Efficacy of antimicrobial lock solutions in preventing catheter-related blood stream infection in haemodialysis patients: a systematic review and meta-analysis of prospective randomised controlled trials

Figures & data

Figure 1: Flowchart of studies selection.

Table 1: Characteristics of studies included in the meta-analysis

Author	Sample size	Catheter days (ALS, controls)	Catheter type	Catheter care	CRBSI definition	ALS
Moran et al. (2012)^34	303	39827, 32933	TCC	Triple antibiotic*	Non-CDC	GTC-0.32 mg/ml, CTR-4%
Saxena et al. (2012)^36	82	14965, 17155	TCC	Non	CDC	CFO-10 mg/ml
Maki et al. (2011)^33	407	25266, 24390	Not clear	NA	Non-CDC	CTR-7.5%, MB, MP, PPP
Davanipur et al. (2011)^32	100	1750, 1625	TCC	NA	NA	CLOX-100 mg/ml
Campos et al. (2011)^31	187	4371, 4376	TCC/NTC	Chlorhexidine/alcohol	CDC	MNC-3 mg/ml, EDTA-30 mg/ml
Mortazavi et al. (2011)^33	30	NA	TCC	Antiseptic/topical mupirocin	CDC	CFO-10 mg/ml
Solomon et al. (2010)^15	107	8129, 9642	TCC	Chlorhexidine/alcohol	Non-CDC	TRD-1.35%, CTR-4%
Al-Hwiesh et al. (2007)^30	63	7212, 7656	TCC	Iodine solution	CDC	VCM-25 mg/ml, GTC-40 mg/ml
MacRae et al. (2008)^29	61	92, 105	TC	NA	Non-CDC	CTR-4%
Saxena et al. (2006)^12	96	18615, 21170	TCC	Oxygen permeable dressing	CDC	CFO-10 mg/ml
Kim et al. (2006)^11	120	1884, 1233	NTC	NA	Non-CDC	CFZ-10 mg/ml, GTC-5 mg/ml
Nori et al. (2006)^10	61	4455, 1734	TCC	NA	CDC	a). GTC-4 mg/ml, CTR-3.13%, or b). MNC-3 mg/ml, EDTA-30 mg/ml
Weijmer et al. (2005)^14	291	8431, 8116	TCC/NTC	NA	CDC	CTR-30%
McIntyre et al. (2004)^9	50	3252, 2470	TCC	Oxygen permeable dressing	CDC	GTC-5 mg/ml
Pervez et al. (2002)^28	36	1613, 1311	TCC	Iodine	Non-CDC	GTC-40 mg/ml, CTR-46.7%
Dogra et al. (2002)^8	83	3280, 2643	TCC	Chlorhexidine/iodine	CDC	GTC-40 mg/ml, CTR-3.13%

*Neomycin, bacitracin and polymyxin

ALS: Antimicrobial lock solution; CRBSI: Catheter related blood stream infection; CDC: Center for Disease Control and Prevention; CFZ: cefazolin; CFO: cefotaxime; CTR: citrate; CLOX: cloxacillin; EDTA: ethylene diamino acetic acid; GTC: gentamicin; MB: methylene blue; MP: methylparaben; MNC: minocycline; NA: not available; NTC: Non-tunneled cuffed catheter; PPP: propylparaben; TRD: taurolidine; TCC: tunneled cuffed catheter; VCM: vancomycin

