Ceftazidime-Avibactam versus Colistin for the Treatment of Infections Due to Carbapenem-Resistant Enterobacterales: A Multicenter Cohort Study

Figures & data

Table 1 Demographic and Clinical Characteristics of Study Patients

Characteristics	CAZ-AVI n = 149	IV Colistin n = 81	P value
Demographic
Age in years (mean ± SD)	59 ± 18	57.5 ± 20	0.474
Male, n (%)	93 (62)	50 (61)	0.918
Study site
KFMC	48 (32)	33 (41)	0.196
KAMC	39 (26)	20 (25)	0.806
KFSHRC	24 (16)	9 (11)	0.302
KSUMC	17 (12)	10 (12)	0.833
SFH	21 (14)	9 (11)	0.521
Comorbidity, n (%)
AIDS	1 (0.7)	1 (1)	0.660
Cerebrovascular disease	43 (29)	19 (23)	0.378
Chronic heart failure	24 (16)	5 (6)	0.030
Chronic obstructive pulmonary disease	10 (7)	3 (4)	0.345
Connective tissue disease	8 (5)	1 (1)	0.122
Dementia	11 (7)	2 (2)	0.123
Diabetes mellitus	71 (48)	47 (58)	0.133
Endocrine disorder^#	46 (31)	23 (28)	0.695
Hemiplegia or paraplegia	13 (9)	4 (5)	0.294
History of myocardial infarction	17 (11)	7 (9)	0.512
Hypertension	89 (60)	48 (59)	0.944
Immunosuppressed^†	33 (22)	16 (20)	0.672
Liver disease	14 (9)	4 (5)	0.229
Moderate to severe chronic renal failure	34 (23)	14 (17)	0.324
Neurological disease	34 (23)	13 (16)	0.224
Peptic ulcer disease	7 (5)	2 (2)	0.405
Peripheral vascular disease	13 (9)	1 (1)	0.023
Charlson comorbidity index, median (IQR)	5 (3–7)	4 (2–6)	0.013
Baseline serum creatinine in µmol/L, median (IQR)	94 (57–160)	73 (44–130)	0.032
Baseline creatinine clearance in mL/min, median (IQR)	60 (33–99)	75 (36–120)	0.112
Indwelling invasive devices, n (%)
Central venous catheter	77 (52)	33 (41)	0.113
Foley catheter	93 (62)	42 (52)	0.120
Mechanical ventilation	76 (51)	35 (43)	0.258
Severity of illness, n (%)
Intensive care unit at infection onset	93 (62)	53 (65)	0.650
No sepsis	20 (13)	11 (14)	0.973
Sepsis	90 (61)	51 (63)	0.703
Septic shock	39 (26)	19 (23)	0.650
APACHE II score, median (IQR)	16 (11–20)	15 (11–19)	0.327
Site of infection, n (%)
HAP	40 (27)	20 (25)	0.722
UTI	30 (20)	14 (17)	0.600
Wound	24 (16)	13 (16)	0.991
Intraabdominal	21 (14)	9 (11)	0.521
VAP	13 (9)	9 (11)	0.557
CLABSI	5 (3)	3 (4)	0.891
Other	16 (11)	13 (16)	–
Presence of bacteremia, n (%)	43 (29)	17 (21)	0.194
Type of CRE, n (%)
Klebsiella pneumoniae	136 (91)	65 (80)	0.016
E. coli	9 (6)	12 (15)	0.027
Other	4 (3)	4 (5)	–
Polymicrobial infection, n (%)	69 (46)	34 (42)	0.528
Infectious diseases consultation, n (%)	144 (97)	76 (94)	0.317
Time to active therapy in hours, median (IQR)	48 (20–79)	43 (32–67)	0.945
Time to study drug in hours, median (IQR)	60 (48–99)	57 (24–90)	0.142
Combination therapy, n (%)*	34 (23)	57 (70)	< 0.001
Combination with more than one agent, n (%)	0	15 (19)	–
Type of combination therapy
Aminoglycoside	7 (5)	6 (7)
Aztreonam	3 (2)	0
Carbapenem	0	47 (58)
Cephalosporin	0	2 (3)
Fluoroquinolone	5 (3)	3 (4)
Inhaled colistin	3 (2)	0
Piperacillin/tazobactam	0	6 (7)
Tigecycline	16 (11)	8 (10)
Susceptible to at least one combination agent, n (%) ^±	13 (38)	16 (28)	0.314
Duration of therapy in days, median (IQR)	12 (8–19)	11 (7–17)	0.213
Overall duration of hospitalization in days, median (IQR)	60 (30–90)	62 (34–124)	0.121
Years of use during the study period	2017–2020	2015–2020	-

Notes: ^#Any endocrine disorder except diabetes. ^†Neutropenic, chronic treatment with corticosteroids, active chemotherapeutic management of malignancy, or solid organ/bone marrow transplant patients on immunosuppressant therapy. *Given concurrently with the study drug for at least 48 hours. ^±Denominator represents patients who received combination therapy.

Abbreviations: AIDS, acquired immunodeficiency syndrome; APACHE II, Acute Physiology and Chronic Health Evaluation; CAZ/AVI, ceftazidime/avibactam; CLABSI, central line-associated bloodstream infection; CRE, carbapenem-resistant Enterobacterales; IQR, interquartile range; KAMC, King Abdulaziz Medical City; KFMC, King Fahad Medical City; KFSHRC, King Faisal Specialist Hospital and Research Center; KSUMC, King Saud University Medical City; SFH, Security Forces Hospital; HAP, hospital-acquired pneumonia; IV, intravenous; SD, standard deviation; UTI, urinary tract infection; VAP, ventilator-associated pneumonia.

