The Etiological and Drug Resistance Characteristics of Multidrug-Resistant Pathogens in Patients Requiring Extracorporeal Membrane Oxygenation: A Retrospective Cohort Study

Figures & data

Figure 1 The flowchart.

Abbreviations: VA-ECMO, Veno-Arterial Extracorporeal Membrane Oxygenation; VV-ECMO, Veno-Venous Extracorporeal Membrane Oxygenation; Group R, Multidrug-resistant bacterial infections Group; Group N, Non Multidrug-resistant bacterial infection bacterial Group; n, the number of patients in each group.

Table 1 The Clinical Characteristics of ECMO Patients With or Without MDR Infections

Characteristics	VA-ECMO			VV-ECMO
	Group R (n=31)	Group N (n=30)	P value	Group R (n=23)	Group N (n=6)	P value
Demographic characteristics:
Age (y)^a	63±16	56±18	0.086	48±19	48±16	0.975
Female^c	9 (29)	4 (13.3)	0.236	5 (21.7)	3 (50)	0.305
Reasons for initiating ECMO:
ARDS^c	5 (16.1)	2 (15)	0.449	23 (100)	6 (100)	/
Cardiac factors^c	18 (58.1)	24 (80)	0.116	0 (0.0)	0 (0.0)	/
Pulmonary embolism^c	8 (25.8)	3 (10)	0.203	0 (0.0)	0 (0.0)	/
Condition states:
Pneumonia	26 (83.9)	21 (70)	0.001	22 (95.7)	6 (100)	/
Sepsis	6 (19.4)	0 (0.0)	/	10 (43.5)	4 (66.7)	0.068
Diabetes^c	10 (32.3)	13 (43.3)	0.372	3 (13)	0 (0.0)	/
Autoimmune disorders^c	2 (6.5)	2 (6.7)	0.999	1 (4.3)	2 (33.3)	0.100
Tumor^c	4 (12.9)	1 (3.3)	0.371	6 (26.1)	0 (0.0)	/
SOFA	13.3±3.5	11.9±4.7	0.197	13.5±3.9	10.5±1.7	0.147
APACHE II	29±6.2	28.7±7.3	0.864	27.7±6.9	23.5±2.6	0.250
Vasoactive drug^c	22 (71)	27 (90)	0.122	8 (34.8)	4 (66.7)	0.198
CRRT^c	18 (58.1)	15 (50)	0.527	14 (60.9)	2 (33.3)	0.364
Laboratory indicators:
WBC (×10^9/L)^b	12.8 (8–17.9)	11.3 (8.4–17.4)	0.729	9.4 (7.5–20.2)	8.2 (4.8–24.8)	0.896
N (%)^a	84.6±14.0	78.5±14.9	0.104	87.7±6.3	88.7±4.3	0.705
LY (×10^9/L)^a	1.1±0.9	1.8±1.2	0.013	0.7±0.4	0.7±0.7	0.781
PCT (ng/mL)^b	3.1 (0.6–12.9)	1.1 (0.5–10.1)	0.190	3.1 (1.1–14.9)	1.6 (0.5–11.7)	0.408
CRP (μg/mL)^a	49±86	20±19	0.231	143±121	99±78	0.416
ESR (mm/h)^b	8 (5–10)	3 (2–9)	0.061	10 (3–31)	9 (5–18)	0.820
AST (U/L)^b	254 (98–579)	209 (67–513)	0.516	37 (20–94)	13 (11–32)	0.410
ALT (U/L)^b	396 (222–842)	450 (114–998)	0.913	43 (25–132)	30 (15–83)	0.356
TB (μmol/L)^b	13.7 (10.5–19.5)	12.3 (7.7–17)	0.139	15.3 (10.8–21.7)	33.2 (4.43–41.9)	0.414
DB (μmol/L)^b	5.5 (3.7–10.1)	3.3 (2.8–6.8)	0.019	11.5 (4.5–16)	9.9 (2.7–26.2)	0.854
TP (g/L)^a	47.4±9.1	45.7±10.8	0.514	48.6±6.2	50.5±6.6	0.985
ALB (g/L)^a	30.1±6.7	28.8±6.8	0.442	29.6±3.9	33.5±6.7	0.074
BNP (pg/mL)^b	258 (57–1172)	145 (12–304)	0.074	177 (29–1090)	153 (20–970)	0.655
PT (%)^a	20.4±8.2	20.7±8.5	0.860	16.2±1.7	16±1.7	0.856
APTT (sec)^b	118.1 (74.8–180)	119.9 (56–180)	0.301	48.4 (42.9–65.9)	63.8 (43.8–109.2)	0.356
Fig (g/L)^b	2.2 (1.6–3.4)	2.1 (1.5–3.4)	0.735	4.1 (2.4–6.2)	2.5 (2.2–4.3)	0.356
D-D (mg/L)^b	2.8 (0.7–10)	3.8 (1.6–8.7)	0.870	2.1 (0.5–6.8)	1.1 (0.5–2)	0.239
PaO2 (mmHg)^b	208 (131–384)	165 (138–251)	0.086	94 (76–144)	107 (79–165)	0.733
PaCO2 (mmHg)^a	36.9±10.4	37.0±9.8	0.981	38.5±8.7	34.6±6.8	0.333
Lac (mmol/L)^b	6.9 (3.5–8.2)	5.4 (2.9–10.2)	0.457	2.3 (1.9–4.1)	2.9 (1.5–3.3)	0.854
Prognosis indicators:
Time on mechanical ventilator (h)^b	249 (156–367)	44 (24–108)	0.001	285 (174–368)	163 (83–251)	0.031
Duration of ECMO support (h)^b	127 (77–194)	44 (23–95)	0.001	164 (123–210)	75 (68–149)	0.047
ECMO weaning^c	22 (71)	8 (26.7)	0.001	15 (65.2)	4 (66.7)	0.999
ICU stay time (d)^b	13 (7–20)	3 (1–8)	0.001	15 (7–22)	9 (4–16)	0.158
Length of hospital stay (d)^b	13 (7–20)	5 (2–10)	0.001	15 (7–22)	9 (4–27)	0.388
In-hospital mortality^c	27 (87.1)	24 (80)	0.687	16 (69.6)	4 (66.6)	0.999

