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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 22
| Issue : 4 | Page : 216-223 |
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Pattern of vascular access-related infection in hemodialysis patients
Montasser Mohamed Zeid, Amina Amal Mahmoud, Mohamed Yehia Khalil, Noha Mohamed Elkohly
Department of Internal Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| Date of Submission | 12-Sep-2021 |
| Date of Acceptance | 21-Dec-2021 |
| Date of Web Publication | 22-Sep-2022 |
Correspondence Address:
Dr. Noha Mohamed Elkohly
Internal medicine and nephrology, Department of Internal Medicine, Faculty of Medicine, University of Alexandria, Alexandria, 21647
Egypt
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jesnt.jesnt_26_21
Background Vascular access-related infections (VARI) represent a substantial burden for patients undergoing hemodialysis (HD) that is unfortunately inevitable. The spectrum of causative organisms varies between different regions and centers, so it is necessary for each dialysis unit to have its database. This prospective descriptive multicenter study was conducted over a 6-month duration to delineate the pattern of VARI among patients undergoing HD units of Alexandria University Hospitals, and to determine the possible relationship between VARI, type of vascular access, pattern of causative organisms, and various risk factors. Materials and methods The study enrolled all patients with documented clinical and bacteriological evidence of VARI. Infection incidence-rate event/1000 dialysis session (ds) was calculated. Results During the study period, 877 HD patients were approached. A total of 66 VARI episodes were identified in 62 patients, with 58 bloodstream infection (BSI) episodes and 8 local-access infections, with an overall incidence rate of 4.64/1000 ds. About 64% of isolated organisms were Gram-negative bacilli, 33.3% Gram-positive cocci, and 2.8% fungi. The most frequent isolated pathogens were Klebsiella pneumonia, Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA). Conclusion VARI rate was higher in HD patients with temporary central venous catheter compared with permanent tunneled catheters. Gram-negative microorganisms and MRSA were the most frequent identified organisms. Creation of arteriovenous fistula should not be delayed to avoid the use of temporary catheters, which carry high risk of VARI.
How to cite this article:
Zeid MM, Mahmoud AA, Khalil MY, Elkohly NM. Pattern of vascular access-related infection in hemodialysis patients. J Egypt Soc Nephrol Transplant 2022;22:216-23 |
How to cite this URL:
Zeid MM, Mahmoud AA, Khalil MY, Elkohly NM. Pattern of vascular access-related infection in hemodialysis patients. J Egypt Soc Nephrol Transplant [serial online] 2022 [cited 2023 Jun 8];22:216-23. Available from: http://www.jesnt.eg.net/text.asp?2022/22/4/216/356688 |
| Introduction | |  |
Chronic kidney disease (CKD) is an evolving global health problem.
End-stage renal disease (ESRD) is considered when glomerular-filtration rate is <15 ml/min/1.73 m2 (stage 5) in which patients often necessitate either kidney transplantation or maintenance dialysis to sustain life [1].
Treatment modalities for ESRD include hemodialysis (HD), peritoneal dialysis, and renal transplantation. HD is considered to be the most common dialysis modality worldwide.
Repeated access to the circulation is essential to achieve adequate maintenance of HD. Therefore, reliable vascular access (VA) is the cornerstone of HD therapy, and timely planning for access formation is a major facet of CKD care [2].
The three main types of HD VAs used in practice are central venous catheters (CVC), arteriovenous fistula (AVF), and arteriovenous graft (AVG).
An AVF is considered to be the optimal form of permanent VA for HD; it is associated with the greatest primary patency rate, the lowest rate of infection, thrombosis, and rates of hospitalization than those reported in patients with AVGs or CVCs.
| Vascular access-related infection (VARI) | | |
HD patients are more liable to infections, as uremia causes defects in neutrophil function, cellular immunity, and complement activation [3].
