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Extended-spectrum beta-lactamases (ESBLs)

As described in Part A, beta-lactamases are enzymes capable of breaking open the beta-lactam ring, part of the molecular structure of penicillins and cephalosporins. Extended-spectrum beta-lactamases (ESBLs) are classes of beta-lactamase that render bacteria multidrug resistant, to cephalosporins and penicillins predominantly but also to other antibiotics. They were first reported over 30 years ago but have risen to prominence over the last decade. ESBLs are ‘expressed’ by Gram-negative bacteria (see Chapter 5), mainly those belonging to the genus of bacteria known as Enterobacteriaeceae, in particular Escherichia coli and Klebsiella pneumoniae, as well as Pseudomonas aeruginosa and Acinetobacter bumanii (Dhillon and Clark, 2012). The use of cephalosporins in animal food production has been linked to the emergence of ESBLs associated with cattle, poultry and pigs (DH, 2012).

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Box 10.5 lists some of the risk factors for ESBL acquisition (colonisation and infection).

Fact Box 10.6 Klebsiella outbreak

One documented outbreak of K. pneumoniae involved nearly 300 patients over a period of three and a half years (Hobson et al., 1996).

Box 10.5 Risk factors for ESBL colonisation and infection

Previous treatment with antibiotics

Presence of an invasive indwelling device or open wound

Neonatal Intensive Care Unit or Special Care Baby Unit admission Intensive Care Unit admission

Klebsiella spp.

Klebsiella are opportunistic pathogens implicated in many healthcare-associated infections, with K. pneumoniae a common cause of pneumonia, urinary tract infections, wound infections, blood- stream infections, biliary tract infections and peritonitis (Donnenberg, 2009). Infection is preceded by colonisation (it can be carried by 10% of the ‘healthy’ population as part of the respiratory flora but may cause pneumonia if host immune defences are impaired) (Levinson, 2010) and is associated with length of stay, the severity of the patient’s illness and the manipulation of any invasive indwelling devices (Lucet et al., 1996). Widespread environmental contamination can occur. It is one of the commonest organisms to carry plasmids encoded for multidrug resistance (Donnenberg, 2009).

E. coli

E. coli is a common cause of community and healthcare-associated urinary tract infections (see Chapter 17) and Gram-negative sepsis, and in neonates it can cause meningitis and septicaemia, acquired from the mother during birth (Levinson, 2010).

Fact Box 10.7 E. coli 0157

Verocytotoxin-producing E. coli 0157 (VTEC) is a pathogenic strain of E. coli acquired through consumption of food or water contaminated with faeces from infected animals, by contact with animals that carry VTEC or by exposure to contaminated environments such as farms.

Cases and outbreaks in children have been associated with ‘petting farms’, and guidance on the prevention of VTEC is available on the HPA website at http://www.hpa.org.uk/Infectious- Diseases/InfectionsAZ/Escherichiacoli0157.

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Acinetobacter

Acinetobacter are encapsulated, non-motile, aerobic, Gram-negative coccobacilli, of which there are at least 21 strains (Allen and Hartman, 2009).

Fact Box 10.8 Laboratory identification of Acinetobacter

Their ability to retain crystal violet dye on Gram-staining may lead to them inadvertently being identified as Gram-positive cocci (Allen and Hartman, 2009), and on culture they can be confused with Neisseria (Ryan and Drew, 2010c).

As well as colonising the bowel and skin of humans and animals, they are also widespread within the environment, occurring naturally within drinking and surface waters, soils and sewage.

Compared to many other organisms, they lack the virulence factors that would class them as major pathogens, but they can cause opportunistic infections, particularly in patients who are immunocompromised, and they can affect any body site.

They have been isolated from traumatic wounds of combat soldiers in Iraq and Afghanistan (Peleg et al., 2008) where they have caused serious infections. However, isolation of Acinetobacter in a clinical specimen is not always of clinical significance; the patient’s general condition and the antibiotic susceptibilities of the organism need to be taken into account in order to determine whether or not the patient is colonised or infected.

A. bumannii is the most commonly reported species of Acinetobacter, accounting for approxi- mately 80% of reported infections such as pneumonia, bacteraemia, wound infections and urinary tract infections. These infections tend to occur in already ill hospitalised patients, and they can be spread by direct or indirect contact, contaminated equipment and environmental exposure.

They can be multi-antibiotic resistant, which is defined as resistant to any aminoglycoside, such as gentamicin, as well as resistant to any third-generation cephalosporin, such as cefuroxime and cefotaxime. Some isolates are now also resistant to the carbapenems such as imipenem and meropenem, and these are designated as MRAB-C, a clone which is established within hospitals in London and the southeast of England.

Guidelines on the control and management of multidrug-resistant Acinetobacter which incorporate recommendations on isolation, antibiotic prescribing, environmental cleanliness and decontamination were published in 2005 and updated in 2006 and 2008 (HPA, 2008).

Pseudomonas

Pseudomonas is both a coloniser, causing a variety of opportunistic infections, and a contaminant, and is environmentally extremely resilient (Ryan and Drew, 2010c). There are over 100 species, of which P. aeruginosa is one of the prolific species associated with healthcare infections. It is a common cause of sepsis, pneumonia (including chronic lower respiratory tract infections in patients with cystic fibrosis), wound infections and urinary tract infections. It produces two pigments, a blue pigment (pyocyanin) and a yellow pigment (fluorescin). Combined, these produce a blue-green pigment that is sometimes seen as exudate on wound dressings.

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Box 10.6 summarises DH best-practice advice relating to the use of hand wash stations.

Fact Box 10.9 Contamination by Pseudomonas

P. aeruginosa can contaminate water systems, posing a risk in healthcare facilities, in particular to vulnerable and potentially immunocompromised patients in adult and paediatric intensive care units and burns units (augmented care). In 2012, the DH issued national guidance in Water Sources and Potential Pseudomonas aeruginosa Contamination of Taps and Water Systems.

Advice for Augmented Care.

Box 10.6 Best-practice advice for the use of hand wash stations

Only use the hand wash station for handwashing.

Do not dispose of body fluids at the wash hand basin – use the dirty utility area.

Do not wash any patient equipment in wash hand basins.

Do not use wash hand basins for storing used equipment awaiting decontamination.

Taps should be cleaned before the rest of the hand basin.

Wash patients, including neonates, on augmented care units with water from outlets demon- strated by risk assessments (and, if necessary, by water sampling) as safe.

Do not dispose of used environmental cleaning fluids at wash hand basins.