Bacterial resistance to silver in wound care

doi:10.1016/j.jhin.2004.11.014

Journal of Hospital Infection

Volume 60, Issue 1, May 2005, Pages 1-7

https://doi.org/10.1016/j.jhin.2004.11.014 Get rights and content

Summary

Ionic silver exhibits antimicrobial activity against a broad range of micro-organisms. As a consequence, silver is included in many commercially available healthcare products. The use of silver is increasing rapidly in the field of wound care, and a wide variety of silver-containing dressings are now commonplace (e.g. Hydrofiber^® dressing, polyurethane foams and gauzes). However, concerns associated with the overuse of silver and the consequent emergence of bacterial resistance are being raised. The current understanding of the biochemical and molecular basis behind silver resistance has been documented since 1998. Despite the sporadic evidence of bacterial resistance to silver, there have been very few studies undertaken and documented to ascertain its prevalence. The risks of antibacterial resistance developing from the use of biocides may well have been overstated. It is proposed that hygiene should be emphasized and targeted towards those applications that have demonstrable benefits in wound care. It is the purpose of this review to assess the likelihood of widespread resistance to silver and the potential for silver to induce cross-resistance to antibiotics, in light of its increasing usage within the healthcare setting.

Introduction

Ionic silver (Ag⁺) is considered to be effective against a broad range of micro-organisms, with low concentrations documented to have therapeutic activity.1, 2 Silver has been described as being ‘oligodynamic’ because of its ability to exert a bactericidal effect at minute concentrations.³ Consequently, a large number of healthcare products now contain silver, principally due to its antimicrobial activities and low toxicity to human cells. Such products include silver-coated catheters,4, 5 municipal water systems6, 7 and wound dressings.⁸

Wounds often provide a favourable environment for the colonization of micro-organisms.6, 8, 9, 10 In order to improve the opportunity for wound healing, it is important to create conditions that are unfavourable to micro-organisms and favourable for the host repair mechanisms, and topical antimicrobial agents are believed to facilitate this process. Antiseptic agents are now considered for the treatment of localized skin and wound infections because they have a lower propensity to induce bacterial resistance than antibiotics. One example of the early use of silver in wound care is silver sulphadiazine (AgSD) cream, developed in the 1960s, for the treatment of burns. Recently, a trend towards the use of wound cover dressings that contain silver has been evident, and today, a selection of foam, film, hydrocolloid, gauze and dressings with Hydrofiber^® technology impregnated with silver are commercially available. However, concerns are being expressed regarding the overuse of silver and the possible emergence of bacterial resistance to silver, particularly within the clinical environment.11, 12 Silver-resistant bacteria have been reported since 197513, 14, 15, 16, 17, 18, 19, 20, 21, 22 and research within this area is clearly increasing.²³ A preliminary understanding of the genetics underlying silver resistance has been known since 1998,24, 25 with a greater understanding of the biochemistry documented a year later.²⁶ Clinical evidence of silver-resistant bacteria has been principally in hospitals, specifically in burns wards, where silver salts (in the form of silver nitrate) are used as antiseptic agents.13, 27

Many clinicians and researchers have questioned whether the widespread usage of silver could lead to cross-resistance to antibiotics, as has been suggested with a number of biocides, specifically triclosan, chlorhexidine and quaternary ammonium compounds (QACs).28, 29 However, in reference to the available evidence to date, this appears to represent an unjustifiable concern.

It is the purpose of this review to assess the likelihood of widespread resistance to silver and the potential for silver to induce cross-resistance to antibiotics, in light of its increasing usage within the healthcare setting.

Section snippets

Wound microbiology and antimicrobial agents

Wounds often provide a favourable environment for the colonization of micro-organisms which may both delay healing and cause infection. Bacteria found in wounds originate primarily from the mouth and colon, and constitute a unique collection of organisms that are potentially pathogenic. Consequently, broad-spectrum antimicrobial agents are required to control these mixed species populations to minimize the opportunity for infection. This has been reflected in the increased usage of silver in

Mode of action of Ag⁺

In bacteria, silver ions are known to react with nucleophilic amino acid residues in proteins, and attach to sulphydryl, amino, imidazole, phosphate and carboxyl groups of membrane or enzyme proteins that leads to protein denaturation.1, 19, 35 Silver is also known to inhibit a number of oxidative enzymes such as yeast alcohol dehydrogenase,³⁶ the uptake of succinate by membrane vesicles³⁷ and the respiratory chain of Escherichia coli, as well as causing metabolite efflux³⁸ and interfering with

General resistance mechanisms

Resistance to an antimicrobial agent can occur either by ‘intrinsic’ or ‘acquired’ mechanisms. Acquired resistance can arise by either mutation or the acquisition of various types of genetic material in the form of plasmids, transposons and self-replicating extra-chromosomal DNA.⁵² Acquired resistance to a wide range of antibiotics has been observed in a variety of micro-organisms.⁵³ Intrinsic resistance is a phenotype demonstrated by micro-organisms before the use of an antimicrobial agent,

Link between Ag⁺ usage, resistance and antibiotics

Ag⁺ resistance is most likely to be found in environments where greatest Ag⁺ usage of silver-containing products might be expected, such as in the dental setting where amalgams are known to contain 35% silver,⁷⁴ burns units in hospitals⁷⁵ or the use of silver-coated catheters.⁴

Some biocides disrupt cellular targets, and subsequent mutations in these targets may confer low-level cross-resistance to certain antibiotics used in humans. Whilst a number of laboratory-based studies have indicated a

Use of Ag⁺ in wound care

Silver has been used extensively for the treatment of burns,92, 93 with AgSD incorporated into bandages for use in large open wounds.94, 95 Many silver-coated and silver-containing dressings are now available for the treatment of wounds.

