Topical versus Systemic Antimicrobial Therapy for Treating Mildly Infected Diabetic Foot Ulcers: A Randomized, Controlled, Double‐Blinded, Multicenter Trial of Pexiganan Cream

Lipsky, Benjamin A.; Holroyd, Kenneth J.; Zasloff, Michael

doi:10.1086/593185

Cited by 245 publications

(215 citation statements)

References 28 publications

(45 reference statements)

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“…This was revealed by pexiganan. In a multicentre trial of a cream containing this synthetic antimicrobial peptide for treating mildly infected diabetic foot ulcers, the authors stated that topical pexiganan was an effective alternative to oral antibiotic therapy and offered the opportunity to reduce the risk of selecting antimicrobial-resistant bacteria (Lamb & Wiseman, 1998;Lipsky et al, 2008). However, these antimicrobial peptides, socalled chemical-produced novel antibiotics, have been considered to compromise natural immunity (Habets & Brockhurst, 2012).…”

Section: Potential Use Of Cpc and Mstmentioning

confidence: 99%

Cetylpyridinium chloride and miramistin as antiseptic substances in chronic wound management – prospects and limitations

Fromm‐Dornieden

Rembe

Schäfer

et al. 2015

Journal of Medical Microbiology

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The antimicrobial activity of cetylpyridinium chloride (CPC) and miramistin (MST) solutions at different concentrations (5¾10 "5 to 0.4 %) and a dressing, containing 0.15 % CPC, were tested against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli after 30 (solutions) and 60 min (fleece) incubation, respectively. Furthermore, the cytotoxic effects of CPC and MST were examined in human keratinocyte (HaCaT) and murine fibroblast (L929) cell lines. A dose of 3¾10 "3 % CPC or MST was sufficient to entirely eradicate S. aureus after 30 min incubation. To achieve the same effect, higher concentrations were required against E. coli (0.025 % CPC; 0.0125 % MST) and P. aeruginosa (0.5 % CPC; 0.05 % MST). The CPC-fleece showed a high antiseptic effect against all three bacterial strains, although it did not completely eliminate P. aeruginosa. Both substances showed a high cytotoxic impact at higher tested concentrations (CPC .3¾10 "3 %; MST .8¾10 "4 %). CPC showed high antimicrobial potency at low concentrations against S. aureus, accompanied by low cytotoxic (side) effects at these concentrations, whilst the required minimal concentration to eradicate E. coli and P. aeruginosa was shown to be cytotoxic for keratinocytes and fibroblasts. The necessary antibacterial amounts of MST were lower, but also cytotoxic in direct contact with typical human wound cells. With regard to demographic changes and increasing bacterial resistance, new effective antiseptics, such as CPC and MST, incorporated in wound dressings without releasing an active substance could help to improve the treatment and healing rates of chronic wounds.

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Section: Potential Use Of Cpc and Mstmentioning

confidence: 99%

Cetylpyridinium chloride and miramistin as antiseptic substances in chronic wound management – prospects and limitations

Fromm‐Dornieden

Rembe

Schäfer

et al. 2015

Journal of Medical Microbiology

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“…Based on these properties, antimicrobial peptides have received a lot of attention as alternatives to antibiotics, particularly for topical therapies (4). Utilization for pulmonary infections has been investigated but is complicated by delivery issues and to date has not been successful in clinical trials (5)(6)(7).…”

mentioning

confidence: 99%

Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

Banaschewski

Veldhuizen

Keating

et al. 2015

Antimicrob Agents Chemother

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e Antibiotic-resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a "perfect storm" for multidrug-resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, since they have potent broad-spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is coadministration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways and opening of collapsed lung regions. The objective of this study was to test various surfactant-AMP mixtures with regard to maintaining pulmonary surfactant biophysical properties and bactericidal functions. We compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, and LL-37) suspended in bovine lipid-extract surfactant (BLES) by assessing surfactant-AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against methillicin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. All AMP/surfactant mixtures exhibited an increase of spreading compared to a BLES control. BLES؉CATH-2 mixtures had no significantly different minimum surface tension versus the BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES. The BLES؉CATH-2 mixture appears to be an optimal surfactant-AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia.

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“…The therapeutic use of many AMPs may be limited by potential toxicity and reduced activity in vivo (15). Nevertheless, there are promising AMPs that have reached preclinical or clinical trials (22)(23)(24).…”

mentioning

confidence: 99%

Identification of Cell-Penetrating Peptides That Are Bactericidal to Neisseria meningitidis and Prevent Inflammatory Responses upon Infection

Eriksson

Geörg

Sjölinder

et al. 2013

Antimicrob Agents Chemother

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bMeningococcal disease is characterized by a fast progression and a high mortality rate. Cell-penetrating peptides (CPPs), developed as vectors for cargo delivery into eukaryotic cells, share structural features with antimicrobial peptides. A screen identified two CPPs, transportan-10 (TP10) and model amphipathic peptide (MAP), with bactericidal action against Neisseria meningitidis. Both peptides were active in human whole blood at micromolar concentrations, while hemolysis remained negligible. Additionally, TP10 exhibited significant antibacterial activity in vivo. Uptake of SYTOX green into live meningococci was observed within minutes after TP10 treatment, suggesting that TP10 may act by membrane permeabilization. Apart from its bactericidal activity, TP10 suppressed inflammatory cytokine release from macrophages infected with N. meningitidis as well as from macrophages stimulated with enterobacterial and meningococcal lipopolysaccharide (LPS). Finally, incubation with TP10 reduced the binding of LPS to macrophages. This novel endotoxin-inhibiting property of TP10, together with its antimicrobial activity in vivo, indicates the possibility to design peptide-based therapies for infectious diseases.

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Topical versus Systemic Antimicrobial Therapy for Treating Mildly Infected Diabetic Foot Ulcers: A Randomized, Controlled, Double‐Blinded, Multicenter Trial of Pexiganan Cream

Abstract: Topical pexiganan might be an effective alternative to oral antibiotic therapy in treating diabetic patients with a mildly infected foot ulcer, and might reduce the risk of selecting antimicrobial-resistant bacteria.

Cited by 245 publications

References 28 publications

Cetylpyridinium chloride and miramistin as antiseptic substances in chronic wound management – prospects and limitations

Cetylpyridinium chloride and miramistin as antiseptic substances in chronic wound management – prospects and limitations

Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

Identification of Cell-Penetrating Peptides That Are Bactericidal to Neisseria meningitidis and Prevent Inflammatory Responses upon Infection

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