
==== Front
Ann Med
Ann Med
Annals of Medicine
0785-3890
1365-2060
Taylor & Francis

39239861
10.1080/07853890.2024.2397087
2397087
Version of Record
Research Article
Infectious Diseases
Clinical outcomes and safety of polymyxin B versus tigecycline combination therapy for pneumonia of carbapenem-resistant Klebsiella pneumoniae: a retrospective cohort study
J. Chen et al.
Chen Jing
Xia Binbin
Liu Yang
Sun Wenfang
Liu Fang
Pang Jingyao
Cheng Hua
Department of Pharmacy, Beijing Luhe Hospital, Capital Medical University, Beijing, China
CONTACT Hua Cheng blw_blw@126.com Department of Pharmacy, Beijing Luhe Hospital, Capital Medical University No. 82 Xinhua South Road, Tongzhou District, Beijing, 101149, China.
6 9 2024
2024
6 9 2024
56 1 23970878 7 2024
8 7 2024
23 7 2024
KnowledgeWorks Global Ltd.5 9 2024
published online in a building issue5 9 2024
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
2024
The Author(s)
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

Abstract

Purpose

Infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) has high mortality. There is no clear optimal therapeutic choice for pneumonia caused by CRKP. The aim of this study was to compare the clinical outcomes and safety of the standard doses of polymyxin B-based regimens vs tigecycline-based regimens and to identify risk factors for mortality.

Methods

This retrospective cohort study included patients with pneumonia caused by CRKP between January 1, 2020 and December 31, 2022. The primary outcomes were 7-day bacterial eradication rate and 14- and 28-day all-cause mortality. The secondary outcome was incidence of acute kidney injury.

Results

Seventy-three patients were included in this study, 29 in the polymyxin B-based combination therapy group and 44 in tigecycline-based combination therapy group. There were no significant differences between the two groups in terms of the 7-day bacterial eradication rate (31.03% vs 20.45%, p = 0.409), the 14-day all-cause mortality (37.93% vs 22.73%, p = 0.160), and the incidence of acute kidney injury (14.29% vs 6.82%, p = 0.526). The 28-day all-cause mortality in the polymyxin B-based therapy group was higher than in the tigecycline-based group (75.86% vs 45.45%, p = 0.010). Binary logistic regression analysis revealed that male and previous use of carbapenems were independent factors associated with 28-day all-cause mortality for patients treated with polymyxin B (p < 0.05).

Conclusions

Polymyxin B-based combination therapy at the standard dose should be used with caution for patients with CRKP-induced pneumonia, especially for men who used carbapenems prior to CRKP detection.

Keywords

Carbapenem-resistant Klebsiella pneumoniae
pneumonia
polymyxin B
tigecycline
This study did not receive financial support.
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pmc1. Introduction

Since the Klebsiella pneumoniae carbapenemases were discovered in 1996, carbapenem-resistant Klebsiella pneumoniae (CRKP) has become globally prevalent [1]. Because CRKP infections have high mortality and overburden healthcare systems [2,3], CRKP is an important concern to the World Health Organization [4]. According to the China Antimicrobial Surveillance Network, the prevalence of Klebsiella pneumoniae resistance to meropenem and imipenem increased from 2.9% and 3% in 2005 to 26.3% and 25% in 2018. Chen et al. reported a mortality of 46.1% for patients with nosocomial pneumonia caused by carbapenem-resistant Gram-negative bacteria [5].

Although some novel ß-lactamase inhibitors such as avibactam and vaborbactam have been approved for clinical use, few are available in mainland China [6]. As of October 2023, only ceftazidime-avibactam was offered in China, and its clinical use was limited because of its high cost [7]. Because of the lack of effective antibiotics, tigecycline and polymyxins were considered therapy for infections caused by carbapenem-resistant Gram-negative bacteria [8]. In most hospitals, tigecycline was more accessible than polymyxins, and in mainland China tigecycline-based therapy was the most often used regimen for treating pneumoniae caused by CRKP [9]. Polymyxins have been used as a salvage therapy for CRKP-causing pneumonia.

