Table 4 Summary of real-world evidence with cefiderocol treatment in critically ill patients
Investigation | No. of patients, sex, age (yr) | Species | Cefiderocol (monotherapy or combination therapy) | Comparator | Infection type | Outcome | Other parameters | References |
|---|---|---|---|---|---|---|---|---|
1 | N = 124; 92 M, median age ~ 65.5 yrs | CR AB | 47 cases (15 monotherapy) | Colistin, 77 cases | BSI 79, VAP 35, other 10 | Day 30 ACM 34% versus 55.8%, P = 0.018 8 pts had micro failure with cefiderocol, and 4 pts had resistance | Nephrotoxicity in colistin group, 90% in the ICU, 40% had COVID-19, higher % on ECMO in cefiderocol group during sepsis, similar % had CRRT during sepsis, 8 pts had solid cancer | [90] |
2 | N = 13; 13 M, mean age 61 yrs | CR AB | 13 cases (8 monotherapy) | None | All NP | 30-day clinical success 54% 30-day mortality 46% | 12 pts polymicrobial, 12 pts had COVID-19, 11 pts in the ICU, 1 pt with immunosuppression | [92] |
3 | N = 17; 14 M, 3 F, median age 64 yrs | XDR, DTR PA | 17 cases (3 monotherapy) | None | VAP 7, IAI 4, BSI 1, meningitis 1, empyema 1, NP 1, osteomyelitis 1, ecthyma gangrenosum 1 | Clinical cure 70.6%, Clinical relapse in 3 pts, Eradication 76.5%, Day 30 ACM 23.5% | Pts had prior treatment failure, 88% in ICU; 3 pts had polymicrobial infection (1 PDR AB, 1 SM, 1 CR, CZA-R KP), 5 pts with COVID-19, 7 pts with immunosuppression | [93] |
4 | N = 107; 82 M, 25 F, median age 65 yrs | CR AB | 42 cases (42 monotherapy) | Colistin, 65 cases, 82% combination therapy | BSI 58%, LRTI 41% | Day 28 ACM: Cefiderocol 55% Colistin 58% Clinical cure: Cefiderocol 40% Colistin 36% | Severe COVID-19, 9 pts with immunosuppression | [91] |
5 | N = 13; 8 M, 5 F, mean age 62.2 yrs | XDR AB | 13 cases (10 monotherapy) | None | BSI + VAP 6, VAP 5, BSI 2 | Microbiological failure 54%, Microbiological failure with suboptimal fCmin/MIC 80%, Day 30 mortality 31% | All pts had COVID-19 pneumonia, TDM-driven assessment, 4 pts with ECMO, 2 pts with CRRT | [94] |
6 | N = 1; M, 64 yrs | PA | 1 case (1 combination therapy; colistin + fosfomycin) | None | Empyema, pneumonia | Eradication | COVID-19, thoracostomy drainage, surgical debridement | [95] |
7 | N = 1; F, 55 yrs | PDR AB | 1 case (1 combination therapy; sulbactam–durlobactam) | None | VAP | Clinical status improved and discharged | COVID-19, respiratory failure, mechanical ventilation, vasopressors, thoracostomy tube | [96] |
8 | N = 1; F, 64 yrs | MDR PA | 1 case (1 combination therapy; polymyxin B + tobramycin) | None | Pneumonia, IAI (abscesses), BSI | Clinical improvement | ESRD, ESLivD, combined liver + kidney transplant, ARDS, ECMO, vasopressor and acute tubular necrosis requiring CVVHDF Polymicrobial infection | [97] |
9 | N = 13; NA, 21–72 yrs | CR PA, AB, KP, E. hormaechei | 13 cases (4 monotherapy) | None | RTI 10, IAI 2, osteo-articular 2, SSSI 1, UTI 1 | Clinical cure 54%, Clinical cure was observed among patients with cefiderocol-susceptible isolates, Mortality 23% | 10 pts in the ICU, 7 pts with immunosuppression | [100] |
10 | N = 1; M, 63 yrs | XDR PA | 1 case (1 monotherapy + metronidazole) | None | IAI, BSI | Favorable clinical evolution, and later died due to ischial eschar complication following treatment | Septic shock, diabetic foot ulcer | [101] |
11 | N = 2; M, 60 yrs, F, 70 yrs | Case 1 CR KP, PDR AB and Case 2 XDR AB, XDR PA | 2 cases (2 monotherapy) | None | BSI | Case 1: clinical improvement and clearance of XDR AB Case 2: clinical improvement and clearance of XDR AB, XDR PA Both patients died from additional complications | 2 polymicrobial cases, CRRT in both patients, Septic thrombosis post cardiothoracic surgery + myelotoxicity Persistent bacteremia | [102] |
12 | N = 10; F 60%, M 40%, Median 75.5 yrs | CR AB, SM, NDM-producing KP | 10 cases (9 monotherapy, 1 combination therapy; fosfomycin) | None | BSI 60%, VAP 40% | Clinical success 70%, Day 30 mortality 10%, 2 cases of recurrent AB BSI | 10 pts had mechanical ventilation, 2 pts with CRRT 5 pts had COVID-19, 4 pts had burns, 1 pt had colon perforation, 1 pt with cancer | [103] |
13 | N = 1; F, 10 yrs | PDR Achromobacter | 1 case (1 combination therapy; meropenem–vaborbactam + bacteriophage) | None | RTI, acute pulmonary exacerbations | Eradication, improvement in respiratory function | CF with respiratory failure, declining respiratory function | [104] |
14 | N = 1; F, 45 yrs | XDR PA | 1 case (1 monotherapy) | None | Empyema (esophageal–pleural fistula, pneumothorax) | Clinical improvement, but resistance emerged during treatment with cefiderocol | Complicated patient, cranial surgery | [105] |
