Increased Incidence and Risk Factors of Infections by Extended-Spectrum β-Lactamase-Producing Enterobacterales During the COVID-19 Pandemic: A Retrospective Case-Control Study

Figures & data

Table 1 Univariate Analysis of Risk Factors for Extended-Spectrum β-Lactamase Producing Enterobacterales (ESBL-E), n (%)

Variables	Case group (n=107)	Control group (n=214)	p value
General Characteristics
Male	52 (48.6%)	103 (48.1%)	0.937
Age, M (P25, P75), (years)	67 (52, 81)	67 (52, 81)	0.983
Length of hospitalization, days			< 0.001
<15	63 (58.9%)	203 (94.9%)
≥15	44 (41.1%)	11 (5.1%)
Previous hospitalization	48 (44.9%)	98 (45.8%)	0.874
ICU admission	21 (19.6%)	14 (6.5%)	< 0.001
COVID-19	61 (57.0%)	88 (41.1%)	0.007
Nutritional status (≥3 points)	28 (26.2%)	26 (12.1%)	0.002
Underlying diseases
Hypertension	48 (44.9%)	83 (38.8%)	0.297
Diabetes mellitus	30 (28.0%)	37 (17.3%)	0.026
COPD	4 (3.7%)	18 (8.4%)	0.118
Chronic kidney disease	13 (12.1%)	8 (3.7%)	0.004
Comorbidities
Sepsis	11 (10.3%)	4 (1.9%)	0.001
Respiratory failure	25 (23.4%)	17 (7.9%)	< 0.001
Hypoproteinemia	49 (45.8%)	38 (17.8%)	< 0.001
Laboratory tests
Albumin (< 40 g/L)	95 (88.8%)	170 (79.4%)	0.038
WBC (> 9.5×10^9/L)	51 (47.7%)	47 (22.0%)	< 0.001
Serum lactate level (> 2.2 mmol/L)	34 (31.8%)	51 (23.8%)	0.128
Invasive operations
Mechanical Ventilation	22 (20.6%)	7 (3.3%)	< 0.001
Central venous placement	30 (28.0%)	17 (7.9%)	< 0.001
Retained urinary catheter	37 (34.6%)	26 (12.1%)	< 0.001
Tracheal intubation	22 (20.6%)	5 (2.3%)	< 0.001
Treatment and drug use
Blood transfusion	20 (18.7%)	15 (7.0%)	0.002
Surgery	28 (26.2%)	73 (34.1%)	0.149
Use of antimicrobial drugs	101 (94.4%)	100 (46.7%)	< 0.001
Length of antimicrobial drug use, days			< 0.001
<7	40 (37.4%)	191 (89.3%)
≥7	67 (62.6%)	23 (10.7%)
Antibacterial drug combination			< 0.001
Not used	6 (5.6%)	114 (53.3%)
Single use	67 (62.6%)	88 (41.1%)
Two or more	34 (31.8%)	12 (5.6%)
Types of antibacterial drugs			< 0.001
Not used	6 (5.6%)	114 (53.3%)
1 type	43 (40.2%)	85 (39.7%)
2 types	32 (29.9%)	14 (6.5%)
≥3 types	26 (24.3%)	1 (0.5%)
Use of hormonal drugs	43 (40.2%)	23 (10.7%)	< 0.001
Length of hormonal drug use, days			0.001
<7	95 (88.8%)	209 (97.7%)
≥7	12 (11.2%)	5 (2.3%)

Notes: The nutritional status was obtained from the nutritional risk screening scale. A score of less than 3 indicates that the patient’s nutritional status is re-evaluated weekly if he or she will undergo major surgery; A score greater than or equal to 3 indicates that the patient is at risk of malnutrition and requires nutritional support therapy. P values in bold are statistically significant (P < 0.05).

Abbreviations: M, median; ICU, intensive care unit; COPD, chronic obstructive pulmonary disease; WBC, white blood cell.

Figure 1 Interrupted time series analysis of the incidence of infections by ESBL-E. Baseline: weeks 1–8 are the weekly incidence of infections by ESBL-E before COVID-19 (December 8, 2021 to February 1, 2022); Intervention stage: weeks 9–16 are the weekly incidence of infections by ESBL-E during the COVID-19 pandemic (December 8, 2022 to February 1, 2023). The black dots indicate the actual weekly incidence of infection by ESBL-E; The dotted line indicates the start of the intervention, which is the beginning of the COVID-19 pandemic; The solid line indicates the incidence of infection by ESBL-E as predicted by the ITSA model.

Figure 2 LASSO Logistic regression. (a) LASSO coefficient profiles of the 27 variables. As the value of λ decreases, the function of the model to select important variables is enhanced; (b) The cross-validation results. The left dashed line corresponds to the parameter lambda.min, and the right dashed line corresponds to the parameter lambda.1se. The left solid line was chosen as the best λ value. 13 variables were selected when λ = 0.021.

Table 2 Multivariate Logistic Regression Analysis of Risk Factors for Extended-Spectrum β-Lactamase Producing Enterobacterales (ESBL-E), OR (95% CI)

Variables	Model 1	Model 2	Model 3	Model 4
COVID-19	1.90 (1.19–3.04)**	1.23 (0.69–2.20)	0.81 (0.43–1.52)	0.61 (0.30–1.28)
Length of hospitalization ≥ 15 days		10.49 (4.83–22.81)***	8.80 (3.92–19.72)***	2.98 (1.07–8.28)*
Diabetes mellitus		1.83 (0.95–3.54)	2.09 (1.07–4.11)*	1.58 (0.66–3.80)
COPD		0.27 (0.07–0.99)*	0.25 (0.07–0.95)*	0.14 (0.03–0.66)*
Chronic kidney disease		3.41 (1.17–9.92)*	3.35 (1.12–10.00)*	4.25 (1.32–13.70)*
Hypoproteinemia		2.68 (1.44–5.02)**	2.23 (1.17–4.25)*	1.25 (0.57–2.76)
Serum lactate level (> 2.2 mmol/L)		0.89 (0.47–1.72)	0.94 (0.48–1.84)	1.73 (0.80–3.76)
WBC (> 9.5×10^9/L)		2.96 (1.65–5.34)***	3.25 (1.76–5.97)***	3.04 (1.54–6.01)**
Blood transfusion			1.88 (0.74–4.74)	1.67 (0.64–4.40)
Surgery			0.66 (0.33–1.33)	0.59 (0.26–1.33)
Use of hormonal drugs			4.06 (1.99–8.29)***	2.38 (1.04–5.43)*
Length of antimicrobial drug use ≥ 7 days				2.14 (0.97–4.72)
Antibacterial drug combination				0.66 (0.25–1.77)
Antibacterial drug use 1 type				5.38 (2.04–14.21)**
Antibacterial drug use 2 types				23.05 (6.71–79.25)***
Antibacterial drug use ≥ 3 types				88.35 (8.55–912.63)***

Notes: In model 1, only the COVID-19 variable was included; Eight variables were included in model 2, including COVID-19, length of hospitalization days ≥15 days, diabetes mellitus, COPD, chronic kidney disease, hypoproteinemia, serum lactate level, WBC; In model 3, three variables were added, including blood transfusion, surgery, and use of hormonal drugs; In Model 4, three variables were added, including length of antimicrobial drug use, antibacterial drug combination, and the type of antimicrobial drug used. The COVID-19 variable is the reference variable. *P < 0.05, **P < 0.01, ***P < 0.001.

Abbreviations: COPD, chronic obstructive pulmonary disease; WBC, white blood cell; OR, odds ratio; CI, confidence interval.