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 7% 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
Possibly up to100,000 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 it’s thought they could be reduced by up to 30%

6. Impact of nosocomial infections
Longer stays in hospital – bed occupancy
Outbreaks leading to ward closures especially norovirus and C. difficile
Pain and anxiety for patients and families
Loss of earnings

7. Where is the money spent?

8. Best to be proactive rather than reactive!!

9. Why are we more likely to get an infection in hospital?
Consider 4 important factors…
The host
The microbes
The environment
Treatment

10. 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 cancer chemotherapy)

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

13. 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?

14. 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

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

16. 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

17. 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)

18. ENVIRONMENTAL SOURCES OF PATHOGENS IN THE HEALTHCARE SETTING
Bacteria
Viruses
Fungi
Air
Gram-positive cocci (originating from skin)
Tuberculosis
Varicella zoster (chickenpox),
Influenza
Aspergillus
Water (tap and bath)
Gram-negative bacteria (Pseudomonas aeruginosa, Aeromonas hydrophilia, Burkholderia cepacia, Stenotrophomonas maltophilia, Serratia marcescens, Flavobacterium meningosepticum, Acinetobacter calcoaceticus, and Legionella pneumophila) Mycobacteria (Mycobacterium xenopi, Mycobacterium chelonae, or Mycobacterium avium-intracellularae)
Molluscum contagiosum Human papillomavirus (bath water)
Noroviruses
Exophiala jeanselmei
Food
Salmonella species, Staphylococcus aureus,
Clostridium perfringens,
Clostridium botulinum, Bacilluscereus and other aerobic spore-forming bacilli Escherichia coli Campylobacter jejuni ,Yersinia enterocolitica, Vibrio parahaemolyticus, Vibrio cholerae, Aeromonas hydrophilia, Streptococcus species Listeria monocytogenes
Rotavirus
Caliciviruses

19. 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

20. Sites of HAIs

21. 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

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

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

24. Causes of death Primary bloodstream infection Pneumonia
Infection of surgical site

25. 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 antibiotics…some are not…

26. MRSA Methicillin (Meticillin) Resistant Staphylococcus aureus
S aureus carried by 30% of us (nose/ skin)
MRSA is more difficult to treat compared to MSSA
Resistance due to mecA gene – encodes PBP2a, doesn’t react with Penicillins
Emerging Vancomycin resistance is a concern
The Biomedical Scientist Jan 2008 p39-41

27. MRSA bacteraemia

28. 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

29. 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

30. Use of SCCmec/orfX PCR MRSA MSSA MR CN-Staph PCR product mecA
SCC 3` end
orfX
MRSA
No PCR product
MSSA
orfX
No PCR product
MR CN-Staph
mecA
SCC 3` end
Cuny & Witte Clin Microbiol Infect (2005) 11:

31. Vancomycin Resistant Enterococci

32. Extended spectrum β-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 carbapenems

34. 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

36. 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 ppm hypochlorite – highly caustic and damaging to surfaces. There may be rapid re-contamination of environment.

37. Nosocomial transmission of C. difficile
Contamination rates after contact with CDAD patients:
Physicians & medical Students % of the time
Dialysis Technicians % of the time
Nurses % of the time
Physiotherapists % of the time
Underside of fingernails %
Fingertips and Palms %
Underside of Rings %
C difficile spores remain in environment in 34-58% of sites after “detergent” cleaning
CDC 2005

38. 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 and of course lives

39. 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

40. Transmission Contact – most common Airborne Transmission
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)

41. The Cycle of Contagion Susceptible person Infection or colonisation
Transmission
Pathogen

42. X The Cycle of Contagion Immunisation or prophylaxis
Individual treatment
Infection control hygiene
Susceptible person
Infection or colonisation
Transmission
Pathogen X

43. Role of infection control teams
Education and training
Development and dissemination of infection control policy
Monitoring and audit of hygiene
Clinical audit

44. Isolation & barrier precautions
Decontamination of equipment
Prudent use of antibiotics
Hand washing
Decontamination of environment

45. The 5 pillars of infection control
Isolation & barrier precautions
Decontamination of equipment
Prudent use of antibiotics
Hand washing
Decontamination of environment

46. Cleanyourhands campaign
An initiative that was rolled out in 2004
Increased procurement of alcohol rub in wards
Poster campaign
Evaluation of this published in BMJ May

47. Tabloid sensationalism?

48. 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.

49. 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
Include soap as well as alcohol rub on wards

50. Some progress
In recent years there has been a steady decline in cases and deaths caused by both MRSA and C. difficle
Is our infection control policy paying off?

56. Resistant Gram negative bacteria
The emphasis is switching to multi-resistant Gram negative pathogens e.g.
CTX-M ESBL producers, seen in E. coli and other Enterobacteriacae providing resistance to 3rd generation cephalosporins
CRE – Carbapenem Resistant Enterobacteriacae e.g. NDM-1 - very few treatment options here (colistin)

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

58. 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

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

60. Surveillance reports published in CDR weekly http://www. hpa. org
But how do Biomedical Scientists help with this work?
Isolating and identifying the pathogens - hospitals
Typing – specialist laboratories

61. 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)

62. 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

63. 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

64. 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

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

66. 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

67. 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

68. Pulsed Field Gel Electrophoresis
Used to separate large DNA fragments >10 kb
Chromosomal DNA digested with restriction enzyme and fragments separated by PFGE
Banding pattern is strain specific – used e.g in MRSA typing

69. 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

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

71. 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?