Notes: ^aThe continuous variables following normal distribution are presented as mean ± standard deviation, and analyzed by t-test or adjusted t-test. ^bThe continuous variables not conforming to normal distribution, are presented as the median [inter- quartile range], and analyzed by non-parametric test. ^cThe dichotomous variables are presented as number (percentage), and analyzed by chi-square or Fisher exact probability (FET) tests. P values < 0.05 were significant and indicated in bold.

Abbreviations: ECMO, Extracorporeal Membrane Oxygenation; VV-ECMO, Veno-Venous Extracorporeal Membrane Oxygenation; VA-ECMO, Veno-Arterial Extracorporeal Membrane Oxygenation; MDR, Multidrug-Resistant; Group R, Multidrug-Resistant bacterial infections Group; Group N, Non Multidrug-Resistant bacterial infection bacterial Group; ARDS, Acute Respiratory Distress Syndrome; SOFA, Sequential organ Failure Assessment; APACHE II, Acute Physiology and Chronic Health Evaluation II; CRRT, Continuous Renal Replacement Therapy; WBC, White Blood Cells; N, Neutrophil; LY, Lymphocyte; PCT, Procalcitonin; CRP, C-reactive Protein; ESR, Erythrocyte Sedimentation Rate; AST, Aspartate Aminotransferase; ALT, Alanine Aminotransferase; TB, Total Bilirubin; DB, Direct Bilirubin; TP, Total Protein; ALB, Albumin; BNP, Brain Natriuretic Peptide; PT, Prothrombin Time; APTT, Activated Partial Thromboplastin Time; Fig, Fibrinogen; D-D, D-Dimer; PaO₂, Arterial Oxygen Partial Pressure; PaCO₂, Arterial Partial Pressure of Carbon Dioxide; Lac, Lactic Acid; ICU, Intensive Care Unit.

Table 2 The Partial Correlation Analysis of MDR Bacterial Infection and Prognosis Indicators

ECMO Modes	Prognosis Indicators	Length of Hospital Stay	ICU Stay Time	Time on Mechanical Ventilator	Duration of ECMO Support	ECMO Weaning	In-Hospital Mortality	With or Without MDR Infections
VA-ECMO	Length of hospital stay	/	0.974**	0.661**	0.192	0.59**	0.314	0.329*
	ICU stay time	/	/	0.722**	0.246	0.653**	0.36*	0.415*
	Time on mechanical ventilator	/	/	/	0.312	0.483*	0.28	0.612**
	Duration of ECMO support	/	/	/	/	0.127	−0.068	0.504*
	ECMO weaning	/	/	/	/	/	0.49*	0.422*
	In-hospital mortality	/	/	/	/	/	/	0
VV-ECMO	Length of hospital stay	/	0.956**	0.593*	0.029	0.488*	0.236	0.147
	ICU stay time	/	/	0.604*	0.071	0.448*	0.272	0.259
	Time on mechanical ventilator	/	/	/	0.156	0.416*	−0.167	0.402
	Duration of ECMO support	/	/	/	/	−0.333	−0.377	0.465*
	ECMO weaning	/	/	/	/	/	0.497*	−0.05
	In-hospital mortality	/	/	/	/	/	/	−0.053

Notes: The results of partial correlation analysis of Table 1 after 1:1 propensity score matching for VA-ECMO patients and 1:3 propensity score matching for VV-ECMO patients. *P values < 0.05 and **P values < 0.001 were significant.

