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Nosocomial Infections

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Title: Nosocomial Infections


1
Nosocomial Infections
  • Patrick Kimmitt

2
Today we are going to cover
  • The factors that contribute to nosocomial
    infections
  • Examples of nosocomial infections and the
    organisms which cause them
  • Control of nosocomial infections
  • Surveillance of nosocomial infections

3
Nosocomial infections
  • The word derives from the Greek nosokomeian,
    meaning hospital
  • These days the terms hospital acquired and
    healthcare associated are used
  • A very emotive subject with the public, driven by
    the press
  • Do hospitals really deserve to be blamed for all
    cases of hospital infection?

4
Nosocomial infections are
  • Infections that are acquired in hospital (48
    hours or more after admission)
  • Approx 9 of patients will suffer from an
    infection whilst in hospital the risk increases
    with length of stay
  • A significant financial burden on NHS

5
Impact of nosocomial infections
  • 100,000 infections per year in UK
  • A cause of 5,000 deaths with nosocomial
    infections playing a role in 15,000 others
  • Costs the NHS 1 billion 9 of its in-patient
    budget
  • Cannot be eradicated but its thought they could
    be reduced by up to 30 (saving 300,000,000!)

6
Where is the money spent?
7
Best to be proactive rather than reactive!!
8
Why are we more likely to get an infection in
hospital?
  • Consider 4 important factors
  • The host
  • The microbes
  • The environment
  • Treatment

9
The host 1
  • People in hospital are already sick!
  • They may have poor general resistance to
    infection
  • Lack of immunity
  • Extremes of age
  • Immunocompromised (eg HIV, cancer chemotherapy)

10
The host 2
  • Reduced immunity
  • Diabetes, severe burns
  • Poor local resistance
  • Poor blood supply to tissues
  • Surgery
  • Wounds, sutures
  • Medical devices
  • Catheters, prostheses, tubing etc

11
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12
The microbes
  • Virtually any infection can be acquired in
    hospital
  • However a number of usual suspects predominate
  • What are they, where do they come from and why do
    they cause nosocomial infection?

13
Opportunistic infections
  • Nosocomial infections are often caused by
    opportunistic pathogens i.e. those which do not
    normally cause infection in healthy people
  • May be a reflection of reduced defences of host
    or access to sites not normally colonised by
    organisms
  • May be from normal flora or environment
  • Antibiotic resistance is a problem

14
Opportunistic pathogens
  • Pseudomonas aeruginosa
  • staphylococci
  • E. coli and other coliforms
  • streptococci and enterococci
  • Bacteroides fragilis
  • Candida albicans
  • Herpes simplex virus
  • Cytomegalovirus

15
Biofilms
  • Biofilms are microbial communities (cities)
    living attached to a solid support eg catheters/
    other medical devices
  • Biofilms are involved in up to 60 of nosocomial
    infections
  • Antibiotics are less effective at killing
    bacteria when part of a biofilm

16
The Environment
  • There are many different sources of pathogens
    when in hospital
  • Our own normal flora (endogenous infection)
  • Infected patients
  • Movement of staff and visitors
  • Environment e.g. fungi, Legionella
  • Blood products (v. rare)
  • Surgical instruments eg vCJD (v. rare)

17
Treatment
  • There is continuous usage of antibiotics in
    hospitals especially in ICU
  • As a result there will be a natural selection for
    strains that are antibiotic resistant
    infections are getting harder to treat
  • This has led to problems with multi-resistant
    bacteria e.g. MRSA, VRE, ESBLs
  • Antibiotic treatment can also lead to alterations
    in normal flora and allow pathogens cause
    infection eg C. difficile

18
Integrons
  • Of increasing concern in hospitals
  • Large genetic elements which carry multiple
    antibiotic resistance genes
  • Integrons can spread to bacteria by horizontal
    gene transfer
  • Organisms such as P. aeruginosa and Acinetobacter
    baumanii are especially prone to carry integrons

19
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20
Bloodstream nosocomial infections
  • Coagulase-negative staphylococci
  • Enterococci
  • Fungi e.g Candida albicans
  • Staphylococcus aureus
  • E. coli and other coliforms
  • Pseudomonas aeruginosa
  • Acinetobacter baumannii with substantial
    antimicrobial resistance - Reported with
    increasing frequency

21
Urinary Tract Infections
  • E. coli and other coliforms
  • Candida albicans
  • Enterococcus
  • Staphylococcus
  • Pseudomonas

22
Surgical site infections
  • S. aureus
  • Pseudomonas aeruginosa
  • Coagulase-negative staphylococci
  • Enterococcus
  • Candida albicans
  • E. coli

23
Causes of death
  1. Primary bloodstream infection
  2. Pneumonia
  3. Infection of surgical site

24
Staphylococcus aureus
  • A common coloniser of the skin and mucosa (e.g.
    the nose) it is a classic opportunist
  • Causes skin and wound infections as well as
    septicaemia, urinary tract infections and
    pneumonia
  • Most strains are sensitive to many
    antibioticssome are not

