TABLE 1

Patient characteristics and clinical outcomes across treatment groups

CharacteristicaTreatment groupbP value
C-A (n = 13)CB+AG (n = 25)CB+COL (n = 30)Otherc (n = 41)
Patient demographics
    Male (n [%])7 (54)16 (64)18 (60)21 (51)0.75
    Age (median [range])66 (32–91)57 (32–87)59 (26–84)62 (25–90)0.63
Underlying disease
    Diabetes (n [%])4 (31)8 (32)8 (27)15 (37)0.85
    Chronic liver disease (n [%])0 (0)9 (36)9 (30)13 (32)0.11
    Chronic respiratory disease (n [%])5 (38)5 (20)8 (27)8 (20)0.51
    Immunocompromised (n [%])5 (38)13 (52)14 (47)22 (54)0.78
    Solid-organ transplant recipient (n [%])3 (23)11 (44)9 (30)17 (41)0.46
Severity of illness
    ICU at time of bacteremia (n [%])6 (46)13 (52)12 (40)25 (61)0.36
    RRT (n [%])2 (15)7 (28)7 (23)8 (20)0.79
    Pitt bacteremia score (median [range])4 (1–6)4 (0–9)4 (0–9)4 (0–9)0.74
    APACHE II score (median [range])20 (16–33)17 (8–38)16 (7–36)19 (4–34)0.46
Strain characteristic
    Presence of KPC (n [%])13 (100)24 (96)30 (100)39 (95)0.56
        KPC-29192429
        KPC-345610
    Primary bacteremia (n [%])3 (23)6 (24)5 (17)14 (34)0.41
    Secondary bacteremia (n [%])10 (77)19 (76)25 (83)27 (66)0.41
        Abdominal2121620
        Respiratory3263
        Urinary tract5224
        Soft tissue0310
Treatment characteristic
    ≥2 active agentsd (n [%])5 (38)e10 (40)f9 (30)8 (20)0.28
    Time to active treatment (median [IQR])55.7 (25–67)52.5 (28–64)67.9 (30–133)65.0 (35–95)0.23
    Duration of treatment (median days [range])13 (5–23)12 (3–28)14 (3–96)10 (3–47)0.31
Patient outcome
    Clinical success (n [%])11 (85)12 (48)12 (40)15 (37)0.02g
    30-Day survival (n [%])12 (92)17 (68)21 (70)28 (68)0.37
    90-Day survival (n [%])12 (92)14 (56)19 (63)20 (49)0.04h
    Persistent bacteremia (n [%])0 (0)1 (4)5 (17)8 (20)0.13
    Recurrent bacteremia (n [%])2 (15)5 (20)3 (10)9 (22)0.60
Drug toxicityi
    Acute kidney injury at 48 h (n [%])1 (9)0 (0)7 (30)4 (12)0.10
    Acute kidney injury at 7 days (n [%])1 (9)3 (17)10 (43)4 (12)0.02
    Acute kidney injury at end of treatment (n [%])2 (18)8 (44)13 (57)6 (18)0.01
    Initiation of renal replacement therapy (n [%])0 (0)0 (0)5 (22)3 (9)
    Time to start of RRT (median days [range])5 (2–8)8 (5–8)
  • a ICU, intensive care unit; IQR, interquartile range; RRT, renal replacement therapy.

  • b AG, aminoglycoside; C-A, ceftazidime-avibactam; CB, carbapenem; COL, colistin.

  • c Other regimens included patients treated with monotherapy (n = 29) or combination therapy (n = 12). Monotherapy consisted of an AG (n = 11), CB (n = 8), COL (n = 4), tigecycline (n = 4), and ciprofloxacin (n = 2). Combination regimens were COL+tigecycline (n = 3), AG+tigecycline (n = 2), and 1 each of AG+cefepime, AG+COL+tigecycline, COL+aztreonam, COL+cefepime, COL+ciprofloxacin, CB+doxycycline, and CB+tigecycline.

  • d Active agents were defined by in vitro susceptibility according to CLSI interpretive criteria for all agents except the carbapenems, which were defined as active in vitro if the MIC was ≤8 μg/ml.

  • e Five patients received gentamicin in combination with C-A.

  • f Six patients received CB+AG+COL.

  • g Patients treated with C-A had higher rates of clinical success than those treated with CB+AG (P = 0.04), CB+COL (P = 0.009), or other regimens (P = 0.004). Clinical success rates were higher among patients treated with C-A than in those treated with all other regimens (P = 0.006).

  • h Patients treated with C-A had higher rates of 90-day survival than those treated with CB+AG (P = 0.03) or other regimens (P = 0.008); there was a trend toward higher 90-day survival for C-A compared with CB+COL (P = 0.07). The 90-day survival rates were higher among patients treated with C-A than in those treated with all other regimens (P = 0.01).

  • i Among patients not requiring RRT at baseline, which included those receiving CA (n = 11), CB+AG (n = 18), CB+COL (n = 23), or other regimens (n = 33). Acute kidney injury was defined by KDIGO criteria as a ≥0.3-mg/dl increase in serum creatinine from baseline at 48 h and as a 1.5× increase in serum creatinine from baseline at 7 days or the end of treatment.