Although resistance to heavy metals, such as Ag⁺, has been studied and reported, exact mechanisms are not known and there is little current evidence of emerging microbial resistance to silver. Increased use of Ag⁺ in wound care has created some concern regarding

References (95)

A.D. Russell et al.
Antimicrobial activity and action of silver
Prog Med Chem
(1994)
L.A. Sampath et al.
Infection resistance of surface modified catheters with either short-lived or prolonged activity
J Hosp Infect
(1995)
S. Silver
Bacterial silver resistance: molecular biology and uses and misuses of silver compounds
FEMS Microbiol Rev
(2003)
H.J. Klasen
A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver
Burns
(2000)
A.E. Aiello et al.
Antibacterial cleaning and hygiene products as an emerging risk factor for antibiotic resistance in the community
Lancet Infect Dis
(2003)
N. George et al.
Silvazine (silver sulfadiazine and chlorhexidine) activity against 200 clinical isolates
Burns
(1997)
M. Subrahmanyam
A prospective randomised clinical and histological study of superficial burn wound healing with honey and silver sulfadiazine
Burns
(1998)
J.F. Fraser et al.
An in vitro study of the anti-microbial efficacy of a 1% silver sulphadiazine and 0.2% chlorhexidine digluconate cream, 1% silver sulphadiazine cream and a silver coated dressing
Burns
(2004)
P.J. Snodgrass et al.
Effects of silver and mercurials on yeast alcohol dehydrogenase
J Biol Chem
(1960)
M.K. Rayman et al.
Transport of succinate in Escherichia coli: characteristics of uptake and energy coupling with transport in membrane preparations
J Biol Chem
(1972)

A.L. Semeykina et al.

Submicromolar Ag⁺ increases passive Na⁺ permeability and inhibits the respiration-supported formation of Na⁺ gradient in Bacillus FTU vesicles

FEBS Lett

(1990)

M. Hayashi et al.

Properties of respiratory chain-linked Na(+)-independent NADH-quinone reductase in a marine Vibrio alginolyticus

Biochim Biophys Acta

(1992)

R.U. Nesbitt et al.

Solubility studies of silver sulfadiazine

J Pharm Sci

(1977)

D. Kucken et al.

Association of qacE and qacE1 with multiple resistance to antibiotics and antiseptics in clinical isolates of Gram-negative bacteria

FEMS Microbiol Lett

(2000)

U. Tattawasart et al.

Outer membrane changes in Pseudomonas stutzeri resistance to chlorhexidine diacetate and cetylpyridinium chloride

Int J Antimicrob Agents

(2000)

D.G. White et al.

Biocides, drug resistance and microbial evolution

Curr Opin Microbiol

(2001)

L. Thomas et al.

Development of resistance to chlorhexidine diacetate in Pseudomonas aeruginosa and the effect of a ‘residual’ concentration

J Hosp Infect

(2000)

S. Silver

Bacterial resistance to toxic metal ions

Gene

(1996)

D.H. Nies

Efflux-mediated heavy metal resistance in prokaryotes

FEMS Microbiol Rev

(2003)

F. Baquero

Low level antibacterial resistance: a gateway to clinical resistance

Drug Resist Update

(2001)

H.J. Klasen

Historical review of the use of silver in the treatment of burns. Part I. Early uses

Burns

(2000)

T.M. Barbosa et al.

The impact of antibiotic use on resistance development and persistence

Drug Resist Update

(2000)

W.W. Monafo et al.

Topical therapy for burns

Surg Clin North Am

(1987)

N. George et al.

Silvazine (silver sulfadiazine and chlorhexidine) activity against 200 clinical isolates

Burns

(1997)

J.B. Wright et al.

Efficacy of topical silver against fungal burn wound pathogens

Am J Infect Control

(1999)

A.B.G. Lansdown et al.

Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat

Br J Dermatol

(1997)

J.L. Clement et al.

Antibacterial silver

Met Based Drugs

(1994)

M.K. Dasgupta

Silver peritoneal catheters reduce bacterial colonization

Adv Perit Dial

(1994)

C.W. Chambers et al.

Bactericidal effect of low concentrations of silver

J Am Water Works Assoc

(1962)

J.L. Kool et al.

Hospital characteristics associated with colonization of water systems by Legionella and risk of nosocomial legionnaires' disease: a cohort study of 15 hospitals

Infect Control Hosp Epidemiol

(1999)

A.P. Adams et al.

