Table A4.
Studies using dynamic in vitro PK/PD models.
| Study-Combinations | Method | Synergy % (n/N) | Comments |
|---|---|---|---|
| Lenhard, J.R., 2017 [61,62] | |||
| PMB/MEM | HFIM | 0 (0/1) | Doses simulating human regimens were used (PMB 3.33 mg/kg then 1.43 mg/kg every 12 h, MEM 2 gr every 8 h as 3 h infusions, SAM 8/4 g every 8 h as 3 h infusions). |
| PMB/SAM | 0 (0/1) | ||
| MEM/SAM | 0 (0/1) | ||
| PMB/MEM/SAM | 100 (1/1) | ||
| Yuan, Z., 2010 [102] and Lim, T.P., 2008 [107] | |||
| AMK/LVX | HFIM | 0 (0/1) | Regrowth despite initial killing at 4 h. |
| AMK/FEP | 0 (0/1) | Regrowth despite initial killing at 4 h. | |
| Córdoba, J., 2015 [73] | |||
| CST/IMP | Other dynamic in vitro PK/PD model | 0 (0/1) | Simulation of human treatment regimens |
| CST/DAP | 100 (1/1) | ||
| IMP/ETP | 0 (0/3) | ||
| RIF/CFS | 0 (0/7) | ||
| Housman, S.T., 2013 [87] | Simulated regimens: SAM 9 g q8 h (3 h inf), DOR 2 gr q8 h (4 h inf), TGC 200 mg q12 h (0.5 h inf). | ||
| TGC/DOR | Other dynamic in vitro PK/PD model | 0 (0/2) | |
| SAM/DOR | 0 (0/3) | Increased killing with SAM/DOR vs. monotherapies against all 3 strains but with regrowth by 24 h. | |
| SAM/TGC | 0 (0/1) | ||
| Lee, H.J., 2013 [88] | |||
| CST/RIF | Other dynamic in vitro PK/PD model | 100 (1/1) | Regimens mimicking human serum concentration after usual doses in critically-ill patients. |
Abbreviations: AMK = amikacin, CFS = cefoperazone/sulbactam, CHBD = checkerboard assay, CST = colistin, CZA = ceftazidime/avibactam, DAP = daptomycin, DOR = doripenem, ETP = ertapenem, FEP = cefepime, FOF = fosfomycin, HFIM = hollow-fiber infection model, IMP = imipenem, LVX = levofloxacin, MEM = meropenem, n/N = number of isolates against which synergy was demonstrated/total number of eligible isolates, PK/PD = pharmacokinetic/pharmacodynamic, PMB = polymyxin-B, RIF = rifampicin, SAM = ampicillin/sulbactam, TGC = tigecycline.