Table 3.
In vitro activities of ceftaroline-avibactam and selected antimicrobial agents tested against a well-characterized collection of β-lactamase-producing Enterobacteriaceae, non-fermentative Gram-negative bacilli, and S. aureus strains, including MRSA strains
| Organism or group, enzyme(s) (no. of strains tested), and antimicrobial agent | MIC (μg/ml) |
% Susceptible/% resistanta by: |
|||
|---|---|---|---|---|---|
| 50% | 90% | Range | CLSI | EUCAST | |
| Enterobacteriaceae | |||||
| ESBL (33) | |||||
| Ceftaroline-avibactam | 0.12 | 0.25 | ≤0.015–1 | NA | NA |
| Ceftaroline | >64 | >64 | 0.25–>64 | 3.0/97.0b | NA |
| Ceftriaxone | >32 | >32 | ≤0.25–>32 | 3.0/93.9 | 3.0/93.9 |
| Ceftazidime | >16 | >16 | ≤16–>16 | 30.3/63.6 | 27.3/69.7 |
| Meropenem | ≤0.12 | ≤0.12 | ≤0.12–0.25 | 100.0/0.0 | 100.0/0.0 |
| Piperacillin-tazobactam | 16 | >64 | ≤8–>64 | 54.5/27.3 | 30.3/45.5 |
| Gentamicin | ≤4 | >8 | ≤4–>8 | 75.8/18.2 | 69.7/24.2 |
| Levofloxacin | >4 | >4 | ≤0.5–>4 | 42.4/51.5 | 39.4/57.6 |
| Plasmid-mediated AmpC (36) | |||||
| Ceftaroline-avibactam | 0.12 | 0.25 | 0.06–1 | NA | NA |
| Ceftaroline | 16 | 64 | 4–>64 | 2.8/97.2b | NA |
| Ceftriaxone | 16 | >32 | 8–>32 | 0.0/88.9 | 0.0/88.9 |
| Ceftazidime | >16 | >16 | 16–>16 | 5.6/94.4 | 0.0/94.4 |
| Meropenem | ≤0.12 | 0.12 | ≤0.06–0.25 | 100.0/0.0 | 100.0/0.0 |
| Piperacillin-tazobactam | 16 | >64 | 2–>64 | 63.9/25.0 | 44.4/36.1 |
| Gentamicin | ≤4 | >8 | ≤2–>8 | 72.2/13.9 | 44.4/27.8 |
| Levofloxacin | >4 | >4 | ≤0.5–>4 | 41.7/52.8 | 41.7/58.3 |
| Ceftazidime-resistant AmpC-producing speciesb (27) | |||||
| Ceftaroline-avibactam | 0.12 | 0.5 | 0.03–0.5 | NA | NA |
| Ceftaroline | 64 | >64 | 0.25–>128 | 0.0/100.0b | NA |
| Ceftriaxone | 32 | >32 | ≤8–>32 | 0.0/100.0 | 0.0/100.0 |
| Ceftazidime | >16 | >16 | ≤16–>16 | 0.0/100.0 | 0.0/100.0 |
| Meropenem | ≤0.06 | 0.12 | ≤0.12–0.12 | 100.0/0.0 | 100.0/0.0 |
| Piperacillin-tazobactam | 64 | >64 | ≤8–>64 | 14.8/44.4 | 14.8/85.2 |
| Gentamicin | ≤2 | >8 | ≤4–>8 | 74.1/18.5 | 74.1/25.9 |
| Levofloxacin | ≤0.5 | >4 | ≤0.5–>4 | 77.8/18.5 | 70.4/22.2 |
| Carbapenemase (32) | |||||
| Ceftaroline-avibactam | 0.5 | 2 | 0.06–4 | NA | NA |
| Ceftaroline | >64 | >64 | 2–>64 | 0.0/100.0b | NA |
| Ceftriaxone | >32 | >32 | 0.5–>32 | 6.3/93.8 | 6.3/93.8 |
| Ceftazidime | >16 | >16 | ≤16–>16 | 6.3/87.5 | 3.1/93.8 |
