) in MDR Pseudomonas aeruginosa pneumonia. Twenty-one pigs with pneumonia caused by an XDR P. aeruginosa strain (susceptible to C/T but resistant to TZP) were ventilated for up to 72 h. Twenty-four hours after bacterial challenge, animals were randomized to receive 2-day treatment with either intravenous saline (untreated) or 25 to 50 mg of C/T per kg body weight (AEAT) or 200 to 225 mg of TZP per kg (IEAT) every 8 h. The primary outcome was the P. aeruginosa burden in lung tissue and the histopathology injury. P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage (BAL) fluid, the development of antibiotic resistance, and inflammatory markers were secondary outcomes. Overall, P. aeruginosa lung burden was 5.30 (range, 4.00 to 6.30), 4.04 (3.64 to 4.51), and 4.04 (3.05 to 4.88) log10CFU/g in the untreated, AEAT, and IEAT groups, respectively (P = 0.299), without histopathological differences (P = 0.556). In contrast, in tracheal secretions (P < 0.001) and BAL fluid (P = 0.002), bactericidal efficacy was higher in the AEAT group. An increased MIC to TZP was found in 3 animals, while resistance to C/T did not develop. Interleukin-1β (IL-1β) was significantly downregulated by AEAT in comparison to other groups (P = 0.031). In a mechanically ventilated swine model of XDR P. aeruginosa pneumonia, appropriate initial treatment with C/T decreased respiratory secretions' bacterial burden, prevented development of resistance, achieved the pharmacodynamic target, and may have reduced systemic inflammation. However, after only 2 days of treatment, P. aeruginosa tissue concentrations were moderately affected.
The rising frequency of multidrug-resistant and extensively drug-resistant (MDR/XDR) pathogens is making more frequent the inappropriate empirical antimicrobial therapy (IEAT) in pan class="Disease">nosocomial pneumonia, which is associated with increased mortality. We aim to determine the short-term benefits of appropriate empirical antimicrobial treatment (AEAT) with ceftolozane/tazobactam (C/T) compared with IEAT with piperacillin/tazobactam (TZP) in MDR Pseudomonas aeruginosa pneumonia. Twenty-one pigs with pneumonia caused by an XDR P. aeruginosa strain (susceptible to C/T but resistant to TZP) were ventilated for up to 72 h. Twenty-four hours after bacterial challenge, animals were randomized to receive 2-day treatment with either intravenous saline (untreated) or 25 to 50 mg of C/T per kg body weight (AEAT) or 200 to 225 mg of TZP per kg (IEAT) every 8 h. The primary outcome was the P. aeruginosa burden in lung tissue and the histopathology injury. P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage (BAL) fluid, the development of antibiotic resistance, and inflammatory markers were secondary outcomes. Overall, P. aeruginosa lung burden was 5.30 (range, 4.00 to 6.30), 4.04 (3.64 to 4.51), and 4.04 (3.05 to 4.88) log10CFU/g in the untreated, AEAT, and IEAT groups, respectively (P = 0.299), without histopathological differences (P = 0.556). In contrast, in tracheal secretions (P < 0.001) and BAL fluid (P = 0.002), bactericidal efficacy was higher in the AEAT group. An increased MIC to TZP was found in 3 animals, while resistance to C/T did not develop. Interleukin-1β (IL-1β) was significantly downregulated by AEAT in comparison to other groups (P = 0.031). In a mechanically ventilated swine model of XDR P. aeruginosa pneumonia, appropriate initial treatment with C/T decreased respiratory secretions' bacterial burden, prevented development of resistance, achieved the pharmacodynamic target, and may have reduced systemic inflammation. However, after only 2 days of treatment, P. aeruginosa tissue concentrations were moderately affected.
Authors: Gurudatt Chandorkar; Jennifer A Huntington; Mark H Gotfried; Keith A Rodvold; Obiamiwe Umeh Journal: J Antimicrob Chemother Date: 2012-07-06 Impact factor: 5.790
Authors: Daniele Roberto Giacobbe; Matteo Bassetti; Francesco Giuseppe De Rosa; Valerio Del Bono; Paolo Antonio Grossi; Francesco Menichetti; Federico Pea; Gian Maria Rossolini; Mario Tumbarello; Pierluigi Viale; Claudio Viscoli Journal: Expert Rev Anti Infect Ther Date: 2018-03-09 Impact factor: 5.091
Authors: Carlos M Luna; Sebastián Baquero; Sebastián Gando; Juan Risso Patrón; Joaquín García Morato; Oriol Sibila; Rubén Absi; Angela Famiglietti; Carlos A Vay; Florencia Von Stecher; Carlos Agustí; Antoni Torres Journal: Chest Date: 2007-08 Impact factor: 9.410
Authors: Kimberly C Claeys; Evan J Zasowski; Trang D Trinh; Abdalhamid M Lagnf; Susan L Davis; Michael J Rybak Journal: Infect Dis Ther Date: 2017-11-21