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Askina ® Calgitrol ® Paste Technical Brochure Wound Management
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Page 1: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

Askina® Calgitrol® PasteTechnical Brochure

Wound Management

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Page 2: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

Areas of Unmet Needs in Acute and 3

and Chronic Wound Management

Development and Mechanism of Action of 4

Askina® Calgitrol® Paste

Rationale 4

Mechanism of Action 5

Targets and Mechanisms of Bacterial Cell Kill 7

by Ionic Silver

Antimicrobial Activity 8

Safety and Tolerability 9

Systemic Safety 9

Local Tolerability 9

Appropriate Wound Types and 10

Application Instructions

In Summary 10

References 11

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Page 3: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

Wounds are a major cause of morbidity in a number of patient populations. They may be acute or chronic in nature, frequently becoming susceptible to infection and requiring extensive levels of daily care. Patients with peripheral vascular diseases (eg, venous and arterial ulcers), diabetes (eg, diabetic foot ulcers), and burns, as well as geriatric populations (eg, pressure ulcers) are particularly susceptible to wound infections. [Frykberg RG 2003; Gist S et al 2009]

The demographic changes occurring in many countries, with increases in the aged population and prevalence of type 2 dia-betes, are expected to lead to an increase in the number of such patients at risk from wound infections. [Frykberg RG 2003; Gist S et al 2009]

Evidence shows that, particularly in the hospital setting, wounds may become infected with antibiotic resistant microorganisms difficult to treat with systemic or topical antibiotics. For example, a loss of antimicrobial activity against Gram-positive and Gram-negative bacteria has been observed as a consequence of bac-terial exposure to the sulphonamide component of silver sulfadi-azine (SSD). [Lowbury EJL et al, 1976]

Treatment-resistant wound infections may therefore result in serious complications, including sepsis and/or amputation. [Bridges K et al 1977; Driver VR et al 2004; White RJ and Cooper R 2005]

The use of ionic silver−containing antimicrobial wound dressings has become a well established therapeutic approach in response to the challenge of antibiotic resistant wound infections. Accor-dingly, a wide variety of fiber-, foam- and mesh-based dressings, that topically deliver silver to the wound site are available. How-ever, the rigid form of these dressings may impose limitations to their effectiveness, particularly in difficult-to-treat wounds. In these cases, the lack of intimate contact between the dressing and the wound often prevents the silver ions from reaching all potentially infected areas within the wound bed. These limita-tions prompted the development of Askina® Calgitrol® Paste, a new, innovative, and unique product that allows more intimate contact between the wound and the antimicrobial silver ions contained in the Calgitrol® Paste. The paste complements the ex-isting range of Askina® Calgitrol® dressings that are more suited to flat or superficial wounds (Table 1).

Askina® Calgitrol Ag Foam + silver alginate matrix

Askina® Calgitrol THIN Silver alginate matrix in thin form

Askina® Calgitrol Paste Amorphous silver alginate matrix

Table 1. Calgitrol® Ag dressing range: One technology, three products

Areas of Unmet Needs in Acute and Chronic Wound Management

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Page 4: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

Askina® Calgitrol® Ag and THIN, which are standard flat dressing forms, and Askina® Calgitrol® Paste consist of a complex silver alginate matrix with recognized and proven clinical applicability and effectiveness. The silver alginate matrix is composed of inter-stitial layers of calcium and silver alginate molecules, inter-spersed with bonded water (8 % −10 % of the matrix). Upon exposure to the wound exudate, absorption of moisture by the matrix leads to softening and swelling of the alginate structure, which facilitates a controlled and steady state release of ionic silver into the wound without losing the structural integrity of the matrix itself. The Askina® Calgitrol® range of products do not require the use of sterile water to prime antimicrobial activity as they contain bonded water, and the silver ions are evenly distri-buted in the matrix readily available for wound treatment (Table 2).

The ionic silver−containing Askina® Calgitrol® Ag dressing has demonstrated antimicrobial effectiveness in a randomized clinical trial involving patients with infected chronic (pressure ulcers, venous ulcers, diabetic foot ulcers) and acute wounds. [Trial C et al 2010]

Further studies have demonstrated clinical benefits in the management of patients with partial-thickness burns and other chronic and acute wounds. [Ricci E et al 2007; Opasanon S et al 2010; Aramwit P et al 2010]

Development and Mechanism of Action of Askin a® Calgitrol® PasteRationale

The clinical value and success of the Askina® Calgitrol® Ag flat dressings prompted the design and development of Askina® Calgitrol® Paste. Calgitrol® Paste is, therefore, a highly conform-able paste composed of the same ionic silver alginate matrix used in the Askina Calgitrol® Ag flat dressings. The paste, however, contains a greater water content (43 %) than the Calgitrol® Ag dressings, conferring unique moisturizing features to Calgitrol® Paste (Table 2).

