Table 2 Summary of included studies
From: Real-world use of ceftolozane/tazobactam: a systematic literature review
Citation, study design, location | N C/T | Patient/infection description | Disease severity | C/T treatment | Outcome, % (n/N) | ||
|---|---|---|---|---|---|---|---|
Clinical | Micro | Mortality | |||||
2020 Studies | |||||||
Peer-reviewed literature | |||||||
Bassetti et al. 2020 [18] Retrospective, multicenter Italy | 153 | ESBL-producing Enterobacterales infections, including NP (30.0%), cUTI (22.2%), and cIAI (16.3%) | ICU N = 74 CCI mean = 4.9 | Dose C/T: 1.5 g q8h (75.0; of which 6 patients received creatinine clearance adjusted dose) or 3 g q8h (24.8%) Empiric C/T: 30.0% Confirmed C/T: 70.0% Duration: med. (range): 14 (8–25) days | 83.7 (128/153) | – | 9.8 (15/153) |
Bosaeed et al. 2020 [19] Retrospective, single center Saudi Arabia | 19 | MDR PsA infections, including NP (32%), CLABSI (21%), and ABSSSI (16%), and cIAI (16%) | ICU N = 12 | Dose C/T: 1.5 g q8h (42.1%) or 3 g q8h (10.5%) or creatinine clearance adjusted (47.4%) Duration: med. (range): 14 (7–35) days | 95 (18/19) | 74 (14/19) | 21 (4/19) |
Buonomo et al. 2020 [20] Retrospective, single center case series Italy | 4 | PsA (50% MDR; 50% XDR) cSSTI in patients with chronic kidney disease | - | Dose C/T: creatine clearance adjusted (100.0%)—0.75 g q8h (75%), 0.375 g q8h (25%) Empiric C/T: 0.0% Confirmed C/T: 100.0% Duration: med. (range): 14 (14) days | 100.0 (4/4) | - | 0 |
Jones et al. 2020 [21] Retrospective single center, case series US | 7 | PsA (57.1% non-MDR; 42.9% MDR) infections (one patient also had an E. coli infection), including pneumonia (42.9%), cUTI (28.6%), and bacteremia (14.3%) | – | Dose C/T: 4.5 g qd (CI; 85.7%), 9 g qd (CI; 14.3%) Duration: med. (range): 14 (6–42) days | 85.7 (6/7) | 100.0 (3/3) | 0a |
Jorgensen et al. 2020 [22] Retrospective, multicenter US | 259 | MDR gram-negative infections (91.1% PsA; 23.2% Enterobacterales) including, RTIs (62.9%), SSTIs (10.8%), and UTIs (10.0%). Patients with MDR PsA infections (N = 226) were used as the primary analysis set | ICU N = 131 IMC N = 23 APACHE II med. = 21 CCI med. = 3 SOFA med. = 5 | Dose C/T: 1.5 g q8h (36.3%) or 3 g q8h (63.7%), creatinine clearance adjusted (30.5%) Duration: med. (IQR): 10 (6–15) days | MDR PsA (N = 226) Clinical failure: 37.6 (85/226) | - | MDR PsA (N = 226) 17.3 (39/226) |
Vena et al. 2020 [23] Retrospective, multicenter, case–control Italy | 16 | Drug-resistant PsA (62.5% MDR; 37.5% XDR) pneumonia and bacteremia | ICU N = 2 | Duration: mean (SD): 12.1 (5.8) days | 81.3 (13/16) | - | 18.8 (3/16) |
Conference proceedings | |||||||
Caffrey et al. 2020 [80] Retrospective, multicenter, cohort US | 57 | MDR PsA infections, including RTIs (36.8%), UTIs (22.8%), and SSTIs (17.5%) | ICU N = 36 APACHE II med. = 40 CCI med. = 4 | Duration med. (IQR): 12 (5–18) days | - | 31.0 (13/42) | 17.5 (10/57) |
Gudiol et al. 2020 [79] Retrospective, multicenter International | 31 | PsA (90.3% MDR; 41.9% XDR) bloodstream infections in neutropenic cancer patients | ICU N = 7 IMC N = 31 | Empiric C/T: 25.8% Confirmed C/T: 96.8% | - | - | 16.1 (5/31) |