International Consensus Guidelines for the Optimal Use of the Polymyxins recommend a loading dose of 20000 ∼ 25000 IU/kg, with a maintenance intravenous dose of 12500 ∼ 15000 IU/kg every 12 h for patients with normal renal function [10]. This recommended dose is significantly greater than the standard dose prescribed in the drug instructions. Pharmacokinetic studies of tigecycline revealed that the standard dose of tigecycline resulted in suboptimal concentrations in lung (0.34 mg/L), which is insufficient to control infections caused by carbapenem-resistant pathogens [11]. And in a meta-analysis, Zha et al. showed that the high-dose tigecycline (200 mg loading dose following 100 mg per 12 h) regimen was associated with decreased mortality of patients who had hospital-acquired pneumonia or ventilator-associated pneumonia [12]. But many patients do not receive the guideline recommended dose in clinical treatment. Some studies suggest that polymyxin B/tigecycline combination is superior to monotherapy [13–15].

The aim of our study was to compare the clinical outcomes and safety of polymyxin B-based combination regimens vs tigecycline-based combination regimens at the standard dose for pneumonia caused by CRKP and to identify risk factors for mortality.

2. Methods

2.1. Study design and patients

This retrospective cohort study was conducted in the Beijing Luhe Hospital, Capital Medical University, a 1200-bed tertiary hospital, between January 1, 2020 and December 31, 2022. Patients were included as follows: (1) age ≥18 years; (2) diagnosis of pneumonia; (3) isolated CRKP ≥2 times on different days from qualified sputum specimen (the number of neutrophils >25 per low-power field (LPF), the number of epithelial cells <10/LPF, or the ratio between neutrophils and epithelial cells >2.5:1) or bronchoalveolar lavage fluid.Patients were excluded as follows: (1) CRKP was considered as colonization strains according to the clinical manifestations; (2) CRKP was detected in other specimens; (3) polymyxin B or tigecycline antimicrobial regimens < 48 h and other targeted treatment options after CRKP isolation; (4) incomplete clinical data.

2.2. Treatment regimens of polymyxin B and tigecycline

Polymyxin B in our study was the standard dose: a loading dose of 100, 0000 IU, and then an intravenous maintenance dose of 50, 0000 IU every 12 h. Tigecycline also was the standard dose: a loading dose of 100 mg, and then an intravenous maintenance dose of 50 mg every 12 h.

2.3. Data collection

Eligible patient data were collected from the electronic medical record system. The following data were collected: demographic characteristics, including age, sex, underlying disease, Charlson Comorbidity Index (CCI) [16], antibiotic use prior to CRKP infection, site of the first CRKP isolated, days from admission to detection of CRKP, concomitant microbiological data, invasive procedures such as mechanical ventilatory support, renal replacement during hospitalization, treatment duration, combination therapy regimen, Acute Physiology and Chronic Health Evaluation II (APACHEII) score of first day on CRKP infection [17], laboratory variables of first day on CRKP infection, details of polymyxin B use (loading dose, duration of treatment), bacterial clearance after 7-days, and all-cause mortality after 14 and 28 days. The safety indicator was the incidence of acute kidney injury (AKI) defined as an increase in SCr by 0.3 mg/dl within 48 h [18].

2.4. Outcomes and definitions

The primary outcomes were 14- and 28-day all-cause mortality. The secondary outcome was 7-day bacteria eradication rate. The indicator of safety was AKI during targeted therapy.

Microbiological efficacy was defined as the clearance of CRKP within 7 days, demonstrated by negative microbial culture of samples from the same site after targeted antimicrobial therapy.

All-cause mortality was defined as all-cause death.

CRKP is defined as a susceptibility test showing Klebsiella pneumoniae resistance to either ertapenem, meropenem or imipenem (or a combination). According to the guidelines of the Clinical and Laboratory Standards Institute (2017), carbapenem resistance is defined as a minimum inhibitory concentration (MIC) of ≥2 mg/L for ertapenem or MIC ≥4 mg/L for imipenem or an inhibition zone diameter ≤19 mm for meropenem. Isolates with a MIC ≤2 mg/L were considered susceptible to tigecycline.

2.5. Statistical analysis

All statistical analyses were performed with IBM SPSS software 25.0. The normality of continuous variables was determined by Kolmogorov Smirnov’s test. The normal continuous variables were represented by the mean ± standard deviation, and the non-normal continuous variables were represented by median and interquartile range. T-test and Mann-Whitney U test were used, respectively, for normally distributed data and non-normally distributed data of inter-group tests. Categorical variables are expressed as numbers of patients and percent and were analyzed by chi-square test. Multivariate logistic regression was used to assess potential independent predictors of 28-day death. Factors with p < 0.05 by univariate analysis were entered into the multivariate logistic analysis. p < 0.05 was considered significant.

