Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Van den Bosch, 2022

Study characteristics and results are extracted from the SR, unless stated otherwise

SR and meta-analysis of  RCTs

Literature search up to 15 February 2021

A: Gudiol, 2020

B: Longo, 2017

C: Wouters, 2018

D: Tribler, 2017

E: Klek, 2015

F: Bisseling, 2010

Study design: RCT, double blind or open, parallel groups.

Setting and Country:

Not specified per study

Source of funding and conflicts of interest:

This research did not receive any specific grant from funding

agencies in the public, commercial, or not-for-profit

sectors.

Conflict of interest statement: None.

Inclusion criteria SR: original RCTs comparing the efficacy of TLs with any other lock solution for the prevention of CVC-related bloodstream infections in all patient populations were included.

Exclusion criteria SR: non-RCTs, studies describing <10 patients and studies using TLs as treatment instead of prevention.

9 studies included, 6 of which in current analysis

Important patient characteristics at baseline:

N, mean age (I/C)

A: 141, 56/57

B: 160, 62/61

C: 105, 59-47/55-47

D: 41, 56/58

E: 30, 44/46

F: 30, 55/49

Sex:

Not reported

CVC type:

A: Non-tunnelled

B: VAP

C: (Non)-tunnelled,

VAP

D: Tunnelled

E: Tunnelled

F: Tunnelled, VAP

Population:

A: Oncology

B: Oncology

C: Total parenteral nutrition

D: Total parenteral nutrition

E: Total parenteral nutrition

F: Total parenteral nutrition

Groups were comparable at baseline

Taurolidine containing lock

A: Taurolidine 1.35%,  Citrate 4% Heparin 100 IU/mL

2.5 mL 3x/week

B: Taurolidine 1.35% Citrate 4%; 3.0 mL after use

C: Taurolidine 2%; 5.0 mL 2-7x/week

D: Taurolidine 1.35% Citrate 4% Heparin 100 IU/mL; 2.0-4.0 mL 2-7x/week

E: Taurolidine 2% and Taurolidine 1.35%, Citrate 4%; dose and frequency not specified

F: Taurolidine 2%; 5.0 mL, frequency not specified

Citrate/heparin/saline lock

A: Heparin 100 IU/mL

B: Saline 0.9%

C: Saline 0.9%

D: Heparin 100 IU/mL

E: Saline 0.9%

F: Heparin 150 IU/mL

End-point of follow-up:

Not specified

For how many participants were no complete outcome data available?

(intervention/control)

Not specified

Infection events (primary outcome)

A: I 2/719; C 1/690

IRR 1.92 (0.18, 20.66), p=1.00

B: 1/10000; C 4/10000

IRR 0.23 (0.03, 2.06), p=0.21

C: I 5/15318; C 18/12493

IRR 0.23 (0.07, 0.63), P<0.01

D: I 0/9622; C 7/6956

IRR N/A

E: I1 0/3658, I2 1/3650; C 0/3660

IRR N/A

F: I 1/5370; C 10/4939

Infection per patient (data from original publications)

A: I 3/72 (4.1%); C 7/69 (10.1%)

B: TIVAP-BSI: I 1/84 (1%); C 4/76 (5%)

C: I 5/52; C 18/50

D: I 0/20; C 7/21

E: tauro: 0/10; tauro+citr 1/10 (10%); C 0/10

F: I 1/16 (6%); C 10/14 (71%)

Quality of life

Not reported

Patient satisfaction

Not reported

Number of catheter-related interventions per year

Not reported

Antibiotic resistance

Not reported

Adverse events

Number of patients when reported, otherwise number of events

A: I 0/72; C 0/69

B: I Local paresthesia (9),

body warm sensation (4),

unpleasant taste (1),

pain (1); C not specified

C: I Unpleasant taste (1),

dizziness (1), erhythema

exit-site (1); C Flushing (1)

D: I Unpleasant taste (8),

paresthesia (3), nausea/

vomiting (2); C Heartburn/acid reflux (1), paresthesia (1),

dizziness (1)

E: I 0/10; C 0/10

F: I 0/16; C 0/14

Authors’ conclusions

The use of TLs might be promising for the prevention of CVC-related bloodstream

infections. Large-scale RCTs are needed to draw firm conclusions on the efficacy of

TLs.

VAP: vascular access port

Zhang, 2019

PROSPERO registration number CRD42015027833

Study characteristics and results are extracted from the SR, unless stated otherwise

SR and meta-analysis of  RCTs

Literature search up to March, 2018

A: Salonen, 2017

B: Sanders, 2008

C: Slobbe, 2010

D: Worth, 2014

Study design:

A: prospective double blind randomized controlled study

B: prospective double-blind randomized trial

C: randomized, placebo-controlled trial

D:

randomized trial

Setting and country:

A: USA

B: New Zealand

C: the Netherlands

D: Australia

Setting was not reported in SR

Source of funding and conflicts of interest:

The authors received no specific funding for this work. There was no additional external funding received for this study.

