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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2015  |  Volume : 26  |  Issue : 3  |  Page : 477-481
The effectiveness of systemic antibiotic therapy with and without ethanol-locked solution in the treatment of hemodialysis-related catheter infection


1 Department of Internal Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2 Dana Pharmaceutical Company, Dana Company, Tabriz, Iran
3 Hemodialysis Center, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
4 Central Laboratory, Imam Reza Hospital, Tabriz, Iran

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Date of Web Publication20-May-2015
 

   Abstract 

Bacterial overgrowth in the inner layer of the catheter as a biofilm is highly encountered in routine medical care, and it may occur in a few days after inserting a catheter as an access in hemodialysis (HD) patients. Catheter-induced bacteremia is often due to the development of biofilms. Locking catheters with antimicrobial agents is an effective way of reducing the risk of catheter-related infection. In a controlled, randomized clinical trial, 64 chronic HD patients (32 men and 32 women with a mean age of 57.5 ± 15.6 years) were divided into case and control groups, with 32 patients in each group. The case group received systemic antibiotic and a lock of catheters with 60% ethanol and the control group received only systemic antibiotic. The results were evaluated after three weeks of treatment. The success rate of clearing infection in group A (29 patients) and group B (18 patients) was 90.6% and 56.2%, respectively (P = 0.002). We conclude that the significant difference in the success rate of clearing catheter infection in HD patients is due to the use of 60% ethanol-lock along with antibiotic therapy, and suggest this for routine use.

How to cite this article:
Khosroshahi HT, Mahdipur H, Parkhideh S, Basmenji S, Khalilzadeh M, Tozihi M. The effectiveness of systemic antibiotic therapy with and without ethanol-locked solution in the treatment of hemodialysis-related catheter infection. Saudi J Kidney Dis Transpl 2015;26:477-81

How to cite this URL:
Khosroshahi HT, Mahdipur H, Parkhideh S, Basmenji S, Khalilzadeh M, Tozihi M. The effectiveness of systemic antibiotic therapy with and without ethanol-locked solution in the treatment of hemodialysis-related catheter infection. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 Jun 23];26:477-81. Available from: https://www.sjkdt.org/text.asp?2015/26/3/477/157315

   Introduction Top


Catheter-related bacteremia (CRB) is one of the major causes of morbidity with potential lethal hazards in patients undergoing hemodialysis (HD), resulting in conditions such as septic shock, endocarditis, septic arthritis, osteomyelitis or epidural abscess. [1]

Bacterial growth in the inner layer of the catheter as a biofilm is highly encountered in routine medical care, and it may occur in a few days after inserting the catheter. [2] Catheter-induced bacteremia is often due to the biofilms. [3] The relative risk of hospitalization due to catheter infection and correspondent mortality is two to three times higher in patients undergoing dialysis through catheters in comparison with those undergoing dialysis through AV fistulas. [4]

The best practice to reduce the incidence rate of bacteremia is reducing the number of patients using catheters for HD. [5] As an alternative, antiseptic/antimicrobial catheter locks are efficiently used to reduce the risk of catheter infection. [6],[7] Bacterial resistance and incomplete disinfection, while the catheter is still in use, are the main concerns related to this method. [7]

Generally, administration of systemic antibiotics per se is an inadequate remedy. Immediate catheter removal plus catheter replacement using a guide wire to change the catheter or the use of antibiotic lock had almost similar results, while antibiotic lock is a less-invasive intervention. [8]

This study aimed to evaluate the effectiveness of systemic antibiotic therapy with and without ethanol-locked solution in the treatment of HD-related catheter infection


   Materials and Methods Top


We studied, in a controlled, randomized clinical trial, 64 chronic HD patients using central venous cuffed catheters (Arrow International Inc., 2400 Bemville Road Reading, PA 19605 USA) that were placed in the internal jugular veins. The education and clinical centers affiliated to the Tabriz University of Medical Sciences were selected as sites for this trial that took place from May 2009 till May 2011. The whole process, including data gathering, patients' collection and evaluation and outcome analysis, lasted for 24 months.

In the following circumstances the patients were excluded from the study: (1) extra catheter source of infection, (2) catheter removal due to AV fistula maturation and (3) any cause of death except catheter infection.

To determine the sample size, we used a pilot study. Fever as a heralding sign had faded away in 80% of the patients in the pilot study. The total sample size for this trial that is capable of detecting 5% difference, with 80% power and α = 0.05, was approximately 60 patients. Because the possibility of loss of some participants existed, and to strengthen the power of the study, we considered 32 patients in each group (case and control). Eligible consenting patients were randomized to one of the two treatment groups (www.randomizer.org).

