Ceftazidime/Avibactam versus Polymyxin B in the Challenge of Carbapenem-Resistant Pseudomonas aeruginosa Infection

Figures & data

Table 1 Comparison of Clinical Characteristics Between CAZ/AVI and Polymyxin B in Patients with CRPA Infection

Characteristics	Total (n=136)	CAZ/AVI (n=51)	Polymyxin B (n=85)	P value
Demographic variables
Male sex	100 (73.5)	37 (72.5)	63 (74.1)	0.841
Age (years)	61.5 (51.25–70)	65 (58–70)	58 (48–69)	0.052
BMI	23.55±4.47	23.28±5.07	23.71±4.10	0.588
CCI	3 (2–4)	3 (2–4)	3 (2–4)	0.248
aCCI	4 (3–6)	5 (3–6)	4 (3–6)	0.493
APACHE II score	16 (12–22)	15 (12–19)	18 (12–22)	0.175
SOFA score	6 (4–8)	5 (4–7)	7 (4–8)	0.054
Comorbidities
Cardiovascular disease	46 (33.8)	17 (33.3)	29 (34.1)	0.925
Chronic pulmonary disease	35 (25.7)	25 (49.0)	10 (11.8)	<0.001
Chronic kidney disease	7 (5.1)	3 (5.9)	4 (4.7)	1
Chronic liver disease	9 (6.6)	3 (5.9)	6 (7.1)	1
Cerebrovascular disease	39 (28.7)	10 (19.6)	29 (34.1)	0.070
Gastrointestinal diseases	15 (11.0)	7 (13.7)	8 (9.4)	0.437
Hypertension	57 (41.9)	20 (39.2)	37 (43.5)	0.622
Diabetes mellitus	32 (23.5)	13 (25.5)	19 (22.4)	0.676
Solid tumor	16 (11.8)	5 (9.8)	11 (12.9)	0.582
Hematologic malignancy	2 (1.5)	1 (2.0)	1 (1.2)	1
Organ transplant	27 (19.9)	21 (41.2)	6 (7.1)	<0.001
Chemotherapy	2 (1.5)	1 (2.0)	1 (1.2)	1
Immunosuppressants use	32 (23.5)	22 (43.1)	10 (11.8)	<0.001
Corticosteroid use	58 (42.6)	31 (60.8)	27 (31.8)	0.001
Surgical history	101 (74.3)	45 (88.2)	56 (65.9)	0.004
Invasive procedures
Endotracheal intubation	122 (89.7)	43 (84.3)	79 (92.9)	0.109
Tracheotomy	81 (59.6)	30 (58.8)	51 (60.0)	0.892
Mechanical ventilation	136 (100)	51 (100)	85 (100)	1
Central venous catheter	118 (86.8)	48 (94.1)	70 (82.4)	0.050
CRRT	66 (48.5)	20 (39.2)	46 (54.1)	0.092
Septic shock	57 (41.9)	16 (31.4)	41 (48.2)	0.054
Infection variables
Pulmonary infection	135 (99.3)	51 (100)	84 (98.8)	1
Bloodstream infection	49 (36.0)	12 (23.5)	37 (43.5)	0.019
Intra-abdominal infection	4 (2.9)	0 (0)	4 (4.7)	0.294
Other infection sites	29 (21.3)	13 (25.5)	16 (18.8)	0.358
Treatment variables
Duration of therapy	9 (5–14)	10 (6–17)	9 (5–12)	0.108
Time to initiation of treatment	6.5 (4–12.75)	6 (4–15)	7 (3.5–10.5)	0.580
Outcomes
The length of ICU (days)	28 (17–44.5)	38 (25–74)	23 (14–33)	<0.001
The length of hospitals (days)	34 (22.67–61)	48 (33–83)	29 (19–43)	<0.001
14-day mortality	26 (19.1)	3 (5.9)	23 (27.1)	0.002
30-day mortality	47 (34.6)	7 (13.7)	40 (47.1)	<0.001
In-hospital mortality	66 (48.5)	15 (29.4)	51 (60.0)	0.001
Bacterial eradication	34 (25.0)	23 (45.1)	11 (12.9)	<0.001

Notes: Data are expressed as number (%) or mean± SD or median (IQR).