Regarding catheter-related infections, they can be classified into localized or systemic. As for the localized form, infection may affect the catheter-insertion site or may spread subcutaneously. Exit-site infection has the highest incidence among HD patients, particularly in nontunneled catheters. Concerning tunnel infection, erythema, induration, tenderness, or exudate are noted at more than 2 cm from the exit site or throughout the subcutaneous route of the tunneled CVC [4]. Many reports have identified diabetes mellitus (DM) and poor patient hygiene as risk factors for development of exit-site infections [5].
The most serious infectious complication is catheter-related bloodstream infection (CRBSI), which is defined as the presence of bacteremia in a patient with HD catheter with no other source for the positive blood culture [6–8].
| Catheter-related bloodstream infection-associated microorganisms | | |
The majority of CRBSI-associated isolates are reported to be Gram-positive organisms (52%–84%). Staphylococcus aureus (S. aureus) and coagulase-negative staphylococci are the most common microorganisms implicated (27.7%–50.0%) [9].
Up to one-third of CRBSIs are caused by methicillin-resistant S. aureus (MRSA) in some HD units.
Gram-negative species (enteric bacilli, Pseudomonas aeruginosa) are isolated in 27%–36% of episodes, whereas fungal isolates (Candida spp.) are less common (≤10%) [6]. No study has shown any viral or parasitic cause of CRBSI [10].
All pathogens can form a biofilm on the walls of CVC, which render them very resistant to antibiotic action [10].
Infection Diseases Society of America 2009 guidelines recommend that at least one of two microbiological methods to be used to confirm the diagnosis of CRBI:
- (1) Quantitative blood cultures from the CVC with at least three-times higher number of colonies (CFU per ml) than cultures from the peripheral vein [4].
- (2) Blood cultures from catheter lumen meeting criteria of differential time to positivity with growth of the microorganism at least 2 h earlier than cultures from the peripheral vein [4].
- (3) HD catheter tip growing the same microorganisms as the peripheral venous culture [4].
| Aim of the work | | |
This cross-sectional observational descriptive single-center study was conducted to delineate the pattern of VARI among patients undergoing HD at the three main dialysis units of Alexandria University Hospitals, and to determine the possible relationship between VARI and the type of VA, the pattern of causative organisms, as well as the various risk factors.
Participants
The present study enrolled all patients with documented clinical and bacteriological evidence of VARI receiving HD at the three main dialysis units (Main university, El Mowasah, and Smouha) of Alexandria University Hospitals, during a 6-month study period from November 2018 to April 2019.
Patients with malignancy or those with coexistence of infective sources other than VA were excluded.
| Methods | | |
This study was approved by the institutional ethics committee and an informed written consent was taken from all participants in the study.
Case definitions
Vascular access-related infection
National Healthcare Safety Network (CDC-NHSN) Dialysis Event Surveillance defined VARI as either a local-access site infection or an access-related bloodstream infection (ARBSI) [11].
- (1) Local-access site infection: defined by the presence of pus, redness, or increased swelling at the VA site and ARBSI is not present.
- (2) ARBSI: defined as positive blood culture with reported VA as the suspected source of infection.
- (3) AVF/AVG-related BSI: defined by two positive blood cultures with the same organism drawn from peripheral veins, separated by at least 15 min, and the presence of local signs of infection at the site of cannulation or along the fistula [12].
Incidence rate
- (1) Infection incidence-rate event was calculated. The number of the VARI episodes during the study period were used as the numerator and the total cumulative number of dialysis sessions for the same period as denominator.
- (2) Rates of VARI were expressed as the number of infection events per 1000 dialysis sessions [13,14].
- (3) Multidrug resistance (MDR) was defined as acquired nonsusceptibility to at least one agent in three or more antimicrobial categories.
- (4) Pan-drug resistance (PDR) was defined as nonsusceptibility to all agents in all antimicrobial categories.
The study protocol was applied when the patient exhibited symptoms or signs suspicious of VARI before or during the HD session. All patients with suspected VARI were subjected to:
- (1) Thorough history taking and clinical examination:
- (a) Demographic data (age, sex, residence, and smoking status).
