Nosocomial Infections

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Nosocomial Infections

• Patrick Kimmitt

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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

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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?

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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

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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!)

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Where is the money spent?
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Best to be proactive rather than reactive!!
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Why are we more likely to get an infection in
hospital?

• Consider 4 important factors
• The host
• The microbes
• The environment
• Treatment

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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)

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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

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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?

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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

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Opportunistic pathogens

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

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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

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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)

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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

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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

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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

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Urinary Tract Infections

• E. coli and other coliforms
• Candida albicans
• Enterococcus
• Staphylococcus
• Pseudomonas

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Surgical site infections

• S. aureus
• Pseudomonas aeruginosa
• Coagulase-negative staphylococci
• Enterococcus
• Candida albicans
• E. coli

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Causes of death

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

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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

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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

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MRSA bacteraemia
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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

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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

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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
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Vancomycin Resistant Enterococci
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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

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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

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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.

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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
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• Fingertips and Palms
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• Underside of Rings
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• C difficile spores remain in environment in
  34-58 of sites after detergent cleaning
• CDC 2005

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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!

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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

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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)

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The Cycle of Contagion
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The Cycle of Contagion
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Role of infection control teams

• Education and training
• Development and dissemination of infection
  control policy
• Monitoring and audit of hygiene
• Clinical audit

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The 5 pillars of infection control
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Tabloid sensationalism?

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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.
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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

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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.

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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?

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Surveillance

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

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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

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Epidemiology

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

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• 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

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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)

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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

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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

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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

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Biotyping

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

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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

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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

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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

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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

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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?

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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?

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