Risk factors and pathogenic bacteria of central venous catheter-associated bloodstream infection in patients with emergency hemorrhagic shock: a single-center retrospective Study from 2016 to 2022 in a Teaching Hospital in China

doi:10.21203/rs.3.rs-3338368/v1

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Research Article

Risk factors and pathogenic bacteria of central venous catheter-associated bloodstream infection in patients with emergency hemorrhagic shock: a single-center retrospective Study from 2016 to 2022 in a Teaching Hospital in China

https://doi.org/10.21203/rs.3.rs-3338368/v1

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Objective

To investigate and analyze the risk factors and pathogenic bacteria of central venous catheter-associated bloodstream infection in patients with emergency hemorrhagic shock.

Methods

According to the inclusion criteria, 249 patients with hemorrhagic shock and central venous catheterization admitted to the emergency department of Shanghai General Hospital from June 2016 to June 2022 were retrospectively analyzed, and divided into the infection group (54 cases) and the non-infection group (195 cases) according to whether catheter-related bloodstream infection occurred.Multivariate Logistic regression was used to analyze the relationship between central venous catheter-related bloodstream infection and various influencing factors. The etiological and drug susceptibility test data of peripheral venous blood culture, puncture site samples and catheter tip samples from patients with central venous catheter-associated bloodstream infection were statistically analyzed.

Results

There were significant differences in age, catheterization location, ultrasound-guided puncture, APACHE ⅱ score, catheter indwelling time and application of broad-spectrum antibiotics between the infected group and the non-infected group (P < 0.05). Staphylococcus epidermis accounted for 44.6%, Escherichia coli 23.2%, and fungi 12.5% in 54 infected patients. The lowest resistance rate of Gram-positive cocci was to vancomycin(3.4%),followed by tetracycline 34.5%,and the highest resistance rate was to amoxicillin 100.0%.

Conclusion

The risk factors of central venous catheter-related bloodstream infection in patients with emergency hemorrhagic shock include advanced age,femoral vein catheterization,non-ultrasound-guided puncture,high APACHE ⅱ score,catheter retention time,and application of broad-spectrum antibiotics.Staphylococcus epidermis the common pathogen of central venous catheterization related infection in emergency hemorrhagic shock patients.

Hemorrhagic shock

Central vein catheterization

Catheter-related bloodstream infection

Etiology

Drug resistance

In recent years, the incidence of catheter-related blood stream infection (CRBSI) has declined, but remains high, with the highest morbidity and mortality, especially in the intensive care unit^[1–4].CRBSI patients lack characteristic clinical manifestations, usually fever is the principal manifestation, and redness, swelling, pain and pus at the insertion site are highly specific. Other clinical manifestations include hemodynamic instability, catheter dysfunction and sudden sepsis^[5].The occurrence of CRBSI in patients not only prolongs hospital stay, increases medical costs, but also increases the difficulty of clinical treatment, thus adversely influencing the prognosis of patients^[6–7].Therefore, in recent years, how to reduce the infection rate of CRBSI is a topic that clinicians are actively studying^[8–11]. Central vein catheterization is a major rescue measure for hemorrhagic shock ^[12–13]. There have been many reports on complications related to central vein catheterization in patients with emergency hemorrhagic shock ^[14–15], however, there are few reports on the occurrence of CRBSI in patients with hemorrhagic shock in emergency. Patients with hemorrhagic shock are in urgent condition, so there is not sufficient time to make a comprehensive assessment of their condition. The emergency physicians are busy with rescuing patients and neglect strict aseptic operation standards. In addition, the occurrence of catheter-related infection and the distribution of pathogenic bacteria in patients with hemorrhagic shock in emergency department also deserve our attention. In this study, 249 patients diagnosed with emergency hemorrhagic shock in our hospital from June 2016 to June 2022 who underwent central venous catheterization were chosen as the study objects, and the risk factors and pathogenic bacteria leading to catheter-associated infection were analyzed. To investigate the risk factors and pathogenic bacteria distribution of CRBSI in patients with central venous catheterization in emergency hemorrhagic shock, so as to give sufficient and reliable basis for its treatment and prevention.

