Lock therapy in prevention and treatment of catheter-associated bloodstream infection: integrative review

Tresso, Karina Angélica; Santos, Bruna Nogueira dos; Braga, Fernanda Titareli Merizio Martins; Margatho, Amanda Salles; Mendes, Karina Dal Sasso; Silveira, Renata Cristina de Campos Pereira

doi:10.37689/acta-ape/2023AR012211

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Review Article • Acta Paul Enferm 36 • 2023 • https://doi.org/10.37689/acta-ape/2023AR012211 copy

Lock therapy in prevention and treatment of catheter-associated bloodstream infection: integrative review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To synthesize knowledge on the use of lock therapy for prevention and treatment of long-term central vascular access devices-associated bloodstream infection in hospitalized adult and elderly patients.

Methods

Integrative review conducted in CINAHL, Cochrane Central, Embase, LILACS, PubMed, Scopus, and Web of Science databases, from January 1st, 2010 to September 28th, 2021, without language restrictions. Data were analyzed descriptively.

Results

Sixteen studies were identified, six (37.5%) on the use of lock therapy for prevention of bloodstream infection associated with central vascular access devices, and ten (62.5%) on treatment. The articles on prevention reported the use of non-antibiotic solutions. Nine of the ten studies that addressed lock therapy as treatment used antibiotic solutions. Two studies assessed the effectiveness of lock therapy in a short duration (three to four days), seven in a longer duration (between 10 and 14 days), and one did not specify the length of time. Each study described an intervention technique and the length of stay of the intraluminal solution. Regarding the risk of bias, five randomized clinical trials, two non-randomized clinical trials, and eight observational studies were rated as low risk. Only one observational study was classified as moderate risk.

Conclusion

The use of non-antibiotic solutions such as ethanol was identified for prevention of bloodstream infection. For treatment, intravenous daptomycin was used. While the studies included in this review on prevention did not show statistical evidence, the ten studies on treatment demonstrated that lock therapy is an effective complement to systemic treatment, showing good catheter salvage rates.

Central venous catheters; Catheters, indwelling; Vascular access device; Catheter-related infecions; Nursing care; Anti-bacterial agents; Anti-infective agents; Lock therapy; Ethanol

