TABLE 15.
β-Lactam–β-lactamase inhibitor combinations in development processa
| Drug | Spectrum of activity (references) | Limitations in spectrum (reference[s])b | Tested for:c | Dosed |
|---|---|---|---|---|
| Cefepime-tazobactam | Enterobacterales, including those with β-lactamases: class A, ESBL, K1; class B, VIM (∼75%); class C, AmpC; class D, OXA-48 (232, 233) | No activity against class B except VIM; KPC mostly R; For P. aeruginosa, same activity as meropenem (232, 233) | cUTI | 2 g/2 g every 8 h |
| Cefepime-enmetazobactam | Enterobacterales, including those with β-lactamases: class A, ESBL, some KPC (limited evidence); class C, AmpC; class D, OXA-48 (limited evidence) (239, 323) | No activity against class B; no additional coverage for P. aeruginosa over cefepime (239, 323) | cUTI | 2 g/500 mg every 8 h |
| Cefepime-zidebactam | Enterobacterales, including those with β-lactamases: class A, ESBL, KPC; class B, MBLs (IMP, VIM, NDM); class C, AmpC; class D, OXA-48; highly active against P. aeruginosa, including carbapenem R (243, 244, 324) | Activity against Acinetobacter spp. probably limited (244) | NA | NA |
| Aztreonam-avibactam | Enterobacterales, including those with β-lactamases: class A, ESBL, KPC; class B, any MBL; class C, AmpC; class D, OXA-48 (248–250) | No enhanced activity over aztreonam alone for P. aeruginosa; no in vitro activity against A. baumannii (248–250) | HABP/VABP, cUTI |
CrCL >50 ml/min: LD, 500 mg/167 mg; ELD, 1,500 mg/500 mg; MD, 1,500 mg/500 mg every 6 h CrCL 31–50 ml/min: LD, 500 mg/167 mg; ELD, 1,500 mg/500 mg; MD, 750 mg/250 mg every 6 h CrCL 16–30 ml/min: LD, 675 mg/225 mg; ELD, 675 mg/225 mg; MD, 675 mg/225 mg every 8 h |
| Sulbactam-durlobactam | Acinetobacter baumannii, including carbapenem R (256) | Limited data on potential activity against Enterobacterales (255) | Any UTI; HABP/VABP, BSI caused by A. baumannii | 1 g/1 g every 6 h |
| Meropenem-nacubactam | Potential activity against Enterobacterales, including those with β-lactamases: class A, ESBL, KPC; class B, NDM; class C, AmpC; class D, OXA-48 (259, 262, 264) | For Pseudomonas and Acinetobacter spp., similar activity to meropenem (264) | NA | NA |
| Cefpodoxime proxetil-ETX0282 | Potential activity against Enterobacterales, including those with β-lactamases: class A, ESBL, KPC; class C, AmpC; class D, OXA-48 (265–267) | No activity described for P. aeruginosa or A. baumannii (265–267) | NA | NA |
| Cefepime-taniborbactam (VNRX-5133) | Potential activity against Enterobacterales, including those with β-lactamases: class A, ESBL, KPC; class B, VIM, NDM, SPM-1, and GIM-1 (but not IMP-1); class C, AmpC; class D, OXA-48; P. aeruginosa, cefepime and carbapenem R (268–270) | cUTI | NA |
a
Data are limited by the fact that there are few available studies to date.
b
R, resistant.
c
cUTI, complicated urinary tract infection; HABP/VABP, hospital-acquired and ventilator-associated bacterial pneumonia; BSI, bloodstream infection; NA, nonapplicable.
d
LD, loading dose; ELD, extended loading dose; MD, maintenance dose; CrCL, creatinine clearance.