Table 2: Assessment of study quality using the GRADE approach

Characteristics of included studies		GRADE Factors
Author	ES	RCT design	Large effect size	Study limitations	Inconsistency	Indirectness	Imprecision	Exposure-response gradient	Plausible confounding	Publication bias	Overall quality
Moran (2012)^34	2.54	✓	✓	✓	✓	✓	✓	NA	✓	✓	++++
Saxena (2012)^36	0.48	✓	X	✓	✓	X	X	NA	✓	✓	++
Maki (2011)^33	0.59	✓	X	✓	✓	✓	X	NA	✓	✓	+++
Davanipur (2011)^32	1.13	✓	✓	✓	✓	X	✓	NA	X	✓	+++
Campos (2011)^31	0.72	✓	X	X	✓	✓	✓	NA	✓	✓	+++
Mortazavi (2011)^35	1.78	✓	✓	X	✓	✓	X	NA	✓	✓	+++
Solomon (2010)^15	0.39	✓	X	X	✓	✓	✓	NA	✓	✓	+++
Al-Hwiesh (2007)^30	1.17	✓	✓	✓	✓	X	X	NA	✓	✓	+++
MacRae (2008)^29	0.15	✓	X	✓	✓	X	X	NA	✓	✓	++
Saxena (2006)^12	0.56	✓	X	✓	✓	X	X	NA	✓	✓	++
Kim (2006)^11	1.09	✓	✓	X	✓	X	X	NA	✓	✓	++
Nori (2006)^10	1.47	✓	✓	✓	✓	✓	X	NA	✓	✓	+++
Nori (2006)^11	1.09	✓	✓	✓	✓	✓	X	NA	✓	✓	+++
Weijmer (2005)^14	0.74	✓	X	✓	✓	✓	✓	NA	✓	✓	++++
McIntyre (2004)^9	1.27	✓	✓	✓	✓	X	X	NA	✓	✓	+++
Pervez (2002)^28	0.59	✓	X	✓	✓	X	X	NA	✓	✓	++
Dogra (2002)^8	1.55	✓	✓	✓	✓	✓	X	NA	✓	✓	+++

✓– No serious limitation, inconsistency, indirectness, imprecision, publication bias, plausible confounding (or presence of large effect size and exposure-response gradient)

X – Presence of serious limitation, inconsistency, indirectness, imprecision, publication bias, plausible confounding (or absence of large effect size and exposure-response gradient)

Overall quality of evidence: + - very low; ++ - low; +++ - moderate; ++++ - high

RR: relative risk; CI: confidence interval; GRADE: Grading of Recommendations Assessment Development and Evaluation; NA: not available; ES: effect size

Figure 2: Forest plot showing RR of developing CRBSI among patients on chronic HD.

Figure 3: Egger’s plot assessing small study effect.

Figure 4: Begg’s Funnel plot assessing publication bias.

Table 3: Assessment of quality of clinical evidence and strength of recommendation using the GRADE approach

		Outcome assessed-efficacy of ALS in preventing CRBSI among HD patients
		All ALS	High dose Gentamicin	Low dose Gentamicin	Cefotaxime	Minocycline	Taurolidine/Citrate
Baseline parameters	Number of studies	Sixteen	Two^8,28	Three^9,10,34	Two^12,36	Two^10,31	Three^14,15,29
	Total sample size	2016	119	414	178	248	459
	Total catheter days	279 701	8 847	84 671	71 905	14 936	126 423
GRADE factors	RCT design	✓	✓	✓	✓	✓	✓
	Plausible confounding	✓	✓	✓	✓	✓	✓
	Study limitations	✓	✓	✓	✓	✓	X
	Inconsistency	X	✓	✓	✓	✓	✓
	Indirectness	✓	✓	✓	✓	✓	✓
	Imprecision	✓	X	✓	✓	✓	✓
	Publication bias	✓	✓	✓	✓	✓	✓
	Large effect size	✓	✓	✓	X	X	X
	Exposure-response gradient	X	X	X	X	X	✓
	Overall quality	+++	+++	++++	+++	+++	+++

✓– No serious limitation, inconsistency, indirectness, imprecision, publication bias, plausible confounding (or presence of large effect size and exposure-response gradient)

X – Presence of serious limitation, inconsistency, indirectness, imprecision, publication bias, plausible confounding (or absence of large effect size and exposure-response gradient)

Overall quality of evidence: +—very low; ++—low; +++—moderate; ++++—high

ALS: Antimicrobial lock solution; CRBSI: Catheter-related blood stream infection; GRADE: Grading of Recommendations Assessment Development and Evaluation; HD: Haemodialysis

Figure 5: Meta-regression of RR of developing CRBSI by catheter days. Slope curve coefficient = 2.35, p = 0.037, 95% CI = -1.1406 to + 0.0001.

Moran J, Sun S, Khababa I, et al. A randomized trial comparing gentamicin/citrate and heparin locks for central venous catheters in maintenance haemodialysis patients. Am J Kidney Dis. 2011;59(1):102–107.