Author, year, country	Study design	Objective	Intervention	Control	Main results
Slobbe et al., 2010.⁽²³⁾ Netherlands	Placebo-controlled randomized clinical trial	To study the efficacy and safety of daily lock therapy with 70% ethanol in the prevention of endoluminal CABSI in hematologic patients with long-stay tunneled catheters.	The lumens of CVAD were locked for 15 min/day with 3 ml of 70% Ethanol daily during hospitalization. Afterwards the lumens were flushed with 10 ml of 0.9% NaCl .	Lock therapy with placebo.	For lock therapy with ethanol, the incidence of endoluminal CABSI per 1000 catheters/day was 0.70 compared to 1.19 in the placebo group, with a non-significant 41% reduction in patients receiving lock therapy with ethanol (p=0.19 For endoluminal CABSI, a non-significant 3.6-fold reduction was found for patients receiving ethanol (2 of 226 versus 7 of 222; p=0.103). More patients receiving ethanol lock therapy discontinued treatment (11 of 226 versus 1 of 222; p=0.006) or continued, with less frequent lock therapy administration (10 of 226 versus 0 of 222; p=0.002), due to non-severe adverse events. Total N=376 patients with 448 catheter
Boersma et al., 2014.⁽²⁴⁾ Netherlands	Randomized clinical trial	To determine the efficacy of lock therapy with TSC compared to heparin in preventing thrombosis and infections associated with tunneled or non-tunneled CVAD in patients with hematologic malignancies undergoing high-dose chemotherapy.	After each catheter use, the lumen was flushed with 10 ml of 0.9% NaCl and locked with 46.7% citrate.	After CVAD use, each lumen received lock therapy with heparin sodium 5,000 U/ml.	34 episodes of CABSI occurred in the 108 patients who were treated with heparin lock therapy compared to 35 episodes in the 99 patients who received lock therapy with TSC (p=0.654). Seven times more CABSI were found with gram-negative batonettes in the heparin lock therapy (p=0.041). Total N=207 patients.
Worth et al., 2014.⁽²⁵⁾ Australia	Randomized clinical trial	To prospectively compare heparinized saline solution with ethanol 70% as lock therapy in hematologic or hematopoietic stem cell transplant patients with tunneled CVAD (prevention).	Each lumen was flushed with 10 ml of saline solution and locked with 2 ml of 70% ethanol, with a dwell time of 2 hours.	Daily lock therapy with heparinized saline solution with a dwell time of 2h in the catheter lumen.	Central catheter-associated bloodstream infection rates were 6.0 in the control group and 4.1 in the intervention group per 1,000 CVAD days (p=0.42). Five CABSI events were identified over 1,917 days of CVAD in the heparinized saline group. Four CABSI events were detected over 1,381 days of CVAD in the ethanol group (p=1.00). Outlet site infection was detected in three patients receiving heparinized saline and in two patients receiving ethanol. N total=85 patients
Gudiol et al., 2020.⁽²⁶⁾ Spain	Multicenter double-blind randomized clinical trial	To test the efficacy of lock therapy with taurolidine-citrate-heparin solution compared to placebo, for prevention of CVAD infection in hematologic neutropenic patients.	Each lumen was locked with 2.5ml of taurolidine 2%, citrate 4% and heparin 500UI/ml solution, three times a week, every 48/72h and dwell time of two hours.	Same procedure with placebo solution. .	Lock therapy with taurolidine-citrate-heparin was associated with less CVAD hub colonization compared to placebo solution: three patients in the intervention group (4.1%) versus seven patients in the placebo group (10.1%). There were no significant differences regarding the incidence of CABSI: two episodes in the intervention group and one in the placebo group. CVAD was removed in 13 patients in each group. N total=141 patients.
Longo et al., 2017.⁽²⁷⁾ France	Randomized, prospective, single-center, phase IV clinical trial	To evaluate the efficacy of lock therapy with taurolidine versus saline solution for prevention of primary infection associated with the fully implanted catheter of oncologic, non-hematologic patients receiving intravenous chemotherapy.	Lock therapy with 3 ml of taurolidine solution	Lock therapy with saline solution.	The incidence rate of CABSI in totally implanted catheter was 0.4% catheters/day in the control group and 0.1% catheters/day in the taurolidine group (p=0.21). Totally implanted catheter-associated infections required 22 days of hospitalization in the taurolidine group versus 106 days in the control group. Taurolidine-related toxicity was transient and classified as grade I. Total number=163 patients
Chaftari et al., 2017.⁽²⁹⁾ USA	Pilot, open-label, prospective study	To evaluate the efficacy and safety of a nonantibiotic and nonheparin nitroglycerin-based lock solution, for the prevention of CABSI in cancer patients using peripherally inserted central catheter.	Lumens were flushed with 0.9% NaCl, followed by infusion of a 2 hour once daily combination of 0.8 to 1 ml of solution composed of 15 or 30 µ Nitroglycerin, 4% sodium citrate and 22% ethanol	Each patient served as his own control while he was not receiving the study solution, but was receiving heparin or saline.	No CABSI was identified during the 619 catheters/day with administration of the lock therapy solution, compared to three episodes of CABSI during the 1,853 days without lock therapy (p=0.32). There were no serious adverse events or episodes of hypotension related to the lock therapy administration. The rate of CABSI was zero on lock therapy days versus 1.6/1,000 catheters/day without lock therapy, compared to a rate of 1.9/1,000 catheters/day in the same patient population. Total N=60 patients.