2019 studies | |||||||
Peer-reviewed literature | |||||||
Bassetti et al. 2019 [25] Retrospective, multicenter Italy | 101 | PsA (70% drug resistant) infections, including NP (31.7%), ABSSSI (20.8%), and cUTI (13.9%) | ICU N = 24 CCI mean = 4.4 | Dose C/T: 1.5 g q8h (69.3%) or 3 g q8h (30.7%) Duration: med. (range): 14 (9–23) days | 83.2 (84/101) | - | 5.0 (5/101) |
Fernández-Cruz et al. 2019 [26] Retrospective, single center, case–control Spain | 19 | PsA (52.6% MDR; 47.4% XDR) infections, including pneumonia (26.3%), catheter-related BSI (21.1%), and primary BSI (21.1%) in patients with hematological malignancy | ICU N = 5 IMC N = 19 CCI mean = 3.0 SOFA mean = 5.4 | Empiric C/T: 15.8% Confirmed C/T: 84.2% Duration: med. (range): 14 (7–18) days | 89.5 (17/19) | - | 5.3 (1/19) |
Gerlach et al. 2019 [24] Retrospective, single center US | 18 | MDR PsA osteomyelitis | ICU N = 11 APACHE II med. = 13.5 CCI med. = 5.5 | Dose C/T: 1.5 g q8h (27.7%) or 3 g q8h (55.6%), or creatinine clearance adjusted (16.7%) Empiric C/T: 0.0% Confirmed C/T: 100.0% Duration: med. (range): 39 (3–98) days | 50.0 (9/18) | 75.0 (3/4) | 22.2 (4/18) |
Pogue et al. 2019 [27] Retrospective, multicenter, case–control US | 100 | MDR or XDR PsA infections, including NP (VABP [52.0%], HABP [12.0%]), cUTIs (16.0%), and wound (13.0%) | ICU N = 70 IMC N = 14 CCI mean = 3 SOFA = 8 | Dose C/T: 3 g q8h (63%), 1.5 g q8h (38%) Duration: med. (IQR): 9.5 (7–14) days | 81.0 (81/100) | - | 20.0 (20/100) |
Rodriguez-Nunez et al. 2019 [28] Retrospective, multicenter International | 90 | Drug-resistant PsA RTIs (76.7% XDR; 23.3% MDR) | CCI med. = 5 | Dose C/T: standard (1.5 g q8h or creatinine clearance adjusted; 40%), high (3 g q8h or double creatinine clearance 60%) Duration: med. (IQR): 14 (10–16) days | 56.7 (51/90) | - | 27.8 (25/90) |
Tan et al. 2019 [29] Retrospective, single center, case series US | 5 | MDR gram-negative (60% PsA; 40% A. baumannii) osteomyelitis | - | Dose C/T: 1.5 g q8h (20%), 3 g q8h (80%) Empiric C/T: 0% Confirmed C/T: 100% Duration mean: 37.8 days | 60.0 (3/5) | - | 20.0 (1/5) |
Conference proceedings | |||||||
Cabrera et al. 2019 [85] Retrospective, multicenter US | 45 | Gram-negative (84.4% PsA; 71.1% MDR PsA) infections, including pneumonia (38%), UTI (20%), wound (9%), and bone (9%) | ICU N = 19 IMC N = 6 | Empiric C/T: 21.7% Confirmed C/T: 78.3% Duration med. (IQR): 8 (4–12) days | 68.9 (31/45) | - | 0 |
Hart et al. 2019 [84] Retrospective, multicenter US | 70 | MDR PsA infections, including pneumonia (56%), wound (11%), IAI (10%) in immunocompromised patients | ICU N = 33 IMC N = 70 APACHE II med. = 18 CCI med. = 5 | Duration mean (SD): 13 (10.8) days | 69 (48/70) | - | 19 (13/70) |
Mills et al. 2019 [83] Retrospective, multicenter cohort US | 62 | MDR PsA pneumonia | ICU N = 49 IMC N = 13 | Duration mean: 16.1 days | 72.6 (45/62) | - | 29 (18/62) |
Sheffield et al. 2019 [82] Retrospective, case series US | 4 | PsA or ESBL-producing E. coli infections, including LVAD infection (50.0%), RTI (25.0%), and IAI (25.0%) | - | Dose C/T med.: 6 g CI qd Duration range: 6–91 days | - | - | 0 |