In patients who developed high-grade fever (BT >38°C) and/or chills during the HD sessions, and had no other clinically documented source of infection (viral or bacterial), two blood cultures of a minimum of 10 mL of blood were obtained through venipuncture, spaced at 30-min intervals, and one blood culture from the central catheter. Culture medium used in this study was biphasic medium, manufactured in Darvash Co. Ltd. (Tehran, Iran). Culturing and antibiogram testing were performed at the central laboratory of the Imam Reza Hospital, Tabriz, Iran. Then, an empirical antibiotic regimen (including vancomycin ± third-generation cephalosporin) was administered immediately and modified thereafter, based on the results of the cultures. Two milliliters of 60% ethanol plus 1 mL heparin were injected into both lines of the central catheter by the HD nurse immediately at the end of each HD session, and removed before the next one (60% ethanol was prepared in 2 mL sterile vial under aseptic conditions in Dana Pharmaceuticals Ltd., Tabriz, Iran, and the concentration of heparin sodium was 5000 unit/mL produced by Caspian Tamin Pharmaceutical Co., Rasht, Iran).

The dialysis physician investigated all the symptoms of the patients, including dyspnea, cough, diarrhea, dysuria, etc. and examined them carefully to identify other possible sources of fever. If no evidence in favor of an alternate source of infection was found, the diagnosis of catheter-related infection was made. In patients with fever or hemodynamic instability 48 h after the initiation of the empiric antibiotic therapy, the trial was considered failed and the catheter was removed promptly. On the other hand, the success in this trial was defined as clinical improvement in signs and symptoms within 48 h of initiating systemic antibiotic in addition to locking the catheter with ethanol.

The patients were given the aforementioned treatment and followed for three weeks by a dialysis physician and nurse. The examining physician was unaware of the treatment allocation. Fever and chills, which were observed at the beginning of the study and during each hemodialysis (HD) session, were considered as the primary consequences and the culture result and catheter removal were defined as the secondary consequences.

This study has been registered on the IRCT website of the Ministry of Health with Registration number 201106062858N4 and approved by the ethic committee of the Tabriz University of Medical Sciences.


   Statistical Analysis Top


The results were presented as mean ± standard deviation, frequencies and percentages. The Student t-test was applied to compare quantitative variables and the chi square test was applied to compare the categorical variables. The collected data were analyzed with the SPSS (version 16) statistical analysis kit and P-values <0.05 were considered significant.


   Results Top


[Table 1] shows the baseline values of all the patients and comparison between the case and control groups; they all completed the study. The patients in the two treatment groups were similar in terms of their mean age and proportion of males to females. The causes of renal failure of both groups were not statistically different between both the case and the control groups (P = 0.61). In group A, 24 (75%) patients had underlying illness that caused renal failure and eight (25%) cases had no apparent cause for kidney disease. In group B, underlying causes of renal failure were found in 24 (75%) patients and none was found in (25%) eight patients. Diabetes and hypertension were the leading causes of renal failure in both groups.
Table 1: Demographic data of patients with catheter-related infection (groups A and B).

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During the study, no episodes of antibiotic or ethanol lock-associated adverse reactions were reported. All the patients in both groups who developed fever or chills during HD had a culture specimen obtained from the indwelling dialysis catheter. The results of blood culture in about 45% of patients in both groups were negative. An insignificant difference was found when positive cultures from the peripheral veins were compared between the two groups (P = 0.62).

[Table 2] shows the results of blood culture and isolated organisms in both the case and the control groups.
Table 2: The results of blood culture and isolated organisms in the treated and control groups.

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In group A, an ethanol-lock protocol was successful for the eradicating infection in 29 of 32 (90.6%) patients; three (9.4%) cases required removal of the dialysis catheter. However, in group B, the systemic antibiotic without the alcohol-lock could eradicate infection in 18 (56.2%) patients; in the remaining 14 (43.8%) patients, the catheters had to be removed. The rates of successful treatment were significantly higher (P = 0.002) with systemic antibiotics plus ethanol-lock catheters (group A) when compared with systemic antibiotics alone (group B).


   Discussion Top


Our results suggest an important role of ethanol-locks in eradicating catheter-related bacteremia in HD patients. Infection is the most common complication leading to removal of transient catheters. The risk of infection is 10.3% within four weeks from implanting catheter. [9] Applying topical and systemic antibiotics may be effective in reducing the incidence of infections theoretically; however, previous studies yielded different results. [10]

Dannenberg et al studied children with catheter-related bacteremia during chemotherapy via a central venous catheter. They received systemic antibiotic along with an ethanol-locked technique and had a higher survival rate than children who received systemic antibiotics only (67% vs. 47%). [7]

Yue et al studied the effects of antimicrobial agents and ethanol to prevent dialysis catheter infection. The results showed, like our study, that 40% ethanol was much more potent than antibiotics alone in the prevention of catheter biofilm formation due to coagulase-negative Staphylococcus. Alcohol is inexpensive and there is no report of alcohol resistance. [11]

