Table 1.
Comparative in vitro activity of meropenem/vaborbactam against Gram-negative clinical isolates
| Pathogen | No. of isolatesa | MEV MIC90a μg/mL | MEV %Sa,b US FDA | MEM MIC90a μg/mL | MEM %Sa,c CLSI/EUCAST | TZP MIC90a μg/ml | TZP %Sa,c CLSI/EUCAST |
|---|---|---|---|---|---|---|---|
| Enterobacteriaceae [25–31] | 46,769 | 0.03 to 0.06 | 98.7–100 | 0.06 | 96.6–98.7/96.9–98.4 | 8–16 | 92.0–93.2/88.8–89.0 |
| Klebsiella pneumonia [25–29] | 5876 | 0.03–0.12 | 97.0–100 | 0.03–0.12 | 88.3–94.3/93.0–95.0 | 32 to > 64 | 87.8–88.2/80.7–82.4 |
| Escherichia coli [25–29] | 11,514 | ≤ 0.015 to 0.03 | 99.8–100 | 0.03 | 99.7–99.8/99.7 | 8 | 94.7–95.7/91.2–93.3 |
| Enterobacter cloacae spp. [25–28] | 2572 | 0.03 | 99.8–100 | 97.2/NR | |||
| CRE [25–29, 31] | 1003 | 0.5–32d | 66.2–100e | > 32 | 0–3.1/6.0–10.4 | > 64 to > 128 | 0–3.0/0–6.7 |
| Serine-CPE [21] | 315 | 1 | 97.8 | > 64 | 2.2/7.3 | ||
| MDR [25] | 1210 | 1 | 32 | 77.7/80.2 | > 64 | 36.6/28.7 | |
| XDR [25] | 161 | 32 | > 32 | 13.0/19.9 | > 64 | 2.5/2.5 | |
| ESBL-phenotype | |||||||
| Enterobacteriaceae [27] | 99 | 0.12 | 100 | 16 | 83.8/85.9 | > 64 | 65.7/50.5 |
| Klebsiella pneumonia [27] | 33 | 0.5 | 100 | ||||
| E. coli [27, 29] | 148 | 0.03 | 100 | 0.06 | 83.7–96.5/NR | 32 | 83.7/NR |
| KPC-producing | |||||||
| Enterobacteriaceae [25, 30, 33, 34] | 1404 | 0.5–8 | 99.0–99.3 | > 32 to > 64 | 0–0.7/3.4–5.2 | > 64 | 0.7/0.7 |
| CRE [28] | 206 | 1 | 99.5 | >32 | 1.9/7.3 | ||
| K. pneumonia [21, 24, 33] | 1207 | 0.5–1 | 96.6–98.9 | >32 to > 64 | 0–7.0/2.4 | ||
| E. coli [21, 33] | 56 | ≤ 0.03 to ≤ 0.06 | 100 | 8–16 | 0–19.1/38.1 | ||
| E. cloacae [21] or Enterobacter spp. [33]f | 68 | 0.12–0.25 | 100 | ≥32 | 0–2.6/10.3 | ||
| non-KPC-producing CRE [25, 28] | 250 | >32 | 31.4 | > 32 | 1.7–3.1/1.7–5.0 | > 64 | 5.4/4.7 |
| CNE [25] | 63 | 4 | 16 | 3.2/7.9 | > 64 | 9.5/7.9 | |
| MBL-producing CREg [28, 30] | 111 | > 32 | 3.8–18.6 | > 32 | 0–8.5/0–1.7 |
Assessed using CLSI broth microdilution methods; agar dilution method used for comparators in one study [24]. Clinical isolates were collected in the USA (2014 [27, 29], 2015 [26]), Europe (2014–2015 [30]), New York city (2013–2014 [24]), China (2006–2012 [34]) and worldwide (2000–2013 [21], 2014 [25], 2014–2015 [33], 2015 [28]). Some data available only as abstract and/or posters [26, 27, 29, 30, 34]
CLSI Clinical and Laboratory Standards Institute, CNE carbapenemase-negative Enterobacteriaceae, CPE carbapenemase-producing Enterobacteriaceae, CRE carbapenem-resistant Enterobacteriaceae, ESBL Extended-Spectrum β-Lactamase, EUCAST European Committee on Antimicrobial Susceptibility Testing, KPC Klebsiella pneumoniae carbapenemase, MDR multidrug resistant, MEM meropenem, MEV meropenem/vaborbactam, MIC90 minimum inhibitory concentration required to inhibit 90% of isolates, NR not reported, S susceptible, TZP piperacillin/tazobactam, XDR extensively drug resistant, MBL metallo-β-lactamase
aAcross all studies; MIC90 and susceptibility not reported for all studies
bSusceptibility estimated based on US FDA susceptibility interpretive criteria
cAccording to CLSI or EUCAST breakpoints
dMIC90 (no. of isolates): 0.5–2.0 µg/mL (n = 15–96) [26, 27, 29], 32 µg/mL (n = 265 [25] and 330 [28]) and NR (n = 281) [31]
eSusceptibility (no. of isolates): 95.8–100% (n = 15–96) [26, 27, 29], 73.9% (n = 330) [28], 66.2% (n = 281) [31] and NR (n = 265) [25]
fIncluding 17 E. cloacae isolates
gIncluding 49 NDM, one IMP-64 and two VIM-producers [28], and 41 NDM-1 and 18 VIM-like producers [30]