Trisler et al. 2019 [81] Retrospective, multicenter US | 35 | PsA infections, including RTI (71.4%), IAI (14.3%), and osteomyelitis (5.7%) in patients with and without CF | - | Empiric C/T: 0.0% Confirmed C/T: 100.0% Duration med. (IQR): CF = 18.5 (14–37.5) days, non-CF = 15.0 (10–25) days | Clinical failure: 54.3 (19/35) | - | - |
2018 studies | |||||||
Peer-reviewed literature | |||||||
Diaz-Cañestro et al. 2018 [30] Prospective, single center Spain | 58 | PsA (86.2% XDR) infections, including RTIs (60.3%), UTIs (17.2%), and IAIs (6.9%) | ICU N = 16 IMC N = 7 CCI med. = 4 SOFA med. = 3 | Dose C/T: 1.5 g q8h (46.6%), 3 g q8h (41.4%), 0.75 g q8h (12.1%) Empiric C/T: 1.7% Confirmed C/T: 91.4% Duration mean (SD): 11.4 (6.2) days | 63.8 (37/58) | - | 27.6 (16/58) |
Dietl et al. 2018 [31] Retrospective, single center, case series Spain | 7 | XDR PsA SSTIs (43%) and osteomyelitis (57%) | CCI med. = 6 | Dose C/T: 1.5 g q8h (43%), 0.75 g q8h (29%), 0.375 g q8h (29%) Empiric C/T: 0% Confirmed C/T: 71% Duration med. (range): SSTI 13 (4–27)/ osteo. 48 (21–66) days | 86 (6/7) | 100 (4/4) | 0 |
Escolà-Vergé et al. 2018 [32] Retrospective, single center Spain | 38 | XDR PsA infections, including RTIs (36.8%), SSTIs (15.8%), and UTIs (15.8%) | ICU N = 12 CCI med. = 3.5 | Dose C/T: 3 g q8h (60.5%), 1.5 g q8h (39.5%) Duration med. (range): 15.5 (3–62) days | 68.4 (26/38) | Micro. recur.: 31.6 (12/38) | 13.2 (5/38) |
Gallagher et al. 2018 [33] Retrospective, multicenter US | 205 | MDR PsA infections, including 59% pneumonia, UTI (13.7%), and wound (12.7%) | ICU N = 105 APACHE II med. = 19 CCI med. = 4 | Dose C/T: 3 g q8h (47.3%), 1.5 g q8h (52.7%) Duration med. (IQR): 10 (7–14) days | 73.7 (151/205) | 70.7 (145/205) | 19.0 (39/205) |
Hakki et al. 2018 [34] Retrospective, single center, case series US | 6 | 7 episodes of MDR PsA infections, including bacteremia (42.9%), pneumonia (42.9%), and soft tissue (14.3%) in patients with hematological malignancy or hematopoietic stem cell transplant | IMC N = 6 | Dose C/T: 3 g q8h (100%) Empiric C/T: 33.3% Confirmed C/T: 66.7% Duration med. (range): 29 (14–103) days | 71.4 (5/7)b | - | 0 |
Xipell et al. 2018 [35] Retrospective, single center, case series Spain | 23 | 24 episodes of MDR PsA infections, including RTI (33.3%), UTI (29.2%). and SSTI (25.0%) | ICU N = 4 | Dose C/T: 3 g q8h or 1.25 g q8h or 0.75 g q8h (% = NR) Empiric C/T: 13% Confirmed C/T: 87% Duration mean (SD): 14.3 (9.4) days | 88 (21/24) | 75 (12/16) | 22 (5/23) |
Conference proceedings | |||||||
Elabor et al. 2018 [97] Retrospective, multicenter US | 65 | MDR PsA infections, including pneumonia, wound/bone/joint infections, UTIs, and IAIs (% NR) in immunocompromised patients | ICU N = 37 IMC N = 65 APACHE II med. = 20 CCI med. = 6 | Dose C/T: 3 g q8h (35.4%), 1.5 g q8h (35.4%), < 1.5 g q8h (29.2%) | 78.4 (51/65) | 75.3 (NR) | 13.9 (9/65) |