In addition, the high conformability of Askina® Calgitrol® Paste al-lows intimate contact between the active ionic silver alginate matrix and the wound bed, which is particularly valuable in diffi-cult-to-manage wounds such as those with tunnels and sinuses, seen in patients with second-degree burns and diabetic foot ul-cers. The synergy created by the intimate wound contact and the sustained release of ionic silver enables rapid killing of wound-infecting microorganisms by Askina® Calgitrol® Paste.

Silver dressings using Calgitrol® technology are ready for use and do not require prior wetting to prime activity

Askina® Calgitrol® Paste is highly conformable allowing inti-mate contact between the ionic silver alginate matrix and the wound bed

Characteristic Calgitrol® Paste Calgitrol® Ag dressing

Formulation Paste Standard dressing forms a surface gel

Silver type 100 % ionic silver 100 % ionic silver

Silver content [Ag] 6.4 - 14.8 mg/g paste 96 - 222 mg/100 cm2

Average [Ag]12 mg/g 180 mg of Ag/15 g tube

141 mg/ 100 cm2

Class Class 3 product Class 3 product

[B. Braun; Report HOSP 263, 2008]

Table 2. Characteristics of Askina® Calgitrol® Paste

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Page 5: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

Askina® Calgitrol® Paste has a high ionic silver content and a unique silver alginate matrix which absorbs wound exudates, maintains molecular integrity, and acts as a reservoir providing a controlled, rapid, and sustained release of ionic silver to the wound over time (Table 3).

Askina® Calgitrol® Paste contains an average of ~12 mg ionic sil-ver per gram of paste (corresponding to ~180 mg/15 g tube of ionic silver) which ensures long-lasting antimicrobial activity. Silver ions in the Askina® Calgitrol® Paste are bound to the poly-saccharide molecules of the alginate matrix. The combination of these moieties acts as a reservoir for the silver ions, which are then steadily released into the wound environment, thus avoiding silver ‘dumping’ and the complications associated with an exces-sive, rapid deposition of ionic silver.

Development and Mechanism of Action of Askin a® Calgitrol® PasteMechanism of Action

Characteristic Calgitrol® Paste Clinical benefit

Silver content ~180 mg of silver/15 g tube Ensures long-term antibacterial action

Linkage of silver ionsSilver ions are linked to the polysaccharide molecules of the alginate, building a complex matrix

The matrix acts as reservoir providing steady release of ionic silver

Controlled bioavailability of silver ions

A silver-sodium ion exchange process controls release of silver ions from the matrix

No systemic toxicity (argyria)

Release of silver ions Controlled diffusion of ionic silverOptimal concentration of ionic silver is main-tained topically, with immediate start of the antibacterial action

Table 3. Properties of Askina® Calgitrol® Paste associated with clinical benefit

In moist wound environments, exudates are typically absorbed into the matrix, leading to a swelling of the alginate and conse- quent dissociation of the silver and calcium alginate bonds (Figure 1). Since the silver-alginate bonds are weaker than the calcium-algi-nate bonds, they rupture first, leading to a preferential, controlled release of silver ions from the matrix. Such release provides for an extended, effective, and steady state delivery of ionic silver to the wound site. Sodium ions from the exudate replace the silver ions in the matrix, which maintains its molecular integrity over time, thus providing a reservoir and continuous source of ionic silver.

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Page 6: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

