TABLE 2.
Activities of ceftazidime-avibactam and comparator antimicrobial agents tested against 701 ESBL-phenotype-positive Enterobacteriaceae isolates collected from 72 U.S. hospitals located in the nine U.S. census regions
| Isolate group (no. of isolates tested) and antimicrobial agent | MIC50 (μg/ml) | MIC90 (μg/ml) | MIC range (μg/ml) | % S/% I/% R according toa: |
|
|---|---|---|---|---|---|
| CLSI | EUCAST | ||||
| KPC producers (118) | |||||
| Ceftazidime-avibactam | 0.5 | 2 | 0.06–4 | –/–/– | –/–/– |
| Ceftazidime | >32 | >32 | 16–>32 | 0.0/0.0/100.0 | 0.0/0.0/100.0 |
| Ceftriaxone | >8 | >8 | 8–>8 | 0.0/0.0/100.0 | 0.0/0.0/100.0 |
| Meropenem | >8 | >8 | 2–>8 | 0.0/4.2/95.8 | 4.2/24.6/71.2 |
| Piperacillin-tazobactam | >64 | >64 | >64 | 0.0/0.0/100.0 | 0.0/0.0/100.0 |
| Levofloxacin | >4 | >4 | ≤0.12–>4 | 10.2/1.7/88.1 | 5.9/4.3/89.8 |
| Gentamicin | 8 | >8 | ≤1–>8 | 47.5/17.8/34.7 | 32.2/15.3/52.5 |
| Tetracycline | 4 | >32 | 1–>32 | 63.6/15.2/21.2 | –/–/– |
| Tigecyclineb | 0.5 | 1 | 0.06–8 | 98.3/0.8/0.9 | 93.2/5.1/1.7 |
| CTX-M-15-like producers (288)c | |||||
| Ceftazidime-avibactam | 0.12 | 0.5 | ≤0.015–2 | –/–/– | –/–/– |
| Ceftazidime | 16 | >32 | 0.5–>32 | 14.6/14.2/71.2 | 2.8/11.8/85.4 |
| Ceftriaxone | >8 | >8 | 8–>8 | 0.0/0.0/100.0 | 0.0/0.0/100.0 |
| Meropenem | ≤0.06 | ≤0.06 | ≤0.06–2 | 99.7/0.3/0.0 | 100.0/0.0/0.0 |
| Piperacillin-tazobactam | 16 | >64 | ≤0.5–>64 | 67.2/17.3/15.5 | 48.3/18.9/32.8 |
| Levofloxacin | >4 | >4 | ≤0.12–>4 | 12.5/4.2/83.3 | 11.5/1.0/87.5 |
| Gentamicin | 2 | >8 | ≤1–>8 | 53.3/2.1/44.6 | 51.6/1.7/46.7 |
| Tetracycline | >32 | >32 | 0.5–>32 | 30.2/0.7/69.1 | –/–/– |
| Tigecyclineb | 0.12 | 1 | 0.06–4 | 98.3/1.7/0.0 | 94.8/3.5/1.7 |
| CTX-M-14-like producers (70)d | |||||
| Ceftazidime-avibactam | 0.12 | 0.25 | 0.03–1 | –/–/– | –/–/– |
| Ceftazidime | 2 | 16 | 0.12–>32 | 74.3/11.4/14.3 | 35.7/38.5/25.7 |
| Ceftriaxone | >8 | >8 | >8 | 0.0/0.0/100.0 | 0.0/0.0/100.0 |
| Meropenem | ≤0.06 | ≤0.06 | ≤0.06–0.25 | 100.0/0.0/0.0 | 100.0/0.0/0.0 |
| Piperacillin-tazobactam | 2 | 8 | ≤0.5–>64 | 92.9/2.8/4.3 | 91.4/1.5/7.1 |
| Levofloxacin | >4 | >4 | ≤0.12–>4 | 17.1/2.9/80.0 | 17.1/0.0/82.9 |
| Gentamicin | 2 | >8 | ≤1–>8 | 55.7/0.0/44.3 | 54.3/1.4/44.3 |
| Tetracycline | >32 | >32 | 0.5–>32 | 22.9/0.0/77.1 | –/–/– |
| Tigecyclineb | 0.12 | 1 | 0.06–4 | 94.3/5.7/0.0 | 94.3/0.0/5.7 |
| SHV ESBL producers (83)e | |||||
| Ceftazidime-avibactam | 0.12 | 0.25 | ≤0.015–0.5 | –/–/– | –/–/– |
