ANALYSIS OF HEALTHCARE ASSOCIATED AND HOSPITAL ACQUIRED INFECTIONS IN CRITICALLY ILL PATIENTS WITH CIRRHOSIS

D’OLIVEIRA, Ricardo Azevedo Cruz; PEREIRA, Lívia Carolina Dourado; CODES, Liana; ROCHA, Mário de Seixas; BITTENCOURT, Paulo Lisboa

doi:10.1590/S0004-2803.202200001-18

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ORIGINAL ARTICLE • Arq. Gastroenterol. 59 (01) • Jan-Mar 2022 • https://doi.org/10.1590/S0004-2803.202200001-18 copy

ANALYSIS OF HEALTHCARE ASSOCIATED AND HOSPITAL ACQUIRED INFECTIONS IN CRITICALLY ILL PATIENTS WITH CIRRHOSIS

Análise das infecções relacionadas aos cuidados de saúde e hospitalares nos pacientes cirróticos críticos

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Background

Bacterial infections occur in 43—59% of cirrhotic patients admitted to the intensive care unit with impact in morbidity and mortality. An increase in the frequency of multidrug-resistant (MDRO) and extensively drug-resistant (XDRO) organisms has been described in bacterial infections in cirrhotic patients with an adverse impact on survival.

Objective

To characterize community-acquired (CA), healthcare-associated (HCA), and hospital-acquired (HA) infections in cirrhotic patients and their impact in the occurrence of adverse outcomes.

Methods

This study included all cirrhotic patients admitted in an intensive care unit specialized in liver and gastrointestinal diseases in Brazil between January 2012 and June 2018. Frequency and topography of infections were retrospectively evaluated, as well as the frequency of MDRO and XDRO organisms, and their impact in occurrence of acute kidney injury, hepatorenal syndrome, acute-on-chronic liver failure, sepsis and mortality.

Results

A total of 374 infections were observed and classified as CA (22%), HCA (34%) and hospital-acquired (44%). Eighty-nine (54%) episodes of hospital-acquired infections were second infections. Spontaneous bacterial peritonitis (32%) and urinary tract infection (23%) were the most common infections. Culture-proven infections were positive in 61% of the cases, mainly gram-negative bacteria (73%). Acute kidney injury, hepatorenal syndrome and sepsis were observed, respectively, in 48%, 15% and 53% of the cases. MDRO and XDRO were seen, respectively, in 35% and 16%, mainly in HCA (48% vs 26% in CA infections, P=0.02) and hospital-acquired (58% vs 26% in CA infections, P=0.0009). Adverse outcomes were more frequently observed in subjects with hospital-acquired infections when compared to HCA and CA infections. Hospital-acquired, HCA and second infections were independently associated with in-hospital mortality.

Conclusion

Hospital-acquired, HCA and second infections are increasingly associated with either MDRO and/or XDRO and are independent predictors of in-hospital mortality. Their recognition and proper selection of appropriate empiric antibiotic regimens are important measures to reduce in-hospital mortality.

Keywords:
Liver cirrhosis; bacterial infections; morbidity; mortality; intensive care unit