The authors have declared that no competing interests exist.

Inclusion criteria SR:

Adults and children with a tunneled or nontunneled CVC as vascular access, regardless of the type of disease; Ethanol lock solutions were used in the intervention group. Solutions were allowed to dwell rather than simply being flushed through the catheter. A control condition (e.g., heparin locks) was used in the control group.

Exclusion criteria SR:

Overlapping study populations, non-RCTs, unavailable full-text.

9 studies included in meta-analysis, 4 of which relevant for current analysis.

Important patient characteristics at baseline:

N, population

A: 38, parenteral nutrition

B: 64, hematology

C: 376, hematology

D: 85, hematology

Sex and age not reported in SR

Catheter type:

A: not reported

B: tunneled

C: tunneled

D: tunneled

Insertion site

A: not reported

B: Subclavian veins

C: Internal jugular vein, subclavian vein, femoral vein

D: Subclavian, internal jugular

veins

Groups were comparable at baseline.

Ethanol lock

A: Ethanol 70%

Patients flushed their catheters with 10 ml 0.9% NaCl after completion of their parenteral nutrition and then locked the catheter with 3 ml 70% ethanol. Prior to administration of the next bag of parenteral nutrition, they again flushed their catheters with 10 mL 0.9% NaCl.

B: Ethanol 70%

Three milliliters of 70% ethanol was injected into each lumen of the catheter daily and left for 2 hours before being entirely removed and replaced with heparinized saline.

C: Ethanol 70%

During hospitalization, every lumen of the CVC was locked with 3 ml 70% ethanol for 15 minutes per day, following which the solution was flushed through with 10 ml 0.9% NaCl. During outpatient settings, ethanol locks were administered once weekly before the replacement of the regular heparin solution.

D: Ethanol 70%

After flushing CVC lumens with 10 ml 0.9% NaCl, 2 ml 70% ethanol was instilled into each CVC lumen daily for inpatients and left in situ for 2 hours. A 5- to 10-ml aliquot was then aspirated from each lumen before locking under positive pressure with 10 mL 0.9% NaCl. Self-caring outpatients were instructed to administer the ethanol lock three times weekly, with 2 hours dwell time.

Control lock

A: heparin

B: heparin

C: 0.9% NaCl

D: heparin

End-point of follow-up:

Not specified in SR

For how many participants were no complete outcome data available?

Not specified in SR

Catheter-related bloodstream infection (primary outcome)

CRBSI (as defined by the study author) per 1000 catheter days

heparin

A: I 4/2597; C 1/3125

OR 4.82 (0.54, 43.14)

B: I 3/5000; C 11/3537

OR 0.19 (0.05, 0.69)

D: I 4/2216; C 5/2657

OR 0.96 (0.26, 3.58)

NaCl

C: I 10/14262; C 16/13483

OR 0.59 (0.27, 1.30)

CRBSI (as defined by the study author) per patient

heparin

A: I 4/18; C 1/20

OR 5.43 (0.55, 54.01)

B: I 3/34; 11/30

OR 0.17 (0.04, 0.68)

D: I 4/42; C 5/43

OR 0.80 (0.20, 3.21)

NaCl

C*: I 2/226; C 7/222

*retrieved from original publication

Exit site infection per 1000 catheter days

heparin

A: not reported

B: I 2/5000; C 1/3537

C: not reported

D: I 2/2216; C 3/2657

Quality of life

Not reported

Patient satisfaction

Not reported

Number of catheter-related interventions per year

Not reported

Antibiotic resistance

Not applicable for this intervention

Adverse events

Not reported at patient level

A: No adverse events in either group

B: I: Dyspnea immediately after the first treatment

(n = 1); C Unusual taste sensation and anxiety (n = 1)

C: I: Facial flushing (n = 39); nausea/vomiting

(n = 20); altered taste (n = 31); dizziness/

drowsiness (n = 41); syncope shortly after the

first treatment (n = 1); C: Facial flushing (n = 17); nausea/vomiting

(n = 17); altered taste (n = 19); dizziness/

drowsiness (n = 10)

D: I: Chest discomfort (3); nausea (n = 1); C: No adverse events.

Authors’ conclusions

The present data indicate that ethanol lock prophylaxis is a potential candidate for the prevention of CRBSI in patients with CVC. However, more attention should be paid to the uniform ethanol lock procedure and toxic effects after long-term ethanol lock exposure.

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Carratala, 1999

Type of study:

RCT

Setting and country:

Single center, Spain

Funding and conflicts of interest:

This study was supported in part by grant 93/1081 from Fondo de

Investigacio´n Sanitaria, Madrid, Spain.

