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      In vitro efficacy of daptomycin and teicoplanin combined with ethanol, clarithromycin or gentamicin as catheter lock solutions

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          Abstract

          Background

          Despite widespread use, optimum choice of antimicrobial agents, concentrations, combinations and exposure times have not been determined for antibiotic lock technique (ALT). Our objective was to evaluate the efficacy of different antibiotic combinations using an in vitro model of catheter-related infection. Daptomycin (DAP) 5 mg/mL, teicoplanin (TEC) 5 mg/mL, both alone and combined with gentamicin (GM) 2.5 mg/mL, clarythromycin (CLA) 5 mg/mL or ethanol 35 % were evaluated against four clinical strains of methicillin resistant coagulase negative staphylococci. Lock solutions were renewed every 24 h.

          Results

          After 72 h catheters were reincubated with culture media to investigate bacterial regrowth. All antibiotic combinations resulted in significant reductions ( p < 0.05) of Log(10) cfu/mL at 72 h for both organisms compared with controls. DAP resulted in significant reductions of Log(10) for all organism versus TEC ( p = 0.001). Only DAP reached the limit of detection at 72 h, however did not prevent regrowth after 24 h of ALT removal. DAP + Ethanol and TEC + ethanol eradicated biofilm at 72 h, but only DAP + ethanol (against all strains) and DAP + CLA (against two strains) prevented regrowth at 24 h after ALT removal.

          Conclusions

          Based on these data, ALT with DAP + ethanol and DAP + CLA should be explored in clinical trials.

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          Most cited references30

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          NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007.

          To describe the frequency of selected antimicrobial resistance patterns among pathogens causing device-associated and procedure-associated healthcare-associated infections (HAIs) reported by hospitals in the National Healthcare Safety Network (NHSN). Data are included on HAIs (ie, central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and surgical site infections) reported to the Patient Safety Component of the NHSN between January 2006 and October 2007. The results of antimicrobial susceptibility testing of up to 3 pathogenic isolates per HAI by a hospital were evaluated to define antimicrobial-resistance in the pathogenic isolates. The pooled mean proportions of pathogenic isolates interpreted as resistant to selected antimicrobial agents were calculated by type of HAI and overall. The incidence rates of specific device-associated infections were calculated for selected antimicrobial-resistant pathogens according to type of patient care area; the variability in the reported rates is described. Overall, 463 hospitals reported 1 or more HAIs: 412 (89%) were general acute care hospitals, and 309 (67%) had 200-1,000 beds. There were 28,502 HAIs reported among 25,384 patients. The 10 most common pathogens (accounting for 84% of any HAIs) were coagulase-negative staphylococci (15%), Staphylococcus aureus (15%), Enterococcus species (12%), Candida species (11%), Escherichia coli (10%), Pseudomonas aeruginosa (8%), Klebsiella pneumoniae (6%), Enterobacter species (5%), Acinetobacter baumannii (3%), and Klebsiella oxytoca (2%). The pooled mean proportion of pathogenic isolates resistant to antimicrobial agents varied significantly across types of HAI for some pathogen-antimicrobial combinations. As many as 16% of all HAIs were associated with the following multidrug-resistant pathogens: methicillin-resistant S. aureus (8% of HAIs), vancomycin-resistant Enterococcus faecium (4%), carbapenem-resistant P. aeruginosa (2%), extended-spectrum cephalosporin-resistant K. pneumoniae (1%), extended-spectrum cephalosporin-resistant E. coli (0.5%), and carbapenem-resistant A. baumannii, K. pneumoniae, K. oxytoca, and E. coli (0.5%). Nationwide, the majority of units reported no HAIs due to these antimicrobial-resistant pathogens.
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            Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm.

            In the setting of catheter-related bloodstream infections, intraluminal antibiotic lock therapy could be useful for the salvage of vascular catheters. In this in vitro study, we investigated the efficacies of the newer antibiotics daptomycin, linezolid, and tigecycline, in comparison with those of vancomycin, minocycline, and rifampin, against methicillin-resistant Staphylococcus aureus (MRSA) embedded in biofilm. We also assessed the emergence of MRSA strains resistant to these antibiotics, alone or in combination with rifampin, after 4-hour daily use for catheter lock therapy. Minocycline, daptomycin, and tigecycline were more efficacious in inhibiting MRSA in biofilm than linezolid, vancomycin, and the negative control (P < 0.001) after the first day of exposure to these antibiotics, with minocycline being the most active, followed by daptomycin and then tigecycline, and with vancomycin and linezolid lacking activity, similar to the negative control. After 3 days of 4-hour daily exposures, daptomycin was the fastest in eradicating MRSA from biofilm, followed by minocycline and tigecycline, which were faster than linezolid, rifampin, and vancomycin (P < 0.001). When rifampin was used alone, it was the least effective in eradicating MRSA from biofilm after 5 days of 4-hour daily exposures, as it was associated with the emergence of rifampin-resistant MRSA. However, when rifampin was used in combination with other antibiotics, the combination was significantly effective in eliminating MRSA colonization in biofilm more rapidly than each of the antibiotics alone. In summary, daptomycin, minocycline, and tigecycline should be considered further for antibiotic lock therapy, and rifampin should be considered for enhanced antistaphylococcal activity but not as a single agent.
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              Management of infections related to totally implantable venous-access ports: challenges and perspectives.

              Use of totally implantable venous-access ports (TIVAPs) is standard practice for patients with diseases such as solid-tumour cancers, haematological malignancies, and chronic digestive diseases. Use of TIVAPs allows long-term administration of venotoxic compounds, improves patients' quality of life, and reduces the risk of infection. Microbial contamination, formation of pathogenic biofilms, and infection, however, are associated with morbidity, mortality, and increased health-care costs. Local and systemic complications or infections related to specific pathogens might lead to device removal. Alternatively, conservative treatment with combined systemic antibiotics and antibiotic lock therapy might be useful. We discuss in-vitro and in-vivo basic and clinical research findings on the epidemiology, diagnosis, and prevention of TIVAP-related infections, the current challenges to management, promising strategies, and some treatments in development that are likely to improve outcomes of TIVAP-related infections, with a particular focus on antibiotic lock therapy.
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                Author and article information

                Contributors
                dprruiz@yahoo.es
                dralexpexa@yahoo.es
                nievescoronado@gmail.com
                jhquero@ugr.es
                +34 958 023 104 , arrapj@gmail.com
                Journal
                BMC Microbiol
                BMC Microbiol
                BMC Microbiology
                BioMed Central (London )
                1471-2180
                30 October 2015
                30 October 2015
                2015
                : 15
                : 245
                Affiliations
                [ ]Laboratorio de Investigación Antimicrobiana, Hospital Universitario San Cecilio. Instituto de Investigación Biosanitaria de Granada, 18012 Granada, Spain
                [ ]Servicio de Microbiología, Hospital Universitario San Cecilio, 18012 Granada, Spain
                [ ]Servicio de Enfermedades Infecciosas, Hospital Universitario San Cecilio. Instituto de Investigación Biosanitaria de Granada, Avda Dr. Olóriz 16, 18012 Granada, Spain
                Article
                585
                10.1186/s12866-015-0585-3
                4628264
                26518881
                09dcc0b4-4c75-483b-8a44-a107d09ca2b1
                © Parra et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 March 2015
                : 23 October 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Microbiology & Virology
                biofilm,central line associated bloodstream infections,antibiotic lock therapy

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