Paste

Intimate contact

Skin Wound bed

2. Swelling of the silver alginate matrix and bond dissociation

3. Controlled and sustained delivery of ionic silver

1. Absorption of exudate into the matrix

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+Ag+

Ag+

Ag+

of ionic silver

Ag+

Ag+Ag+

Ag+

Ag+

Ag+

Ag+

Na +

Na +

Na +Na +Na +

Na +Na +

Na +

Na +

Na +

Na +

NaNa + Na +

Ag Ag

Ca Ca

Ca

Ag

CaCaAg Ag

Ca Ca

Ca

Ag

CaCaAg Ag

Ca Ca

Ca

Ag

CaCaAg Ag

Ca Ca

CaCaCa

Ag Ag

Ca Ca

Ca

Ca

Ag Ag

Ca Ca

CaAg Ag

Ca Ca

CaAg Ag

Ca Ca

CaAg Ag

Ca Ca

Ca

Ag Ag

Ca Ca

Ca

Ag

CaCa

Ca

Ag Ag

AgAgCa Ca

Ag Ag

AgAgCa Ca

Ag Ag

AgAgCa Ca

Ag Ag

Ca Ca

Ag

Ca

CaCaAg Ag

Ca Ca

CaCaAg Ag

Ca Ca

CaCaAg Ag

Ca Ca

CaCaAg Ag

Ca Ca

CaCa

Ag

AgAgCa

Alg Alg Alg Alg Alg

Alg Alg Alg Alg Alg

Ag+Ag+ Ag+ Ag+

Figure 1. Release of ionic silver from the silver alginate matrix

The fl ow of silver ions from the alginate matrix into the wound occurs by mass action law, with silver ions moving from high to low concentration areas. The extended release from the alginate matrix ensures that active ionic silver is delivered steadily over time, reaching immediate and effective antimicrobial concentra-tions in the wound (Figure 1).

This controlled bioavailability of silver ions ensures high antimi-crobial wound activity without the risk of over-delivery of silver ions, the resultant wound discoloration, and potential for sys-temic absorption and toxicity.

Extended release from the alginate matrix ensures that active ionic silver is delivered steadily over time and reaches antimicrobial concentrations in the wound

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Page 7: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

Paste

Intimate contact

Skin Wound bed

2. Swelling of the silver alginate matrix and bond dissociation

3. Controlled and sustained delivery of ionic silver

1. Absorption of exudate into the matrix

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Na +

Na +

Na +Na +Na +

Na +Na +

Na +

Na +

Na +

Na +

NaNa + Na +

Ag Ag

Ca Ca

Ca

Ag

Ag Ag

Ca Ca

Ca

Ag

Ag Ag

Ca Ca

Ca

Ag

Ag Ag

Ca Ca

Ca

Ag Ag

Ca Ca

CaAg Ag

Ca Ca

CaAg Ag

Ca Ca

CaAg Ag

Ca Ca

CaAg Ag

Ca Ca

Ca

Ag Ag

Ca Ca

Ca

Ag

Ag+Ag+ Ag+ Ag+

Figure 2. Sites of ionic silver antimicrobial activity in target bacteria

[Feng QL et al 2000; Lansdown AB 2010]

Targets and Mechanisms of Bacterial Cell Kill by Ionic Silver

The in vitro and in vivo antimicrobial activity of ionic silver is directed against multiple bacterial target sites, thus reducing the probability of generating resistance after repeated use, as it may be observed with the most frequently used antibiotics (eg, sulfonamides). [Bridges K et al 1977; Gupta A et al 1998; Driver VR 2004; Chopra I 2007]

Upon release from the matrix, active ionic silver targets three critical bacterial structures (Figure 2). [Feng QL et al 2000; Lansdown AB 2010]

The bacterial wall, with loss of bacterial integrity and pathogenicity The bacterial protein structure, synthesis, and enzymatic activity, with impairment of the intracellular metabolic pathways and energy stores The bacterial DNA, with inhibition of DNA replication and cell division

Release of ionic silver in the vicinity of wound-infecting bacte-ria induces, in the majority of cases, a bactericidal rather than bacteriostatic effect against multiple bacterial strains including Staphylococcus aureus, Escherichia coli, and Pseudomonas aeru-ginosa. [Feng QL et al 2000; Jung WK et al 2008]

Electron microscopy studies of the Gram-negative bacteria E. coli exposed to ionic silver showed DNA condensation and loss of replication activity, rupture of the bacterial wall, and release of microbial content. X-ray studies demonstrated the presence of silver ions inside the extensively damaged bacteria. Similar changes occurred in Gram-positive microorganisms such as S. aureus, following incubation with ionic silver. [Feng QL et al 2000; Jung WK et al 2008]

Silver dressings that release ionic silver at bactericidal concen-trations are associated with a low risk of inducing resistance in target bacteria. [White R et al 2006; Chopra I 2007]Ionic silver is directed against multiple bacterial target sites,

thus reducing the probability of generating resistance after repeated use

Figure adapted from Molecular Expressions Web site. Michael Davidson and the Florida State University Research Foundation. http://micro.magnet.fsu.edu. Accessed January 2012.