Antibacterial properties of a silver chloride-coated nylon wound dressing

Vet Surg

(1999)

I. Brook

Microbiology and management of sinusitis

J Otolaryngol

(1996)

P.G. Bowler et al.

The microbiology of infected and noninfected leg ulcers

Int J Dermatol

(1999)

J.P. Pirnay et al.

Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone

J Clin Microbiol

(2003)

A. Gupta et al.

Silver resistance genes in plasmids of the IncH incompatibility group and on Escherichia coli chromosome

Microbiology

(2001)

G.L. McHugh et al.

Salmonella typhimurium resistance to silver nitrate, chloramphenicol, and ampicillin

Lancet

(1975)

D.I. Annear et al.

Instability and linkage of silver resistance, lactose fermentation and colony structure in Enterobacter cloacae

J Clin Pathol

(1976)

A.T. Hendry et al.

Silver-resistant Enterobacteriaceae from hospital patients

Can J Microbiol

(1979)

K. Bridges et al.

Gentamicin-silver-resistant Pseudomonas

BMJ

(1979)

R.T. Belly et al.

Silver resistance in microorganisms

Dev Ind Microbiol

(1982)

C. Haefeli et al.

Plasmid-determined silver resistance in Pseudomonas stutzeri isolated from a silver mine

J Bacteriol

(1984)

P. Kaur et al.

Plasmid mediated resistance to silver ions in Escherichia coli

Ind J Med Res

(1985)

P. Kaur et al.

Mechanism of resistance to silver ions in Klebsiella pneumoniae

Antimicrob Agents Chemother

(1986)

M.E. Starodub et al.

Mobilization of Escherichia coli R1 silver-resistance plasmid pJT1 by Tn5-Mob into Escherichia coli C600

Biol Met

(1990)

L.M. Deshpande et al.

Plasmid mediated silver resistance in Acinetobacter baumannii

Biometals

(1994)

A. Gupta et al.

Silver as a biocide: will resistance become a problem?

Nat Biotechnol

(1998)

S. Silver et al.

Silver cations as an antimicrobial agent: clinical uses and bacterial resistance

APUA Newsl

(1999)

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ReviewBacterial resistance to silver in wound care

Summary

Introduction

Section snippets

Wound microbiology and antimicrobial agents

Mode of action of Ag+

General resistance mechanisms

Link between Ag+ usage, resistance and antibiotics

Use of Ag+ in wound care

Prog Med Chem

J Hosp Infect

FEMS Microbiol Rev

Burns

Lancet Infect Dis

Burns

Burns

Burns

J Biol Chem

J Biol Chem

FEBS Lett

Biochim Biophys Acta

J Pharm Sci

FEMS Microbiol Lett

Int J Antimicrob Agents

Curr Opin Microbiol

J Hosp Infect

Gene

FEMS Microbiol Rev

Drug Resist Update

Burns

Drug Resist Update

Surg Clin North Am

Burns

Am J Infect Control

Silver aids healing in the sterile skin wound: experimental studies in the laboratory rat

Br J Dermatol

Antibacterial silver

Met Based Drugs

Silver peritoneal catheters reduce bacterial colonization

Adv Perit Dial

Bactericidal effect of low concentrations of silver

J Am Water Works Assoc

Hospital characteristics associated with colonization of water systems by Legionella and risk of nosocomial legionnaires' disease: a cohort study of 15 hospitals

Infect Control Hosp Epidemiol

Antibacterial properties of a silver chloride-coated nylon wound dressing

Vet Surg

Microbiology and management of sinusitis

J Otolaryngol

The microbiology of infected and noninfected leg ulcers

Int J Dermatol

Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone

J Clin Microbiol

Silver resistance genes in plasmids of the IncH incompatibility group and on Escherichia coli chromosome

Microbiology

Salmonella typhimurium resistance to silver nitrate, chloramphenicol, and ampicillin

Lancet

Instability and linkage of silver resistance, lactose fermentation and colony structure in Enterobacter cloacae

J Clin Pathol

Silver-resistant Enterobacteriaceae from hospital patients

Can J Microbiol

Gentamicin-silver-resistant Pseudomonas

BMJ

Silver resistance in microorganisms

Dev Ind Microbiol

Plasmid-determined silver resistance in Pseudomonas stutzeri isolated from a silver mine

J Bacteriol

Plasmid mediated resistance to silver ions in Escherichia coli

Ind J Med Res

Mechanism of resistance to silver ions in Klebsiella pneumoniae

Antimicrob Agents Chemother

Mobilization of Escherichia coli R1 silver-resistance plasmid pJT1 by Tn5-Mob into Escherichia coli C600

Biol Met

Plasmid mediated silver resistance in Acinetobacter baumannii

Biometals

Silver as a biocide: will resistance become a problem?

Nat Biotechnol

Silver cations as an antimicrobial agent: clinical uses and bacterial resistance

APUA Newsl

Review
Bacterial resistance to silver in wound care

Mode of action of Ag⁺

Link between Ag⁺ usage, resistance and antibiotics

Use of Ag⁺ in wound care