Author, year, country	Study design	Objective	Intervention	Control	Main results
Ahmad et al., 2019.⁽¹⁵⁾ denmark	Retrospective, non-interventional quality control study	To analyze the dwell time of the tunneled catheter after hydrochloric acid installation in adult hematologic patients with CABSI (treatment).	Each lumen was flushed with 10 ml of 0.9% NaCl; administered hydrochloric acid 2.5 mmol/ml according to lumen volume; 10 minutes of dwell time; 5 ml aspirated from each lumen; flushed with 10 ml of 0.9% NaCl; the procedure was repeated two more times.	Not applicable.	After lock therapy with hydrochloric acid, the CVAD was not removed due to infection in 49 of 71 patients (69%). 22 patients (31%) kept their CVAD until the end of treatment. Non-infectious mortality (19/71), accidental removal (2/71) or mechanical dysfunction of the CVAD (6/71) were additional reasons for premature catheter removal. Twenty-two catheters (31%) had to be removed because of infection. The median time from CVAD insertion to hydrochloric acid lock therapy was 39 days. The median time from hydrochloric acid lock therapy to CVAD removal was 58 days. N total=75 patients
Bookstaver et al., 2010.⁽¹⁶⁾ USA	Retrospective analysis of a case series	To analyze the outcomes associated with antimicrobial lock therapy as adjuvant treatment of CABSI.	Lumens were maintained with lock solution whenever the CVAD was not in use, and subsequently, suctioned. In double lumen CVAD, one was maintained with locking solution for 24h, alternating every other day.	Not applicable.	Most patients received vancomycin, daptomycin or gentamicin combined with heparin as lock therapy. Negative blood culture was achieved in 69.2% of cases and negative blood culture plus CVAD maintenance was achieved in 11 cases (42.3%). Longer length of antimicrobial lock therapy was significantly correlated with negative blood culture (p=0.077). Total N=26 cases in 15 patients.
Freire et al., 2018.⁽¹⁷⁾ Brazil	Prospective study	To analyze long-term CVAD associated infections from risk factors for unfavorable outcomes and the impact of lock antimicrobial therapy, including multidrug-resistant bacteria infection (treatment).	Vancomycin (5mg/ml) and Amikacin (2mg/ml) administered in all lumens, changed every 24h.	Systemic treatment, no lock therapy.	296 infections associated with long-term CVAD were identified, 212 (71.6%) were bloodstream infections. The success rate of antimicrobial lock therapy was 75.9%. Despite high incidence of infection by multidrug-resistant bacteria, antimicrobial lock therapy improved the outcome of long-term CVAD-associated infection in cancer patients.Total number: 275 patients with 296 infections
Haag et al., 2011.⁽¹⁸⁾ Germany	Retrospective analysis of a case series	To evaluate lock therapy with taurolidine in combination with systemic antibiotic in the management of CABSI.	CVAD was locked for 3 to 4 consecutive days with TauroLock^TM Hep 100R solution (cyclotaurolidine 1.4%, citrate solution 0.4% and heparin 100UI/ml).	Not applicable.	Treatment was successful in 16 of 24 events (67%). CVAD removal was required in 8 cases (33%). In four patients, the conservative approach was discontinued prematurely due to persistent fever. N total=23 patients with 24 episodes of infections
Soman et al., 2016.⁽¹⁹⁾ Índia	Exploratory study	To explore the use of new antimicrobials for lock therapy in long term catheter (treatment).	Antibiotic solution associated with N-acetylcystin 20%- 2ml and heparin 50-100UI in a volume sufficient to fill the catheter lumen, remaining for 24h, 14 consecutive days.	Not applicable.	Treatment with lock therapy was successful in 30 (81.08%) of 37 episodes of CABSI/symptomatic colonization. The catheter was saved in 26 (86.66%) of the 30 episodes caused by GNB and in 2 of 4 episodes caused by GPC. Lock therapy failure was evidenced in CABSI by Stenotrophomonas, Pseudomonas, Acinetobacter baumanii, methicillin-resistant Staphylococcus aureus and coagulase negative Staphylococcus. Two patients had the catheter removed due to obstruction, both had negative catheter tip cultures. In two episodes Colistin was successfully used in lock therapy. N total=29 patients with 37 episodes of infection.