Capsule

Nucleoid

Cytoplasm

Cell wall

CytoplasmicMembrane

Pili

Bacterial cell wallLoss of bacterial integrity

Bacterial proteinsImpairment of bacterial metabolism

Energy stores depletion

Bacterial DNA proteinsInhibition of bacterial division

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+

Ag+Ag+Ag+Ag+Ag+

Ag+Ag+Ag+

Ag+

Ag+

Ag+Ag+Ag+Ag+

Ag+Ag+

Ag+Ag+Ag+

Ag+

Ag+

Ag+

Ag+Ag+

Ag+Ag+Ag+Ag+

Ag+Ag+Ag+

Ag+Ag+Ag+Ag+

Ag+

Ribosomes

7

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Page 8: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

Figure 3. Antimicrobial activity of Askina® Calgitrol® Paste - In vitro kill rates against (A) MRSA, (B) E. coli, and (C) P. aeruginosa

The ability of ionic silver to kill a large spectrum of Gram-positive, Gram-negative, aerobic and anaerobic bacteria, as well as methi-cillin-resistant S. aureus (MRSA) and vancomycin-resistant Entero-coccus underlies its usefulness in the treatment of infected or at risk wounds. [Thomas S and McCubbin P 2003; Driver VR 2004; Weller C and Sussman G 2006]

In vitro testing has demonstrated the effectiveness of Askina® Calgitrol® Paste against multiple Gram-positive and Gram-negative bacterial strains including MRSA, P. aeruginosa, and E. coli. [B. Braun; Reports HOSP 283A, 2011 and HOSP 303, 2011]

Askina® Calgitrol® Paste induced a 4-log reduction against MRSA in 2 hours, and a >7 to >9-log reduction against E. coli and P. aeruginosa over a period of 3 hours. The Askina® Calgitrol® Paste kill rates were similar to those for SSD, which is recognized as a standard of care for burns (Figure 3).

Resistance to topical silver has been addressed, but is of no im-portance for clinical practice [Percival SL et al 2005]. Conversely, substantial resistance rates have been induced by the sulfon-amide component of SSD. [Bridges K and Lowbury EJL 1977; Gupta A et al 1998; White RJ and Cooper R

2005]

CFU, colony-forming units [B. Braun; Reports HOSP 283A, 2011 and HOSP 303, 2011]

Antimicrobial Activity

B. E. coliTime (hours)

Log (CFU) Reduction

12

10

8

6

4

2

010,5 1,5 2,52 3 43,5 4,5 5,55 6 24

12

10

8

6

4

2

010,5 1,5 2,52 3 43,5 4,5 5,55 6 24

12

10

8

6

4

2

010,5 1,5 2,52 3 43,5 4,5 5,55 6 24C. P. aeruginosa Time

(hours)

Askina® Calgitrol® PasteSilver sulfadiazine

Log (CFU) Reduction

12

10

8

6

4

2

010,5 1,5 2,52 3 43,5 4,5 5,55 6 24

12

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6

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010,5 1,5 2,52 3 43,5 4,5 5,55 6 24

12

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2

010,5 1,5 2,52 3 43,5 4,5 5,55 6 24

A. MRSATime (hours)

Log (CFU) Reduction 12

10

8

6

4

2

010,5 1,5 2,52 3 43,5 4,5 5,55 6 24

12

10

8

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2

010,5 1,5 2,52 3 43,5 4,5 5,55 6 24

12

10

8

6

4

2

010,5 1,5 2,52 3 43,5 4,5 5,55 6 24

Askina® Calgitrol® Paste demonstrates antimicrobial effec-tiveness against Gram-positive and Gram-negative strains //

//

//

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Page 9: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

It is important to consider the potential risk of systemic and local silver-related toxicity when envisioning use of a silver-containing topical formulation. Substantial absorption of ionic silver can lead to systemic silver toxicity, also known as argyria.