- (b) Comorbidities: DM, hypertension, and inflammatory disorders (vasculitis and systemic autoimmune conditions).
- (c)Prior antimicrobial use was defined as every previous antimicrobial treatment for at least 48 h in the previous 3 months [15].
- (d)VA: type, location, duration, center where access was performed, and presence of other VA.
- (e)HD: duration and frequency.
- (f)Presence of fever, chills, malaise, hypotension, or change of mental status.
- (g)Signs of infection at VA.
- (2)Laboratory investigations included
- (a) Complete blood count.
- (b) Kidney-function tests (serum creatinine and urea).
- (c) Liver enzymes (alanine transaminase (ALT) and aspartate aminotransferase (AST)).
- (d) Serum albumin.
- (e) Fasting blood sugar.
- (f) Estimation of C-reactive protein level.
- (3) Doppler ultrasound assessment of the VA when needed.
- (4) Plain X-ray or computed tomography (CT) chest when needed.
- (5) Echocardiography was performed for patients with suspected infective endocarditis.
- (6) Bacteriological study:
- (a) Blood cultures were collected as soon as possible after clinical symptom onset and before the administration of antimicrobial therapy.
- (b) Blood samples were taken before dialysis session. According to CDC Surveillance criteria, in patients with suspected CRBSI, blood cultures were drawn, one from a peripheral vein and the other from the HD catheter.
- (c) Culture and sensitivity for nasal swab were performed in cases with positive S. aureus blood culture.
Statistical analysis of data
Data were fed to the computer and analyzed using IBM SPSS software package version 20.0 (IBM Corp., Armonk, NY). Qualitative data were described using number and percent. The Kolmogorov–Smirnov test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, and SD (if parametric). Median and interquartile range was used for nonparametric quantitative data. Significance of the obtained results was judged at the 5% level.
| Results | | |
This cross-sectional observational descriptive single-center study was carried out over a 6-month duration from November 2018 to April 2019, at the three main dialysis units (Main university, El Mowasah, and Smouha) of Alexandria University Hospitals.
A total of 877 HD patients were approached during the study period. They were distributed as 715 patients in the Main university HD unit, 149 patients in El Mowasah HD units, and 13 patients in Smouha HD unit.
The age of patients ranged between 16 and 92 years with a mean age of 49.1 ± 14.7 years, 81.7% were below 65 years, and 50.6% were males.
The distribution of study patients according to the VA types used in the three participating HD units illustrates that the most frequently used VA type in the Main university HD unit was temporary catheters (95.6%) of which up to 100% of patients initiating HD used temporary catheters. AVFs constituted 83.4% and 85.7% in El Mowasah and Smouha HD units, respectively.
In relation to the site of catheter insertion, an internal jugular catheter was the most reported site of VARI with 50 (75.8%) episodes compared with femoral and subclavian CVC, 11 (16.7%) and 5 (7.6%) VARI episodes, respectively.
The comorbid conditions associated with VARI encountered were hypertension (66.1%) and diabetes (58.1%) being the most frequently encountered comorbidities. Previous episodes of VARI were recorded in 11 (17.7%) patients, recent hospitalization in 39 (59.1%) patients, and history of prior antibiotics use in 81.1% of patients. Antibiotic lock solution was not reported in any of the studied patients.
The median duration of temporary and tunneled CVC groups was 2.9 (interquartile range (IQR) 1.8–4.3) weeks and 12.9 (IQR 4.3–34.0) weeks. The highest frequency of VARI episodes occurred between 2 and 4 weeks for temporary catheter (37.3%), and ≥6 months for tunneled catheter (40%).