	CA infections (n=81)	HCA infections (n=129)	HA infections (n=164)	P
Age (years)	68±11	68±12	69±10	0.50
Child-Pugh Score
A	2 (3%)	0 (0%)	0 (0%)	—
B	27 (33%)	32 (25%)	41 (25%)	0.30
C	52 (64%)	97 (75%)	123 (75%)	0.15
MELD	23±7	23±8	23±8	0.80
APACHE II	14±5	16±8	17±7	0.01^b
Charlson Comorbidities Index	8±3	8±3	8±2	0.08
SOFA	5±3	5±2	5±3	0.60
Types of infections
Spontaneous bacterial peritonitis	27 (33%)	51 (40%)	40 (24%)	0.02^c
Urinary tract infection	19 (23%)	33 (26%)	34 (21%)	0.60
Pneumonia	6 (7%)	16 (12%)	31 (19%)	0.04^b
Skin and soft tissue infection	14 (17%)	9 (7%)	5 (3%)	<0.001^a,b
Infection with undefined site	6 (7%)	10 (8%)	9 (5%)	0.70
Spontaneous bacteremia	2 (2%)	7 (5%)	17 (10%)	0.05 ^b
Primary bloodstream infection	0 (0%)	0 (0%)	16 (10%)	—
Secondary bacterial peritonitis	2 (2%)	1 (1%)	6 (4%)	0.20
Tracheobronchitis	0 (0%)	0 (0%)	4 (2%)	—
Ventilator-associated pneumonia	0 (0%)	0 (0%)	2 (1%)	—
Other infections	5 (6%)	2 (2%)	0 (0%)	—
Microbiological results
Positive cultures (n=230)	35 (43%)	70 (54%)	125 (76%)	<0.001^b,c
Bacterial profile
Gram-negative	25 (71%)	48 (69%)	95 (76%)	0.50
Gram-positive	10 (29%)	22 (31%)	30 (24%)	0.50
Multidrug-or extensively drug resistant organisms	9 (26%)	34 (48%)	72 (58%)	0.003^a,b
Multidrug-resistant organisms	7 (20%)	22 (31%)	51 (41%)	0.03^b
Extensively drug-resistant organisms	2 (6%)	13 (19%)	21 (17%)	0.20

	All (n=230)	CA infections (n=35)	HCA infections (n=70)	HA infections (n=125)
Gram-negative bacteria	169 (73%)	26 (74%)	48 (69%)	95 (76%)
Klebsiella pneumoniae	13 (6%)	3 (9%)	3 (4%)	7 (6%)
Escherichia coli	29 (13%)	10 (29%)	10 (14%)	9 (7%)
Aeromonas hydrophila	3 (1%)	2 (6%)	—	1 (1%)
Enterobacter cloacae	5 (2%)	—	2 (3%)	3 (2%)
Pseudomonas aeruginosa	8 (3%)	—	2 (3%)	6 (5%)
Burkholderia cepacia	4 (2%)	1 (3%)	—	3 (2%)
Stenotrophomonas maltophilia	3 (1%)	—	—	3 (2%)
Proteus mirabilis	2 (1%)	—	—	2 (2%)
Others	9 (4%)	2 (6%)	1 (1%)	6 (5%)
Acinetobacter Baumanni	2 (1%)	—	—	2 (2%)
MDR Gram-negative bacteria	60 (26%)	6 (17%)	19 (27%)	35 (28%)
ESBL-producing Klebsiella pneumoniae	34 (15%)	6 (17%)	10 (14%)	18 (14%)
ESBL-producing Escherichia coli	16 (7%)	—	8 (11%)	8 (6%)
Enterobacter cloacae	3 (15)	—	—	3 (2%)
Brevundimonas diminuta	2 (1%)	—	—	2 (2%)
Proteus mirabilis	3 (1%)	—	—	3 (2%)
Others	2 (1%)	—	1 (1%)	1 (1%)
XDR Gram-negative bacteria	31 (13%)	2 (6%)	11 (16%)	18 (14%)
Carbapanemase-producing Klebsiella pneumoniae	25 (11%)	2 (6%)	10 (1%)	13 (10%)
Carbapanemase-producing Escherichia coli	3 (1%)	—	—	3 (2%)
Others	3 (1%)	—	1 (1%)	2 (2%)
Gram-positive cocci	61 (27%)	9 (26%)	22 (31%)	30 (24%)
Streptococcus pneumoniae	10 (4%)	4(12%)	6 (9%)	—
Staphylococcus aureus	8 (3%)	2 (6%)	4 (6%)	2 (2%)
Coagulase negative Staphylococcus	9 (4%)	—	4 (6%)	5 (4%)
Enterococcus faecalis	9 (4%)	2 (6%)	3 (4%)	4 (3%)
MDR Gram-positive cocci	20 (9%)	1 (3%)	4 (6%)	15 (12%)
Methicilin-resistant Staphylococcus aureus	4 (2%)	—	2 (3%)	2 (2%)
Coagulase negative Staphylococcus	11 (5%)	—	1 (1%)	10 (8%)
Enterococcus faecalis	5 (2%)	1 (3%)	1 (1%)	3 (2%)
XDR Gram-positive cocci	5 (2%)	—	1 (1%)	4 (3%)
Coagulase negative Staphylococcus	1 (0%)	—	—	1 (1%)
Enterococcus faecalis	4 (2%)	—	1 (1%)	3 (2%)

