Key Points Resistant bacteria, particularly methicillin-resistant Staphylococcus aureus MRSAare an ever-increasing global threat that has reached epidemic proportions and is extremely costly, both in terms of human suffering and the financial burden it places on healthcare systems. The battle against bacterial resistance should focus on preventing the spread of contamination by reducing the risk of infection, educating both staff and patients in infection control, and improving standards of hygiene.
The problem of resistant bacteria has been exacerbated by the uncontrolled use of antibiotics, so a range of alternative measures are required to prevent the development of further resistance and manage infections. These include antibacterial preparations and dressings that contain silver.
This article is supported by an educational grant from Smith and Nephew. The views expressed in this article are those of the authors and do not necessarily reflect those of Smith and Nephew. Further information on MRSA can be found at www. Nov Last updated: Abstract The spread of antibiotic-resistant strains of micro-organisms such as methicillin-resistant Staphylococcus aureus MRSA represents an ever-increasing threat to the health of vulnerable people throughout the world who are obliged to spend extended periods in healthcare tetracycline animal mrsa. The organism is also responsible for increasing the financial burden placed on such centres and the wider community at large, with the result that precious financial resources are diverted from other areas of need to deal with the consequences of infection.
There is general agreement that the problem of resistance has been exacerbated by the overuse or misuse of antibiotics so, wherever possible, alternative methods are now required to tetracycline animal mrsa topical infections caused by antibiotic-resistant organisms.
Open wounds act as an important focus for cross-infection, necessitating the application of appropriate measures to eliminate or prevent the spread of bacteria from such lesions. Some topical products that can be used in the treatment of wound infections are described, with particular emphasis on the potential value of silver-containing dressings.
Introduction Staphylococcus aureus is a gram-positive bacterium that exists as a skin commensal in a significant proportion of the population.
Despite its ubiquitous nature, it is a recognised potential pathogen with the ability to cause a wide range of infections from localised skin eruptions to life-threatening conditions such as bacteraemia, endocarditis and pneumonia . Another important feature of the bacterium is its ability to develop resistance to commonly used antibiotics and antiseptics.
The development of resistance to penicillin by S. By the early s, however, isolated reports of resistance to these agents began to appear in the literature, even before the antibiotics were used in clinical practice . The emergence in of ciprofloxacin-resistant S. Twenty-four of the 55 patients involved had been treated previously with ciprofloxacin and MRSA was shown to be a contributing factor in at least five of 21 deaths.
The reconstruction and stabilization plan and historical by which resistance develops are complex and have been described in detail elsewhere but it has been demonstrated that resistance is associated with the production of a unique, low-affinity penicillin-binding protein PBP2a encoded by the chromosomal gene mecA.
Neither the protein nor the mecA gene is present in methicillin-sensitive S. That the development of resistance can be accelerated by inappropriate or excessive use of antibiotics was illustrated graphically by Fukatsu et alwho described how the overuse of third-generation cephalosporins led to a serious outbreak of MRSA in a university teaching hospital .
MRSA can also develop resistance to families of antibiotics other than the penicillins. In one reported case, oral rifampicin not only failed to eradicate the organism in four patients who were carrying it but also produced isolates that were highly resistant to the drug .
Some strains of MRSA readily spread from patient to patient and are therefore called epidemic methicillin-resistant S, tetracycline animal mrsa. This term does not relate to the antimicrobial resistance of the organism but rather to its behaviour tetracycline animal mrsa an epidemiological context . In the laboratory, EMRSA are classified according to antibiotic susceptibility, phage reactions and toxin production.
These vary in virulence and their propensity to cause infections in specific tissues . Of particular concern are reports of the emergence in Japan, the USA and Eastern Europe of tetracycline animal mrsa with low levels of resistance to vancomycin, currently the treatment of choice for systemic infections due to MRSA .
The risk of mortality associated with a staphylococcal bacteraemia was analysed by Conterno and colleagues  after a study was carried out at a general teaching hospital with a high prevalence of MRSA strains in Sao Paulo, Brazil, tetracycline animal mrsa. Multivariate analysis identified three variables that were significantly and independently associated with mortality: The first tetracycline animal mrsa caused by EMRSA occurred in eastern Australia in the late s and this, or a closely related organism, first became a clinical problem in England inin the north-east Thames region .
A survey conducted over a six-month period by the Staphylococcus Reference Laboratory revealed that by this strain EMRSA-1 was affecting 50 different hospitals.
