In vitro pharmacokinetics of antimicrobial cationic peptides alone and in combination with antibiotics against methicillin resistant Staphylococcus aureus biofilms

Döşler, Sibel; Mataracı, Emel

doi:10.1016/j.peptides.2013.08.008

Cited by 102 publications

(64 citation statements)

References 26 publications

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“…Although the data do not allow statistical analysis, the pattern of MBEC values for S. epidermidis appears to be more consistent with proportion of vancomycin in the formulation rather than synergy between tobramycin and vancomycin, consistent with the tolerance to tobramycin above 8000 lg/mL. Our data support previous reports that MBECs are very high compared with MICs [1,4] but challenge reports that MBECs are immeasurable [1,5,17].…”

Section: Discussionsupporting

confidence: 85%

Biofilm Antimicrobial Susceptibility Increases With Antimicrobial Exposure Time

Castaneda

McLaren

Tavaziva

et al. 2016

Clinical Orthopaedics &Amp; Related Research

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Background The antimicrobial concentration required to kill all the bacteria in a biofilm, known as the minimum biofilm eradication concentration (MBEC), is typically determined in vitro by exposing the biofilm to serial concentrations of antimicrobials for 24 hours or less. Local delivery is expected to cause high local levels for longer than 24 hours. It is unknown if longer antimicrobial exposures require the same concentration to eradicate bacteria in biofilm. Questions/purposes Does MBEC change with increased antimicrobial exposure time? Methods Biofilms were grown for 24 hours using five pathogens (methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa) and then exposed to four antimicrobials regimens: tobramycin, vancomycin, and tobramycin combined with vancomycin in 3:1 and 1:1 ratios by weight in concentrations of 62.5, 125, 250, 500, 1000, 2000, 4000, and 8000 lg/mL for three durations, 1, 3, and 5 days, in triplicate. MBEC was measured as the lowest concentration that killed all bacteria in the biofilm determined by 21-day subculture. Results MBEC was lower when antimicrobial exposure time was longer. For the staphylococcus species, the MBEC was lower when exposure time was 5 days than 1 day in 11 of 12 antimicrobial/microorganism pairs. The MBEC range for these 11 pairs on Day 1 was 4000 to[8000 lg/mL and on Day 5 was \ 250 to 8000 lg/mL. MBEC for tobramycin/P. aeruginosa was 2000 lg/mL on Day 1 and B 250 lg/mL on Day 5, and for E. coli, 125 lg/mL on Day 1 and B 62.5 on Day 5. Conclusions Although antimicrobial susceptibility was lower for longer exposure times in the microorganisms we studied, confirmation is required for other pathogens. Clinical Relevance One-day MBEC assays may overestimate the local antimicrobial levels needed to kill organisms in biofilm if local levels are sustained at MBEC or above for longer than 24 hours. Future studies are needed to confirm that antimicrobial levels achieved clinically from local delivery are above the MBEC at relevant time points and to confirm that MBEC for in vitro microorganisms accurately represents MBEC of in vivo organisms in an clinical infection.

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Section: Discussionsupporting

confidence: 85%

Biofilm Antimicrobial Susceptibility Increases With Antimicrobial Exposure Time

Castaneda

McLaren

Tavaziva

et al. 2016

Clinical Orthopaedics &Amp; Related Research

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“…Most of these compounds take part in the prevention of biofilm formation, but little information is available regarding compounds that are able to disrupt established wound biofilm. One of the potential agents responsible for biofilm destruction is bee (Apis melifera)-derived antibacterial peptide defensin-1 (Def-1), as it has been shown recently that antimicrobial cationic peptides destroy bacterial biofilm (Dosler & Mataraci, 2013;Dosler & Karaaslan, 2014). Def-1 is one of the main regular but quantitatively variable antibacterial components of honey (Kwakman et al, 2011;Majtan et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Antibiofilm efficacy of honey and bee-derived defensin-1 on multispecies wound biofilm