 PubMed Web of Science ®Google Scholar

Saxena AK, Al-hafiz A, Abu-Oyun B, et al. Cefotaxime-heparin lock prophylaxis against hemodialysis catheter-related sepsis among Staphylococcus aureus nasal carriers. Saudi J Kidney Dis Transpl. 2012;23(4):743–754.10.4103/1319-2442.98154

 PubMedGoogle Scholar

Maki DG, Ash SR, Winger RK, et al. AZEPTIC Trial Investigators. A novel antimicrobial and antithrombotic lock solution for hemodialysis catheters: a multi-center, controlled, randomized trial. Crit Care Med. 2011 April;39(4):613–620.

 PubMed Web of Science ®Google Scholar

Davanipur M, Pakfetrat M, Roozbeh J. Cloxacillin as an antibiotic lock solution for prevention of catheter-associated infection. IJKD. 2011;5:328–331.

 Web of Science ®Google Scholar

Campos RP, do Nascimento M, Chula DC, et al. Minocycline-EDTA lock solution prevents catheter-related bacteremia in hemodialysis. J Am Soc Nephrol. 2011 October;22(10):1939–1945.10.1681/ASN.2010121306

 PubMed Web of Science ®Google Scholar

Solomon LR, Cheesbrough JS, Ebah L, et al. A randomized double-blind controlled trial of taurolidine-citrate catheter locks for the prevention of bacteremia in patients treated with hemodialysis. Am J Kidney Dis. 2010;55:1060–1068.10.1053/j.ajkd.2009.11.025

 PubMed Web of Science ®Google Scholar

Al-Hwiesh AK, Abdul-Rahman ISA. Successful prevention of tunneled, central catheter infection by antibiotic lock therapy using vancomycin and gentamicin. Saudi J Kidney Dis Transplant. 2007;18:239–247.

 PubMedGoogle Scholar

MacRae JM, Dojcinovic I, Djurdjev O, et al. Citrate 4% versus Heparin and the reduction of thrombosis study (CHARTS). Clin J Am Soc Nephrol. 2008 Mar;3(2):369–374.10.2215/CJN.01760407

 PubMed Web of Science ®Google Scholar

Saxena AK, Panhotra BR, Sundaram DS, et al. Tunneled catheters’ outcome optimization among diabetics on dialysis through antibiotic-lock placement. Kidney Int. 2006;70:1629–1635.10.1038/sj.ki.5001776

 PubMed Web of Science ®Google Scholar

Kim SH, Song KI, Chang JW, et al. Prevention of uncuffed hemodialysis catheter-related bacteremia using an antibiotic lock technique: a prospective, randomized clinical trial. Kidney Int. 2006;69:161–164.10.1038/sj.ki.5000012

 PubMed Web of Science ®Google Scholar

Nori US, Manoharan A, Yee J, et al. Comparison of low-dose gentamicin with minocycline as catheter lock solutions in the prevention of catheter-related bacteremia. Am J Kidney Dis. 2006;48:596–605.10.1053/j.ajkd.2006.06.012

 PubMed Web of Science ®Google Scholar

Weijmer MC, van den Dorpel MA, Van de Ven PJ, et al. Randomized, clinical trial comparison of trisodium citrate 30% and heparin as catheter-locking solution in hemodialysis patients. J Am Soc Nephrol. 2005;16:2769–2777.10.1681/ASN.2004100870

 PubMed Web of Science ®Google Scholar

McIntyre CW, Hulme LJ, Taal M, et al. Locking of tunneled hemodialysis catheters with gentamicin and heparin. Kidney Int. 2004;66:801–805.10.1111/j.1523-1755.2004.00806.x

 PubMed Web of Science ®Google Scholar

Pervez A, Ahmed M, Ram S, et al. Antibiotic lock technique for prevention of cuffed tunnel catheter associated bacteremia. J Vasc Access. 2002;3:108–113.

 PubMedGoogle Scholar

Dogra GK, Herson H, Hutchison B, et al. Prevention of Tunneled Hemodialysis Catheter-Related Infections Using Catheter-Restricted Filling with Gentamicin and Citrate: A Randomized Controlled Study. J Am Soc Nephrol. 2002;13:2133–2139.10.1097/01.ASN.0000022890.29656.22

 PubMed Web of Science ®Google Scholar

Mortazavi M, Alsaeidi S, Sobhani R, et al. Successful prevention of tunneled, central catheter infection by antibiotic lock therapy using cefotaxime. J Res Med Sci. 2011 March;16(3):303–309.

 PubMed Web of Science ®Google Scholar