A Real-World Study Comparing Various Antimicrobial Regimens for Bloodstream Infections Caused by Carbapenem-Resistant Gram-Negative Bacilli in a Tertiary Hospital, Shanghai, China, from 2010 to 2017

Figures & data

Table 1 Characteristics of Individuals with Bloodstream Infections Caused by CR-GNB According to All-Cause 28-Day Mortality

Variables	Survived (n = 140)	Died (n = 35)	P value
Age (years), mean (SD)	52.7 (17.6)	62.1 (15.1)	0.004
Male, no. (%)	105 (75.0)	24 (68.6)	0.440
Comorbidities, no. (%)
Solid tumour	27 (19.3)	7 (20.0)	0.924
Haematological malignancy	7 (5.0)	3 (8.6)	0.421
Liver disease
Cirrhosis	13 (9.3)	1 (2.9)	0.307
Hepatitis	20 (14.3)	3 (8.6)	0.576
Post transplantation (solid organ/stem cell)	17 (12.1)	1 (2.9)	0.129
Chronic pulmonary disease	6 (4.3)	3 (8.6)	0.386
Chronic renal failure	6 (4.3)	0 (0.0)	0.601
Acute renal failure	4 (2.9)	3 (8.6)	0.144
Cardiac dysfunction	1 (0.7)	5 (14.3)	0.001
Diabetes	20 (14.3)	8 (22.9)	0.216
Hypertension	41 (29.3)	15 (42.9)	0.124
Vascular disease
Cardiovascular	7 (5.0)	4 (11.4)	0.234
Cerebrovascular	24 (17.1)	14 (40.0)	0.003
Others (macrovascular/peripheral vascular/intestinal vascular)	9 (6.4)	1 (2.9)	0.689
Intracranial infection	16 (11.4)	3 (8.6)	0.769
Non-neoplastic/infectious neurologic diseases	9 (6.4)	0 (0.0)	0.207
Post cardiopulmonary resuscitation	5 (3.6)	0 (0.0)	0.584
Autoimmune diseases	2 (1.4)	3 (8.6)	0.055
Skin disease	3 (2.1)	0 (0.0)	1.000
Gastrointestinal disease
Perforation	2 (1.4)	5 (14.3)	0.004
Others (obstruction/hemorrhage)	11 (7.9)	2 (5.7)	1.000
Trauma	28 (20.0)	7 (20.0)	1.000
Clinical findings
Immunocompromise, no. (%)	56 (40.0)	15 (42.9)	0.758
Neutropenia, no. (%)	6 (4.3)	1 (2.9)	1.000
Septic shock, no. (%)	23 (16.4)	15 (42.9)	0.001
APACHE II score, median (IQR)	18 (13–23)	25 (20–34)	<0.001
Surgical procedure besides transplantation, no. (%)	59 (42.1)	14 (40.0)	0.818
Indwelling invasive devices, no. (%)
Central venous catheter/PICC	106 (75.7)	32 (91.4)	0.042
Other catheter (tracheal catheter/nasogastric tube/bladder catheter/surgical drain)	113 (80.7)	33 (94.3)	0.053
Length of hospital stay, median (IQR)	34.5 (23.5–69)	26 (18–42)	0.001
Length of ICU stay, median (IQR)	17.5 (0–44)	18 (7–26)	0.728
Days of mechanical ventilation, median (IQR)	1 (0–16.5)	13 (6–19)	0.001
Treatment variables
Time to initiation targeted regimen ≤48 h, no. (%)	79 (56.4)	23 (65.7)	0.319
Sustained positivity of blood culture, no. (%)	12 (12.2)	8 (26.7)	0.082
Days to negativity of blood culture, median (IQR)	6 (2–10)	4 (3–6)	0.100
Peak temperature during BSI (°C), mean (SD)	39.4 (0.9)	39.9 (0.9)	0.006
Persistent fever, no. (%)	40 (28.8)	29 (82.9)	<0.001
Days to defervescence, median (IQR)	8 (4–17)	7 (2–10)	0.369
WBC after targeted regimen (×10^9/L), median (IQR)
D1	10.9 (7.1–15.2)	11.3 (6.7–18.4)	0.490
D3	9.6 (7.1–13.1)	13.3 (7.2–17.6)	0.069
D7	8.8 (6.1–12.4)	13.4 (9.9–16.9)	0.027
ANC after targeted regimen (×10^9/L), median (IQR)
D1	8.7 (5.7–12.5)	10.1 (5.9–16.0)	0.205
D3	7.8 (5.3–10.3)	11.3 (6.1–17.5)	0.007
D7	7.2 (4.2–9.8)	12.0 (7.9–15.3)	0.010

Abbreviation: PICC, peripherally inserted central catheter.

Figure 1 Flowchart of the study selection process.

Figure 2 Percentages of resistance to carbapenems among GNB isolates in BSIs throughout the study period.