Subjects

A total of 249 patients with hemorrhagic shock treated in Shanghai General Hospital from June 2016 to June 2022 were selected, all of whom received central venous catheterization in the emergency room of our hospital and met the inclusion criteria(FIGURE 1).

Criteria for diagnosis of hemorrhagic shock: (1) systolic blood pressure < 90mmHg or more than 30% lower than the basal level or pulse pressure < 30mmHg; (2) conscious disorders, such as irritability, indifferent expression or vague consciousness, coma; (3) cold and wet limbs or mottled skin, pale mucous membranes or cyanosis; (4) Pulse > 100 beats /min or not palpable. When the first is combined with any of the last three, hemorrhagic shock is diagnosed.

Diagnostic criteria for CRBSI ^[16]: The same pathogenic bacteria are isolated from peripheral blood and catheter tip, and the positive culture of catheter tip is 2h earlier than that of peripheral blood, and the patient shows signs of infection, then CRBSI can be diagnosed. Patients in whom fever alleviated within 48 hours post-CVC removal without any other source of infection were defined as “possible” CRBSI, irrespective of negative laboratory cultures.

Inclusion criteria: (1) Patients who received central venous catheterization in the emergency department of our hospital and met the diagnostic criteria for hemorrhagic shock. (2) Age ≥ 20 years old. (3) Central venous catheter was left in place for more than 48 hours. (4) When the same patient has multiple diagnoses, only the first diagnosis is selected. (5) Patients with complete clinical records.

Exclusion criteria: (1) patients with organic lesions of heart, lung, liver, kidney and other organs; (2) Patients receiving immunosuppressive drugs or antibiotics within 1 month prior to central venous catheter placement; (3) patients who died, were transferred to another hospital or gave up treatment during hospitalization; (4) Patients with infection symptoms such as fever or chills 48 hours before deep vein catheterization. All patients signed informed consent and voluntarily participated in the study. The study protocol was approved by the hospital ethics committee(Medical Ethics Committee of Shanghai General Hospital).The guidelines outlined in the declaration of Helsinki were followed in this study.

Research methods

Collection of medical history data

The clinical medical records of 249 patients were retrospectively analyzed, and the cases were retrieved by the medical record inquiry system of the hospital. Two researchers entered the forms and one reviewed them. The specific content of relevant data included gender, age, location of catheterization, blood loss, cause of shock, body mass index (BMI), APACHE II score, time of indentation of deep vein catheter, application of broad-spectrum antibiotics, ultrasound-guided puncture or not, and related blood test results. According to the occurrence of catheter-related bloodstream infection, 54 cases were into infection group and 195 cases were into non-infection group.

Specimen collection and pathogen culture methods

All catheters were subjected to routine bacterial culture and peripheral blood culture was retained at the time of removal. After disinfecting the skin around the CVC puncture site, pull out the catheter and cut the proximal tip 4–5 cm with sterile scissors. Samples were collected and placed in a sterile container and sent to the microbiological laboratory within 15 minutes at room temperature. The tip of the catheter was cultured by semi-quantitative culture technique. The BactecTMFX40 blood culture instrument produced by Becton Dickinson Company in the United States was used for blood culture, and the pathogen was identified by phoenix 100 automatic bacterial identification drug sensitive system produced by Becton Dickinson Company in the United States.

Statistical Analysis

SPSS 21.0 software was used to analyze the data. The measurement data is represented by mean ± standard deviation(‾χ ± s), and the counting data was expressed as a percentage. Chi-square test was used for comparison between groups, and Logistic regression was used for multivariate analysis. For P < 0.05 the difference was considered statistically significant.