Subgroup univariate analysis has been used to determine the relationship between different risk factors and the duration of catheter insertion till onset of VARI revealed that types of catheter (P<0.01), sites of catheter insertion (P<0.01), HD duration (P<0.01), presence of DM (P<0.05), recent hospitalization (P<0.01), and hemoglobin level (P<0.05) were statistically significant factors influencing time of VARI onset, whereas age, hypertension (HTN), autoimmune disease, previous VARI, and serum albumin level showed insignificant difference (P>0.05).
Furthermore, multivariate linear-regression analysis revealed that the independent risk factors for early onset of VARI were DM (P<0.05), lower level of hemoglobin (P<0.05), and the type of VA, which was the most important predictor.
Among 66 VARI episodes, 60.6% were due to Gram-negative bacilli, 36.4% Gram-positive cocci, and 3.03% fungi.
In 60 VARI episodes (90.9%), a single microorganism was isolated. In 34 (51.5%) of them, a single Gram-negative bacilli was identified, with Klebsiella pneumoniae 13 (19.7%) and Escherichia More Details coli (E. coli) 12 (18.2%) that were the most frequent. In 24 (36.4%) episodes, a single Gram-positive organism was detected, with MRSA that accounted for 21.2%, whereas Candida spp. was responsible for 2 (3.03%) episodes.
| Discussion | | |
AVF, AVG, and CVC are the three main types of dialysis VA commonly used in practice [16]. An AVF is considered to be the optimal form of VA for HD.
For HD catheters, infection is one of the major and most serious complications [16,17].
In the current study, 877 HD patients were approached during the 6-month study period from November 2018 to April 2019.
In the present study, the use of temporary catheters for initiation of HD in the Main university HD unit was very high up to 100%, as compared with other studies, which varied from 15% to 60% [18]. Delayed diagnosis, late presentation, or late referral led to unplanned dialysis initiation and hence, acute HD catheter (temporary catheters) insertion in such patients was obligatory.
In this respect, previous studies documented higher rates of bacterial colonization of femoral and jugular temporary catheters compared with subclavian catheters, a factor to be an important step in the pathogenesis and risk of catheter-infectious complications [19].
The higher colonization rate with internal jugular catheter has been accused to the shorter subcutaneous tunnel of the internal jugular site, and closer proximity to the nasal microflora [19]. On the other hand, the skin at the subclavian vein is flat, which is easier to clean and disinfect, resulting in late CRBSI onset [19].
Proximity to the perineal area with higher density of skin-flora colonization are possible factors responsible for the higher risk of femoral catheter-associated infection [20,21].
Concerning the microbiological profile of VARIs in patients receiving HD, the current study demonstrated high prevalence of Gram-negative microorganisms responsible for 60.6% of VARI episodes, with Klebsiella pneumoniae (27.3%) and E. coli (24.2%) being the most frequent. The explanation of higher incidence of Gram-negative VARI in the current study can be attributed to unfortunately, the more common use of nontunneled catheters together with impaired immunity of HD patients as well as the presence of comorbidities such as DM and malnutrition, all these factors tend to increase the virulence and adherence properties of hospital-acquired Gram-negative bacteria. Another important factor is poor patient hygiene and less-strict infection-control measures followed in HD units.
Internal jugular catheter was the most reported site of VARI with 50 (75.8%) episodes compared with femoral and subclavian CVC, 11 (16.7%) and 5 (7.6%) VARI, respectively [20].
The postulated explanation for the higher frequency of internal jugular VARI episodes (75.8%) could be largely attributable to the guidelines’ recommendation of considering internal jugular access as the site of choice for CVC insertion. Consequently, internal jugular insertion was the first option for most of our HD patients compared with the other access sites.
In the present study, different catheter-insertion sites showed insignificant difference regarding the distribution pattern of isolated pathogens. In contrast, several previous studies showed variation in the predominance of isolated bacteria from the different access sites with Gram-positive bacteria more prevalent among internal jugular catheters compared with Gram-negative bacteria in femoral catheters [21].