3. Results

3.1. Clinical characteristics of the two groups

Of 295 patients with pneumonia caused by CRKP, 222 were excluded according to the inclusion and exclusion criteria. Seventy-three patients were enrolled in this study, 29 patients in the polymyxin B-based combination group and 44 patients in the tigecycline-based combination group (Figure 1). The median age was 75 (range: 67–84) years. Fifty-eight patients (79.4%) were men. Common underlying diseases included 33 patients (45.2%) with cerebrovascular disease, 28 patients (38.3%) with hemiplegia, and 25 patients (34.2%) with diabetes. The mean CCI score was 5.44 ± 2.55. More than three antibiotics were used for 50 patients (68.5%) before the CRKP was isolated. The median days from admission to CRKP isolation was 10 (range: 5–22) days. At least two carbapenem-resistant pathogens were isolated at the same specimen site of 58 patients (79.5%). After CRKP isolation, the worst mean APECHE II score was 23.70 ± 6.57. The median hospitalization was 33 days (range 23–63 days). CRKP susceptibility for polymyxin B was unknown. Table 1 shows the baseline characteristics of the two groups.

Figure 1. Schematic of patient screening process. BALF = bronchoalveolar lavage fluid.

Table 1. Demographic and clinical characteristics of study patients.

Characteristics	PMB-based combination (n = 29)	TGC-based combination (n = 44)	P	
Demographic	
Age, median (IQR)	73.5(65-85)	76(69-82)	0.861	
Male, n(%)	23(79.3%)	35(79.5%)	0.981	
Comorbidity	
CCI score(mean ± SD)	5.9 ± 2.6	5.14 ± 2.51	0.216	
Invasive procedures, n (%)	
Nasal feeding	28(96.5%)	44(100%)	0.833	
Foley catheter	29(100%)	44(100%)	–	
Central venous catheter	25(86.2%)	37(84.1%)	1.000	
Peripheral arterial catheter	1(3.44%)	7(15.9%)	0.199	
CRRT	4(13.8%)	3(6.82%)	0.559	
Tracheotomy	7(24.1%)	8(18.2%)	0.538	
Gastroenterostomy	2(6.9%)	0(0)	0.301	
Mechanical ventilation	21(72.4%)	34(77.3%)	0.637	
Tracheoscopy	19(65.5%)	21(47.7%)	0.135	
Parenteral nutrition	21(72.4%)	23(52.3%)	0.085	
Overall duration of hospitalization in days, median (IQR)	30(20.5-48)	36(24.25-67)	0.154	
Time to CRKP detected in days, median (IQR)	7(2.5-19.5)	10.5(6.00-25.75)	0.167	
Multi-Carbapenem-resistant pathogens, n (%)	25(86.21%)	33(75%)	0.246	
Antimicrobial susceptibility	
MIC ≥ 8mg/L for ertapenem	43(97.7%)	28(96.6%)	1.000	
MIC ≥ 16 mg/L for imipenem	40(90.9%)	28(96.6%)	0.642	
Inhibition zone diameter ≤6mm for meropenem	32(72.7%)	19(65.5%)	0.511	
MIC ≤ 2 mg/L for TGC	43(97.7%)	28(96.6%)	1.000	
Previous antibiotics regimens before CRKP deteced,n(%)	
Previously use of Carbapenem	21(72.4%)	29(65.91%)	0.558	
Previously use of β-lactam/β-lactamase inhibitors	20(68.96%)	27(61.36%)	0.507	
Previously use of quinolones	10(34.48%)	19(43.18%)	0.457	
Previously use of aminoglycoside	5(17.24%)	2(4.54%)	0.163	
Severity, mean ± SD	
APACHE II score (mean ± SD)	23.69 ± 7.03	23.70 ± 6.33	0.993	
Laboratory variables of CRKP isolated, median (IQR)	
WBC, median(IQR)	9.11(6.96-15.87)	9.90(7.17-13.59)	0.857	
N%, median(IQR)	86.8(79.45-90.43)	83.56(75.72-87.43)	0.152	
PLT, median(IQR)	157(107-226.5)	186.5(124.75-265)	0.234	
CRP, median(IQR)	73.77(39.76-151.87)	73.77(58.24-106.41)	0.790	
ALT, median(IQR)	28(13.5-81.5)	24(12.5-58.25)	0.491	
Tbil, median(IQR)	10.70(7.55-17.4)	10.8(7.35-16.1)	0.672	
ALB, median(IQR)	30.2(27.75-32.1)	29.85(27.8-32.57)	0.888	
Cr, median(IQR)	66(43.5-143)	84(63.25-145.75)	0.151	
CK, median(IQR)	56(32-172.5)	68.5(28-287.25)	0.652	
PCT, median(IQR)	0.45(0.28-4.94)	0.45(0.45-0.72)	0.609	
PMB, polymyxin B; TGC, tigecycline; CCI, Charlson Comorbidity Index; CRRT, continuous renal replacement therapy; APACHE II, Acute Physiology and Chronic Health Evaluation II; WBC, white blood cell; N%, percent of neutrophils; PLT, platelet count; CRP, C-reactive protein; ALT, alanine transaminase; Tbil, total bilirubin; ALB, albumin; Cr, serum creatinine; CK, creatine kinase; PCT, procalcitonin.