Abbreviations: CAZ/AVI, Ceftazidime/avibactam; BMI, Body mass index; CCI, Charlson comorbidity index; aCCI, age-adjusted Charlson comorbidity index; CRRT, Continuous renal replacement therapy; ICU, Intensive care unit; IQR, Interquartile range.

Figure 1 Study flow chart.

Abbreviations: CRPA, Carbapenem-resistant Pseudomonas aeruginosa; CAZ/AVI, ceftazidime/avibactam.

Table 2 Comparison of Clinical Characteristics Between CAZ/AVI and Polymyxin B in Patients with CRPA Infection After Adjustment

Characteristics	Total (n=56)	CAZ/AVI (n=28)	Polymyxin B (n=28)	P value
Demographic variables
Male sex	42 (75.0)	20 (71.4)	22 (78.6)	0.537
Age (years)	62.5 (48.25–70.75)	62.5 (58–70)	62.5 (47.25–71)	0.780
BMI	23.24±4.02	23.84±4.77	22.63±3.07	0.264
CCI	3 (2–4)	3 (2–3)	3 (1.25–5)	0.363
aCCI	4.70±2.51	4.57±2.22	4.82±2.80	0.713
APACHE II score	16 (12.25–20)	15.5 (14–24.25)	16 (10.5–19.5)	0.485
SOFA score	6 (4–8)	6 (4–8)	6 (4–8)	0.954
Comorbidities
Cardiovascular disease	17 (30.4)	9 (32.1)	8 (28.6)	0.771
Chronic pulmonary disease	11 (19.6)	6 (21.4)	5 (17.9)	0.737
Chronic kidney disease	5 (8.9)	3 (10.7)	2 (7.1)	1
Chronic liver disease	5 (8.9)	1 (3.6)	4 (14.3)	0.349
Cerebrovascular disease	16 (28.6)	8 (28.6)	8 (28.6)	1
Gastrointestinal diseases	5 (8.9)	2 (7.1)	3 (10.7)	1
Hypertension	23 (41.1)	11 (39.3)	12 (42.9)	0.786
Diabetes mellitus	11 (19.6)	7 (25.0)	4 (14.3)	0.313
Solid tumor	8 (14.3)	3 (10.7)	5 (17.9)	0.703
Hematologic malignancy	1 (1.8)	1 (3.6)	0 (0.0)	1
Organ transplant	10 (17.9)	5 (17.9)	5 (17.9)	1
Chemotherapy	1 (1.8)	1 (3.6)	0 (0.0)	1
Immunosuppressants use	11 (19.6)	6 (21.4)	5 (17.9)	0.737
Corticosteroid use	27 (48.2)	14 (50.0)	13 (46.4)	0.789
Surgical history	46 (82.1)	22 (78.6)	24 (85.7)	0.485
Invasive procedures
Endotracheal intubation	50 (89.3)	23 (82.1)	27 (96.4)	0.195
Tracheotomy	37 (66.1)	19 (67.9)	18 (64.3)	0.778
Mechanical ventilation	56 (100)	28 (100)	28 (100)	1
Central venous catheter	50 (89.3)	26 (92.9)	24 (85.7)	0.666
CRRT	27 (48.2)	12 (42.9)	15 (53.6)	0.422
Septic shock	25 (44.6)	13 (46.4)	12 (42.9)	0.788
Infection variables
Pulmonary infection	55 (98.2)	28 (100)	27 (96.4)	1
Bloodstream infection	18 (32.1)	10 (35.7)	8 (28.6)	0.567
Intra-abdominal infection	2 (3.6)	0 (0)	2 (7.1)	0.471
Other infection sites	15 (26.8)	9 (32.1)	6 (21.4)	0.365
Treatment variables
Duration of therapy	9 (5.25–14.75)	10 (6–16.75)	8.5 (5–11)	0.109
Time to initiation of treatment	7 (4–14.5)	10.5 (4–18)	6 (4–10.5)	0.366
Outcomes
The length of ICU (days)	28 (17–43.75)	32.5 (19.52–72)	24.5 (14–32.5)	0.021
The length of hospitals (days)	33.5 (24.3–60.5)	46 (27.5–78.5)	29.5 (19–43.25)	0.008
14-d mortality	9 (16.1)	2 (7.1)	7 (25.0)	0.146
30-d mortality	16 (28.6)	4 (14.3)	12 (42.9)	0.018
In-hospital mortality	25 (44.6)	10 (35.7)	15 (53.6)	0.179
Bacterial eradication	16 (28.6)	12 (42.9)	4 (14.3)	0.018

