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Intravascular Antimicrobial Lock Therapy

Cather lock therapy is the medical procedure whereby an antibiotic solution is injected into the catheter to prevent the development of a biofilm or to eliminate a biofilm that has developed in the catheter. Biofilms that consist of pathogenic bacteria or fungi have the potential of growing on the inside of the catheter and can cause serious infections in a patient. A limited number of antimicrobial and antifungal therapies have shown a decrease in BSIs.

Intravascular catheters are among the most commonly inserted medical devices and they are known to cause of catheter related bloodstream infections (BSIs). Cather biofilms are associated with chronic infections. One of these organisms is the fungus Candida albicans. It has shown to be one of the leading causes of catheter-related BSIs. The presence of biofilm on intravascular catheters provide increased tolerance against antimicrobial treatments, thus alternative treatment strategies are sought. Traditionally, many strategies, such as application of combined antimicrobials, addition of antifungals, and removal of catheters, have been practiced, but they were not successful in eradicating BSIs. Since these fungal infections can result in significant morbidity, mortality, and increased healthcare cost, other promising preventive strategies, including antimicrobial lock therapy, chelating agents, alcohol, and biofilm disruptors, have been applied. In this review, current success and failure of these new approaches, and a comparison with the previous strategies are discussed in order to understand which preventative treatment is the most effective in controlling the catheter-related BSIs.

Medical uses
Catheter related bloodstream infections have been shown to originate from biofilms that develop inside an intravascular catheter. Biofilms can develop in the catheter and are associated with chronic infections. A leading cause of catheter-related bloodstream infections is the fungus Candida albicans. Historically other stratedgies for preventing bsi have included the application of combined antimicrobils, addition of antifungals, removal of catheters but were not found to be successful.10.3390/pathogens4030457

Catheter lock therapy (CLT) is used to reduce treatment failure during the other medical procedures. A small dose of antimicrobial agent is put into the catheter lumen. The amount of the antibiotic is very small typicall less than 1.5 milliliters. The antibiotic solution is kept in the catheter for an extended period, often hours or even days. The high concentration in the catheter remains at the site of biofilm infection.

The purpose of the lock is not to actually treat infection and is not assumed to treat infections outside of the catheter or on the external surface. It also is not used to treat catheter-associated thrombus. Because the antibiotic does not enter the blood stream and remains localized to the catheter lumen, vancomycin concentrations of up to 5 mg/mL, which is 1000 times higher than the usual minimum concentration, can be injected into the catheter. Administration of the antibiotic only targets microorganisms present inside the catheter and has not improved treatment outcomes for infections outside the catheter or present in other internal biofilms.

Microorganisms associated with catheter related bloodstream infections

 * Escherichia coli
 * Staphylococcus aureus
 * Staphlococcus areus (HRSA)
 * Staphylococcus aureus (MRSA)
 * Acinetobacter baumannii
 * Pseudomonas aeruginosa
 * Candida albicans

Agents
Antibiotic lock therapy (ALT) is used with:
 * vancomycin
 * daptomycin
 * ceftriaxone
 * aminoglycosides
 * ciprofloxacin
 * ethanol

In some instances a combination of antibiotics are used. Some health care settings allow the use of heparin and antibiotic mixtures, though none are currently available pre-mixed or in commercially available and standardized doses. ALT is well-tolerated in adults, but the use with neonates is often difficult and the efficacy has not been firmly established.

The Infectious Diseases Society of America treatment guidelines for ALT recommends the use of ALT for adults and children to minimize the risk of infection but it is always used with standardized antibiotic treatment and not used unless an infection has been identified. However, the uptake of ALT use in pediatric practice seems to be inconsistent. This may be related to concerns about the development of antibiotic resistance, a limited range of studied antibiotics, a paucity of pediatric safety data, the potential for heparin overdose in infants, the need for prolonged dwell times and the lack of commercially available lock solutions. Antibiotic solutions for ALT are produced extemporaneously and usually admixed with heparin to prevent catheter occlusion. Recommended heparin concentrations vary from 0 to 5000 units/mL depending on the antibiotic, but high concentrations are contraindicated in small infants due to the risk of systemic anticoagulation. More data are needed before a strong recommendation can be made on the routine use of adjunctive ALT in pediatrics, and ALT should not be considered mandatory in children.

Ethanol lock therapy (ELT) for the treatment of CLABSI has not been studied in published randomized trials. Ethanol penetrates biofilm and rapidly kills microorganisms, including common CLABSI pathogens such as S. aureus, S. epidermidis, Klebsiella pneumoniae, P. aeruginosa and Candida spp., by protein denaturation. In vitro studies suggest that maximum killing occurs during the first 2 hours of exposure to 70% ethanol.

ALT with ethanol demonstrates fewer treatment failures. Treatment of candida with ethanol lock therapy has been reported but remains inconclusive. Expected success in controlling Candida is expected because of the historically poor history of cure of these infections.

Episodes of self-limiting nausea, headache and taste of alcohol have been associated with ELT, but more serious side effects, such as respiratory distress, are rare. These effects are likely reduced by minimizing the ELT dose and aspirating the lock after the dwell period and seem to be less common in children. Reports on catheter occlusion or intraluminal clot formation during the use of ELT, especially in children, have raised concerns that ELT may contribute to occlusion, but the frequency and clinical significance of this are unknown.

Hydrochloric acid lock therapy has been trialed as a treatment for in children with long-term entral venous catheters. There are positive results between hydrochloric acid lock therapy use and successful removal of biofilms in catheters. but routine use of hydrochloric acid lock therapy for the treatment is not recommended at this time.

Risks/Complications
Skill is needed when setting an antimicrobial lock. A leak in the catheter may allow toxic concentrations of the antibiotic into bloodstream. This could lead to toxicity and possible death. Another concern is antii-microbial resistance developing. At this point, ethanol could be an optimal lock solution It has a broad spectrum effectiveness, it is low cost and it lacks the ability for microorganisms to become resistant to it.