Outcomes	Community-acquired	Healthcare-associated	Hospital-acquired	P
	infections (n=81)	infections (n=129)	infections (n=164)
ICA-AKI	36 (44%)	65 (50%)	75 (46%)	0.70
Hepatorenal syndrome	5 (6%)	12 (9%)	25 (15%)	0.07^b
Dialysis requirement	8 (10%)	11 (9%)	27 (16%)	0.09 ^c
ACLF	28 (35%)	64 (50%)	75 (46%)	0.09^a
Sepsis	22 (27%)	41 (32%)	89 (54%)	<0.01^b,c
Septic shock	13 (16%)	31 (24%)	76 (46%)	<0.01^b,c
Hospital length of stay (days)	11 (7—15)	11 (8—17)	17 (11—28)	<0.001^b,c
ICU length of stay (days)	5 (3—11)	6 (3—10)	10 (4—15)	<0.001^b,c
Mortality	15 (19%)	32 (25%)	78 (48%)	<0.001^b,c

	OR	95%CI		P
Healthcare-associated infections	2.30	1.00	5.29	0.04
Pneumonia	2.71	1.11	6.61	0.03
Second infections	2.47	1.11	5.47	0.03
Hospital-acquired infections	3.64	1.46	9.11	0.006
Female sex	2.24	1.05	4.77	0.04
MELD	1.15	1.09	1.21	<0.001
In-ICU length of stay	1.13	1.06	1.20	<0.001
APACHE II	1.12	1.06	1.19	<0.001
Spontaneous bacterial peritonitis	0.24	0.12	0.52	<0.001

Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia e Outras Especialidades - IBEPEGE. Rua Dr. Seng, 320, 01331-020 São Paulo - SP Brasil, Tel./Fax: +55 11 3147-6227 - São Paulo - SP - Brazil
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[1] Corresponding author: Ricardo Azevedo Cruz D’Oliveira^. E-mail: gastroricardo@gmail.com

Age (years)	67±11
Male sex	147 (72%)
Etiology of cirrhosis
Alcohol liver disease	68 (33%)
Undefined	49 (24%)
Hepatitis C virus	39 (19%)
Non-alcoholic steatohepatitis	24 (12%)
Mixed	11 (6%)
Others	12 (6%)
Child-Pugh Score	11±2
CPS A	2 (1%)
CPS B	75 (26%)
CPS C	208 (73%)
MELD score	23±8
Apache II score	16±7
SOFA	5±3
Charlson Comorbidities Index	8±3
Concurrent hepatocellular carcinoma	63 (22%)
Main reason for ICU admission
Bacterial Infection with sepsis or septic shock	108 (38%)
Hepatic encephalopathy	91 (32%)
Ascitis	54 (19%)
Variceal hemorrhage	28 (10%)
Other causes	4 (1%)
Outcomes
Acute Kidney Injury	138 (48%)
Hepatorenal syndrome	42 (15%)
Dialysis during hospitalization	46 (16%)
ACLF	128 (45%)
Sepsis	152 (53%)
Septic shock	120 (42%)
ICU length of stay	8 (3—12)
Hospital length of stay (days)	8 (8—19)
Mortality	125 (44%)