3.2. Targeted treatment regimes

Polymyxin B-based combination group:10 patients of polymyxin B + carbapenems, 9 patients of polymyxin B + β-lactams,7 patients of polymyxin B + quinolones,3 patients of polymyxin B + aminoglycosides, 18 (62.1%) patients were given loading doses. Treatment duration time was 7(range: 5–12) days. Tigecycline-based combination group: 21 patients of tigecycline + β-lactams,12 patients of tigecycline + meropenem, 5 patients of tigecycline + aminoglycosides,3 patients of tigecycline + minocycline,3 patients of tigecycline + other activated antimicrobial agents. All patients were given loading doses. Treatment duration time was 9(range:6-14)days.

3.3. Outcomes

After targeted treatment, there were no significant differences between the two groups in terms of the 7-day bacterial eradication rate (31.03% vs 20.45%, p = 0.409) and the 14-day all-cause mortality (37.93% vs 22.73%, p = 0.160). The 28-day all-cause mortality was higher in the polymyxin B-based combination group compared with the tigecycline-based combination group (75.86% vs 45.45%, p = 0.010) (Table 2).

Table 2. Outcomes for patients who received polymyxin B-based combination vs tigecycline-based combination.

Outcomes	PMB-based combination (n = 29)	TGC-based combination (n = 44)	P	
7-day microbiologic Eradication	9(31.03%)	9(20.45%)	0.409	
14-day all-cause mortality	11(37.93%)	10(22.73%)	0.160	
28-day all-cause mortality	22(75.86%)	20(45.45%)	0.010	
Acute kidney injury	4(14.29%)	3(6.82%)	0.526	
PMB, polymyxin B, TGG, tigecycline.

To eliminate the effect of continuous renal replacement therapy (CRRT) on serum creatinine values, we excluded one patient who underwent CRRT within 48 h after targeted treatment. AKI occurred in 7 patients (9.72%). Incidence of acute kidney injury were no significant differences between the two groups (14.29% vs 6.82%, p = 0.526) (Table 2).

3.4. Risk factors associated with 28-day all-cause mortality

In the univariate logistic regression analysis, being male, CCI score, previous use of carbapenems, APACHE II, and polymyxin B were associated with 28-day all-cause mortality (p < 0.05) (Table 3).

Table 3. Risk factors associated with 28-day mortality.

