Risk Factors and Outcomes of Multidrug-Resistant Bacteria Infection in Infected Pancreatic Necrosis Patients

Figures & data

Figure 1 Patient inclusion flow chart.

Abbreviations: AP, acute pancreatitis; MAP, mild acute pancreatitis; CT, computed tomography; IPN, infected pancreatic necrosis; MDRB, multidrug resistant bacteria; EPI, extra-pancreatic infection; PCT, procalcitonin.

Table 1 Definitions of the Clinical Factors

Clinical Factors	Definition
Acute pancreatitis^Citation7	Fulfillment of two of the following three criteria: 1) acute onset of epigastric pain radiating to the lower back; 2) blood amylase and/or lipase levels >3 times higher than normal; and 3) imaging examination (eg, abdominal ultrasound, enhanced CT, and MRI) revealing typical findings of acute pancreatitis.
Necrotizing pancreatitis^Citation14	Presence of varying density shadows in the pancreatic parenchyma on contrast-enhanced CT, with no enhancement in the pancreatic parenchyma in the early stages of disease. The degree of pancreatic necrosis in necrotizing pancreatitis patients was divided into <30%, 30–50%, and > 50%.
Infected pancreatic necrosis^Citation7	Fulfillment of either of the following two criteria: 1) abdominal enhanced CT scan displaying the “bubble sign” in pancreatic and/or peripancreatic tissues; 2) development of positive pancreatic necrotic bacterial or fungal cultures with fine-needle aspiration (FNA) or other micro-invasive procedures.
Extra-pancreatic infection^Citation15,Citation16	Occurrence at sites other than the pancreas. When AP patients display symptoms of infection with no definite signs of infection (bubble syndrome) are found to have necrotic pancreatic tissue on imaging but the necrotic tissue and pus puncture and drainage culture are negative, the patient may be suspected of having infection in other parts of the pancreas, which can be confirmed or excluded by multiple or multiple sites of pathogen culture. Common sites include the blood, respiratory tract, urinary tract, abdominal cavity, biliary tract, and surgical incision sites.
Multidrug-resistant bacteria^Citation17,Citation18	Bacteria that are resistant to three or more classes of commonly used antimicrobial drugs.
Organ failure
Pulmonary failure	PaO2/ FIO2 <300, or need for mechanical ventilation.
Circulatory failure	Circulatory systolic blood pressure <90 mm Hg, despite adequate fluid resuscitation, or need for inotropic catecholamine support.
Renal failure	Creatinine level ≥177 umol/L after rehydration or new need for hemofiltration or hemodialysis.
New-onset organ failure	First onset of organ failure requiring intervention at any time in a 24 hour period.
Multiple organ failure	Number of organs in failure ≥2.
Surgical complications
Intraabdominal hemorrhage	Persistent bleeding fluid in the drainage tube or around the wound, requiring surgical, radiologic, or endoscopic intervention.
Gastrointestinal fistula	Secretion of fecal material from a percutaneous drain or inflow into the necrotic cavity, either from small or large bowel; confirmed by endoscopy, imaging or during surgery.
Gastrointestinal obstruction	Gastrointestinal symptoms (eg abdominal distention, abdominal pain, dyspepsia, etc.) caused by pressure on surrounding organs by pancreatic necrotic material.
Pancreatic fistula	Amylase content in drainage tube or exudate around wound ≥3 times the serum amylase level.
Abdominal compartment syndrome	An increase in intra-abdominal pressure (≥20 mmHg) caused by various factors leading to the dysfunction of digestive, circulatory, respiratory and urinary systems.
Referral time	The time for patients to present to our hospital for treatment since the onset of disease, including direct visits to our hospital and referral from other secondary hospitals.
Infected pancreatic necrosis diagnosed before admission	Infected pancreatic necrosis diagnosed before the patient was referred to our hospital.

Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; AP, acute pancreatitis.

Table 2 Comparison of Baseline Data on Admission Between MDRB and Non-MDRB Groups