Eleven other epidemic strains were also identified during the survey, each affecting up to eight hospitals . In one year a single strain of EMRSA, prevalent in south-east England, produced 40 infections, tetracycline animal mrsa, including bacteraemia, pneumonia, surgical wounds, and skin and urinary tract infections, and three attributable deaths in one acute hospital .
Inover a six-month period, 61 patients at a university hospital became colonised or infected with MRSA , tetracycline animal mrsa. MRSA represents a particular hazard for burns patients and has the potential to cause significant morbidity and mortality in this patient group because disruption of the normal skin barrier and depression of the immune system makes them more vulnerable to colonisation and infection .
MRSA can also present a problem in the community, particularly in nursing care and residential homes , tetracycline animal mrsa.
In such environments the main risk factors for colonisation and infection include age, underlying conditions, nasal colonisation and the presence of in-dwelling devices such as catheters, tetracycline animal mrsa, tracheostomies and nasogastric tubes . Although there is evidence of in-home transmission MRSA colonisation appears to be more strongly associated with recent hospital admission . Over the years the number of centres that have encountered resistant strains has risen sharply and the management of patients with tetracycline animal mrsa infections tetracycline animal mrsa do not respond to conventional treatments represents a significant clinical problem.
During the period tothe percentage of S. Although many patients become colonised with MRSA, not all develop an infection and many attempts have been made to identify the risk factors that predispose an individual to infection. Soon after the emergence of MRSA it was recognised that patients in intensive care units were particularly vulnerable to infection. About two-thirds of nosocomial cases and outbreaks tetracycline animal mrsa occurred in critical care facilities, tetracycline animal mrsa, and once MRSA has become endemic extraordinary efforts may be required to prevent nosocomial transmission .
In 23 of these patients, MRSA was the main pathogen, producing either pneumonia, bacteraemia or wound infections. In eight patients death was directly related to MRSA infection. It has been shown that patients with MRSA infections in an acute care facility are more likely to have a prolonged hospital stay, have received prior antibiotics and have severe underlying disease than patients infected with MSSA .
Intensive care setting, the administration of three or more antibiotics, ulcers, surgical wounds, nasogastric or endotracheal tubes, drains, and urinary or intravenous catheterisation were all associated with an increased risk of MRSA infection. The risk of developing an infection in an intensive care unit was investigated in a large-scale point prevalence survey involving 10, patients in 1, ICUs in 17 western European countries .
The presence of MRSA infection also reduced the chance of survival, particularly in association with lower respiratory tract infections, as the risk of mortality was three times higher in patients with MRSA than in those with MSSA. Cost of MRSA The cost of managing the problems associated with emerging drug resistance is considerable.
Treatment costs escalate dramatically as a result of increased antibiotic usage and extended hospital stays, with the side effects that result from the use of more tetracycline animal mrsa antibiotics adding to the cost in human terms. For all these reasons, prevention remains better than cure. The report of the UK working party on hospital infection and more recently the report by the National Audit Office recommended that despite practical problems, where infection control facilities may be inadequate or in situations where MRSA has become endemic, active intervention to prevent the further spread of the organism is of benefit and should be encouraged, tetracycline animal mrsa.
Hospitals are therefore instructed to devise policies and procedures for dealing with the prevention and control of MRSA based on the advice contained within the report . Active surveillance and investigation of healthcare associated infection and antimicrobial-resistant organisms Reducing infection risk by controlling the use of invasive devices, instruments and other equipment Reducing reservoirs of infection by improving bed management and isolation facilities Adopting high standards of hygiene and clinical practice Prudent use of antibiotics to minimise the emergence of antibiotic-resistant organisms Improving senior management commitment, local infrastructure and systems Research and development to ensure that technological breakthroughs in prevention and control are rapidly translated into benefits for patients.
It is widely recognised that some bacteria can survive in the environment for extended periods and viable organisms are often isolated from rooms occupied by patients with MRSA. This means that healthcare professionals can easily transfer bacteria from one patient area to another on inanimate objects such as their clothing, instruments or pens.
An outbreak of mupirocin resistance in a dermatology unit was thought to be associated with a contaminated blood pressure cuff and communal shower area . Measured ozone concentrations reached 0, tetracycline animal mrsa. This is enough to cause mild pulmonary toxicity, but although bacterial counts were reduced in the vicinity of the gas generator, tetracycline animal mrsa, the effect elsewhere in the room was limited.
MRSA also appeared more resistant to the effects of ozone than MSSA, leading the authors to conclude that the device tested would be inadequate for the decontamination of hospital side rooms.