In another study by Raad et al, the effect of a combination of agents including minocyclin, ethylene diaminetetraacetic acid (EDTA) and 25% ethanol in the prevention of dialysis catheter infection was evaluated, and they found that the combination was much more effective than each agent alone. Also, this combination had a potent effect on the eradication of colonized methcillin-resistant Staphylococcus aureus over the catheter surface in comparison with minocyclin-EDTA mixture or EDTA in 25% ethanol alcohol. [12]

Carratala et al [13] studied the antibiotic-locked technique in the treatment of the catheter infection and it was effective in the treatment of 82% of HD catheter infection. Nonetheless, more thorough studies were recommended for better comparison between this approach and using systemic antibiotics. In contrast to Carratala's study, we used systemic antibiotic in the treatment of catheter infection in our study and reviewed the effectiveness of systemic antibiotic with and without ethanol. As mentioned above, the success rate of systemic antibiotic in combination with ethanol was statistically more significant than systemic antibiotic alone (P = 0.002).

However, our study had some limitations. The results of blood culture were positive only in 55% patients in both groups that may be due to previous use of antibiotics in other centers in addition to the small proportion of patients with catheter infection, which prolonged the sampling period.

We conclude that the significant difference in the success rate of clearing catheter infection in HD patients is due to the use of 60% ethanol-lock along with antibiotic therapy, and suggest this for routine use.


   Acknowledgment Top


The authors of this article appreciate and share their success with people who helped in this research and are thankful for their teamwork.

 
   References Top

1.
Beladi S, ShahbazianH. Survival at 1, 3, and 5 years in diabetic and nondiabetic hemodialysis patients. Iran J Kidney Dis 2010;4:74-7.  Back to cited text no. 1
    
2.
Tanriover B, Carlton D, Saddekni S. Bacteremia associated with tunneled dialysis catheters: Comparison of two treatment strategies. Kidney Int 2000;57:2151-5.  Back to cited text no. 2
    
3.
Balestrino D, Souweine B, Charbonnell N, Lautrette A, Aumeran C, Traor' e O, Forestier C. Eradication of microorganisms embedded in biofilm by an ethanol based catheter lock solution. Nephrol Dial Transplant 2009;24: 3204-9.  Back to cited text no. 3
    
4.
Pastan S, Soucie M, McClellan WM. Vascular access and increased risk of death among hemodialysis patients. Kidney Int 2002;62:620-6.  Back to cited text no. 4
    
5.
Laura L, Ralph C, Michel J. Preventing hemodialysis catheter-related bacteraemia with an antimicroboial lock solution. Nephrolo Dial Transplant 2007;23:1666-72.  Back to cited text no. 5
    
6.
Koenraad J, John V, Bart DM, Hilde K. Trisodium citrate 30% vs heparin 5% as catheter lock in the interdialytic period in twinor doublelumen dialysis catheters for intermittent hemodialysis. Kidney Int 2001;16:1521-2.  Back to cited text no. 6
    
7.
Dannenberg C, Bierbach U, Rothe A, Beer J, Korholz D. Ethanol-lock technique in the treatment of bloodstream infections in pediatric oncology patients with Broviac catheters. J Pediatr Hematol Oncol 2003;25:616-21.  Back to cited text no. 7
    
8.
Poole CV, Carlton D, Bimbo L, Allon M. Treatment of catheter related bactraemia with an antibiotic lock protocol: Effect of bacterial pathogen. Nephrol Dial Transplant 2004;19: 1237-44.  Back to cited text no. 8
    
9.
Kairaitis LK, Gottlieb T. Outcome and complication of temporary hemodialysis catheter. Nephrol Dial Transplant 1999;14:1710-6.  Back to cited text no. 9
    
10.
Lok CE, Mokrzycki MH. Prevention and management of catheter-related infection in hemodialysis patients. Kidney Int 2011;79: 587-98.  Back to cited text no. 10
    
11.
Yue Q, Istivan T, Deighton M. Comparison of various antimicrobial agents as catheter lock solutions: Preference for ethanol in eradication of coagulase-negative staphylococcal biofilms. J of Med Microbiol 2009;58:442-50.  Back to cited text no. 11
    
12.
Raad I, Hanna H, Dvorak T, Chaiban G Hachem R. Optimal antimicrobial catheter lock solution, using different combinations of Minocycline, EDTA, and 25-percent Ethanol, rapidly eradicates organisms embedded in biofilm. Antimicrob Agents Chemother 2007; 51:78-83.  Back to cited text no. 12
    
13.
Carratala J. The antibiotic-lock technique for therapy of" highly needed" infected catheters. Clin Microbiol Infect 2002;8:282-9.  Back to cited text no. 13
    

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Correspondence Address:
Dr. Hosein Mahdipur
Department of Internal Medicine, Tabriz University of Medical Sciences, Tabriz
Iran
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DOI: 10.4103/1319-2442.157315

PMID: 26022017

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