Tatarelli et al., 2015.⁽²⁰⁾ Italy	Retrospective analysis of a case series	To analyze the efficacy of daptomycin administered systemically and as lock therapy in the treatment of CABSI.	5 ml of daptomycin solution diluted in Ringer’s lactate at a dose of 1mg/ml administered into each lumen, remaining for 12h/day.	Not applicable.	Seven patients failed previous therapy with Vancomycin and one patient with cefazolin. Daptomycin was successful in six (75%) of the eight cases (clinical improvement and microbiological eradication). The mean duration of daptomycin therapy was 13 days (range 7-16). N total=8 patients
Vassallo et al., 2017.⁽²¹⁾ France	Retrospective cohort study	To evaluate the efficacy of the antibiotic lock therapy combined with systemic daptomycin for conservative treatment of implanted catheters in patients with CoNS infection	5 ml of daptomycin, 25 mg solution diluted in lactated ringer’s solution at a dose of 5mg/ml administered into each lumen, maintained for 18h daily for three consecutive days.	Not applicable	21 episodes of CABSI were analyzed among 20 patients. The mean duration of antibiotic lock therapy combined with systemic daptomycin was three days, with rifampicin for four days, followed by switching to oral medications, most commonly cotrimoxazole or linezolid to a mean of 14 days of treatment. Clinical success and failure rates were 76% and 24%, respectively. Total N=20 patients with 28 episodes of infection.
Zanwar et al., 2018.⁽²²⁾ Índia	Retrospective study	To analyze the incidence, microbiological and treatment patterns, and efficacy of antibiotic lock therapy for colonized tunneled catheters (Hickman) and CABSI in patients undergoing hematopoietic stem cell transplantation (treatment).	Catheter contents suctioned; catheter flushed with saline solution; antibiotic administered according to the microorganism sensitivity, in a volume appropriate to the lumen; dwell time of 24 hours; procedure repeated after 24 hours.	Not applicable.	Incidence of catheter colonization was 9.8%, and in 45% of the cases the microorganism was BGN. The incidence of CABSI was 10.7%, and in 83% of cases the microorganism was BGN. Hickman catheter salvage rate in patients with CABSI submitted to antibiotic lock therapy combined with systemic antibiotic therapy was 86% compared to 55% rate in patients without lock therapy (p=0.06). There was no increase in resistant strains subsequent to CABSI. N total=224
Raad et al., 2016.⁽²⁸⁾ USA	Phase II Pilot Study	To evaluate the efficacy of the triple combination of 1 mg/ml minocycline and 30 mg/ml EDTA in 25% ethanol (MLT) to rescue catheters with CABSI, allowing the treatment of these infections without removal of the CVAD.	Each catheter lumen was filled with 0.8 to 1 ml of the MLT solution for 2h, once a day, for a total of 7 doses. Five were in the first five subsequent days and the last two doses in the following two weeks.	Patients with CABSI who have had the catheter removed, with the insertion of a new CVAD.	The time for fever remission and microbiological eradication were similar in both groups. Patients in the intervention group received systemic antibiotic therapy for a shorter time than patients in the control group (median 11 days versus 16 days, respectively; p<0.0001). Patients who received lock therapy maintained the catheter for a median of 74 days (4-240 days) after the onset of bacteremia. No patients who received lock therapy had infectious or mechanical complications compared to the control group, where seven infectious and six mechanical complications were found. N total=90 patients
Alonso et al., 2020⁽³⁰⁾ Spain	Retrospective study	To evaluate the success of lock therapy with vancomycin solution combined with systemic antimicrobials for the treatment of patients with staphylococcal CABSI.	Each catheter lumen or reservoir was locked daily with 2 ml of solution containing vancomycin (5 mg/ml) and heparin (60 IU) for a period of 8-12 to 24 h for 7-14 days.	Not applicable.	42.1% of 72 patients on vancomycin solution lock therapy remained with CVAD after CRBS. When considering the dwell time until catheter replacement or end of therapy, the success rate was higher (71.1%). No significant differences regarding catheter type, age, length of hospital stay, minimum inhibitory concentration of vancomycin, and Staphylococcus species was found. Although the crude mortality rate was 53.9%, the mortality rate attributable to CRBS was 1.3%.

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[1] Corresponding author: Renata Cristina de Campos Pereira Silveira E-mail: recris@eerp.usp.br