Characteristics	MDRB (n = 124)	No-MDRB (n= 143)	Total (n= 267)	P value
Age [year mean ± SD]	50.11 ± 14.42	51.32 ± 15.55	50.72 ± 14.94	0.554
Sex [n (%)]				0.897
Male	81 (65.32)	95 (66.43)	176 (65.92)
Female	43 (34.68)	48 (33.56)	91 (34.08)
Etiology [n (%)]				0.288
Gallstones	66 (53.23)	78 (54.55)	144 (53.93)
Hyperlipidemia	41 (33.06)	37 (25.87)	78 (29.21)
Others	17 (13.71)	28 (19.58)	45 (16.85)
BMI [kg/m^2 mean ± SD]	24.75 ± 3.58	25.24 ± 4.55	25.00 ± 4.09	0.207
ASA [score, median (range)]	2 (1~3)	1 (1~3)	2 (1~3)	0.186
Transfer time [days, median (range)]	30 (1~120)	25 (1~150)	30 (1~150)	0.01*
Transfer [n (%)]	115 (92.74)	130 (90.91)	245 (91.76)	0.659
IPN diagnosed at a different facility				0.704
Yes	44 (35.48)	56 (39.16)	100 (37.45)
No	80 (64.52)	87 (60.84)	167 (62.55)
Admission temperature [mean ± SD]	37.14 ± 0.89	36.91 ± 0.89	37.03 ± 0.89	0.191
CTSI [score, median(range)]	8 (4~10)	6 (2~10)	6 (2~10)	0.001*
Extent of necrosis [n (%)]				0.001*
<30%	10 (8.06)	56 (39.16)	66 (24.72)
30–50%	79 (63.71)	66 (46.15)	118 (54.31)
>50%	35 (28.23)	21 (14.69)	56 (20.97)
Admission laboratory indicators [mean ± SD]
WBC (× 10^9/L)	12.10 ± 5.76	11.25 ± 6.70	11.67 ± 6.24	0.318
Percentage of neutrophils (%)	82.28 ± 8.78	81.49 ± 9.86	81.91 ± 9.21	0.664
Hb (g/L)	94.49 ± 32.05	112.36 ± 28.34	102.75 ± 31.40	0.003*
Hct (%)	29.39 ± 6.78	32.64 ± 8.31	31.02 ± 7.73	0.002*
Alb (g/L)	27.76 ± 5.39	30.27 ± 6.55	28.92 ± 6.03	0.033*
CRP (mg/L)	186.27 ± 122.88	165.43 ± 122.97	176.07 ± 122.71	0.249
PCT (ng/mL)	1.65 ± 1.39	0.82 ± 0.79	1.25 ± 1.19	0.001*
IL-6 (pg/mL)	239.48 ± 210.65	186.50 ± 160.11	213.43 ± 188.35	0.058

Note: *P<0.05.

Abbreviations: MDRB, multidrug resistant bacteria; BMI, body mass index; ASA, American Society of Anesthesiologists; IPN, infected pancreatic necrosis; WBC, white blood cell count; Hb, hemoglobin; CTSI, computer tomography severity index; Hct, hematocrit; CRP, C-reactive protein; Alb, albumin; PCT, procalcitonin; IL-6, interleukin; ERCP, endoscopic retrograde cholangiography.

Table 3 Clinical Management and Prognosis Comparison by Group

Characteristics	MDRB (n = 124)	No-MDRB (n = 143)	Total (n = 267)	P value
Duration of nutritional support [days (mean ± SD)]
Parenteral nutrition	32.07 ± 26.92	20.71 ± 18.61	26.31 ± 23.67	0.001*
Enteral nutrition	30.25 ± 27.44	20.07 ± 19.08	25.03 ± 23.96	0.001*
Nutritional support [n (%)]				0.001*
Only parenteral nutrition	24 (19.35)	73 (51.05)	97 (36.33)
Combined nutrition	100 (80.65)	70 (48.95)	170 (63.67)
Need antibiotic treatment [n (%)]
Yes	110 (88.71)	105 (73.43)	215 (80.52)	0.002*
No	14 (11.29)	38 (26.57)	52 (19.47)
Outside intervention [n (%)]				0.152
Yes	46 (37.10)	41 (28.67)	87 (32.58)
No	78 (62.90)	102 (71.33)	180 (67.42)
Minimally invasive intervention [n (%)]				0.001*
Yes	110 (88.71)	93 (65.03)	203 (76.03)
No	14 (11.29)	50 (34.97)	64 (23.97)
Number of surgical interventions [times, median (Range)]	2 (1–10)	2 (1–7)	2 (1–10)	0.014*
Surgical complications [n (%)]	29 (23.39)	17 (11.89)	46 (17.23)	0.015*
Intraabdominal hemorrhage	12 (9.68)	8 (5.59)	20 (7.49)
Gastrointestinal fistula	8 (6.45)	4 (2.80)	12 (4.49)
Gastrointestinal obstruction	6 (4.84)	2 (1.40)	8 (3.00)
Others	3 (2.42)	3 (2.10)	6 (2.25)
Preoperative organ failure	40 (32.26)	41 (28.67)	81 (30.34)	0.594
New organ failure after surgery	14 (11.29)	2 (1.40)	16 (5.99)	0.001*
Time of confirmed infection [days (mean ± SD)]	10.84 ± 7.79	14.61 ± 12.65	12.73 ± 10.64	0.009*
EPI infection [n (%)]	79 (63.71)	49 (34.27)	128 (47.94)	0.001*
Fungal infection [n (%)]	44 (35.48)	28 (19.58)	72 (26.97)	0.004*
Pancreatic origin	8 (6.45)	5 (3.50)	13 (4.87)
Extra-pancreatic origin	36 (29.03)	23 (16.08)	59 (22.10)
ICU stay [days (mean ± SD)]	30.13 ± 28.67	17.94 ± 13.72	23.79 ± 19.75	0.001*
Hospital stay [days (mean ± SD)]	49.98 ± 31.08	28.99 ± 21.45	36.59 ± 27.25	0.001*
Mortality [n (%)]	30 (24.19)	20 (13.99)	50 (18.73)	0.041*