Argyria is usually associated with environmental exposure to high quantities of silver and chronic overload (silver body burden equal to 3.8 g or higher). Argyria is characterized by the deposi-tion of inert silver in connective tissues, vessels, and the dermis, and with potentially extensive discolouration of the skin and nail beds, particularly in light-exposed areas. [Lansdown AB 2010]

Systemic absorption of silver and clinical argyria has been report-ed with the use of SSD in patients with large area burns. [Flamazine Cream Product Information; Smith & Nephew 2009]

In contrast, systemic absorption of silver from Askina® Calgitrol® Paste has been shown to be insignificant in a preclinical model, with blood serum silver levels remaining ≤ 0.012 ppm over a pe-riod of 7 days (Figure 4). [B. Braun; Report HOSP 257, 2009]

Up to almost 30 times higher blood silver levels (0.05 − 0.31 ppm) have been detected in burns patients without signs of silver-related toxicity. [Wan AT et al 1991]

Skin contact studies have shown that Askina® Calgitrol® Paste is well-tolerated after topical application, with little or no local irritation. Its use is not associated with a significant risk of sen-sitization and no staining of the skin surrounding the application area has been reported in patients treated with Askina® Calgitrol® Paste. [B. Braun; Report HOSP 257, 2009]

Safety and TolerabilitySystemic Safety Local Tolerability

0.36

0.30

0.24

0.18

0.12

0.06

0Day 1 Day 3 Day 7

Figure 4. Leachable silver detected in the blood stream

[NAMSA Report HOSP 257; Wan AT et al 1991]Time (days)

Silver concentration (ppm)

Askina® Calgitrol® Paste

No evidence of toxicity in this range of silver concentrations

Askina® Calgitrol® Paste is well-tolerated after topical ap-plication, and systemic absorption of silver has been shown to be very low.

//

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Page 10: Askina Calgitrol Paste Technical Brochure€¦ · buted in the matrix readily available for wound treatment (Table 2). The ionic silver−containing Askina ® Calgitrol Ag dressing

Askina® Calgitrol® Paste is indicated for external use for the management of

Partial- to full-thickness wounds

Stage I−IV pressure wounds

Venous and arterial ulcers

Diabetic foot ulcers

Second-degree burns

The ease of use of Askina® Calgitrol® Paste makes it ideal for si-nuses and tunnel wounds often seen in patients with burns, and for other difficult-to-manage wounds, ie, diabetic foot ulcers. In addition, the moisture donating properties of Askina® Calgitrol® Paste may provide a soothing effect on burns.

Compatibility with a variety of secondary dressings and the po-tential need for less frequent dressing changes contribute to the versatility of Askina® Calgitrol® Paste and a potential reduction in the burden of care for nursing personnel.

After cleansing the wound with 0.9 % saline or Prontosan® solu-tion, the Askina® Calgitrol® Paste can be easily applied in a thick layer to the entire wound bed. Askina Calgitrol® Paste is easily removed with 0.9 % saline or Prontosan® solution, by simple rins-ing.

Askina® Calgitrol® Paste should be reapplied at each dressing change with a daily or up to three days frequency. A change may also be advisable if wound exudates leak through the secondary dressing.

Askina® Calgitrol® Paste should not be used in patients with known hypersensitivity to alginates or silver, and in patients with ulcers resulting from tuberculosis, syphilis, or deep fungal infec-tions. [Askina® Calgitrol® Paste Instructions for Use; B. Braun 2011]

In SummaryAskina® Calgitrol® Paste has a highly conformable product form. This conformability allows for intimate contact between the ionic silver alginate matrix and the wound bed; the prod-uct helps to maintain a moist wound healing environment and does not require any activation by water prior to use.

The silver alginate matrix provides effective, controlled, and sustained release of active ionic silver and a broad antimicro-bial activity over the entire wound bed area.

Askina® Calgitrol® Paste has an antimicrobial activity similar to that of SSD without the emerging issues of antimicrobial resistance and systemic toxicity.

Askina® Calgitrol® Paste is an ideal formulation for difficult to manage wound shapes, tunnel wounds, and small sinuses as found in diabetic foot ulcers and second-degree burns.

Askina® Calgitrol® Paste is easy to apply and can be used with a variety of secondary dressings including low adherent inter-face and gauze types.

Appropriate Wound Types and Application Instructions

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Aramwit P, Muangman P, Namviriyachote N, Srichana T. In vitro evaluation of the antimicrobial effectiveness and moisture binding properties of wound dressings. Int J Mol Sci. 2010;11(8):2864-2874.

Askina® Calgitrol® Ag. Instructions for Use [P1067-00]. B. Braun Hospicare Ltd. Sligo, Ireland; 2011.

Askina® Calgitrol® Paste. Instructions for Use [P1056-00]. B. Braun Hospicare Ltd. Sligo, Ireland; 2011.

B. Braun. Measurement of serum silver from Askina® Calgitrol® Paste in a swine dermal wound model. (Testing carried out by NAMSA); Report HOSP 257. B. Braun Hospicare Ltd, 2009.