Abbreviations: ECMO, Extracorporeal Membrane Oxygenation; VV-ECMO, Veno-Venous Extracorporeal Membrane Oxygenation; VA-ECMO, Veno-Arterial Extracorporeal Membrane Oxygenation; MDR, Multidrug-Resistant; ICU, Intensive Care Unit.

Figure 2 Outcomes of ECMO patients displayed separately according to whether they were infected by MDR bacteria.

Table 3 The Species of MDR Pathogens in ECMO Patients

Pathogen Species	VA-ECMO n (%)	VV-ECMO n (%)	ECMO n (%)
Staphylococcus aureus	1 (2.2)	0 (0)	1 (1.2)
Escherichia coli	2 (4.4)	2 (5.4)	4 (4.9)
Klebsiella pneumoniae	7 (15.6)	13 (35.1)	20 (24.4)
Pseudomonas aeruginosa	4 (8.9)	4 (10.8)	8 (9.8)
Acinetobacter baumannii	24 (53.3)	16 (43.3)	40 (48.8)
Burkholderia cepacia	7 (15.6)	2 (5.4)	9 (10.9)
Total	45 (100)	37 (100)	82 (100)

Note: The variables are presented as number (percentage).

Abbreviations: MDR, Multidrug-Resistant; ECMO, Extracorporeal Membrane Oxygenation; VV-ECMO, Veno-Venous Extracorporeal Membrane Oxygenation; VA-ECMO, Veno-Arterial Extracorporeal Membrane Oxygenation.

Table 4 The Sources of MDR Pathogens in ECMO Patients

Sources	VA-ECMO n (%)	VV-ECMO n (%)	ECMO n (%)
Drainage fluid	2 (4.4)	0 (0)	2 (2.4)
Bronchoalveolar lavage	1 (2.2)	0 (0)	1 (1.2)
Catheter blood	1 (2.2)	0 (0)	1 (1.2)
Secretion	1 (2.2)	1 (2.7)	2 (2.4)
Urine	1 (2.2)	2 (5.4)	3 (3.7)
Blood	5 (11.1)	5 (13.5)	10 (12.2)
Sputum	34 (75.7)	29 (78.4)	63 (76.9)
Total	45 (100)	37 (100)	82 (100)

Note: The variables are presented as number (percentage).

Abbreviations: MDR, Multidrug-Resistant; ECMO, Extracorporeal Membrane Oxygenation; VV-ECMO, Veno-Venous Extracorporeal Membrane Oxygenation; VA-ECMO, Veno-Arterial Extracorporeal Membrane Oxygenation.

Figure 3 Species and sources of MDR pathogens in ECMO patients. The left part of the figure shows the species and sources of MDR pathogens in VA-ECMO patients. The right part of the figure shows the species and sources of MDR pathogens in VV-ECMO patients. Each column represents a patient with MDR infection and each row the bacterium detected. The pathogens were divided into three categories: GPB (Gram-positive bacteria) and GNB (Gram-negative bacteria). The different colors of blocks represent the source of MDR pathogen. The specific meaning of colors are shown in the color indicator on the right of the figure.

Figure 4 The variety of MDR-GNB of ECMO and other ICU patients.