CRBSI basic information ：There were 54 cases of CRBSI (49 patients with confirmed CRBSI and 5 patients with "suspected" CRBSI), and the infection rate was about 21.7%. The occurrence time of CRBSI is shown in Figure 2. When CRBSI was suspected, the central venous catheter was removed under sterile conditions (catheter tip culture and blood culture were performed), the catheter was replaced, and the location of the central venous catheter was changed. According to the culture results, appropriate antimicrobial therapy was given to the patients. All CRBSI cases recovered completely after central venous catheter removal and no CRBSI-related deaths occurred.

Baseline data for both groups: There was no significant difference between the infected group and the non-infected group in gender, cause of shock, body mass index (BMI) and related blood test indexes(P＞0.05),while there were statistically significant differences in age, location of central venous catheters, blood loss, APACHE ⅱ score, the duration of deep venous catheter indwelling、application of broad-spectrum antibiotics and ultrasound-guided puncture between the two groups (P < 0.05) (Table 1).

Table 1. Basic data of catheter-associated infection in patients with central venous catheterization in emergency hemorrhagic shock

Project	Infection group（ｎ＝54）	No infection group （ｎ＝195）	χ^２／ｔ	Ｐ
gender(Male/female)	31/23	123/72	0.576	0.448
Age	31/23
＜60 years of age	36	160	5.974	0.015
≥60 years of age	18	35	5.974	0.015
Blood loss
＜1500ml	32	147	5.441	0.020
≥1500ml	22	48	5.441	0.020
BMI(kg/m2)	21.73±3.84	22.40±3.65	0.896	0.462
APACHEⅡscore	20.04±3.22	15.40±3.01	9.566	＜0.001
Indwelling time of catheter (d)
＜14d	32	150	8.697	0.003
≥14d	22	41	8.697	0.003
Use broad-spectrum antibiotics (Y/N)	17/37	33/162	5.585	0.018
Tube placement location
Internal jugular or subclavian vein	35	155	5.035	0.025
Femoral vein	19	40	5.035	0.025
Ultrasound-guided puncture
Y	7	57	5.860	0.015
N	47	138	5.860	0.015
Hemoglobin (g / L)	83.9±16.6	84.0±14.6	-0.024	0.981
PLT( ×10⁹/ L)	100.4±21.2	104.6±22.8	-0.787	0.434
D-dimer (μg / ml)	1.25±0.61	1.10±0.52	1.170	0.246
Calciumions (mmol / L)	1.86±0.28	1.90±0.27	-0.515	0.608
Fib (g / L)	1.13±0.32	1.16±0.34	-0.462	0.646

BMI：Body Mass Index.APACHE II Score : acute physiology and chronic health evaluations Ⅱ.Non-femoral vein：Internal jugular or subclavian vein.

Multivariate Logistic regression analysis of risk factors of central venous catheter-associated bloodstream infection: Central venous catheter-associated bloodstream infection was taken as the dependent variable, and assigned: infection = 1, no infection = 0. Age, location of central vein catheterization, blood loss, APACHEⅡ score, indwelling time of deep vein catheter, application of broad-spectrum antibiotics, and ultrasound-guided puncture were independent variables. Age, APACHEⅡ score at admission, duration of indwelling of catheter were input as original values, and other independent variables were input as yes =1, no = 0. Age, location of central venous catheterization, APACHEⅡ score, indwelling time of deep venous catheterization, application of broad-spectrum antibiotics and ultrasound-guided puncture were the risk factors for central venous catheter-related bloodstream infection in patients with hemorrhagic shock(P<0.05) (Table 2).

Table 2. Multivariate Logistic analysis of CRBSI in patients with hemorrhagic shock.