No conflict of interest statement.

Inclusion criteria:

Hospitalized patients with a nontunneled, multilumen,

polyurethane CVC in place and who

were to receive chemotherapy designed to produce severe neutropenia were eligible for participation in the trial

Exclusion criteria:

Patients were

excluded if they had clinical or microbiologic evidence of infection or had a

known allergy to vancomycin. Patients already receiving antibiotics or parenteral

nutrition were also excluded.

N total at baseline:

Intervention: 60

Control: 60

Important prognostic factors²:

Age, mean ± SD:

I: 42

C: 44

Sex:

I: 51.7% M

C: 68.4% M

Type of catheter

Double lumen

I: 66.7%

C: 61.4&

Triple lumen

I: 33.3%

C: 38.6%

Duration of catheterization

prior to randomization

(days)

I: 25

C: 24

Groups were comparable at baseline.

Lock solution containing heparin at 10 U/ml and vancomycin at 25 mg/ml.

Lock solution containing heparin at 10 U/ml

Catheters were inserted into the subclavian vein by physicians who wore masks, caps, sterile gloves, and surgical gowns and who used large sterile drapes. Study catheters were not exchanged over guidewires. At the time of catheter insertion, the skin insertion site was disinfected with 4% chlorhexidine gluconate (Hibiscrub; ICI Farma, Pontevedra, Spain), which was applied by scrubbing for at least 30 s. The insertion sites were covered with sterile gauze.

Length of follow-up:

28 days

Loss-to-follow-up:

Intervention:

0/60 (0%)

Control:

0/57 (0%)

Incomplete outcome data:

Not specified.

Catheter infection

Significant colonization of

catheter hub (primary outcome)

I: 0/60 (0%)

C: 9/57 (15.8%)

P=0.001

Catheter-related bacteremia

I: 0/60 (0%)

C: 4/57 (7.0%)

P=0.05

Quality of life

Not reported

Patient satisfaction

Not reported

Number of catheter-related interventions per year

Not reported

Antibiotic resistance

No vancomycin-resistant organism was isolated

from any source during the study period

Adverse events

Not reported

Authors’ conclusions:

Our study shows that a solution containing heparin and vancomycin administered by using an antibiotic-lock technique effectively prevents catheter hub colonization

with gram-positive bacteria and subsequent bacteremia during chemotherapy-induced neutropenia in patients

with hematologic malignancy.

Study

First author, year

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/not applicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Potential conflicts of interest reported?⁹

Yes/no/unclear

Zhang, 2019

Yes

Yes

No

Excluded studies were not.described.

Yes

N/A

Yes

Yes

No

Unclear

Not specified for included studies

Van den Bosch, 2022

Yes

Yes

No

Excluded studies were not.described.

Yes

N/A

Yes

Yes

Yes

Unclear

Not specified for included studies

Study reference

(first author, publication year)

Was the allocation sequence adequately generated?

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

LOW

Some concerns

HIGH

Carratala, 1999

Definitely yes;

Reason: For study solution allocation a computer-generated list of random numbers, which was available only to the pharmacist, was used.

Definitely yes;

Reason: The two solutions were indistinguishable to

medical personnel and were dispensed in 20-ml vials that were numerically coded

and that were kept refrigerated. The code list was kept in the hospital pharmacy

and was opened only after the study was completed.

Definitely yes;

Reason: The

patients’ physicians and nurses, the clinical investigators, and the research microbiologists

who processed all cultures were blinded to each study group.

Probably yes;

Reason: Loss to follow-up was infrequent.

Probably yes;

Reason: All relevant outcomes were reported.

Probably yes;

Reason: No other problems noted.

LOW

Reference

Reason for exclusion

Dang FP, Li HJ, Wang RJ, Wu Q, Chen H, Ren JJ, Tian JH. Comparative efficacy of various antimicrobial lock solutions for preventing catheter-related bloodstream infections: A network meta-analysis of 9099 patients from 52 randomized controlled trials. Int J Infect Dis. 2019 Oct;87:154-165. doi: 10.1016/j.ijid.2019.08.017. Epub 2019 Aug 20. PMID: 31442627.

wrong P: includes hemodialysis

Gudiol C, Arnan M, Aguilar-Guisado M, Royo-Cebrecos C, Sánchez-Ortega I, Montero I, Martín-Gandul C, Laporte-Amargós J, Albasanz-Puig A, Nicolae S, Perayre M, Berbel D, Tebe C, Riera J, Sureda A, Cisneros JM, Carratalà J. A Randomized, Double-Blind, Placebo-Controlled Trial (TAURCAT Study) of Citrate Lock Solution for Prevention of Endoluminal Central Venous Catheter Infection in Neutropenic Hematological Patients. Antimicrob Agents Chemother. 2020 Jan 27;64(2):e01521-19. doi: 10.1128/AAC.01521-19. PMID: 31712211; PMCID: PMC6985755.