Effective manual procedures laid down for the cleaning of these areas must therefore be closely followed to eliminate potential sources of infection . Experience suggests that the spread of MRSA can be reduced by attention to simple hygiene procedures. Particularly important is regular handwashing with an effective antibacterial agent such as an iodine-containing soap  or a preparation containing triclosan tetracycline animal mrsa, .
Aqueous-based hand disinfectants containing chlorhexidine are sometimes used, but are much more effective if they also contain alcohol . The National Audit Report  therefore emphasises the need for: Education and training in infection control for all groups of staff, particularly doctors Compliance with guidance on issues such as hand hygiene, catheter care and aseptic technique Controlled antibiotic prescribing in hospitals Improved hospital cleanliness Consultation with the infection control team on wider trust activities such tetracycline animal mrsa new building projects.
In addition to inanimate objects, tetracycline animal mrsa, the transmission of viable micro-organisms in the nose and other areas of the body, both by patients and healthy subjects carriersmust not be overlooked.
In healthy individuals, three patterns of carriage can be distinguished over time: Casewell described how, inWilliams and colleagues established for the first time that nasal carriers of S.
Subsequent acquisition of tetracycline-resistant strains was associated with even higher rates of infection. The parallels with MRSA are obvious.
Much attention has therefore been focused on the possibility of screening for and then eradicating the organism from the anterior nares of both patients and hospital staff, tetracycline animal mrsa. It has been demonstrated that tetracycline animal mrsa acquisition of MRSA by patients may result from exposure to hospital personnel who regularly carry the organism. The elimination of perioperative nasal carriage of S. In a study to assess the impact of the use of mupirocin ointment tetracycline animal mrsa colonisation, transmission and infection with MRSA in a long-term care facility, all residents were monitored from June to June .
MRSA-colonised patients received mupirocin ointment to nares tetracycline animal mrsa the first seven months of the study, and to nares and wounds in the following five months. Overall, the MRSA colonisation rate did not change when mupirocin was used in nares only, but was halved when the drug was used in nares and wounds. Mupirocin-resistant MRSA strains tetracycline animal mrsa isolated in The authors conclude that although mupirocin ointment is effective in decreasing tetracycline animal mrsa with MRSA, its long-term use led to the emergence of mupirocin-resistant MRSA strains.
The drug should therefore be reserved for use during outbreaks and should not be used over the long term in facilities with endemic MRSA colonisation. In a randomised placebo-controlled double-blind trial, Harbarth and colleagues found that nasal mupirocin was only marginally effective in eradicating multi-site MRSA carriage in a setting where MRSA was endemic .
Although the incidence of mupirocin resistance is generally low, in one hospital five out of nine MRSA strains isolated in were resistant to mupirocin, which may signal a serious threat for the future . Changes in mupirocin resistance over an extended period were revealed after surveillance for mupirocin sensitivity in all MRSA strains isolated from colonised or infected patients in a bed public teaching hospital during an epidemic and for three years after it. Mupirocin resistance increased markedly over this period from 2, tetracycline animal mrsa.
In Brazil, an epidemic strain of MRSA, which has acquired a novel mupirocin resistance gene, has been reported . In Uberlandia university hospital, also in Brazil, where mupirocin usage was rare, tetracycline animal mrsa, the resistance rate was 6.
Commenting on the development of resistance to mupirocin, Eltringham suggests that any strategy to limit the increase of mupirocin resistance in MRSA should emphasise the importance of controlled antibiotic use of both mupirocin and other agents .
The nose is not the only site tetracycline animal mrsa carriage of Tetracycline animal mrsa. The perineum was the major site of carriage, with Although most authors appear to support measures to slow the spread of MRSA, and some have reported a significant reduction in the number of carriers and infections following the implementation of measures to control its spread others remain less convinced.
Tetracycline animal mrsa latter argue that, despite occasional reports of local successes, the steadily increasing prevalence of strains of S. They argue, somewhat controversially, that efforts to control the spread of methicillin resistance are counterproductive, and that instead energy should be directed towards the control of outbreaks of disease and prevention of the emergence of antibiotic resistance.
Psychological effects of MRSA infections The potentially serious psychological effects of enforced isolation after a prolonged MRSA infection on patients who may already be depressed as a result of illness or separation from their families are often overlooked.
In one study carried out at the National Spinal Injuries Centre at Stoke Mandeville Hospital, Buckinghamshire, 16 MRSA-positive patients with spinal cord injuries aged between 18 and 65 and their matched controls completed a series of questionnaires to measure aspects of the psychological impact on them.
The measures used were functional independence, tetracycline animal mrsa, depression, anxiety, and the affective states of anger, vigour, fatigue and confusion.