Elsevier

Nutrition

Volume 14, Issue 5, May 1998, Pages 427-432
Nutrition

Original Articles
Elimination of Intraluminal Colonization by Antibiotic Lock in Silicone Vascular Catheters

Presented at the 20th Clinical Congress of the American Society for Parenteral and Enteral Nutrition, Washington, DC, January 16, 1996.
https://doi.org/10.1016/S0899-9007(98)00013-6Get rights and content

Abstract

An in vitro model was designed to evaluate the efficacy of instilled antimicrobials to reduce or eliminate intraluminal microbial colonization. Minimal inhibitory concentration and minimal bactericidal concentration activity of appropriate test anti-infectives were determined using standard methodology against clinically derived and reference test strains commonly associated with catheter-related infection. Drug activity was validated by bioassay for the test anti-infectives. Reference and clinical test strains were inoculated to the intraluminal surface of silicone catheter segments and incubated for 30 min, after which the inoculum was replaced with total parenteral nutrition (TPN) solution and reincubated for 12 h. For 7 d, instillation of antibiotic and TPN solution was alternated every 12 h to simulate clinical conditions. On days 1, 4, and 7, catheter segments were rinsed, bisected, and sonicated for quantitative plate count to determine mean microbial counts per centimeter of catheter surface. Catheter segments were also prepared for scanning electron microscopy. A significant decrease in staphylococcal intraluminal colonization after instillation of nafcillin, ceftriaxone, gentamicin, and vancomycin was demonstrated (P < 0.001). Aztreonam, ceftriaxone, and gentamicin completely eliminated gram-negative catheter colonization (P < 0.001). Yeast was eradicated from the internal catheter surface after treatment with amphoteracin B, and fluconazole significantly decreased intraluminal colonization (P < 0.001). Results show a significant decrease in staphylococcal, gram-negative, and fungal intraluminal colonization after instillation of appropriate antimicrobial. In vitro results support early clinical success using this technique. Future studies are warranted to identify optimal drug concentrations and dosing intervals.

Introduction

Surgically placed cuffed tunneled silicone catheters, such as the Hickman catheter, are used to facilitate long-term intravenous therapy. Infection is the most frequent complication, with catheter-associated sepsis accounting for up to 70% of infections, the remainder being either exit site or tunnel infections.[1]

The treatment of catheter-associated sepsis remains controversial. Currently, catheter removal is the only definitive treatment for catheter-associated sepsis. Because catheter replacement is not without risk and may become limited by the availability of access sites, catheter salvage becomes an important consideration in long-term venous access devices. Parenteral antibiotic therapy is often the initial treatment.[1] During the last decade, published reviews document successful catheter salvage rates of 30–65% using conventional regimens.2, 3, 4, 5

Messing et al.[6] in 1988 reported the use of a new modality for in situ treatment of catheter-related sepsis resulting in a 91% catheter salvage rate. This strategy is called “antibiotic lock” (AL) and involves the static instillation of a highly concentrated antibiotic solution into the catheter in a volume adequate to fill the lumen. The antibiotic remains within the catheter for an extended period, usually 12 h. Duration of clinical therapy is typically 7 d.[7] The purpose of this treatment strategy is to decontaminate the intraluminal surface of the catheter.

In a select group of outpatients followed up by the authors, AL treatment was successful 92% of the time.[7] Others have reported8, 9, 10, 11, 12, 13 similar findings using this technique to decontaminate the internal surface of catheters. In these reports, differing drugs in a wide range of concentrations for varying duration of therapy were used in small patient populations.

Studies to date demonstrating the in vitro efficacy of AL to eliminate microbial contamination of vascular access devices have been limited.[8] The purpose of this study was to evaluate the efficacy of instilled antibiotics to reduce or eliminate intraluminal microbial colonization using a laboratory model, thereby enhancing our understanding of the therapeutic usefulness of the AL in the clinical setting.

Section snippets

Bacterial Strains

The following strains of staphylococci were used: Staphylococcus aureus ATCC 29213, originally isolated from a wound; S. epidermidis CP, recovered from an infected Hickman catheter; and S. epidermidis M187sp11 and M187sn3, mutant strains generated through transposon mutagenesis from a parent strain M187 that was isolated from a catheter-associated infection.[14] M187sp11 is a highly adherent biofilm-producing strain, whereas M187sn3 is a poorly adherent nonbiofilm-producing mutant. Enteric

Results

All test anti-infectives were stable and active for a 12-h time span, with less than a 10% loss of therapeutic activity. Reference and clinical test strains, planktonic or adherent (sessile) to catheter segments, were sensitive to each of the appropriate test anti-infectives (Table I).

Test strains adhered rapidly to the intraluminal surface of silastic catheter segments (Fig. 2A,B). Differences in microbial recovery among the test strains colonizing the intraluminal surface demonstrate that

Discussion

The success of AL in the clinical setting is predicated on three premises: (1) that the catheter is colonized intraluminally, (2) that adequate drug can be delivered to the site of colonization, and (3) that the drug can reduce or eliminate surface colonization.

It is recognized that microorganisms can adhere to the catheter surface either extraluminally or intraluminally.[19] Currently, there is controversy surrounding the etiology of catheter colonization. Debate recently has focused on

Summary

In conclusion, anti-infectives tested remained stable and active intraluminally for up to 12 h. MIC and MBC were documented for microorganisms adherent to silicone catheter segments, and test strains were shown to be sensitive to antimicrobial activity. We demonstrated a significant decrease in staphylococcal intraluminal colonization (slime−/slime+) after installation of nafcillin, ceftriaxone, and vancomycin (P < 0.001) after 7 d. The agents aztreonam, ceftriaxone, and gentamicin completely

Acknowledgements

Acknowledgments

This study was supported in part by a grant from the Rhoads Research Foundation of the American Society for Parenteral and Enteral Nutrition and Pfizer Pharmaceuticals Inc., New York, NY.

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