Related factors and assignment	β	S.E	Waldχ^２	Ｐ	OR	95%CI
Age	1.387	0.349	8.354	0.022	2.016	1.109-12.438
Tube placement location	1.391	0.360	9.172	0.018	2.671	1.110-13.544
Indwelling time of deep venous catheter	1.447	0.430	12.320	0.007	4.503	1.116-19.228
Ultrasound-guided puncture	-0.893	0.332	8.811	0.009	0.307	0.114-0.925
Blood loss	1.214	0.207	2.570	0.069	1.124	0.912-3.103
APACHEⅡscore	2.844	0.410	14.875	＜0.001	3.066	2.150-10.396
Use broad-spectrum antibiotics	2.302	0.495	5.032	0.024	1.542	1.304-3.974

APACHE II Score: acute physiology and chronic health evaluations Ⅱ.

Distribution of infectious pathogens：A total of 56 strains of pathogenic bacteria were isolated from 49 patients with CRBSI, of which 53.6% were gram-positive bacteria, 33.9% were gram-negative bacteria and 12.5% were fungi. Staphylococcus epidermis accounted for 44.6% of the pathogens detected, and Candida albicans was the main fungus detected（Table 3）.

Table 3. Distribution and composition of pathogenic bacteria in CRBSI patients (%).

Pathogenic bacteria	number	constituent ratio
Ｇ^－ negative	19	33.9%
E. coli	13	23.2%
Klebsiella pneumoniae	4	7.1%
Others	2	3.6%
Ｇ^＋ negative	30	53.6%
Staphylococcus epidermis	25	44.6%
Staphylococcus aureus	3	5.4%
Enterococcus faecium	2	3.6%
Fungus	7	12.5%
Candida albicans	4	7.1%
Candida.tropical	1	1.8%
Candida.glabrata	2	3.6%

Drug susceptibility test：The resistance rate of Gram positive bacteria to vancomycin was the lowest (3.4%), followed by tetracycline (34.5%) and amoxicillin (100%). The resistance rate of gram negative bacteria to amikacin and ceftriaxone was relatively high (94.7%)（Table 4,5）.

Table 4. Drug resistance rate of 30 strains of gram-positive cocci to antibiotics(%)

Antibacterial drugs	Number	Drug resistance rate (%)
Amikacin	18	94.7
Aztreonam	13	68.4
Ampicillin	15	78.9
Ceftazidime	17	89.5
Ceftriaxone	18	94.7
Cefotaxime	14	73.7
Ciprofloxacin	11	57.9
Imipenem	8	42.1
Piperacillin	15	78.9
Sulfamethoxazole/trimethoprim	13	68.4
Tobramycin	10	52.2

Table 5. Drug resistance rate of 19 strains of gram-negativebacilli to antibiotics (%)

Antibacterial drugs	Number	Resistance rate（%）
Amoxicillin	29	100
Ampicillin	27	93.1
Cefotaxime	24	82.8
Clindamycin	11	37.9
Erythromycin	23	79.3
Imipenem	19	65.5
Gentamicin	18	62.1
Rifampicin	14	48.3
Tetracycline	10	34.5
Vancomycin	1	3.4

Therapeutic effect：According to the etiological detection and drug sensitivity results of the patients, the patients were treated with appropriate antibacterial drugs, and the duration of antibacterial drugs was (8.1±1.3) days. The infection of all patients was controlled, and the clinical symptoms disappeared. The bacterial culture results of the confirmed CRBSI patients were negative, and they were finally cured and discharged.

Patients with hemorrhagic shock are in critical condition and need rapid and large amounts of blood transfusion and fluid rehydration ^[17–18]. Central vein catheterization is one of the essential operations and has been widely used in clinical rescue of patients ^[19]. However, central vein catheterization technology, as an invasive operation technology, causes catheter-associated infection, which is a difficult problem for clinical medical staff ^[20].