Table 2 Outcomes in Patients Receiving Ceftazidime-Avibactam versus Intravenous Colistin

Outcome ^a	CAZ-AVI n = 149	IV Colistin n = 81	P value	Odds Ratio (95% CI)
Clinical cure	106 (71)	42 (52)	0.004	2.29 (1.31–4.01)
In-hospital mortality	52 (35)	36 (44)	0.156	0.67 (0.39–1.16)
Acute kidney injury	23 (15)	27 (33)	0.002	0.37 (0.19–0.69)
Risk	14	11	–	–
Injury	4	7	–	–
Failure	4	7	–	–
RRT	1	2	–	–
Microbiologic outcome ^b
Eradication	81 (67)	37 (55)	0.113	1.64 (0.89–3.03)
Persistence	40 (33)	30 (45)
Infection-related mortality	42 (28)	27 (33)	0.418	0.79 (0.44–1.41)
30-day readmission ^c	15 (16)	5 (11)	0.488
30-day readmission due to infection ^c	7 (7)	2 (4)	0.528
30-day recurrence ^c	10 (10)	5 (11)	0.885
90-day recurrence ^c	11 (11)	6 (13)	0.734
Length of hospital stay from onset of infection (days)	36 (20–60)	33 (20–72)	0.797
Length of ICU stay from onset of infection (days)^d	17 (6–39)	14 (7–26)	0.109
Duration of mechanical ventilation (days)^e	11 (5–22)	12 (5–24)	0.483

Notes: ^aData represented n (%) or median (IQR). ^bOnly included patients who had repeated cultures (n = 121 in ceftazidime-avibactam arm and 67 in colistin arm). ^cOnly included patients who survived (n = 97 in ceftazidime-avibactam arm and 45 in colistin arm). ^dIncluded only patients who were in the ICU at infection onset. ^eIncluded only patients who were mechanically ventilated during the infection episode.

Abbreviations: CAZ-AVI, ceftazidime-avibactam; CI, confidence interval; ICU, intensive care unit; RRT, renal replacement therapy.

Table 3 Univariate Analysis of Factors Associated with Clinical Cure

Variable	Clinical Failure n = (82)	Clinical Cure n = (148)	P value
Demographic
Age in years (mean ± SD)	60 ± 19	57 ± 17	0.232
Male, n (%)	51 (62)	92 (62)	0.996
Comorbidity, n (%)
Cerebrovascular disease	29 (36)	33 (22)	0.032
Chronic heart failure	12 (15)	17 (12)	0.491
Chronic obstructive pulmonary disease	4 (5)	9 (6)	0.705
Connective tissue disease	3 (4)	6 (4)	0.882
Dementia	7 (9)	6 (4)	0.159
Diabetes mellitus	39 (48)	79 (53)	0.370
Endocrine disorder	34 (41)	35 (24)	0.005
Hemiplegia or paraplegia	4 (5)	13 (9)	0.267
History of myocardial infarction	8 (10)	16 (11)	0.802
Hypertension	53 (65)	84 (57)	0.244
Immunosuppressed	17 (21)	32 (22)	0.875
Liver disease	8 (10)	10 (7)	0.417
Moderate to severe chronic renal failure	19 (23)	29 (20)	0.523
Neurological disease	20 (24)	27 (18)	0.268
Peripheral vascular disease	4 (5)	10 (7)	0.568
Charlson comorbidity index, median (IQR)	5 (4–7)	4 (2–6)	0.029
Indwelling invasive devices, n (%)
Central venous catheter	46 (56)	64 (43)	0.062
Foley catheter	49 (60)	86 (58)	0.808
Mechanical ventilation	49 (60)	62 (42)	0.009
APACHE II score, median (IQR)	18 (12–25)	15 (9–19)	0.005
Site of infection, n (%)
HAP	23 (28)	37 (25)	0.614
UTI	15 (18)	29 (20)	0.810
Wound	15 (18)	22 (15)	0.498
Intraabdominal	12 (15)	18 (12)	0.594
VAP	4 (5)	18 (12)	0.072
CLABSI	1 (1)	7 (5)	0.164
Presence of bacteremia, n (%)	26 (32)	34 (23)	0.148
Polymicrobial infection, n (%)	40 (49)	63 (43)	0.364
Time to active therapy in hours, median (IQR)	48 (24–80)	44 (24–75)	0.379
Time to study drug in hours, median (IQR)	55 (24–80)	62 (48–97)	0.074
Duration of therapy in days, median (IQR)	11 (7–18)	12 (9–18)	0.193

Abbreviations: APACHE II, Acute Physiology and Chronic Health Evaluation; CLABSI, central line-associated bloodstream infection; IQR, interquartile range; HAP, hospital-acquired pneumonia; SD, standard deviation; UTI, urinary tract infection; VAP, ventilator-associated pneumonia.

Table 4 Analysis of Significant Factors Associated with Clinical Cure Using Logistic Regression Model

Variable	Odds Ratio	95% Conf. Interval	P value
CAZ-AVI	2.75	1.28–5.91	0.009
Cerebrovascular disease	0.67	0.27–1.62	0.371
Endocrine disorder	0.48	0.20–1.11	0.080
Mechanical ventilation	0.54	0.25–1.17	0.119
Charlson comorbidity index	0.88	0.76–1.03	0.121
APACHE II score	0.93	0.89–0.98	0.011

Abbreviations: APACHE II, Acute Physiology and Chronic Health Evaluation; CAZ-AVI, ceftazidime-avibactam.