Successful Salvage of Central Venous Catheters in Patients with Catheter-Related or Central Line-Associated Bloodstream Infections by Using a Catheter Lock Solution Consisting of Minocycline, EDTA, and 25% Ethanol

Abstract

In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites. In vitro and animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line-associated bloodstream infections (CLABSI) while retaining the catheter in situ. Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively; P < 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.) L ong-term central venous catheters have become a lifeline for patients with cancer, those undergoing transplant, or longterm hemodialysis patients. More than five million central venous catheters (CVCs) are inserted annually in the United States, resulting in approximately 400,000 episodes of central line-associated bloodstream infections (CLABSI) and catheter-related bloodstream infections (CRBSI) (1, 2), each associated with an attributable mortality of 12 to 35% (3, 4) and an attributable cost of $34,508 to $56,000 per episode (5). For CLABSI/CRBSI associated with long-term CVCs (including cuffed/tunneled CVCs or ports with a dwell time of Ͼ30 days), the lumen of the catheter is the major source of colonization and subsequent bacteremia (6).The conventional standard of care in the management of CLABSI/CRBSI involves removal of the infected CVC and replacement with a new catheter at a different vascular site (7). However, in cancer, transplant, and hemodialysis patients with long-term catheters, removal of the CVC and reinsertion of a new catheter at a different site might be difficult or even impossible because of the unavailability of accessible vascular sites. Furthermore, these seriously ill patients with CLABSI/CRBSI and sepsis often have underlying thrombocytopenia or coagulopathy, which would make reinsertion of a new CVC at a different site risky given these comorbidities and related mechanical complications, such as blee...

Targeting microbial biofilms: current and prospective therapeutic strategies

“…Given the devastating consequences if a biofilm infection persists, surgeons are undertaking earlier and more aggressive treatment, including revisiting ‘old’ last-resort antibiotics such as colistin 10 . Another established approach used for intravenous catheter-related infections is lock therapy 11 . Following a decision to treat rather than remove certain types of catheters, the potential to leave biofilms intact (but containing dead cells) includes the potential to promote colonization by other microorganisms.…”

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections

“…The in vitro biofilm eradication model highly correlated with clinical microbiological eradication from catheter cultures obtained from CLABSI patients that had their catheters locked for 2 h daily with a minocycline-EDTA-ethanol lock solution (13). We reported the efficacy of 0.01% glyceryl trinitrate (GTN; nitroglyc-erin)-7% citrate-20% ethanol as a potential ACLS.…”

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

“…Because there is no RCT to compare the effect of EDTA in preventing CRT. Moreover, a major concern related to CLSs is the increasing need for thrombolytic interventions to maintain catheter patency (Sofroniadou et al, 2017;Raad et al, 2016). So, there should be more research on CRT in the future.…”

“…A limitation of this study is that seven of the studies included (Raad et al, 2016;Moghaddas et al, 2015;Dümichen et al, 2012;Boersma et al, 2015;Souweine et al, 2015;Goossens et al, 2013;Wouters et al, 2018) were deemed to have a high overall risk of bias (13.5%). In three of these (Raad et al, 2016;Dümichen et al, 2012;Souweine et al, 2015), this was due to the high risk of bias resulting from the failure to blind participants or outcome assessment, and in another three (Boersma et al, 2015;Goossens et al, 2013;Wouters et al, 2018), it was due to the attrition rate, which was greater than 5% of the total sample size. In the remaining study, the risk was high because the random method used the first letter of the name (Moghaddas et al, 2015).…”