TABLE 7.
Studies evaluating CAZ-AVI for MDR Enterobacterales and P. aeruginosa infections
| Study ID; main pathogen(s) tested (reference)a | Design | No. included (p/i)b | Comp (no. [%]) | No. and source(s) of infectionc | No. of isolates by type | No. of isolates by susceptibility | No. with combination treatment | Outcomes (no. [%])d |
|---|---|---|---|---|---|---|---|---|
| Enterobacterales | ||||||||
| Caston 2017; CRE CPE in hematological patients (315) | Retrospective comparative study | 31 p with hematological malignancy, 8 C-A, 23 comp | Combination in 17/23 (94)e | 31 BSI | C-A: 7 Klebsiella spp., 1 E. coli; comp: 20 Klebsiella spp., 2 S. marcescens, 1 E. cloacae | All CPE, C-A: 5 OXA-48, 3 KPC; comp: 14 OXA-48, 9 KPC | All 8 in the C-A group |
Mortality: C-A, 2/8 (25); comp, 12/23 (52.2) Clinical cure 14 days: 6/8 (75) vs 8/23 (34.8) |
| King 2017; CRE (93) | Retrospective study | 60 p | 23 BSI, 17 UTI, 16 LRTI, 4 IAI, 10 others | 50 K. pneumoniae, 5 E. coli, 5 others | CRE, mechanism not reported | 19 |
Mortality: 19/60 (32) Clinical cure EOT: 9/60 (65) Microbiol cure EOT: 2/60 (53) |
|
| Shields 2017; CRE (∼80% CPE) (74) | Retrospective study | 37 p, 37 i | 10 BSI, 4 UTI, 4 IAI, 12 LRTI, 4 SSTI, 3 others | 31 K. pneumoniae, 3 E. coli; 3 Enterobacter spp. | All CRE, 29 KPC | 11 |
Mortality: 9/37 (24.3) Clinical success 30 days: 22/37 (59) Microbiol cure 7 days: 27/37 (73) |
|
| Shields 2017; CRE CPE, KPC (92) | Retrospective study | 109 p, 13 C-A, 96 comp | Combination in 67/96 (70)c | 109 BSI | K. pneumoniae | CRE KPC, C-A: 9 KPC-2, 4 KPC-3; comp, 72 KPC-2, 21 KPC-3 | 5 |
Mortality: C-A, 1/13 (7.7%); comp, 30/96 (31.3) Clinical success 30 days: C-A, 5/13 (38.4); comp, 39/96 (40.6) |
| Temkin 2017; CRE CPE, KPC, OXA-48 (316) | Case series (salvage treatment C-A) | 38 p, 38 i | IAI mostly, 26 BSI | 36 p CRE infection (35 Klebsiella sp., 1 E. coli), 2 p with CRf P. aeruginosa | 23 KPC, 13 OXA-48, 2 P. aeruginosa | 25 |
Mortality: 15/38 (39.5) Clinical cure: 26/38 (68.4) Microbiol cure: 24/38 (63.2) |
|
| Sousa 2018; CRE CPE, OXA-48-producing Enterobacterales (317) | Prospective study (noninterventional) | 57 p | 16 IAI, 15 LRTI, 14 UTI, 26, BSI, 6 others | 54 K. pneumoniae, 2 E. coli, 1 Enterobacter cloacae | OXA-48 | 11 |
Mortality: 13/57 (22) Clinical cure 7 days: 44/57 (77) Microbiol cure 7 days: 37/57 (65) |
|
| van Duin 2018; CRE CPE (90) | Prospective comparative study (noninterventional) | 38 p C-A, 99 p colistin | Colistin | 63 BSI (15 C-A, 48 colistin), 30 LRTI (9 C-A, 21 colistin), 44 others | K. pneumoniae: 37 C-A, 96 colistin 96; Enterobacter sp.: 1 C-A, 3 colistin | 54 isolates tested: 28 KPC-2 (52%), 24 KPC-3 (44%) | 24 C-A, 93 colistin | Mortality: C-A, 3/38 (8); colistin, 33/99 (33) |
| Alraddadi 2019; CRE CPE (32) | Retrospective comparative study | 38 p: 10 p C-A, 28 p comp | Combination in 25/28 (89)c | C-A: 5 LRTI, 3 UTI, 3 IAI, 2 SSTI, 7 BSI; comp: 14 LRTI, 8 UTI, 5 IAI, 3 SSTI, 15 BSI | K. pneumoniae: 7 C-A, 3 comp; E. coli: 3 C-A, 5 comp | OXA-48-8 C-A: 19 comp; NDM: 1 C-A, 5 comp; NDM+OXA-48: 0 C-A, 1 comp; no carbapenemase gene: 1 C-A, 3 comp | None |
Mortality: C-A, 5/10 (50); comp, 16/28 (57.1) Clinical cure 30 days: C-A, 4/10 (40); comp, 11/28 (39) |
| De la Calle 2019; CRE CPE, OXA-48 (33) | Retrospective study | 23 p, 24 e (9 salvage) | 7 IAI, 6 UTI, 5 LRTI, 5 other, 6 BSI | 23 e K. pneumoniae, 1 e E. coli | OXA-48 | 10 e |
