Outcomes of Adjunctive Therapy with Intravenous Cefoperazone-Sulbactam for Ventilator-Associated Pneumonia Due to Carbapenem-Resistant Acinetobacter baumannii

Figures & data

Figure 1 Flowchart of study enrollment.

Table 1 Comparison of Clinical Features Between Patients with Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia

Parameter	Patients with VAP Due to CEP-SUL-Resistant CRAB (n=260)	Patients with VAP Due to CEP-SUL-Susceptible CRAB				P-value^C
		CEP-SUL^– (n=28)	P-value^A	CEP-SUL^+ (n=52)	P-value^B
Demographics
Age, median (IQR)	46 (41,62)	44 (40,56)	0.326	45 (42,74)	0.457	0.232
Male sex	182 (70)	21 (75)	0.582	33 (64)	0.354	0.423
Comorbidities	161 (62)	15 (54)	0.391	34 (65)	0.638	0.427
Immunocompromised status	66 (25)	6 (21)	0.647	18 (35)	0.173	0.331
Clinical characteristic
Initial emergent admission (not mutually exclusive) Intensive care unit	135 (52)	14 (50)	0.847	25 (48.1)	0.613	0.999
APACHE II score, median (IQR)	19 (15,23)	18 (15,21)	0.104	21 (18,22)	0.047	0.023
Bacteremia	50 (19)	5 (18)	0.861	10 (19)	1.000	0.999
Concomitant infections (not included bacteremia)	67 (26)	6 (21)	0.617	19 (37)	0.115	0.255
Meropenem MIC ≥32 μg/mL	230 (88)	24 (86)	0.669	41 (79)	0.065	0.652
CEP-SUL MIC ≥4 μg/mL	260 (100)	20 (71)	<0.001	38 (73)	<0.001	0.999
Treatment
Adjunctive treatment
Imipenem or meropenem	128 (49)	10 (36)	0.178	24 (46)	0.686	0.507
Tigecycline	51 (20)	4 (14)	0.498	10 (19)	0.949	0.760
Other antibiotic(s)	90 (35)	14 (50)	0.112	25 (48)	0.068	0.870
Appropriate empirical treatment	117 (45)	12 (43)	0.829	21 (40)	0.541	0.999
Empirical treatment with CEP-SUL	9 (3)	0(0)	0.601	2 (4)	0.891	0.508
Duration of treatment, median (IQR)	14 (10,14)	14 (12,14)	0.897	14 (11,14)	0.878	0.632
Dosage of colistin (MIU/day) (IQR)	5 (4,6)	5 (4,6)	0.899	5 (4,6)	0.874	0.856

Notes: ^APatients with VAP due to CEP-SUL-resistant CRAB versus patients with VAP due to CEP-SUL-susceptible CRAB and did not receive CEP-SUL; ^Bpatients with VAP due to CEP-SUL-resistant CRAB versus patients with VAP due to CEP-SUL-susceptible CRAB and received CEP-SUL; ^Cpatients with VAP due to CEP-SUL-susceptible CRAB and received CEP-SUL versus patients with VAP due to CEP-SUL-susceptible CRAB and did not receive CEP-SUL. Other antibiotic(s) included piperacillin-tazobactam, ciprofloxacin, levofloxacin, gentamicin, amikacin, vancomycin and fosfomycin. Boldface entries indicate values that reached the significance level set at 0.05.

Abbreviations: CEP-SUL⁺, patients who received cefoperazone-sulbactam; CEP-SUL^–, patients who did not receive cefoperazone-sulbactam; IQR, interquartile range; APACHE II, Acute Physiology and Chronic Health Evaluation; MIC, minimum inhibitory concentrations; CEP-SUL, cefoperazone-sulbactam; VAP, ventilator-associated pneumonia; CEP-SULS, cefoperazone-sulbactam-susceptible.

Table 2 Comparison of Outcomes Between Patients with Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia

Outcomes	Patients with VAP Due to CEP-SUL-Resistant CRAB (n=260)	Patients with VAP Due to CEP-SUL-Susceptible CRAB			P-value ^B	P-value^C
		CEP-SUL^– (n=28)	P-value^A	CEP-SUL^+ (n=52)
Clinical outcomes
Mortality
14-day	71 (27)	11 (39)	0.155	9 (17)	0.154	0.058
30-day	128 (49)	17 (61)	0.203	18 (35)	0.079	0.045
In-hospital	137 (53)	19 (68)	0.076	20 (39)	0.089	0.023
After the end of treatment	70 (27)	8(29)	0.851	11 (21)	0.400	0.454
Side effects
Renal insufficiency	22(8)	2 (7)	0.812	3 (6)	0.521	0.999
Bone marrow suppression	12 (5)	1 (4)	0.802	2 (4)	0.808	0.999
Bleeding disorder	3 (1)	0 (0)	0.867	0 (0)	0.815	0.999
Non-clinical outcomes
Length of hospital stay after end of VAP treatment (days) [median (IQR)]	35 (32,47)	35 (33,45)	0.897	25 (24,36)	0.023	0.014
No. of ventilator days since diagnosis of VAP [median (IQR)]	16 (13,19)	15 (13,18)	0.784	11 (8,13)	0.002	0.002
Cost (baht) [median (IQR)]
Total hospital	255,654 (165,745–312,441)	243,454 (153,456–309,343)	0.097	198,765 (124,778–223,443)	0.025	0.041
Antimicrobial	36,885 (26,987–39,771)	35,432 (28,554–38,442)	0.245	34,564 (27,887–39,002)	0.086	0.106
Non-antimicrobial	221,754 (189,214–288,235)	225,887 (197,654–276,221)	0.654	176,990 (159,400–208,731)	0.003	0.002

Notes: ^APatients with VAP due to CEP-SUL-resistant CRAB versus Patients with VAP due to CEP-SUL-susceptible CRAB and did not receive CEP-SUL; ^Bpatients with VAP due to CEP-SUL-resistant CRAB versus Patients with VAP due to CEP-SUL-susceptible CRAB and received CEP-SUL; ^Cpatients with VAP due to CEP-SUL-susceptible CRAB and received CEP-SUL versus patients with VAP due to CEP-SUL-susceptible CRAB and did not receive CEP-SUL. Boldface entries indicate values that reached the significance level set at 0.05.

Abbreviations: CEP-SUL⁺, patients who received cefoperazone-sulbactam; CEP-SUL^–, patients who did not receive cefoperazone-sulbactam; IQR, interquartile range; VAP, ventilator-associated pneumonia; CEP-SULS, cefoperazone-sulbactam-susceptible; CEP-SUL, cefoperazone-sulbactam.

Table 3 Factors Influencing 30-Day Mortality Among 80 Patients with Ventilator-Associated Pneumonia Due to Carbapenem-Resistant and Cefoperazone-Sulbactam-Susceptible Acinetobacter baumannii

Variables	Values		Crude OR (95% CI)	Adjusted OR (95% CI)	P-value
	Survivors (n = 45)	Non-Survivors (n = 35)
Age (years) [median (IQR)]	45 (41,68)	45 (42,71)	1.00 (1.02,1.08)	1.00 (0.97,1.03)	0.865
Male sex	30 (67)	24 (67)	1.02 (0.42,2.78)	1.2 (0.34,4.16)	0.766
Comorbidities	31 (69)	18 (51)	0.47 (0.19,1.19)	0.3 (0.10,1.05)	0.055
Immunocompromised status	15 (33)	9 (26)	0.69 (0.26,1.85)	0.79 (0.23,2.70)	0.712
APACHE II score [median (IQR)]	20 (15,22)	20 (18,23)	1.07 (0.95,1.2)	1.15 (1.00,1.33)	0.050
Initial intensive care unit admission	22 (49)	17 (49)	0.9 (0.40,2.38)	0.96 (0.29,3.12)	0.952
Meropenem MIC ≥32 μg/mL	38 (84)	27 (77)	0.62 (0.20,1.92)	0.70 (0.17,2.94)	0.637
CEP-SUL MIC ≥4 μg/mL	35 (78)	23 (66)	0.55 (0.20,1.47)	0.25 (0.14,1.72)	0.266
Appropriate empirical antimicrobial agents	19 (42)	14 (40)	0.9 (0.52,2.22)	0.71 (0.24,2.08)	0.531
Adjunctive treatment with carbapenem(s)	19 (42)	15 (43)	1.03 (0.42,2.5)	1.11 (0.34,3.57)	0.862
Adjunctive treatment with tigecycline	9 (20)	5 (14)	0.6 (0.2,2.22)	1.35 (0.16,3.33)	0.691
Adjunctive treatment with cefoperazone-sulbactam	34 (76)	18 (51)	0.34 (0.13,0.88)	0.24 (0.07,0.82)	0.019
Duration of antimicrobial agents	14 (12,15)	13 (10,14)	0.86 (0.74,1)	0.85 (0.71,1.02)	0.059

Note: Boldface entries indicate values that reached the significance level set at 0.05.

Abbreviations: IQR, interquartile range; APACHE II, Acute Physiology and Chronic Health Evaluation; MIC, minimum inhibitory concentrations; CEP-SUL, cefoperazone-sulbactam; OR, odds ratio; CI, confidence interval.

Figure 2 Survival of patients with VAP due to CRAB who received CEP-SUL and did not receive CEP-SUL.