| Meropenem | >8 | >8 | ≤0.06–>8 | 9.4/84.4 | 15.6/53.1 |
| Piperacillin-tazobactam | >64 | >64 | 32–>64 | 0.0/93.8 | 0.0/100.0 |
| Gentamicin | 8 | >8 | ≤2–>8 | 48.4/45.2 | 35.5/51.6 |
| Levofloxacin | >4 | >4 | ≤0.5–>4 | 37.0/59.3 | 22.2/63.0 |
| Carbapenemase in AmpC-producing speciesb (37) | |||||
| Ceftaroline-avibactam | 1 | 2 | 0.06–4 | NA | NA |
| Ceftaroline | >64 | >64 | ≤0.12–>64 | 2.7/86.5b | NA |
| Ceftriaxone | >32 | >32 | ≤8–>32 | 18.9/81.1 | 18.9/81.1 |
| Ceftazidime | >16 | >16 | ≤16–>16 | 18.9/78.4 | 18.9/81.1 |
| Meropenem | 8 | >8 | 0.12–>8 | 2.7/83.8 | 16.2/40.5 |
| Piperacillin-tazobactam | >64 | >64 | 1–>64 | 24.3/70.3 | 24.3/75.7 |
| Gentamicin | 8 | >8 | ≤2–>8 | 38.9/44.4 | 36.1/61.1 |
| Levofloxacin | 4 | >4 | ≤0.5–>4 | 39.4/48.5 | 27.3/60.6 |
| Metallo-β-lactamase (8) | |||||
| Ceftaroline-avibactam | >32 | – | >32 | NA | NA |
| Ceftaroline | >128 | – | 32–>128 | 0.0/100.0b | NA |
| Ceftriaxone | >32 | – | 16–>32 | 0.0/100.0 | 0.0/100.0 |
| Ceftazidime | >32 | – | 32–>32 | 0.0/100.0 | 0.0/100.0 |
| Meropenem | 8 | – | 1–>8 | 12.5/75.0 | 25.0/37.5 |
| Piperacillin-tazobactam | 64 | – | 32–>64 | 0.0/50.0 | 0.0/100.0 |
| Gentamicin | ≤2 | – | ≤2–>8 | 75.0/12.5 | 75.0/25.0 |
| Levofloxacin | 1 | – | ≤0.5–>4 | 62.5/37.5 | 50.0/37.5 |
| Multiple β-lactamases (57) | |||||
| Ceftaroline-avibactam | 0.12 | 0.5 | ≤0.015–2 | NA | NA |
| Ceftaroline | >64 | >64 | 4–>64 | 0.0/100.0b | NA |
| Ceftriaxone | >32 | >32 | ≤0.25–>32 | 3.5/94.7 | 3.5/94.7 |
| Ceftazidime | >16 | >16 | ≤16–>16 | 29.8/70.2 | 12.3/70.2 |
| Meropenem | ≤0.12 | ≤0.12 | ≤0.12–4 | 98.2/1.8 | 98.2/0.0 |
| Piperacillin-tazobactam | 16 | >64 | ≤8–>64 | 52.6/35.1 | 43.9/47.4 |
| Gentamicin | >8 | >8 | ≤4–>8 | 38.6/50.9 | 35.1/61.4 |
| Levofloxacin | 4 | >4 | ≤0.5–>4 | 47.4/47.4 | 42.1/52.6 |
| Multiple β-lactamases, including KPC (15) | |||||
| Ceftaroline-avibactam | 0.5 | 2 | 0.25–4 | NA | NA |
| Ceftaroline | >64 | >64 | 64–>64 | 0.0/100.0b | NA |
| Ceftriaxone | >32 | >32 | 16–>32 | 0.0/100.0 | 0.0/100.0 |
| Ceftazidime | >16 | >16 | 16–>16 | 0.0/100.0 | 0.0/100.0 |
| Meropenem | >8 | >8 | 4–>8 | 0.0/100.0 | 0.0/66.7 |
| Piperacillin-tazobactam | >64 | >64 | >64 | 0.0/100.0 | 0.0/100.0 |
| Gentamicin | 4 | >8 | ≤2–>8 | 53.3/20.0 | 33.3/46.7 |
| Levofloxacin | >4 | >4 | ≤0.5–>4 | 20.0/80.0 | 13.3/80.0 |
| Multiple β-lactamases in AmpC-producing speciesb (27) | |||||
