Ethanol-Lock Technique in the Treatment of Bloodstream Infections in Pediatric Oncology Patients With Broviac Catheter

Dannenberg, C.; Bierbach, Uta; Rothe, Antje; Beer, J; Körholz, Dieter

doi:10.1097/00043426-200308000-00006

Cited by 146 publications

(175 citation statements)

References 21 publications

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“…To evaluate the in vivo efficacy of tetrasodium EDTA as a potential adjuvant in ALT, we tested different gentamicin-based lock solutions against bioluminescent methicillin-susceptible S. aureus (MSSA) biofilms growing in TIVAP implanted in rats (n ϭ 5 rats for each treatment). In addition to solutions containing gentamicin alone, EDTA alone, or combined gentamicin-EDTA, we evaluated 70% ethanol, which was shown to be an effective antibacterial lock agent both in vitro and in vivo (12,24). We first used ALT instillations renewed every 24 h for 5 Results for CFU are means Ϯ standard deviations.…”

Section: Resultsmentioning

confidence: 99%

Full and Broad-Spectrum In Vivo Eradication of Catheter-Associated Biofilms Using Gentamicin-EDTA Antibiotic Lock Therapy

Chauhan

Lebeaux

Ghigo

et al. 2012

Antimicrob Agents Chemother

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Biofilms that develop on indwelling devices are a major concern in clinical settings. While removal of colonized devices remains the most frequent strategy for avoiding device-related complications, antibiotic lock therapy constitutes an adjunct therapy for catheter-related infection. However, currently used antibiotic lock solutions are not fully effective against biofilms, thus warranting a search for new antibiotic locks. Metal-binding chelators have emerged as potential adjuvants due to their dual anticoagulant/antibiofilm activities, but studies investigating their efficiency were mainly in vitro or else focused on their effects in prevention of infection. To assess the ability of such chelators to eradicate mature biofilms, we used an in vivo model of a totally implantable venous access port inserted in rats and colonized by either Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, or Pseudomonas aeruginosa. We demonstrate that use of tetrasodium EDTA (30 mg/ml) as a supplement to the gentamicin (5 mg/ml) antibiotic lock solution associated with systemic antibiotics completely eradicated Gram-positive and Gramnegative bacterial biofilms developed in totally implantable venous access ports. Gentamicin-EDTA lock was able to eliminate biofilms with a single instillation, thus reducing length of treatment. Moreover, we show that this combination was effective for immunosuppressed rats. Lastly, we demonstrate that a gentamicin-EDTA lock is able to eradicate the biofilm formed by a gentamicin-resistant strain of methicillin-resistant S. aureus. This in vivo study demonstrates the potential of EDTA as an efficient antibiotic adjuvant to eradicate catheter-associated biofilms of major bacterial pathogens and thus provides a promising new lock solution.C entral venous catheters are routinely used to administer medication or fluids to patients admitted to oncology, nephrology, and intensive care units (2, 47, 52). Although these devices greatly improve patient health, their use is often associated with medical complications due to colonization by pathogenic microorganisms (38). This leads to development of complex bacterial or fungal biofilm communities that display strong tolerance toward antimicrobials (15,37,45). Biofilms are difficult to eradicate; moreover, they constitute a potential source of bloodstream infections, a leading cause of health care-associated infections in critically ill patients (29). Currently, there is no fully efficient method for treating catheter-related biofilms aside from traumatic and costly removal of colonized devices (5,11,42,49). However, recent clinical practice guidelines recommended the use of antibiotic lock therapy (ALT) for treatment of uncomplicated long-term catheter-related infections (31). ALT relies on the instillation of highly concentrated antibiotic solutions (up to 1,000 times the MIC) left to dwell in the catheter for 12 to 24 h in order to prevent or eradicate biofilm formation. Although ALT shows a high success rate for coagulase-negative staphyl...

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Section: Resultsmentioning

confidence: 99%

Full and Broad-Spectrum In Vivo Eradication of Catheter-Associated Biofilms Using Gentamicin-EDTA Antibiotic Lock Therapy

Chauhan

Lebeaux

Ghigo

et al. 2012

Antimicrob Agents Chemother

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“…‫,ء‬ P Ͻ 0.001; #, P Ͻ 0.05 compared to biofilm formed in the absence of ethanol (0% ethanol control). (15,54,59). Although the focus of our study was not to test the efficacy of ethanol as a therapeutic alternative in the treatment of catheter-associated infections, the fact that ethanol does not affect bacterial biofilm formed on catheters in vivo suggests caution in the random use of ethanol lock therapy.…”