Note: *P <0.05.

Abbreviations: MDRB, multidrug resistant bacteria; POF, persistent organ failure; EPI, extra-pancreatic infection; ICU, intensive care unit.

Table 4 Microbiological Profile of Organisms in IPN Patients

Organism	Total, n (%)
	MDRB	Non-MDRB	Total
Gram positive
Enterococcus faecium	19 (1.91)	79 (7.94)	98 (9.85)
Staphylococcus epidermidis	12 (1.21)	45 (4.52)	57 (5.73)
Staphylococcus hominis	7 (0.70)	31 (3.12)	38 (3.82)
Staphylococcus aureus	10 (1.01)	12 (1.21)	22 (2.21)
Others	8 (0.80)	41 (4.12)	49 (4.92)
Gram negative
Acinetobacter bowman	85 (8.84)	32 (3.22)	117 (11.76)
Klebsiella pneumoniae	79 (7.94)	39 (3.92)	118 (11.86)
Pseudomonas aeruginosa	38 (3.82)	80 (8.04)	118 (11.86)
Escherichia coli	32 (3.22)	56 (5.63)	88 (8.84)
Others	17 (1.71)	143 (14.37)	160 (16.08)
Fungal
Candida albicans	30 (3.02)	17 (1.71)	47 (4.72)
Candida parapsilosis	16 (1.61)	7 (0.70)	23 (2.31)
Candida glabrata	17 (1.71)	3 (0.30)	20 (2.01)
Candida tropicalis	17 (1.71)	6 (0.60)	23 (2.31)
Others	15 (1.51)	2 (0.20)	17 (1.71)
Total, n (%)	402 (40.40)	593 (59.60)	995 (100)

Abbreviation: MDRB, multidrug resistant bacteria.

Table 5 Multivariable Analysis of Risk Factors for MDRB Infection in IPN Patients

Variables	Univariable Analysis		Multivariable Analysis
	OR (95% CI)	p-value	OR (95% CI)	p-value
EPI	3.947 (2.240–6.957)	0.001*	4.116 (1.381–12.271)	0.011*
Level of admission PCT	2.141 (1.557–2.994)	0.001*	2.728 (1.502–4.954)	0.001*
Degree of pancreatic necrosis	6.347 (2.831–14.227)	0.001*	2.741 (1.109–6.775)	0.029*
Transfer time	1.011 (1.000–1.021)	0.044*	1.107 (0.994–1.04)	0.153
Hb	0.979 (0.965–0.994)	0.006*	0.956 (0.905–1.009)	0.103
Hct	0.943 (0.908–0.980)	0.003*	1.125 (0.907–1.395)	0.284
Alb	0.930 (0.868–0.996)	0.038*	0.997 (0.895–1.109)	0.949
Antibiotic treatment	2.911 (1.425–5.946)	0.003*	0.964 (0.898–1.035)	0.317
Whether surgical intervention	4.364 (2.080–9.156)	0.001*	1.007 (0.980–1.034)	0.622

Notes: After univariate and multivariate Logistic regression analysis found that combined EPI (OR: 4.116, 95% CI: 1.381–12.271, P = 0.011), PCT level at admission (OR: 2.728, 95% CI: 1.502–4.954, P = 0.001), and the degree of pancreatic necrosis (OR: 2.741, 95% CI: 1.109–6.775, P = 0.029) being identified as independent risk factors for MDRB infection in IPN patients. *P < 0.05.

Abbreviations: MDRB, multidrug resistant bacteria; EPI, extra-pancreatic infection; PCT, procalcitonin; Hb, hemoglobin; Hct, hematocrit; Alb, albumin; IPN, infected pancreatic necrosis.

Figure 2 Receiver operating characteristic curve analysis of the prediction of MDRB infection by admission PCT level.

Notes: The ROC analysis of the PCT level at admission found that when the PCT value was 1.055 ng/mL, the sensitivity was 0.636, the specificity was 0.741, and the ROC curve area was 0.705.

Abbreviations: MDRB, multidrug resistant bacteria; PCT, procalcitonin.

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