Gram-positive microorganisms and fungi accounted for 36.4% and 3.03% of VARI episodes, respectively. MRSA VARI episodes were the most frequently recorded Gram-positive isolates (21.2%). None of the blood cultures showed any anaerobic organism.
Antimicrobial resistance is becoming significantly common among the infecting bacterial pathogens.
In this regard, the pattern of antibiotic resistance identified in our study demonstrated that 31.9% of the total isolates were MDR constituting 43.5% and 12.5% of Gram-negative and Gram-positive organisms, respectively. Antibiotic resistance to third- and fourth-generation cephalosporins and fluoroquinolones (ciprofloxacin and levofloxacin) was the most common among MDR Gram-negative isolates, whereas aminoglycosides (37.5%–39.6%) and carbapenems (33.3%–35.4%) showed the least drug resistance.
Because S. aureus is one of the most common pathogens among dialysis patients, the emergence of resistance to methicillin and other antistaphylococcal beta-lactam antibiotics has had a tremendous impact on this population. MRSA accounted up to 51% of the reported S. aureus bloodstream isolates, and 59.3% of those resistant S. aureus were from patients with CVC [22].
In the present study, about 70% of the S. aureus were MRSA. However, only 7.6% of MRSA isolates were resistant to vancomycin, teicoplanin, and linezolid.
The high prevalence of MDR and PDR strains could be explained by the antibiotic abuse observed in our HD patients, where unnecessary antibiotics were used together with starting antibiotics without culture base.
These observations should raise our awareness about an emerging problem, highlighting the need for monitoring these microorganisms to prevent and control the risk of their dissemination.
| Conclusions | | |
From the present study, we can conclude that
- (1) The risk of VARI is access-type-dependent that is the highest with temporary CVC, intermediate with tunneled cuffed catheters, whereas permanent AVFs and AVGs carry the lowest risk.
- (2) Catheter type, site, duration of insertion, HD duration, presence of DM, recent hospitalization, and low hemoglobin (Hb) level are risk factors that significantly influence the onset of VARI.
- (3) Gram-negative microorganisms are the most prevalent pathogens responsible for VARIs in our HD settings.
- (4) MDR organisms constituted a large portion of the isolated pathogens.
- (5) Antibiotic abuse could largely contribute to the high prevalence of MDR and PDR strains in our patients.
Recommendations
- (1) Planning for early AVF creation is a crucial element during pre-ESRD nephrology care for initiation of HD ‘Fistula first catheter last’.
- (2) Tunneled catheters are preferred over temporary catheters.
- (3) Much attention should be paid for establishment of infection-preventive strategies, including staff training, patient education, and standardized infection-prevention protocols.
- (4) Further studies are recommended to conduct this study on a larger sample size and longer duration.
[Table 1][Table 2][Table 3][Table 4][Table 5][Table 6][Table 7][Table 8][Table 9][Table 10][Table 11][Table 12][Table 13][Table 14]  | Table 3: Frequency of the associated systemic and local manifestations and complications in VARI episodes
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 | Table 4: The laboratory investigations at the onset of VARI episodes (n=66)
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 | Table 5: Distribution of the VARI episodes according to duration of catheter insertion (n=66)
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 | Table 8: Distribution of VARI episodes according to the access type and site (n=66)
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 | Table 9: Duration of catheter insertion till onset of VARI (weeks) in relation to catheter type and site of insertion (n=66)
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 | Table 10: Distribution of VARI episodes according to the type of isolated organisms (n=66)
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 | Table 11: Distribution of VARI episodes according to the type of causative organisms regarding type and insertion site of HD catheters and participant HD units (n=66)
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 | Table 14: Frequencies of MDR organisms among isolated Gram −ve (n=46) and Gram +ve pathogens (n=24)
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Acknowledgements
The paper has been read and approved by all the authors, that the requirements for authorship as stated earlier in this document have been met, and that each author believes that the paper represents honest work, if that information is not provided in another form.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13], [Table 14]
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