In this study, 54 of 249 patients with central venous catheter developed CRBSI, with an infection rate of about 21.7%, which was significantly higher than the 13% reported by Bisanti A et al. ^[21] (CRBSI occurred in ICU), indicating to a certain extent that the incidence of CRBS was higher in patients with emergency hemorrhagic shock. The analysis of basic data for infected and non-infected groups(Table 1)and the results of Logistic regression analysis༈Table 2༉showed that age, location of central vein catheterization, APACHEⅡ score, duration of deep vein catheterization, application of broad-spectrum antibiotics and ultrasound-guided puncture were independent risk factors for CRBSI. Due to the patient's advanced age and high APACHEⅡ score, the patient's immunity generally declined, which may be an important reason for the patient's CRBSI ^[22]. With the increase of catheter retention time, substances such as serum protein and fibrin in the blood are easily deposited on the surface of the catheter. The above-mentioned sediments are an ideal medium for pathogenic bacteria and play a role in protecting the pathogenic bacteria from being killed by immune cells and antibacterial drugs, thus promoting the release of a large number of pathogenic bacteria into the blood and eventually causing infection. In the multivariate Logistic regression analysis of this study, the OR value of catheter indwelling time was 4.503, indicating that the longer the catheter indwelling time, the greater the possibility of catheter-related bloodstream infection.Polderman Studies by Polderman KH ^[23] and Pitiriga V^[24] also indicated that catheter indwelling time is an independent risk factor for catheter-related infection, so central venous catheter should be removed as soon as possible if conditions permit. In this study, as some trauma patients had open contaminated wounds, it was necessary to use broad-spectrum antibiotics early to prevent infection, but the use of broad-spectrum antibiotics could not reduce CLABSI^[25]. The data of this study showed that the use of antibiotics was also an important risk factor for CRBSI in patients with hemorrhagic shock (OR = 1.542). Rinke ML et al. ^[26] showed that the history of antibiotic treatment was identified as a risk factor for cathedral-associated bloodstream infection, which may be due to unreasonable timing, drug selection and duration of use. As a result, some patients with bacterial colonization eventually become infected, so the use of broad-spectrum antibiotics can easily lead to the generation of drug-resistant strains, which in turn increases the probability of CRBSI. Guidelines for CLABSI prevention and control issued by the CENTERS for Disease Control and Prevention (CDC) and the Advisory Committee on Hospital Infection Control Practices (HICPAC) in June 2017 also explicitly stated that routine systemic prophylactic use of antibiotics should not be used to prevent catheter bacterial colonization before or during endovascular catheterization^[27].Regarding the role of ultrasound in central venous catheterization, it has been reported that ultrasound-guided central venous catheterization can reduce the incidence of catheter-related bloodstream infection^[28–29]. However, Khera S^[30] suggested that ultrasound-guided central vein catheterization was not associated with catheter-associated bloodstream infection. Buetti^[31] believes that improper ultrasound procedures can increase the incidence of catheter-associated infections. In this study, it was found that the rate of catheter infection in ultrasound-guided central venous catheterization was lower than that in non-ultrasound-guided catheterization. We believe that ultrasound guidance can reduce the incidence of catheter bloodstream infection as long as the strict aseptic operation is performed, which may be mainly due to the higher success rate of puncture under ultrasound, which reduces the number of puncture and tissue damage, thus reducing the probability of catheter infection. In this study, it was also found that the incidence of infection varied with the location of central vein catheterization. The incidence of infection of internal jugular vein or subclavian vein catheterization was lower than that of femoral vein catheterization, which was similar to the findings of Heidenreich D^[32]. Parienti JJ's study identified a low subclavian vein access infection rate but a high likelihood of pneumothorax^[33].Therefore, jugular vein access can be used as the preferred site for catheterization in the absence of obvious contraindications.