Notes: Data are expressed as number (%) or mean± SD or median (IQR).

Abbreviations: CAZ/AVI, Ceftazidime/avibactam; BMI, Body mass index; CCI, Charlson comorbidity index; aCCI, age-adjusted Charlson comorbidity index; CRRT, Continuous renal replacement therapy; ICU, Intensive care unit; IQR, Interquartile range.

Table 3 Comparison of Clinical Characteristics Between 30-Day Survivors and Non-Survivors with CRPA Infection

Characteristics	Total (n=136)	Survivors (n=89)	Non-Survivors (n=47)	P value
Demographic variables
Male sex	100 (73.5)	67 (75.3)	33 (70.2)	0.524
Age (years)	61.5 (51.25–70)	62 (50.5–70.0)	61 (53–71)	0.980
BMI	23.55±4.47	23.76±4.67	23.15±4.10	0.446
CCI	3 (2–4)	3 (1–4)	3 (3–4)	0.015
aCCI	4 (3–6)	4 (3–6)	5 (4–6)	0.045
APACHE II score	16 (12–22)	16 (12–20)	17 (12–23)	0.277
SOFA score	6 (4–8)	6 (4–8)	7 (4–9)	0.338
Comorbidities
Cardiovascular disease	46 (33.8)	33 (37.1)	13 (27.7)	0.270
Chronic pulmonary disease	35 (25.7)	30 (33.7)	5 (10.6)	0.003
Chronic kidney disease	7 (5.1)	5 (5.6)	2 (4.3)	1
Chronic liver disease	9 (6.6)	7 (7.9)	2 (4.3)	0.658
Cerebrovascular disease	39 (28.7)	23 (25.8)	16 (34.0)	0.315
Gastrointestinal diseases	15 (11.0)	10 (11.2)	5 (10.6)	0.916
Hypertension	57 (41.9)	38 (42.7)	19 (40.4)	0.799
Diabetes mellitus	32 (23.5)	19 (21.3)	13 (27.7)	0.409
Solid tumor	16 (11.8)	9 (10.1)	7 (14.9)	0.411
Hematologic malignancy	2 (1.5)	1 (1.1)	1 (2.1)	1
Organ transplant	27 (19.9)	23 (25.8)	4 (8.5)	0.016
Chemotherapy	2 (1.5)	1 (1.1)	1 (2.1)	1
Immunosuppressants use	32 (23.5)	23 (25.8)	9 (19.1)	0.381
Corticosteroid use	58 (42.6)	37 (41.6)	21 (44.7)	0.727
Surgical history	101 (74.3)	73 (82.0)	28 (59.6)	0.004
Invasive procedures
Endotracheal intubation	122 (89.7)	78 (87.6)	44 (93.6)	0.427
Tracheotomy	81 (59.6)	60 (67.4)	21 (44.7)	0. 010
Mechanical ventilation	136 (100)	89 (100)	47 (100)	1
Central venous catheter	118 (86.8)	77 (86.5)	41 (87.2)	0.907
CRRT	66 (48.5)	30 (33.7)	36 (76.6)	<0.001
Septic shock	57 (41.9)	25 (28.1)	32 (68.1)	<0.001
Infection variables
Pulmonary infection	135 (99.3)	88 (98.9)	47 (100.0)	1
Bloodstream infection	49 (36.0)	28 (31.5)	21 (44.7)	0.127
Intra-abdominal infection	4 (2.9)	2 (2.2)	2 (4.3)	0.900
Other infection sites	29 (21.3)	24 (27.0)	5 (10.6)	0.027
Treatment variables
Duration of therapy	9 (5–14)	11 (7–17)	6 (4–9)	<0.001
Time to initiation of treatment	6.5 (4–12.75)	6 (4–15)	7 (3–10)	0.348
CAZ/AVI use	51 (37.5%)	44 (49.4)	7 (14.9)	<0.001
Polymyxin B use	85 (62.5%)	45 (50.6)	40 (85.1)	<0.001
Outcomes
The length of ICU (days)	28 (17–44.5)	34.09 (24.5–58)	18 (13–25)	<0.001
The length of hospitals (days)	34 (22.67–61)	46 (30–78.5)	21 (15–33)	<0.001
Bacterial eradication	34 (25.0)	34 (38.2)	0 (0)	<0.001