| Ceftaroline-avibactam | 0.5 | 2 | 0.12–4 | NA | NA |
| Ceftaroline | 256 | >256 | 1–>256 | 0.0/96.3b | NA |
| Ceftriaxone | >32 | >32 | 16–>32 | 0.0/100.0 | 0.0/100.0 |
| Ceftazidime | 256 | >256 | 1–>256 | 14.8/81.5 | 3.7/85.2 |
| Meropenem | ≤0.12 | 0.5 | ≤0.12–>8 | 96.3/3.7 | 96.3/3.7 |
| Piperacillin-tazobactam | 32 | >64 | ≤8–>64 | 37.0/25.9 | 33.3/63.0 |
| Gentamicin | >8 | >8 | ≤2–>8 | 25.9/59.3 | 14.8/74.1 |
| Levofloxacin | 4 | >4 | ≤0.5–>4 | 44.4/48.1 | 40.7/55.6 |
| P. aeruginosa (25) | |||||
| Ceftaroline-avibactam | 16 | >32 | 2–>32 | NA | NA |
| Ceftaroline | >64 | >64 | 8–>64 | NA | NA |
| Ceftriaxone | >32 | >32 | 16–>32 | 0.0/86.4b | NA |
| Ceftazidime | >16 | >16 | ≤16–>16 | 8.0/56.0 | 8.0/92.0 |
| Meropenem | >8 | >8 | 0.25–>8 | 28.0/68.0 | 28.0/56.0 |
| Piperacillin-tazobactam | 64 | >64 | 4–>64 | 36.0/44.0 | 36.0/64.0 |
| Gentamicin | >8 | >8 | ≤2–>8 | 41.2/52.9 | 41.2/58.8 |
| Levofloxacin | 4 | >4 | ≤0.5–>4 | 41.2/47.1 | 41.2/58.8 |
| Acinetobacter spp. (24) | |||||
| Ceftaroline-avibactam | 32 | >32 | 0.5–>32 | NA | NA |
| Ceftaroline | >64 | >64 | 1–>64 | NA | NA |
| Ceftriaxone | >32 | >32 | ≤8–>32 | 25.0/66.7 | NA |
| Ceftazidime | >16 | >16 | ≤16–>16 | 8.3/62.5 | NA |
| Meropenem | >8 | >8 | ≤0.12–>8 | 29.2/62.5 | 29.2/62.5 |
| Piperacillin-tazobactam | >64 | >64 | ≤0.5–>64 | 29.2/70.8 | NA |
| Gentamicin | >8 | >8 | ≤2–>8 | 41.7/58.3 | 41.7/58.3 |
| Levofloxacin | >4 | >4 | ≤0.5–>4 | 29.2/66.7 | 29.2/70.8 |
| S. aureus (110) | |||||
| Ceftaroline-avibactam | 1 | 2 | 0.25–4 | NA | NA |
| Ceftaroline | 1 | 2 | 0.25–4 | 75.4b,c,d | NA |
| Ceftriaxone | >32 | >32 | ≤8–>32 | 0.0/90.9 | 9.1/90.9 |
| Ceftazidime | >16 | >16 | ≤16–>16 | 0.0/90.9 | 9.1/90.9 |
| Meropenem | 8 | >8 | ≤0.12–>8 | 9.1/90.9 | 9.1/90.9 |
| Piperacillin-tazobactam | 64 | >64 | ≤0.5–>64 | 9.1/90.9 | 9.1/90.9 |
| Imipenem | 8 | >8 | ≤0.12–>8 | 9.1/90.9 | 9.1/90.9 |
| Vancomycin | 1 | 1 | 0.25–2 | NA | NA |
a
Results obtained by the criteria published by the CLSI (2012) (6) or EUCAST (2011) (9a). β-Lactam susceptibility should be guided by the oxacillin test results for S. aureus. NA, not available.
b
U.S. FDA breakpoints were applied (Rocephin package insert, 2010; Genentech, Inc.) for comparison purposes.
c
All S. aureus isolates with SCCmec type IV were susceptible to ceftaroline.
d
Percentage of susceptible isolates.