Mortality: 2/23 (8) Clinical cure 30 days: 15/23 (65.2) |
|
| Guimaraes 2019; CRE CPE, KPC2 coresistant to polymyxin (98) | Case series (salvage treatment C-A) | 29 p, 30 i | 12 BSI, 8 UTI, 2 IAI, 3 LRTI, 2 SSTI | 28 K. pneumoniae, 2 S. marcescens, KPC-2 producers | All KPC-2, coresistant to carbapenems and polymyxin | 14 |
Mortality: 15/29 (51.7) Clinical success EOT: 24/29 (82.7) Microbiol success EOT: 12/29 (41.3) |
|
| Iannaccone 2019; CRE CPE, KPC (109) | Retrospective study | 23 p | 23 BSI | K. pneumoniae | All KPC, K. pneumoniae | 20 |
Mortality: 6/23 (26) Clinical cure in-hospital: 17/23 (73.9) |
|
| Tsolaki 2019; CRE CPE, KPC (91) | Retrospective comparative study | 41 C-A vs 36 BAT | Combination in 35/36 (97)c | C-A: 22 BSI, 19 LRTI, 4 IAI, 3 other; comp: 28 BSI, 7 LRTI, 4 IAI, 2 other | K. pneumoniae | C-A all KPC, BAT, 31/36 p KPC; colistin-susceptible/C-A 17/41, comp 31/36 | 32 |
Mortality: C-A, 6/41 (15); comp, 14/36 (38) Clinical cure 10 days: C-A, 33/41 (80.4); comp, 19/36 (52.8) Microbiol cure 10 days: C-A, 33/35 (94.3); comp, 21/31 (67.7) |
| Tumbarello 2019; CRE CPE (318) | Retrospective comparative study, salvage treatment | 138 p C-A, 104 p BSI, matched 104 p BSI comp | Combination in 77/104 (74)c | 104 BSI, 13 LRTI, 12 IAI, 9 UTI, 3 other | K. pneumoniae | CPE | 109 |
Mortality: 47/138 (34.1) Mortality BSI, 38/104 (36.5); comp, 58/104 (55.7) |
| Enterobacterales and P. aeruginosa | ||||||||
| Jorgensen 2019; CRE and any Pseudomonas spp. (88) | Retrospective study | 203 p | 76 LRTI, 40 UTI, 38 IAI, 39 other, 22 BSI | 159 Enterobacteriaceae (78.3%), 63 Pseudomonas sp. (31.0%) | 117 CRE, 63 any Pseudomonas | 65 (45 CRE, 20 P. aeruginosa) |
Mortality: CRE, 19/117 (16.2); P. aeruginosa, 11/63 (17.5) Clinical response 30 days: CRE, 83/117 (70.9); P. aeruginosa, 44/63 (69.8) |
|
| Rodriguez-Nunez 2018; MDR and XDR P. aeruginosa (89) | Case series | 8 p | 5 LRTI, 3 others, 3 BSI | P. aeruginosa | MDR and XDR | 5 |
Mortality: 1/8 (12.5) Clinical cure: 4/8 (50) |
|
| Stone 2018; MDR Enterobacteriaceae and P. aeruginosa (84) | Post hoc analysis of 5 RCTs | 1,146 p: 565 p C-A, 581 p comp | Carbapenem | C-A: 181 IAI, 237 UTI, 56 LRTI; comp: 207 IAI, 184 UTI, 59 LRTI | E. coli: 323 C-A, 329 other; K. pneumoniae: 123 C-A, 153 other; E. cloacae: 29 C-A, 29 comp; other Enterobacterales: 31 C-A, 28 comp; P. aeruginosa: 56 C-A, 39 comp | MDR Enterobacteriaceae and P. aeruginosa | None |
Clinical cure TOC, Enterobacterales: C-A, 478/560 (85.4); comp, 508/578 (87.9); P. aeruginosa: C-A, 32/56 (57.1), comp, 21/39 (53.8) Microbiol response TOC: C-A, 399/509 (78.4); comp, 388/542 (71.6) |
a
CPE, carbapenem-producing Enterobacterales; CRE, carbapenem-resistant Enterobacterales; KPC, Klebsiella pneumonia carbapenem producing; MDR, multidrug resistant; XDR, extensively drug resistant.
b
p, patient; i, isolate; e, episode; C-A, ceftazidime-avibactam; comp, comparator; BAT, best available therapy; BSI, bloodstream infection.
c
LRTI, lower respiratory tract infection; UTI, urinary tract infection; IAI, intra-abdominal infection; SSTI, skin and soft tissue infection.
d
Microbiol, microbiological; EOT, end of treatment; TOC, test of cure.
e
Combinations or monotherapy with any of aminoglycosides, carbapenems, tigecycline, and/or colistin, and less common fosfomycin, quinolones, trimethoprim-sulfamethoxazole, and aztreonam (1 [3.6%]).
f
CR, carbapenem resistant.