Sojka

Valachová

Bucekova

et al. 2016

Journal of Medical Microbiology

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Many clinically relevant biofilms are polymicrobial. Examining the effect of antimicrobials in a multispecies biofilm consortium is of great clinical importance. The goal of this study was to investigate the effect of different honey types against bacterial wound pathogens grown in multispecies biofilm and to test the antibiofilm activity of honey defensin-1 (Def-1) in its recombinant form. A modified Lubbock chronic wound biofilm formed by four bacterial species (Staphylococcus aureus, Streptococcus agalactiae, Pseudomonas aeruginosa and Enterococcus faecalis) was used for evaluation of honey and recombinant bee-derived Def-1 antibiofilm efficacy. Recombinant Def-1 was prepared by heterologous expression in Escherichia coli. We showed that different types of honey (manuka and honeydew) were able to significantly reduce the cell viability of wound pathogens (Staphylococcus aureus, Streptococcus agalactiae and Pseudomonas aeruginosa) in mature polymicrobial biofilm. None of the tested honeys showed the ability to eradicate Enterococcus faecalis in biofilm. In addition, recombinant Def-1 successfully reduced the viability of Staphylococcus aureus and Pseudomonas aeruginosa cells within established polymicrobial biofilm after 24 and 48 h of treatment. Interestingly, recombinant Def-1 did not affect the viability of Streptococcus agalactiae cells within the biofilm, whereas both natural honeys significantly reduced the viable bacteria. Although Enterococcus faecalis was highly resistant to Def-1, Def-1 significantly affected the biofilm formation of Enterococcus faecalis and Streptococcus agalactiae after 24 h of treatment, most likely by inhibiting its extracellular polymeric substances production. In conclusion, our study revealed that honey and Def-1 are effective against established multispecies biofilm; however, Enterococcus faecalis grown in multispecies biofilm was resistant to both antimicrobials.

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“…Vancomycin concentrations well over 4000 lg/mL are readily obtained in the knee immediately after infusion, and with a daily infusion regimen, this level can be achieved daily for 6 weeks or longer [46]. Moderate concentrations of antibiotics are necessary to prevent biofilm formation [11,12], but once biofilm and persister cells have formed, concentrations of orders of magnitude greater (as high as 4000 lg/ mL) are necessary to eradicate the bacteria within the biofilm [7,8,11,12,17,27,31,45,49,50]. Clearly, some risk of toxicity exists with direct intraarticular infusion of antibiotics, but this method may be the safest way to achieve high antibiotic levels over time [54][55][56] while allowing for the opportunity to decrease the dose, change antibiotics, or stop them altogether in the case of allergic reactions or renal toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Vancomycin was used because of its effectiveness against bacteria in glycocalyx biofilms. This property of vancomycin makes it preferable to cephalosporins when infusing directly into joints that have metal implants [12,27]. Gentamicin was used only in the one patient with a gram-negative bacterium that was sensitive to this antibiotic.…”

Section: Methodsmentioning

confidence: 99%

“…High local antibiotic concentration around the site of an infected THA is a matter of major clinical importance, because bacteria protected by biofilm require concentrations that are orders of magnitude greater than the minimal inhibitory concentration for the planktonic forms of the same bacterium to eliminate resistant organisms that are protected by the glycocalyx [8,11,12,16,32]. Intravenous antibiotics generally do not achieve these levels of concentration in synovial fluid, but instead achieve levels around two to three times the minimal inhibitory concentration (MIC) [46].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

One-stage Revision With Catheter Infusion of Intraarticular Antibiotics Successfully Treats Infected THA

Whiteside

Roy

2017

Clinical Orthopaedics &Amp; Related Research

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Background Two-stage revision surgery for infected total hip arthroplasty (THA) is commonly advocated, but substantial morbidity and expense are associated with this technique. In certain cases of infected THA, treatment with one-stage revision surgery and intraarticular infusion of antibiotics may offer a reasonable alternative with the distinct advantage of providing a means of delivering the drug in high concentrations. Questions/purposes We describe a protocol for intraarticular delivery of antibiotics to the hip through an indwelling catheter combined with one-stage revision surgery and examine (1) the success as judged by eradication of infection at 1 year when treating chronically infected cemented stems; (2) success in treating late-onset acute infections in well-ingrown cementless stems; and (3) what complications were associated with this approach in a small case series. Methods Between

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In vitro pharmacokinetics of antimicrobial cationic peptides alone and in combination with antibiotics against methicillin resistant Staphylococcus aureus biofilms

Cited by 102 publications

References 26 publications

Biofilm Antimicrobial Susceptibility Increases With Antimicrobial Exposure Time

Biofilm Antimicrobial Susceptibility Increases With Antimicrobial Exposure Time

Antibiofilm efficacy of honey and bee-derived defensin-1 on multispecies wound biofilm

One-stage Revision With Catheter Infusion of Intraarticular Antibiotics Successfully Treats Infected THA

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