25
MRSA
  • Methicillin (Meticillin) Resistant Staphylococcus
    aureus
  • S aureus carried by 30 of us (nose/ skin)
  • MRSA is no more virulent than MSSA strains but
    more difficult to treat
  • Resistance due to mecA gene encodes PBP2a,
    doesnt react with Penicillins
  • Emerging Vancomycin resistance is a concern
  • The Biomedical Scientist Jan 2008 p39-41

26
MRSA bacteraemia
27
Epidemic MRSA (EMRSA)
  • Epidemic strains have acquired a selective
    advantage for transmission in hospital
    environments
  • EMRSA-1 was identified in S.E. England in 1984.
  • Subsequent surveys showed further 13
    multi-hospital MRSA (EMRSA-2 to -14)
  • Mid-1990s EMRSA-15 and -16 emerged and spread
    rapdily
  • Approx 60 of MRSA isolates in hospitals are
    EMRSA-15, and 35 EMRSA-16

28
Rapid MRSA screening
  • Current methods for screening for MRSA are based
    on culture and take 48 hours
  • PCR-based screening can generate a result in 2
    hours!
  • mecA is carried on a transferable gene cassette
    called SCCmec but also found in
    coagulase-negative staphylococci
  • PCR developed using primers for SCCmec and orfX
    on the S. aureus chromosome

29
Use of SCCmec/orfX PCR
MRSA
No PCR product
MSSA
orfX
No PCR product
MR CN-Staph
mecA
SCC 3 end
Cuny Witte Clin Microbiol Infect (2005)
11834-837
30
Vancomycin Resistant Enterococci
31
Extended spectrum ß-Lactamases
  • ESBLs are enzymes responsible for resistance to
    3rd generation Cephalosporin antibiotics such as
    Ceftazidime and Cefotaxime
  • Resistance is found in E. coli and other members
    of the Enterobacteriacae
  • Often cross-resistance with other antibiotics
    making treatment difficult use imipenem

32
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33
Clostridium difficile
  • Causes antibiotic-associated diarrhoea and
    pseudomembranous colitis life-threatening
    illnesses
  • Normally affects only the elderly, especially
    those on long-term broad-spectrum antibiotics
  • Produces two powerful toxins and is a
    spore-former difficult to eradicate, resistant
    to alcohol
  • Reasons for the rapid increase in cases is still
    not known

34
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35
Clostridium difficile
  • Nosocomial disease spread primarily by hands of
    staff and outbreaks are common
  • Patients generally respond to discontinuation of
    the inciting agent or therapy with metronidazole
    or vancomycin. Response is rapid but Mtz and Vanc
    may also alter normal flora and may allow disease
    to recur
  • Once the colon is injured it is more susceptible
    to re-infection. Relapse rates are up to approx
    20
  • Almost impossible, at present, to rid the
    environment of C. difficile spores
  • Some use 1000-10000ppm hypochlorite highly
    caustic and damaging to surfaces. There may be
    rapid re-contamination of environment.

36
Nosocomial transmission of C. difficile
  • Contamination rates after contact with CDAD
    patients
  • Physicians medical Students
    75 of the time
  • Dialysis Technicians
    66 of the time
  • Nurses
    56 of the time
  • Physiotherapists
    50 of the time
  • Underside of fingernails
    43
  • Fingertips and Palms
    37
  • Underside of Rings
    20
  • C difficile spores remain in environment in
    34-58 of sites after detergent cleaning
  • CDC 2005

37
Success story
  • Scunthorpe and Goole NHS trust looked at changing
    their antibiotic prescribing policy to reduce the
    incidence of C. difficile disease
  • Cost 12,000 extra to implement
  • Saved 280,000 in staffing, bed occupancy,
    treatment, use of isolation rooms etc, oh, and
    some lives!

38
Infection Control
  • Infections may derive from endogenous
    (auto-infection) or exogenous sources
    (cross-infection)
  • We need to consider the chain of infection and
    the transmission of an infectious agent

39
Transmission
  • Contact most common
  • Direct (physical contact)
  • Indirect (via contaminated objects)
  • Airborne Transmission
  • Droplet respiratory secretions on surfaces
  • Inhalation of infectious particles
  • Blood-borne transmission (v. rare)
  • Food-borne (rare)

40
The Cycle of Contagion
41
The Cycle of Contagion
42
Role of infection control teams
  • Education and training
  • Development and dissemination of infection
    control policy
  • Monitoring and audit of hygiene
  • Clinical audit

43
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44
The 5 pillars of infection control
45
Tabloid sensationalism?