B. Braun. Determination of silver in Askina® Calgitrol® Paste to demonstrate pro-duction homogeneity using Method Number G4AV. (Testing carried out by Shef-field Analytical Services); Report HOSP 263, B. Braun Hospicare Ltd., 2008.

B. Braun. Log Reduction (LR) measure of efficacy of Askina® Calgitrol® Paste, Flamazine Cream and Flaminal® Hydro against Cultures of P. aeruginosa (NCIMB 8626) and E. coli (NCIMB 12416) . (Testing carried out by Institute of Technology, Sligo); Report HOSP 283A, B. Braun Hospicare Ltd., 2011.

B. Braun. Log Reduction (LR) measure of efficacy (results only) of Askina® Calgi-trol® Paste and Flamazine Cream against a Culture of Methicillin Resistant Staph-ylococcus aureus (MRSA, ATCC BAA-44). (Testing carried out by Institute of Tech-nology, Sligo); Report HOSP 303, B. Braun Hospicare Ltd., 2011.

Bridges K, Lowbury EJL. Drug resistance in relation to use of silver sulphadiazine cream in burns units. J Clin Pathol. 1977;30(2):160-164.

Chopra I. The increasing use of silver-based products as antimicrobial agents: a useful development or a cause for concern? J Antimicrob Chemother. 2007;59(4):587-590.

Driver VR. Silver dressings in clinical practice. Ostomy Wound Manage. 2004;50(9A Suppl):11S-15S.

Feng QL, Wu J, Chen GQ, Cui FZ, Kim TN, Kim JO. A mechanistic study of the anti-bacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J Biomed Mater Res. 2000;52(4):662-668.

Flamazine Cream Product Information V.17. Smith & Nephew; 2009.

Frykberg RG. An evidence-based approach to diabetic foot infections. Am J Surg. 2003;186(5A):44S-54S.

Gist S, Tio-Matos I, Falzgraf S, Cameron S, Beebe M. Wound care in the geriatric client. Clin Interv Aging. 2009;4:269-287.

Gupta A, Maynes M, Silver S. Effects of halides on plasmid- mediated silver resistance in Escherichia coli. Appl Environ Microbiol. 1998;64(12):5042-5045.

Jung WK, Koo HC, Kim KW, Shin S, Kim SH, Park YH. Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli. Appl Environ Microbiol. 2008;74(7):2171-2178.

Lansdown AB. A pharmacological and toxicological profile of silver as an antimi-crobial agent in medical devices. Adv Pharmacol Sci. 2010;2010:910686.

Lowbury EJ, Babb JR, Bridges K, Jackson DM. Topical chemoprophylaxis with silver sulphadiazine and silver nitrate chlorhexidine creams: emergence of sulphon-amide-resistant Gram-negative bacilli. Br Med J. 1976;1(6008):493-496.

Opasanon S, Muangman P, Namviriyachote N. Clinical effectiveness of alginate silver dressing in outpatient management of partial-thickness burns. Int Wound J. 2010;7(6):467-471.

Percival SL, Bowler PG, Russel D. Bacterial resistance to silver in wound care. J Hosp Infect. 2005;60(1):1-7.

Ricci E, Pittarello R, Moffa M, Ferrero M, Gonella E, Tonino E. Askina® Calgitrol® Ag: clinical use of an advanced ionic silver dressing. Acta Vulnologica. 2007;5(3):105-111.

Thomas S, McCubbin P. An in vitro analysis of the antimicrobial properties of 10 silver-containing dressings. J Wound Care. 2003;12(8):305-308.

Trial C, Darbas H, Lavigne JP, et al. Assessment of the antimicrobial effectiveness of a new silver alginate would dressing: a RCT. J Wound Care. 2010;19(1):20-26.

Wan AT, Conyers RA, Coombs CJ, Masterton JP. Determination of silver in blood, urine, and tissues of volunteers and burn patients. Clin Chem. 1991;37(10 Pt 1):1683-1687.

Weller C, Sussman G. Wound dressings update. J Pharm Pract Res. 2006;36:318-324.

White RJ, Cutting K. Exploring the effects of silver in wound management. What is optimal? Wounds. 2006;18:307-314.

White RJ, Cooper R. Silver sulphadiazine: a review of the evidence. Wounds UK. 2005;1:51-56.

References

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B. Braun Hospicare Ltd. | Collooney | Co. Sligo | Ireland | www.bbraun.com ZJ01266 Edition: 05/2012

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