Table 5 The Resistance Ratio of MDR Bacteria to Antibiotics in ECMO Patients

Classification of Antibiotics	Antibiotics	Staphylococcus aureus		Escherichia coli		Klebsiella pneumoniae		Pseudomonas aeruginosa		Acinetobacter baumannii		Burkholderia cepacia
		VA (n=1)	VV (n=0)	VA (n=2)	VV (n=2)	VA (n=7)	VV (n=13)	VA (n=4)	VV (n=4)	VA (n=24)	VV (n=16)	VA (n=7)	VV (n=2)
Carbapenem	Imipenem	/	/	100%	100%	57%	92.3%	100%	75%	95.8%	100%	100%	/
	Meropenem	/	/	100%	100%	57%	92.3%	100%	75%	95.8%	100%	100%	100%
	Ertapenem	/	/	100%	100%	57%	91.7%	/	/	/	/	/	/
Cephalosporin	Cefotaxime	/	/	100%	50%	100%	100%	/	100%	100%	100%	/	/
	Ceftazidime	/	/	100%	100%	85.7%	100%	62.5%	50%	87.5%	93.7%	0	0
	Cefuroxime	/	/	100%	50%	100%	100%	/	/	/	/	/	/
	Ceftriaxone	/	/	/	/	/	/	/	100%	100%	100%	100%	/
	Cefixime	/	/	50%	25%	92.9%	75%	/	/	/	/	/	/
	Cefazolin	100%	/	100%	100%	100%	100%	/	/	/	/	/	/
	Cefoperazone sulbactam	/	/	50%	0	78.6%	100%	75%	25%	54.2%	65.6%	/	/
	Cefoxitin	/	/	100%	50%	57.1%	100%	/	/	/	/	/	/
	Cefepime	/	/	/	/	/	/	87.5%	62.5%	95.8%	93.7%	/	/
Penicillin	Ampicillin	100%	/	100%	50%	100%	100%	/	/	/	/	/	/
	Ampicillin sulbactam	/	/	100%	50%	100%	100%	/	/	/	/	/	/
	Piperacillin	/	/	100%	50%	100%	100%	100%	50%	87.5%	93.7%	0	/
	Piperacillin/Tazobactam	50%	/	0	0	78.6%	100%	87.5%	37.5%	79.2%	93.7%	0	/
Quinolone	Ciprofloxacin	/	/	75%	50%	100%	100%	62.5%	75%	95.8%	96.9%	50%	/
	Levofloxacin	/	/	75%	50%	100%	100%	87.5%	75%	93.7%	96.9%	64.3%	87.5%
Aminoglycoside	Amikacin	0	/	0	0	57.1%	77%	50%	25%	68.7%	56.2%	/	/
	Gentamicin	/	/	50%	0	85.7%	69.2%	66.7%	75%	81.2%	73.3%	0	/
Others	Cotrimoxazole	/	/	/	/	40%	40%	100%	100%	58.3%	71.9%	0	0
	Tigecycline	/	/	100%	100%	50%	53.8%	100%	/	58.3%	66.7%	/	/
	Colistin	/	/	/	/	0	0	0	/	0	0	/	/
	Amtriannan	/	/	/	/	0	/	100%	25%	100%	100%	/	/
	Minocycline	/	/	/	/	/	/	100%	0	41.7%	71.9%	0	0
	Ticarcillin clavulanic acid	/	/	/	/	/	/	87.5%	50%	87.5%	0	28.6%	100%
	Tobramycin	/	/	/	/	/	/	50%	50%	81.2%	71.9%	85.7%	/
	Vancomycin	100%	/	/	/	/	/	/	/	/	/	/	/

Note: The “n” indicates the number of pathogens.

Abbreviations: MDR, Multidrug-Resistant; ECMO, Extracorporeal Membrane Oxygenation; VA, Multidrug-Resistant pathogens in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients; VV, Multidrug-Resistant pathogens in veno-venous extracorporeal membrane oxygenation (VV-ECMO) patients.

Figure 5 Heatmap showing the antimicrobial susceptibility results of MDR bacteria in ECMO patients. Each column represented a bacterium detected and each row an antibiotic of antimicrobial susceptibility tests. All of the drugs were divided into six categories according to their functions. The different colors of blocks represent antimicrobial susceptibility to the drugs. The results of antimicrobial susceptibility were divided into three categories: resistant, intermediary and sensitive. The specific meanings of colors are shown in the color indicators on the right of the figure.

Abbreviations: ESBL⁺, Extended-Spectrum β-Lactamases positive; ESBL⁻, Extended-Spectrum β-Lactamases negative.

Figure 6 The comparison of drug resistance profiles of MDR bacteria between ECMO and other ICU patients. (A) The comparison of drug resistance profiles of Klebsiella pneumoniae (MDR-KP) in ECMO and other ICU patients in our department. The left columns of (A) represent the resistance rates of MDR-KP to antibiotics in ECMO and other ICU patients. The columns of (A) on the right are the differences in resistance rates of MDR-KP between ECMO and other ICU patients in our department. (B) The comparison of drug resistance profiles of Acinetobacter baumannii (MDR-AB) in ECMO and other ICU patients in our department. The left columns of (B) represent the resistance rates of MDR-AB to antibiotics in ECMO and other ICU patients. The columns of (B) on the right show the differences in resistance rates of MDR-AB between ECMO and other ICU patients in our department.