46
Government response
Hospital superbug must be halved Bloodstream
infections with the hospital superbug MRSA must
be halved in three years, the government has
said. Health Secretary John Reid tasked NHS
hospitals with achieving a year on year reduction
up to and beyond March 2008.
47
Government meddling??
  • By forcing targets on NHS trusts for reduction of
    MRSA numbers, has this led to an increase in
    infections with other superbugs?
  • Hand washing with alcohol-based antiseptics is
    fine for decontamination of MRSA but have no
    effect on spores of C. difficile - need to wash
    with soap and water

48
Some progress
  • MRSA and C. difficile infections fall by a third,
    16 July 2010
  • There were a total of 1,898 cases of MRSA
    reported between April 2009 and March 2010,
    representing a 35 reduction in cases from the
    previous year when 2,935 cases were reported.
  • In the same period, 25,604 cases of C. difficile
    were reported, representing a 29 reduction from
    the previous year when 36,095 cases were reported.

49
So how are we doing in 2011?
  • Happily the numbers of cases of MRSA and C.
    difficile infections appears to be decreasing.
  • So are the numbers of reported deaths from these
    infections
  • What about ESBLs and multi-resistant Gram
    negatives?
  • Is recent and current infection control policy
    paying off?

50
Surveillance
  • Continuous monitoring of the frequency and
    distribution of infectious diseases
  • Determines the most important causes of
    infectious diseases and identifies at risk groups

51
Uses of surveillance
  • Used to identify new problems
  • Used to identify where resources are most needed
  • Used to determine the burden of disease
  • Used for strategic planning and policies
  • Use surveillance for measuring outcomes of
    intervention strategies

52
Epidemiology
  • Surveillance is also used to detect epidemics and
    outbreaks
  • Epidemiologists at Centre for Infections analyse
    data sent from laboratories throughout the
    country

53
  • Surveillance reports published in CDR weekly
    http//www.hpa.org.uk/cdr/index.html
  • But how do Biomedical Scientists help with this
    work?
  • Isolating and identifying the pathogens -
    hospitals
  • Typing specialist laboratories

54
Typing of pathogens
  • There are many different strains of a bacterial/
    fungal/ viral species so in order to identify a
    possible outbreak and identify the source we need
    to discriminate between organisms of the same
    species
  • This is called typing there are a number of
    methods available
  • Those based on phenotype (traditional)
  • Those based on genotype (recent)

55
Typing methods
  • Typing is usually performed at specialised
    Reference Laboratories such as those at HPA
    Centre for Infections
  • Different methods are used for different
    pathogens use the one which gives best
    discrimination
  • Pathogens of the same type may be part of an
    outbreak, if they are of a different type an
    outbreak can be ruled out

56
Phage Typing
  • Phage (bacteriophage) is a virus that infects and
    kills bacteria
  • Different strains are susceptible to different
    phages
  • Gives a fingerprint that can discriminate between
    strains
  • Used in the typing of S. aureus and Salmonella

57
Serotyping
  • Used to detect variations in certain antigens
    present on the pathogen
  • Use specific antisera and observe a
    Antibody-Antigen reaction (usually a
    precipitation or agglutination reaction)
  • Eg Streptococcus pyogenes M-protein typing M1
    type is important in invasive infections (flesh
    eating etc)
  • H and N typing of influenza eg H5N1, H1N1 etc

58
Biotyping
  • Biotyping explores the metabolism of an organism
    eg a particular enzyme activity or ability to
    ferment a particular sugar
  • Eg. coagulase-negative staphylococci

59
Genotyping
  • There are a number of methods available most
    rely on sequence variation in non-coding
    (intergenic) DNA
  • This variation is characteristic of a particular
    strain (or type)
  • Strains from an outbreak will be the same type
  • Similar to DNA fingerprinting used in CSI and
    paternity disputes

60
Restriction Fragment Length Polymorphism (RFLP)
  • DNA extracted from bacterial isolates is digested
    (cut) with a restriction enzyme eg EcoR I
  • Produces DNA fragments of varying size gel
    electrophoresis
  • Pattern of bands is strain-specific

61
Pulsed Field Gel Electrophoresis
  • Used to separate large DNA fragments gt10 kb
  • Chromosomal DNA digested with restriction enzyme
    and fragments separated by PFGE
  • Banding pattern is strain specific used e.g in
    MRSA typing

62
Repetitive DNA
  • Much of the bacterial genome consists of short
    repeating DNA sequences micro or minisatellites
  • By comparing the number of repeats present at
    specific loci the relationship between strains
    can be investigated
  • Often known as VNTR typing

63
Summary 1
  1. Can you explain in detail why patients in
    hospital are more prone to infection?
  2. Can you define a primary and an opportunistic
    pathogen?
  3. Can you give examples of nosocomial infections,
    with predisposing factors and examples of the
    pathogens which cause them?
  4. Can you discuss infections due to MRSA and C.
    difficile in detail?

64
Summary 2
  • 5. Can you discuss the transmission of infection
    in hospitals, uses of infection control and the
    role of infection control teams?
  • Why is surveillance of nosocomial infections
    important?
  • What is the role of the laboratory in the
    diagnosis and surveillance of nosocomial
    infections?
  • Can you give examples of the methods used in the
    laboratory for diagnosis and surveillance of
    nosocomial infections?

65
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