Gioia et al. 2018 [96] Retrospective, single center Spain | 15 | MDR PsA infections, including RTI (53%), IAI (27%), and wound (13%) | ICU N = 8 IMC N = 9 CCI med. = 4 | Dose C/T: 1.5 g q8h (67%), < 1.5 g q8h (13%), 3 g q8h (20%) Duration med. (range): 23 (2–102) days | 60 (9/15) | 60 (9/15) | 27 (4/15) |
Henry et al. 2018 [95] Retrospective, single center US | 29 | 42 treatment courses for gram-negative infections (86% PsA; 7% Klebsiella spp.; 7% E. coli), including pneumonia (26%), IAIs (21%), and UTI (21%) | ICU N = 15 | Dose C/T: med. (range) = 1.5 g (0.15–3 g) q8h Empiric C/T: 36% Confirmed C/T: 64% Duration med. (range): 10 (2–85) days | 76 (32/42) | - | 38 (11/29) |
Hirsch et al. 2018 [94] Retrospective, multicenter US | 35 | Gram-negative infections (79% PsA: 60.7% MDR; 21.4% XDR), including RTIs (33%), BSIs (21%), and bone/joint infections (18%) | ICU N = 26 | Dose C/T: 3 g q8h (42.9%), 1.5 g q8h (31.4%), 0.75 g q8h (17.1%), 0.375 g q8h (2.9%), Other (5.7%) Empiric C/T: 20% Confirmed C/T: 80% | 77.4 (24/31) | 74.2 (23/31) | 14.3 (5/35) |
Jayakumar et al. 2018 [92] Retrospective, single center US | 22 | PsA (95%; 90% MDR) sepsis and/or bacteremia infections | - | Dose C/T: 3 g q8h (55%), Other (45%) Empiric C/T: 18% Confirmed C/T: 82% Duration med.: 10 days | 77 (17/22) | - | 23 (5/22) |
Jorgensen et al. 2018 [90] Retrospective, multicenter US | 116 | MDR PsA infections, including RTI (65%), UTI (10.3%), and SSTI (9.4%) | ICU N = 72 IMC N = 22 APACHE II med. = 21 CCI med. = 3.5 | - | Clinical failure: 38.8 (45/116) | - | 17.2 (20/116) |
Jorgensen et al. 2018 [91] Retrospective, multicenter US | 137 | MDR PsA infections | ICU N = 87 IMC N = 11 | - | - | - | 18.2 (25/137) |
Pogue et al. 2018 [89] Retrospective, multicenter US | 113 | PsA cUTI (64%) and cIAI (36%) | - | Empiric C/T: 31% Confirmed C/T: early definite 28% and late definite 41% | - | - | 12.4 (14/113) |
Puzniak et al. 2018 [87] Retrospective, multicenter US | 1,490 | Gram-negative infections (78% PsA [202/259 patients with microbiological results]) | ICU N = 824 CCI mean = 3 | - | - | - | 9.1 (NR) |
Puzniak et al. 2018 [88]c Retrospective, multicenter US | 199 | PsA infections, including RTIs (57%) and UTIs (17%) | ICU N = 107 CCI mean = 2.9 | Empiric C/T: 34% Confirmed C/T: early direct 50% and late direct 16% Duration med. (IQR): 8 (4–13) days | - | - | 14 (28/199) |
Tordato et al. 2018 [86] Retrospective, single center Italy | 11 | PsA infections (73% XDR), including RTIs (54%), BSIs (27%), and IAIs (18%) | ICU N = 6 IMC N = 3 CCI med. = 4 | Duration med. (range): 16 (6–27) days | 100.0 (11/11) | - | 36.4d (4/11) |
2017 studies | |||||||
Peer-reviewed literature | |||||||
Álvarez Lerma et al. 2017 [36] Retrospective, single center, case series Spain | 2 | PDR PsA ventilation-associated respiratory infections | ICU N = 2 APACHE II mean = 25.5 | Dose C/T: 1.5 g q8h then 0.75 g q8h (50%), 0.75 g q8h (50%) Empiric C/T: 0% Confirmed C/T: 100% Duration: mean = 15.5 days | 100 (2/2) | 100 (2/2) | 50 (1/2) |