Parameter	Death n = 42	Survive n = 31	P	
Age, median(IQR)	76(66.75-82.25)	73(73-82)	0.373	
Male, n(%)	38(90.48%)	20(64.52%)	0.010	
CCI score (mean ± SD)	6.05 ± 2.75	5.43 ± 2.15	0.016	
Nasal feeding	42(100%)	30(96.77%)	1.000	
Central venous catheter	38(90.48%)	24(77.42%)	0.133	
Peripheral arterial catheter	5(11.90%)	3(9.68%)	0.764	
CRRT	3(7.14%)	4(12.90%)	0.415	
Tracheotomy	8(19.05%)	7(22.58%)	0.712	
Gastroenterostomy	1(2.38%)	1(3.23%)	0.828	
Mechanical ventilation	33(78.57%)	22(70.97%)	0.458	
Tracheoscopy	23(54.76%)	17(54.84%)	0.995	
Parenteral nutrition	25(59.52%)	19(61.29%)	0.879	
Days from admissition to CRKP detected, median (IQR)	10.5(2.75-20.5)	5(2-19)	0.142	
Multi-Carbapenem-resistant pathogens	28(66.67%)	24(77.42%)	0.185	
MIC ≥ 8mg/L for ertapenem	41(97.6%)	30(96.8%)	1.000	
MIC ≥ 16mg/L for imipenem	40(95.2%)	28(90.3%)	0.645	
Inhibition zone diameter ≤6mm for meropenem	30(71.4%)	21(67.7%)	0.734	
MIC ≤ 2 mg/L for TGC	41(97.6%)	30(96.8%)	1.000	
Previously use of carbapenem	35(83.33%)	15(48.39%)	0.002	
Previously use of β-lactamase inhibitor	24(57.14%)	23(74.19%)	0.136	
Previously use of fluoroquinolones	20(47.62%)	9(29.03%)	0.112	
Previously use of aminoglycoside	5(11.90%)	2(6.45%)	0.441	
APACHE II score (mean ± SD)	24.86 ± 6.81	20 ± 6.86	0.048	
WBC, median(IQR)	9.37(6.79-15.44)	8.79(7.84-17.03)	0.756	
N%, median(IQR)	88.65(79.57-90.75)	83.3(78.1-89.74)	0.310	
PLT(mean ± SD)	161.68 ± 88.04	177.43 ± 58.63	0.635	
CRP, median(IQR)	73.77(39.93-137.76)	73.77(27.18-169.86)	0.809	
ALT, median(IQR)	18(12-57)	75(28-129)	0.269	
Tbil, median(IQR)	9.8(7.15-17.1)	12.5(10.7-28.1)	0.074	
ALB(mean ± SD),	29.445 ± 3.21	31.24 ± 3.27	0.070	
Cr, median(IQR)	75(41.5-152.25)	65(45-72)	0.460	
CK, median(IQR)	75(32.5-216.25)	44(31-134)	0.343	
PCT, median(IQR)	0.53(0.39-6.43)	0.22(0.03-1.97)	0.331	
PMB-containing	22(52.38%)	7(22.58%)	0.012	
PMB, polymyxin B; TGG, tigecycline; ICU, intensive care unit; CCI, Charlson Comorbidity Index; CRRT, continuous renal replacement therapy; APACHE II, Acute Physiology and Chronic Health Evaluation II; WBC, white blood cell; N%, percent of neutrophils; PLT, platelet count; CRP, C-reactive protein; ALT, alanine transaminase; Tbil, total bilirubin; ALB, albumin; Cr, serum creatinine; CK, creatine kinase; PCT, procalcitonin.

Binary logistic regression analysis revealed that being male, previous use of carbapenems, and polymyxin B were independent factors associated with 28-day all-cause mortality (p < 0.05) (Table 4).

Table 4. Independent risk factors of 28-day all-cause mortality.

Variable	OR(95%CL)	P	
Male,n(%)	9.983(1.766, 56.421)	0.009	
CCI score(mean ± SD)	1.117(0.883, 1.413)	0.357	
Previously use of Carbapenem	0.180(0.047, 0.685)	0.012	
APACHE II score(mean ± SD)	1.082(0.989, 1.184)	0.087	
PMB-containing	0.192(0.052, 0.708)	0.013	
CCI:Charlson Comorbidity Index; APACHE II, Acute Physiology and Chronic Health Evaluation II; PMB, polymyxin B.

4. Discussion

There are but few studies that compare polymyxin B versus tigecycline for treating pneumonia caused by CRKP. In our retrospective cohort study, we found that 7-day bacterial eradication in the polymyxin B-based combination group was 31.03%, which was consistent with previous reports of 28.4%-39.42% [19,20]. Bacterial eradication rates varied among different bacteria, with lower rates for patients with CRKP infection and higher rates for CR-Acinetobacter baumannii infection [19]. The 7-day bacterial clearance rate was greater in the polymyxin B-based combination group than in the tigecycline-based combination group, which agreed with the previous studies. The microbiologic clearance rate was 64% in the polymyxin B group versus 43% in the tigecycline group [21].