Notes: Data are expressed as number (%) or mean± SD or median (IQR).

Abbreviations: BMI, Body mass index; CCI, Charlson comorbidity index; aCCI, age-adjusted Charlson comorbidity index; CRRT, Continuous renal replacement therapy; ICU, Intensive care unit; IQR, Interquartile range.

Table 4 Univariate and Multivariate COX Regression Analysis Associated with 30-Day Mortality

Variables	Univariate Analysis		Multivariate Analysis
	P value	HR (95% CI)	P value	HR (95% CI)
CCI (1-point increments)	0.040	1.179 (1.008–1.379)
Chronic pulmonary disease	0.012	0.302 (0.120–0.765)
Organ transplant	0.035	0.332 (0.119–0.926)
Surgical history	0.002	0.389 (0.217–0.698)	0.026	0.506 (0.277–0.923)
Tracheotomy	0.004	0.425 (0.239–0.757)
CRRT	<0.001	4.461 (2.266–8.786)	0.003	3.159 (1.479–6.745)
Septic shock	<0.001	3.739 (2.020–6.919)	0.030	2.133 (1.078–4.222)
Other infection sites	0.028	0.353 (0.140–0.894)
Duration of therapy (1-day increments)	<0.001	0.847 (0.785–0.913)	<0.001	0.853 (0.794–0.917)
CAZ/AVI use	<0.001	0.235 (0.105–0.525)	0.028	0.394 (0.172–0.902)

Abbreviations: HR, Hazard ratios; CI, Confidence interval; CCI, Charlson comorbidity index; CRRT, Continuous renal replacement therapy; CAZ/AVI, Ceftazidime/avibactam.

Table 5 Univariate and Multivariate COX Regression Analysis Associated with 30-Day Mortality After Adjustment

	Univariate Analysis		Multivariate Analysis
	P value	HR (95% CI)	P value	HR (95% CI)
Age (1-year increments)	0.033	1.047 (1.004–1.093)	0.022	1.050 (1.007–1.094)
Central venous catheter	0.021	0.262 (0.084–0.816)	0.027	0.268 (0.084–0.859)
Duration of therapy (1-day increments)	0.027	0.871 (0.771–0.984)
CAZ/AVI use	0.031	0.287 (0.092–0.890)	0.016	0.244 (0.078–0.765)

Abbreviations: HR, Hazard ratios; CI, Confidence interval; CAZ/AVI, Ceftazidime/avibactam.

Figure 2 Kaplan–Meier curves of patients with CRPA infection treated with CAZ/AVI or polymyxin B.

Abbreviations: CRPA, Carbapenem-resistant Pseudomonas aeruginosa; CAZ/AVI, ceftazidime/avibactam.