Table 2 Characteristics of Individuals with Bloodstream Infections Caused by CR-GNB According to Treatment Regimen

Variables	Monotherapy (n = 48)	Combination Therapy (n = 127)	P value
Age (years), mean (SD)	58.6 (17.1)	53.1 (17.5)	0.064
Male, no. (%)	35 (72.9)	94 (74.0)	0.883
Comorbidities, no. (%)
Solid tumour	11 (22.9)	23 (18.1)	0.473
Haematological malignancy	3 (6.3)	7 (5.5)	1.000
Liver disease
Cirrhosis	4 (8.3)	10 (7.9)	1.000
Hepatitis	5 (10.4)	18 (14.2)	0.512
Post transplantation (solid organ/stem cell)	5 (10.4)	13 (10.2)	1.000
Chronic pulmonary disease	4 (8.3)	5 (3.9)	0.260
Chronic renal failure	1 (2.1)	5 (3.9)	1.000
Acute renal failure	4 (8.3)	3 (2.4)	0.091
Cardiac dysfunction	2 (4.2)	4 (3.1)	0.666
Diabetes	3 (6.3)	25 (19.7)	0.031
Vascular disease
Cerebrovascular	14 (29.2)	24 (18.9)	0.142
Others (cardiovascular/macrovascular/peripheral vascular/intestinal vascular)	6 (12.5)	15 (11.8)	0.900
Intracranial infection	5 (10.4)	14 (11.0)	0.908
Non-neoplastic/infectious neurologic diseases	1 (2.1)	8 (6.3)	0.447
Autoimmune diseases	2 (4.2)	3 (2.4)	0.616
Gastrointestinal disease
Perforation	2 (4.2)	5 (3.9)	1.000
Others (obstruction/hemorrhage)	3 (6.3)	10 (7.9)	1.000
Trauma	9 (18.8)	26 (20.5)	0.799
Clinical findings
Immunocompromise, no. (%)	22 (45.8)	49 (38.6)	0.383
Neutropenia, no. (%)	3 (6.3)	4 (3.1)	0.394
Septic shock, no. (%)	11 (22.9)	27 (21.3)	0.813
APACHE II score, median (IQR)	19 (15.5–24.5)	19 (13–24)	0.820
Indwelling invasive devices, no. (%)
Central venous catheter/PICC	37 (77.1)	101 (79.5)	0.724
Other catheter (tracheal catheter/nasogastric tube/bladder catheter/surgical drain)	38 (79.2)	108 (85.0)	0.351
Length of hospital stay, median (IQR)	34 (20.5–64)	32 (22–56)	0.786
Length of ICU stay, median (IQR)	17.5 (0–41)	18 (0–36)	0.820
Days of mechanical ventilation, median (IQR)	1.5 (0–14.5)	6 (0–17)	0.365
Treatment variables
Time to initiation targeted regimen ≤48 h, no. (%)	35 (72.9)	67 (52.8)	0.016
Peak temperature during BSI (°C), mean (SD)	39.5 (0.8)	39.5 (1.0)	0.748
D1 WBC after targeted regimen (×10^9/L), median (IQR)	11.2 (6.0–16.7)	10.9 (7.4–15.5)	0.704
D1 ANC after targeted regimen (×10^9/L), median (IQR)	8.4 (4.6–14.2)	8.9 (6.0–13.3)	0.606

Abbreviation: PICC, peripherally inserted central catheter.

Table 3 Clinical Outcomes of Individuals with Bloodstream Infections Caused by CR-GNB, According to Type of Antibiotic Regimen, in vitro Susceptibility Tests, and Time to Initiation of Targeted Regimen Containing at Least One Active Agent

Outcomes	Number (%) of Individuals		P value
	Monotherapy (n = 48)	Combination Therapy (n = 127)
All-cause 14-day mortality	4 (8.3)	17 (13.4)	0.359
All-cause 28-day mortality	7 (14.6)	28 (22.0)	0.271
Mortality due to infection	12 (25.0)	39 (30.7)	0.458
Treatment success or presumed success rate	28 (58.3)	75 (59.1)	0.931
	No active agent (n = 120)	With active agent (n = 55)
All-cause 14-day mortality	17 (14.2)	4 (7.3)	0.193
All-cause 28-day mortality	24 (20.0)	11 (20.0)	1.000
Mortality due to infection	37 (30.8)	14 (25.5)	0.467
Treatment success or presumed success rate	67 (55.8)	36 (65.5)	0.230
	Initiation of at least 1 active agent ≤48 h (n = 18)	Initiation of at least 1 active agent >48 h (n = 37)
All-cause 14-day mortality	2 (11.1)	2 (5.4)	0.590
All-cause 28-day mortality	5 (27.8)	6 (16.2)	0.473
Mortality due to infection	6 (33.3)	8 (21.6)	0.510
Treatment success or presumed success rate	11 (61.1)	25 (67.6)	0.637

Figure 3 Treatment success or presumed success rate associated with different antimicrobial drug regimen categories in patients diagnosed as CR-GNB BSIs with different presenting features (A), with active agent containing or not (B) and with different categories of isolates (C).