Reported in systematic review

Gudiol C, Nicolae S, Royo-Cebrecos C, Aguilar-Guisado M, Montero I, Martín-Gandul C, Perayre M, Berbel D, Encuentra M, Arnan M, Cisneros-Herreros JM, Carratalà J. Administration of taurolidine-citrate lock solution for prevention of central venous catheter infection in adult neutropenic haematological patients: a randomised, double-blinded, placebo-controlled trial (TAURCAT). Trials. 2018 May 2;19(1):264. doi: 10.1186/s13063-018-2647-y. PMID: 29720244; PMCID: PMC5932813.

Wrong study design: protocol

Longo R, Llorens M, Goetz C, Platini C, Eid N, Sellies J, Ouamara N, Quétin P. Taurolidine/Citrate Lock Therapy for Primary Prevention of Catheter-Related Infections in Cancer Patients: Results of a Prospective, Randomized, Phase IV Trial (ATAPAC). Oncology. 2017;93(2):99-105. doi: 10.1159/000470911. Epub 2017 May 3. PMID: 28463827.

Reported in systematic review

Norris LB, Kablaoui F, Brilhart MK, Bookstaver PB. Systematic review of antimicrobial lock therapy for prevention of central-line-associated bloodstream infections in adult and pediatric cancer patients. Int J Antimicrob Agents. 2017 Sep;50(3):308-317. doi: 10.1016/j.ijantimicag.2017.06.013. Epub 2017 Jul 6. PMID: 28689878.

Original publication used

Reitzel RA, Rosenblatt J, Chaftari AM, Raad II. Epidemiology of Infectious and Noninfectious Catheter Complications in Patients Receiving Home Parenteral Nutrition: A Systematic Review and Meta-Analysis. JPEN J Parenter Enteral Nutr. 2019 Sep;43(7):832-851. doi: 10.1002/jpen.1609. Epub 2019 Jun 6. PMID: 31172542.

wrong study design, only observational data

Salonen BR, Bonnes SL, Vallumsetla N, Varayil JE, Mundi MS, Hurt RT. A prospective double blind randomized controlled study on the use of ethanol locks in HPN patients. Clin Nutr. 2018 Aug;37(4):1181-1185. doi: 10.1016/j.clnu.2017.05.009. Epub 2017 May 17. PMID: 28576557.

Reported in systematic review

Taşdelen Öğülmen D, Ateş S. Use of alcohol containing caps for preventing bloodstream infections: A randomized controlled trial. J Vasc Access. 2021 Nov;22(6):920-925. doi: 10.1177/1129729820952961. Epub 2020 Aug 27. PMID: 32854563.

Wrong intervention

van de Wetering MD, van Woensel JB, Lawrie TA. Prophylactic antibiotics for preventing Gram positive infections associated with long-term central venous catheters in oncology patients. Cochrane Database Syst Rev. 2013 Nov 25;2013(11):CD003295. doi: 10.1002/14651858.CD003295.pub3. Update in: Cochrane Database Syst Rev. 2021 Oct 7;10:CD003295. PMID: 24277633; PMCID: PMC6457614.

more recent systematic review used

Vassallo M, Dunais B, Roger PM. Antimicrobial lock therapy in central-line associated bloodstream infections: a systematic review. Infection. 2015 Aug;43(4):389-98. doi: 10.1007/s15010-015-0738-1. Epub 2015 Feb 6. PMID: 25657033.

no usable data in article

Vernon-Roberts A, Lopez RN, Frampton CM, Day AS. Meta-analysis of the efficacy of taurolidine in reducing catheter-related bloodstream infections for patients receiving parenteral nutrition. JPEN J Parenter Enteral Nutr. 2022 Sep;46(7):1535-1552. doi: 10.1002/jpen.2363. Epub 2022 Mar 25. PMID: 35233792.

more complete systematic review used

Worth LJ, Slavin MA, Heath S, Szer J, Grigg AP. Ethanol versus heparin locks for the prevention of central venous catheter-associated bloodstream infections: a randomized trial in adult haematology patients with Hickman devices. J Hosp Infect. 2014 Sep;88(1):48-51. doi: 10.1016/j.jhin.2014.06.007. Epub 2014 Jul 2. PMID: 25063013.

Reported in systematic review

Zacharioudakis IM, Zervou FN, Arvanitis M, Ziakas PD, Mermel LA, Mylonakis E. Antimicrobial lock solutions as a method to prevent central line-associated bloodstream infections: a meta-analysis of randomized controlled trials. Clin Infect Dis. 2014 Dec 15;59(12):1741-9. doi: 10.1093/cid/ciu671. Epub 2014 Aug 25. PMID: 25156111.

more complete systematic review used