Cefiderocol- Compared to Colistin-Based Regimens for the Treatment of Severe Infections Caused by Carbapenem-Resistant Acinetobacter baumannii
Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 202...
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Published in | Antimicrobial agents and chemotherapy Vol. 66; no. 5; p. e0214221 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Microbiology
17.05.2022
|
Subjects | |
Online Access | Get full text |
ISSN | 0066-4804 1098-6596 1098-6596 |
DOI | 10.1128/aac.02142-21 |
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Abstract | Cefiderocol may represent a therapeutic option for carbapenem-resistant
Acinetobacter baumannii
(CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021).
Cefiderocol may represent a therapeutic option for carbapenem-resistant
Acinetobacter baumannii
(CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%,
P
= 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22–0.66,
P
< 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol
versus
6.8% of those receiving colistin (
P
= 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings. |
---|---|
AbstractList | Cefiderocol may represent a therapeutic option for carbapenem-resistant
Acinetobacter baumannii
(CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%,
P
= 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22–0.66,
P
< 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol
versus
6.8% of those receiving colistin (
P
= 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings. Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%, P = 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22-0.66, P < 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol versus 6.8% of those receiving colistin (P = 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings.Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%, P = 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22-0.66, P < 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol versus 6.8% of those receiving colistin (P = 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings. Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%, P = 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22–0.66, P < 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol versus 6.8% of those receiving colistin (P = 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings. Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%, = 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22-0.66, < 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol 6.8% of those receiving colistin ( = 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings. Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%, P = 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22–0.66, P < 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol versus 6.8% of those receiving colistin ( P = 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings. |
Author | Tiseo, Giusy Vecchione, Alessandra Barnini, Simona Menichetti, Francesco Leonildi, Alessandro Farcomeni, Alessio Della Sala, Leonardo Falcone, Marco |
Author_xml | – sequence: 1 givenname: Marco orcidid: 0000-0003-3813-8796 surname: Falcone fullname: Falcone, Marco organization: Department of Clinical and Experimental Medicine, University of Pisa, Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy – sequence: 2 givenname: Giusy surname: Tiseo fullname: Tiseo, Giusy organization: Department of Clinical and Experimental Medicine, University of Pisa, Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy – sequence: 3 givenname: Alessandro surname: Leonildi fullname: Leonildi, Alessandro organization: Microbiology Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy – sequence: 4 givenname: Leonardo surname: Della Sala fullname: Della Sala, Leonardo organization: Department of Clinical and Experimental Medicine, University of Pisa, Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy – sequence: 5 givenname: Alessandra surname: Vecchione fullname: Vecchione, Alessandra organization: Microbiology Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy – sequence: 6 givenname: Simona surname: Barnini fullname: Barnini, Simona organization: Microbiology Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy – sequence: 7 givenname: Alessio surname: Farcomeni fullname: Farcomeni, Alessio organization: Department of Economics and Finance, University of Rome “Tor Vergata,” Rome, Italy – sequence: 8 givenname: Francesco surname: Menichetti fullname: Menichetti, Francesco organization: Department of Clinical and Experimental Medicine, University of Pisa, Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35311522$$D View this record in MEDLINE/PubMed |
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Keywords | bloodstream infections cefiderocol multidrug resistance Acinetobacter baumannii pneumonia antibiotic resistance ventilator-associated pneumonia colistin sepsis |
Language | English |
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Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Undefined-3 The authors declare a conflict of interest. M.F. received grants and/or speaker honoraria from MSD, Angelini, Shionogi, Pfizer, Menarini, Gilead and Nordic Pharma. F.M. has participated in advisory boards and/or received speaker honoraria from Angelini, Correvio, Merck Sharp & Dohme (MSD), Nordic Pharma, Pfizer, Astellas, Gilead, Bristol-Myers Squibb (BMS), Janssen, ViiV, bioMérieux, Biotest, Becton Dickinson, Pfizer, and Shionogi. Declared conflicts of interest are outside the submitted work and did not affect the scientific objectivity of this study. The other authors have none to declare. |
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PublicationTitle | Antimicrobial agents and chemotherapy |
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Publisher | American Society for Microbiology |
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Snippet | Cefiderocol may represent a therapeutic option for carbapenem-resistant
Acinetobacter baumannii
(CRAB) infections, but clinical data are limited. This is an... Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an... |
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SubjectTerms | Acinetobacter baumannii Anti-Bacterial Agents - therapeutic use Antimicrobial Chemotherapy Carbapenems - therapeutic use Cefiderocol Cephalosporins Clinical Therapeutics Colistin - therapeutic use Humans Pneumonia, Ventilator-Associated - drug therapy Retrospective Studies Sepsis - drug therapy |
Title | Cefiderocol- Compared to Colistin-Based Regimens for the Treatment of Severe Infections Caused by Carbapenem-Resistant Acinetobacter baumannii |
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