Castón et al. 2017 [37] Retrospective, multicenter, case series Spain | 12 | MDR PsA infections, including RTIs (50%) and IAIs (25.0%). 83% of patients had septic shock | IMC N = 4 | Dose C/T: 1.5 g q8h (67%), 3 g q8h (33%) Empiric C/T: 0% Confirmed C/T: 100% Duration med. (range): 12 (9–18) days | 75.0 (9/12) | 63.6 (7/11) | 25.0 (3/12) |
Dinh et al. 2017 [38] Retrospective, multicenter, case series France | 15 | XDR PsA infections, including RTIs (46.7%), UTIs (20.0%), and IAIs (13.3%) | ICU N = 8 IMC N = 10 SOFA mean = 7.6 | Dose C/T: med. (range) = 6 g (3–7.5 g) Duration med. (range): 15 (4–63) days | 67 (10/15) | 75 (6/8) | 27 (4/15) |
Haidar et al. 2017 [39] Retrospective, single center, case series US | 21 | MDR PsA infections, including 86% RTIs, 5% cUTIs, 5% cIAIs, and 5% bacteremia | IMC N = 9 CCI med. = 5 SOFA med. = 6 | Dose C/T: 1.5 g q8h (48%), 0.75 g q8h (24%), 0.375 g q8h (5%), Other (23%) Duration med. (range): 14 (3–52) days | Clinical failure: 29 (6/21) | - | 10 (2/21) |
Munita et al. 2017 [40] Retrospective, multicenter US | 35 | CR PsA infections, including pneumonia (51.0%) and secondary BSI (17.1%) | CCI med. = 4 | Dose C/T: 3 g q8h (26%), 0.375–1.25 g q8h (% = NR) Duration med. (range): 16 (5–27) days | 74 (26/35) | 100 (25/25) | 22.8 (8/35) |
Sacha et al. 2017 [41] Retrospective, single center US | 49 | 60 courses of therapy for gram-negative infections (86.7% PsA: 34.6% non-MDR; 40.4% MDR; 25.0% XDR), including NP (56.7%), IAI (18.3%), and bacteremia (6.7%) | ICU N = 37 IMC N = 25 | Dose C/T: 3 g q8h (1.7%), 1.5 g q8h (51.7%), 0.75 g q8h (26.7%), 0.375 g q8h (8.3%), 0.15 g q8h (11.7%) Empiric C/T: 36.7% Confirmed C/T: 63.3% Duration med.: 1–8 dayse | 64.1f (25/39) | 38.5 (5/13) | 16.7 (10/60) |
Xipell et al. 2017 [42] Retrospective, single center, case series Spain | 3 | MDR or XDR PsA infections, including mediastinitis, liver abscess, and septic shock | - | Dose C/T: 1.5 g q8h (100%) Empiric C/T: 0% Confirmed C/T: 100% Duration mean (range): 30.3 (21–42) days | 100 (3/3) | - | 0 |
Conference proceedings | |||||||
Leuthner et al. 2017 [98] Retrospective, single center US | 30 | Gram-negative infections (93% PsA; 3% E. coli; 3% P. stuartii), including RTIs (67%), cUTIs (27%), and BSIs (20%) | ICU N = 8 IMC N = 4 | Dose C/T: 3 g q8h (57%), Other (43%) Empiric C/T: 23% Confirmed C/T: 77% Duration med.: 10 days | 80 (24/30) | 92 (11/12) | 20 (6/30) |
2016 studies | |||||||
Conference proceedings | |||||||
Iovleva et al. 2016 [100] Retrospective, single center, case series US | 2 | Imipenem-resistant PsA HCAP | APACHE II mean = 13 CCI mean = 2 | - | 100 (2/2) | 100 (2/2) | 0 |
Nathan et al. 2016 [99] Retrospective, multicenter US | 28 | Gram-negative infections (68% resistant pathogens, including 36.4% MDR PsA and 15.2% ESBL-producing E. coli), including RTI (28.6%), cIAI (25%), and cUTI (25%) | ICU N = 0 | Duration: med. = 12 days for RTI, 12 days for cIAI and 15 days for cUTI | 89 (24/27) | - | - |
2015 studies | |||||||
Peer-reviewed literature | |||||||
Gelfand et al. 2015 [43] Retrospective, single center, case series US | 3 | MDR PsA pneumonia | IMC = 2 | Dose C/T: 3 g q8h (100%) Duration mean (range): 12.7 (10–14) days | 100 (3/3) | 100 (3/3) | 0 |