| Ceftazidime | >32 | >32 | 1–>32 | 12.0/7.3/80.7 | 2.4/9.6/88.0 |
| Ceftriaxone | >8 | >8 | 0.12–>8 | 9.6/7.3/83.1 | 9.6/7.3/83.1 |
| Meropenem | ≤0.06 | 0.12 | ≤0.06–2 | 98.8/1.2/0.0 | 100.0/0.0/0.0 |
| Piperacillin-tazobactam | >64 | >64 | 1–>64 | 45.8/3.6/50.6 | 36.1/9.7/54.2 |
| Levofloxacin | >4 | >4 | ≤0.12–>4 | 39.8/7.2/53.0 | 37.3/2.5/60.2 |
| Gentamicin | 2 | >8 | ≤1–>8 | 61.4/10.9/27.7 | 51.8/9.6/38.6 |
| Tetracycline | 4 | >32 | 0.5–>32 | 55.4/9.7/34.9 | –/–/– |
| Tigecyclineb | 0.5 | 1 | 0.06–2 | 100.0/0.0/0.0 | 94.0/6.0/0.0 |
| CMY-2-like producers (54)f | |||||
| Ceftazidime-avibactam | 0.12 | 0.5 | 0.03–1 | –/–/– | –/–/– |
| Ceftazidime | 16 | >32 | 2–>32 | 13.0/24.0/63.0 | 0.0/13.0/87.0 |
| Ceftriaxone | >8 | >8 | 0.5–>8 | 1.9/14.8/83.3 | 1.9/14.8/83.3 |
| Meropenem | ≤0.06 | 0.12 | ≤0.06–0.25 | 100.0/0.0/0.0 | 100.0/0.0/0.0 |
| Piperacillin-tazobactam | 4 | >64 | ≤0.5–>64 | 81.5/7.4/11.1 | 72.2/9.3/18.5 |
| Levofloxacin | ≤0.12 | >4 | ≤0.12–>4 | 70.4/1.8/27.8 | 64.8/5.6/29.6 |
| Gentamicin | ≤1 | >8 | ≤1–>8 | 79.6/1.9/18.5 | 77.8/1.8/20.4 |
| Tetracycline | >32 | >32 | 0.5–>32 | 33.3/1.9/64.8 | –/–/– |
| Tigecyclineb | 0.12 | 2 | 0.06–4 | 96.3/3.7/0.0 | 85.2/11.1/3.7 |
| ESBL microarray-negative isolates (70) | |||||
| Ceftazidime-avibactam | 0.12 | 0.5 | ≤0.015–1 | –/–/– | –/–/– |
| Ceftazidime | 1 | 4 | 0.06–8 | 94.3/5.7/0.0 | 50.0/44.3/5.7 |
| Ceftriaxone | 1 | >8 | 0.12–>8 | 55.7/4.3/40.0 | 55.7/4.3/40.0 |
| Meropenem | ≤0.06 | ≤0.06 | ≤0.06–0.5 | 100.0/0.0/0.0 | 100.0/0.0/0.0 |
| Piperacillin-tazobactam | >64 | >64 | 4–>64 | 30.0/7.1/62.9 | 22.9/7.1/70.0 |
| Levofloxacin | ≤0.12 | >4 | ≤0.12–>4 | 78.6/0.0/21.4 | 75.7/2.9/21.4 |
| Gentamicin | ≤1 | 2 | ≤1–>8 | 92.9/0.0/7.1 | 92.9/0.0/7.1 |
| Tetracycline | 2 | >32 | 0.5–>32 | 57.1/10.0/32.9 | –/–/– |
| Tigecyclineb | 0.12 | 1 | 0.03–2 | 100.0/0.0/0.0 | 95.7/4.3/0.0 |
a
Criteria according to the CLSI (15) and EUCAST (16). S, sensitive; I, intermediate; R, resistant. Dashes were used for categories if breakpoint criteria were not available.
b
U.S. FDA breakpoints were applied (21).
c
CTX-M-15-like-producing isolates do not include KPC- or NDM-1-producing isolates.
d
CTX-M-14-like-producing isolates do not include CTX-M-15-like-producing isolates.
e
SHV ESBL-producing isolates do not include CTX-M-15-like-, CTX-M-14-like-, KPC-, or NDM-1-producing isolates.
f
CMY-2-like-producing isolates do not include CTX-M-15-like-, CTX-M-14-like-, KPC-, or NDM-1-producing isolates.