In this study, pathogenic strains were cultured in the samples submitted by 54 patients with catheter-associated infection, and the main pathogen was gram-positive bacteria (53.6%), among which Staphylococcus epidermis had the highest incidence (44.6%), which may be related to bacterial colonization at the site of central venous catheter insertion ^[34–35]. Since all patients with hemorrhagic shock in this study were in critical condition, the disinfection and operation procedures of medical staff during catheterization may be inadequate. In addition, the drug sensitivity results showed that gram-positive coccus had the highest sensitivity to vancomycin. San-Juan R et al. ^[36] concluded that vancomycin should continue to be the preferred treatment for Gram-positive catheter-associated bloodstream infections, especially in hospital centers with low prevalence of strains with reduced vancomycin sensitivity. Vancomycin-resistant Staphylococcus aureus has received increasing attention from the medical community^[37–38]. In this study, amoxicillin was found to have the highest resistance rate, followed by ampicillin. Therefore, in clinical practice, antibiotics are selected according to patients' drug sensitivity. Gram-negative bacilli had the highest sensitivity to imipenem, followed by tobramycin, but the drug resistance rate to amikacin and ceftriaxone was relatively high, which has certain reference value for guiding clinical empirical drug use.For the treatment of CRBSI caused by gram-negative bacteria, current guidelines recommend antibiotic treatment for at least 7–14 days, while recent data suggest that appropriate antibiotic treatment for 7 days or less after central venous catheter removal may be as effective as a longer course of treatment for catheter infection ^[39–40]. A total of 7 patients with fungal infection were detected in this study, mainly Candida albicans. It has been reported that central venous catheters, broad-spectrum antibiotics and candida colonization are risk factors for critical patients with invasive candida infection ^[41–42]. In this study, the duration of use of antibiotics was (8.1 ± 1.3) days, the infection of all patients was controlled, the clinical symptoms disappeared, and the bacterial culture results were negative. Zhong Y et al. ^[43] believed that early central venous catheter re-placement was safe in the case of CRBSI. For patients who still require a Central Line for ongoing treatment, replacement of a new Central Line should not be delayed..

This study was a retrospective analysis, which had certain limitations, such as whether to disinfect hands before puncture, the number of puncture, and the working years of surgeons, which could not be counted. This is a single-center study with a relatively small number of cases, and the results may be biased. In the future, we will further expand the sample size and conduct prospective studies to provide more sufficient and reliable evidence for the prevention of CRBSI in patients with hemorrhagic shock.

In conclusion, the incidence of catheter-related infection in patients with deep vein catheterization in hemorrhagic shock is still high, and Gram-positive bacteria is the main pathogen, which is related to the patient's age, catheterization location, catheter indentation time, APACHEⅡ score, application of broad-spectrum antibiotics, and ultrasound-guided puncture. In clinical work, doctors should strengthen the assessment of the condition of patients with hemorrhagic shock, strictly aseptic operation, as far as possible to select the internal jugular vein or subclavian vein for ultrasound-guided puncture, early withdrawal of the central venous catheter, and strict control of the application of broad-spectrum antibiotics.

Acknowledgements

Not applicable.

Authors’ contributions

Jianping Zhu: This author conceived and designed the study,wrote the manuscript and has approved the publication of this version.He is accountable for the accuracy and integrity of the work.Yanxin Xu:This author participated in data collection,performed the data analysis, wrote the manuscript and has approved the publication of this version.He is accountable for the accuracy and integrity of the work. Shaohong Wu:This author participated in data collection and performed the data analysis.Feiyao Wang:This author participated in the study design,data interpretation and manuscript editing.Weixing Zhang:This author participated in the study design,data interpretation and manuscript editing.Ruilan Wang:This author conceived and designed the study,wrote the manuscript and has approved the publication of this version.All authors read and approved the final manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public,commercial,or not-for-profit sectors.

Availability of data and materials

The datasets used and analysed during the current study available from the corresponding author on reasonable request.

Ethical approval and consent to participate

All patients signed informed consent and voluntarily participated in the study. The study protocol was approved by the hospital ethics committee(Medical Ethics Committee of Shanghai First People's Hospital).The guidelines outlined in the declaration of Helsinki were followed in this study.

Consent for publication

Not applicable.

Conflict of interest

The authors declare that they have no competing interests.

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Risk factors and pathogenic bacteria of central venous catheter-associated bloodstream infection in patients with emergency hemorrhagic shock: a single-center retrospective Study from 2016 to 2022 in a Teaching Hospital in China

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