Section: Vol 74 2006 Deletion Of Adh Results In Increased Biofilm Fmentioning

confidence: 99%

Alcohol Dehydrogenase Restricts the Ability of the Pathogen Candida albicans To Form a Biofilm on Catheter Surfaces through an Ethanol-Based Mechanism

et al. 2006

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Candida biofilms formed on indwelling medical devices are increasingly associated with severe infections. In this study, we used proteomics and Western and Northern blotting analyses to demonstrate that alcohol dehydrogenase (ADH) is downregulated in Candida biofilms. Disruption of ADH1 significantly (P ‫؍‬ 0.0046) enhanced the ability of Candida albicans to form biofilm. Confocal scanning laser microscopy showed that the adh1 mutant formed thicker biofilm than the parent strain (210 m and 140 m, respectively). These observations were extended to an engineered human oral mucosa and an in vivo rat model of catheterassociated biofilm. Inhibition of Candida ADH enzyme using disulfiram and 4-methylpyrazole resulted in thicker biofilm (P < 0.05). Moreover, biofilms formed by the adh1 mutant strain produced significantly smaller amounts of ethanol, but larger amounts of acetaldehyde, than biofilms formed by the parent and revertant strains (P < 0.0001), demonstrating that the effect of Adh1p on biofilm formation is mediated by its enzymatic activity. Furthermore, we found that 10% ethanol significantly inhibited biofilm formation in vitro, with complete inhibition of biofilm formation at ethanol concentrations of >20%. Similarly, using a clinically relevant rabbit model of catheter-associated biofilm, we found that ethanol treatment inhibited biofilm formation by C. albicans in vivo (P < 0.05) but not by Staphylococcus spp. (P > 0.05), indicating that ethanol specifically inhibits Candida biofilm formation. Taken together, our studies revealed that Adh1p contributes to the ability of C. albicans to form biofilms in vitro and in vivo and that the protein restricts biofilm formation through an ethanol-dependent mechanism. These results are clinically relevant and may suggest novel antibiofilm treatment strategies.

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“…Most alcohol-based disinfectants contain ethanol, typically at a concentration of ϳ70 to 85% (vol/vol). As an example, antibiotic lock therapy of implanted intravenous catheters uses alcohol as an antimicrobial disinfectant (9) and is widely applied, particularly in pediatrics (34). Finally, ethanol may also be used for food preservation (35).…”

mentioning

confidence: 99%

Very Low Ethanol Concentrations Affect the Viability and Growth Recovery in Post-Stationary-Phase Staphylococcus aureus Populations

Chatterjee

Somerville

Heilmann

et al. 2006

Appl Environ Microbiol

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Pharmaceuticals, culture media used for in vitro diagnostics and research, human body fluids, and environments can retain very low ethanol concentrations (VLEC) (<0.1%, vol/vol). In contrast to the wellestablished effects of elevated ethanol concentrations on bacteria, little is known about the consequences of exposure to VLEC. We supplemented growth media for Staphylococcus aureus strain DSM20231 with VLEC (VLEC ؉ conditions) and determined ultramorphology, growth, and viability compared to those with unsupplemented media (VLEC ؊ conditions) for prolonged culture times (up to 8 days). VLEC ؉ -grown late-stationaryphase S. aureus displayed extensive alterations of cell integrity as shown by scanning electron microscopy. Surprisingly, while ethanol in the medium was completely metabolized during exponential phase, a profound delay of S. aureus post-stationary-phase recovery (>48 h) was observed. Concomitantly, under VLEC ؉ conditions, the concentration of acetate in the culture medium remained elevated while that of ammonia was reduced, contributing to an acidic culture medium and suggesting decreased amino acid catabolism. Interestingly, amino acid depletion was not uniformly affected: under VLEC ؉ conditions, glutamic acid, ornithine, and proline remained in the culture medium while the uptake of other amino acids was not affected. Supplementation with arginine, but not with other amino acids, was able to restore post-stationary-phase growth and viability. Taken together, these data demonstrate that VLEC have profound effects on the recovery of S. aureus even after ethanol depletion and delay the transition from primary to secondary metabolite catabolism. These data also suggest that the concentration of ethanol needed for bacteriostatic control of S. aureus is lower than that previously reported.

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Ethanol-Lock Technique in the Treatment of Bloodstream Infections in Pediatric Oncology Patients With Broviac Catheter

Cited by 146 publications

References 21 publications

Full and Broad-Spectrum In Vivo Eradication of Catheter-Associated Biofilms Using Gentamicin-EDTA Antibiotic Lock Therapy

Full and Broad-Spectrum In Vivo Eradication of Catheter-Associated Biofilms Using Gentamicin-EDTA Antibiotic Lock Therapy

Alcohol Dehydrogenase Restricts the Ability of the Pathogen Candida albicans To Form a Biofilm on Catheter Surfaces through an Ethanol-Based Mechanism

Very Low Ethanol Concentrations Affect the Viability and Growth Recovery in Post-Stationary-Phase Staphylococcus aureus Populations

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