15 | N = 1; M, 62 yrs | XDR AB | 1 case (1 combination therapy; colistin + daptomycin + fluconazole) | None | Empyema | Complete resolution of fever, radiological signs, pleural cavity, urine culture | Invasive ventilation, hemothorax, surgery, AKI, polymicrobial infection | [106] |
16 | N = 1; M, 46 yrs | MDR PA | 1 case (1 monotherapy + metronidazole) | None | IAI (abscess) | Clinical resolution | Hemodialysis, ESRD, polymicrobial infection | [107 |
17 | N = 1; F, 68 yrs | CR KP | 1 case (1 combination therapy; ceftazidime–avibactam, polymyxin B) | None | BSI, IAI | Eradication from blood, clinically stabilized, but fatal due to subsequent condition | Kidney transplant, ESRD, hemodialysis, polymicrobial infection | [108] |
18 | N = 1; M, adult | XDR AB, KPC KP | 1 case (1 monotherapy + linezolid) | None | VAP, BSI | Complete resolution of fever, lung infiltrates | ECMO for respiratory failure due to viral pneumonia, treatment failure on prior colistin + AKI | [109] |
19 | N = 1; F, 78 yrs | ESBL, XDR PA + rectal colonization OXA-48 KP + OXA-23/OXA-51 AB | 1 case (1 combination therapy; meropenem + colistin) | None | BSI, endocarditis | Eradication | Intermittent hemofiltration, sepsis, travel history | [110] |
20 | N = 1; M, 65 yrs | E. coli, XDR AB | 1 case (1 combination therapy; ampicillin–sulbactam + tigecycline) | None | VAP | Microbiological cure with recurrence | CVVHDF, COPD, thoraco-abdominal aortic aneurysm surgical repair | [98] |
21 | N = 24; 17 M, 7 F, median age 66.5 yrs | AB 58%, PA 42%, KP 17%, SM 8% | 24 cases (16 monotherapy, 8 combination therapy; minocycline, gentamycin, colistin, tobramycin) | None | VAP 79%, wound infection 17%, cUTI 4%, driveline infection 4%, concurrent BSI 21% | Clinical success 46%, clinical failure 54%, Day 30 ACM 42% | 5 pts had COVID-19 pneumonia, mechanical ventilation and bacterial superinfection, 8 pts received hemodialysis | [99] |
22 | N = 13; 11 M, 2 F, median age 63 yrs | 10 CR AB, 1 KPC-KP, 2 XDR PA | 13 cases (13 combination therapy; colistin, fosfomycin, tigecycline, meropenem) | None | BSI 8, VAP/ pneumonia 3, abscess 2, neurosurgical wound infection 1, perihepatic abscess 1 | All patients had clinical or microbiological cure, Day 30 ACM 23% | 7 pts had history of COVID-19, 4 pts with post-surgical infection, 4 pts with immunosuppression | [111] |
23 | N = 5; 4 M, 1 F, age 35–76 yrs | MDR & CR AB, MDR PA, CFDC-R PA | 5 cases (5 monotherapy) | None | CAP 20%, HAP 60%, sepsis 20% | Microbiological cure 60%, clinical cure 20%, death 40% | 3 pts had CVVHD, 2 pts had ECMO, 2 pts had COVID-19, 2 pts were immunocompromised, 1 PA isolate was resistant to cefiderocol prior to treatment | [53] |
24 | N = 10; 9 M, 1 F, age 33–78 yrs | XDR/DTR PA, MDR PA, MDR E. coli, MDR A. xylosoxidans | 10 cases (3 monotherapy, 7 combination therapy) | None | Bacteremia 40%, VAP 40%, other 20% | Clinical cure 90%, microbiological cure 80%, recurrence 10%, Day 30 ACM 10% | All patients were treated with CFDC as last resort, 5 pts had sepsis, 2 pts had septic shock, 1 pt had CVVHDF, 4 pts with immunosuppression | [112] |
25 | N = 1; M, 64 yrs | CR PA, SM | 1 case (1 monotherapy) | None | RTI | Clinical cure, microbiological eradication, survival | SARS-CoV-2 infection, respiratory failure, ICU admission, venovenous ECMO | [58] |
26 | N = 3; 3 M, age 45–71 yrs | 3 DTR AB, plus E. faecalis and E. faecium 1 pt, KP 1 pt | 3 cases (1 monotherapy, 2 combination therapy; fosfomycin, nebulized colistin) | None | VAP 100%, sepsis 33.3%, BSI 66.7% | Clinical improvement 100%, microbiological eradication 100%, new infection 1 pt, death 1 pt | All 3 pts had acute renal injury requiring CVVH, mechanical ventilation, septic shock, vasopressor support 1 pt had bilateral lung transplant | [113] |
27 | N = 1; M, 57 yrs | Achromobacter xylosoxidans | 1 case (1 combination therapy; fosfomycin, trimethoprim–sulfamethoxazole) | None | Endocarditis, sepsis | Clinical cure | SARS-CoV2 infection, ARDS Stage IVB Non-Hodgkin lymphoma | [114] |
28 | N = 10; 8 M, 2 F, age 30–85 yrs | 6 PA, 1 AB, 1 SM, 1 Burkholderia cenocepacia, 1 P. putida complex | 10 cases (4 monotherapy, 6 combination therapy; colistin, amikacin) | None | VAP 40%, UTI 20%, cholangitis 10%, otitis media 10%, central catheter infection 20%, secondary BSI 40% | Clinical response 20%, Microbiological failure 60%, Day 30 mortality 60% | 6 pts with septic shock, 8 pts with immunosuppression | [115] |