There were no significant differences in 14-day all-cause mortality between the two groups, akin to a study by Chang et al. [15]. In our study, the 28-day all-cause mortality of the polymyxin B-based combination was significantly greater than the tigecycline-based combination. However, in their retrospective cohort study, Chang et al. found that appropriate polymyxin B therapy resulted in significantly lower 28-day mortality compared with an appropriate tigecycline therapy for patients with hospital-acquired pneumonia caused by carbapenem-resistant organisms [15]. The reasons for the higher mortality in the polymyxin B group in our study were as follows: First, according to the average Chinese body weight of 60 kg, the dose in our study was lower than recommended [10]. In a study of polymyxin B-based Regimens for infection with carbapenem-resistant Gram-negative bacteria, Qu found that a loading dose of polymyxin B ≥ 2.0 mg/kg was an independent protective factor for poor clinical efficacy [20]. Because of the low concentration of polymyxin B in the lungs, it is recommended that intravenous polymyxin B should be administered in combination with aerosol inhalation [22]. Some studies suggest that a combination of aerosol inhalation plus intravenous polymyxin B is associated with improved favorable clinical outcome [23,24]. But there is no aerosol dose form polymyxin B in China, and combined atomization inhalation was not used in our study. In addition, the sensibility of CRKP to polymyxin B was unknown. Polymyxin-resistant CRKP occurs in China, and the main resistance gene is blaKPC [25,26].

The incidence of acute kidney injury among patients exposed to polymyxin B was 14.29% in our study, which was lower than previous findings [27,28]. The main reason for this difference was that the polymyxin B dose in our study was 10,000 IU/day, lower than high-dose polymyxin B (∼30,000 IU/kg/day).

Several studies have shown that nephrotoxicity of polymyxin B is closely related to daily dose and cumulative dose [29–32].

We concluded that being male, previous use of carbapenems, and polymyxin B-containing with pneumoniae caused by CRKP were independent risk factors for death in 28-days. Most studies did not reveal a correlation between sex and 28-day death [33,34]. Lou et al. found a correlation between being female and 28-day death [35]. However, Vardakas et al. found a correlation between being male and 28-day death, which was consistent with our study [36]. The correlation between sex and mortality may be related to the sample and needs to be confirmed in a large size sample study.Teo et al. reported that prior polymyxin and carbapenem exposure were independent risk factors for isolation of polymyxin-resistant carbapenem-resistant Enterobacteriaceae [37]. Wang et al. found that low-dose and long-term use of polymyxins increased the resistance of CRKP to polymyxins [38]. Therefore, it is particularly important to ensure the rational use of polymyxin B in clinical practice to limit the generation of polymyxin B-resistant bacteria.

Our study had some limitations. The study was a single center retrospective cohort study, and the patient number was small. Nevertheless, we focused mainly on pulmonary infections caused by CRKP, for which there is relatively few investigations. Large-scale random controlled trials are needed to assess treatment options for site-specific CRKP infections. Also, because of the limited number of patients, we did not conduct sub-group analysis (e.g. multi-carbapenem-resistant pathogens, different antibiotic combinations). Lastly, the susceptibility of bacteria to polymyxin B was unknown; thus, the dose could not be adjusted according to the MIC value.

5. Conclusion

Empirical use of a polymyxin B-based combination regimen should be used with caution for patients with CRKP-induced pneumonia if polymyxin B was administered at a standard dose. Because a polymyxin B-based combination regimen may lead to a higher 28-day all-cause mortality, especially for men who used carbapenems before CRKP detection.

Acknowledgements

The authors thank AiMi Academic Services (www.aimieditor.com) for English language editing and review services.

Authors contributions

JC and HC contributed to study design and writing original draft. BBX contributed to the study methodology and data analysis. FWS, YL, YJP and FL contributed to data collection. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval and consent to participate

The Medical Ethics Committee of Beijing Luhe Hospital Affiliated to Capital Medical University approved this study. Approval number: 2023-LHKY-013-01). As this was a retrospective study, the informed consent was waived.

Data availability statement

The datasets generated and/or analyzed during the current study are not publicly available due to privacy requirements; however, the data are available from the corresponding author on reasonable request.
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