HCAI - Prevalence and Trends Flashcards

1
Q

How is the HSE dealing with HCAI infections at the moment

A

HSE following the Antimicobial Resistance Infection Control (AMRIC) Action Plan 2022-2025

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2
Q

What are the five aims of the AMRIC action plan?

A

Improved patient outcomes
Improved patient safety
Staff education and training
Improved staff safety
Awareness and deeper understanding

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3
Q

Give some recent examples of why we need infection control

A

Major outbreaks of CPE prior to covid in tallagha and limerick

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4
Q

What is a HCAI

A

Infections which are contracted while a person is in a hospital or nursing homes and other health-care facilites
They are neithe present nor incubating when the patient enters the hospital
HCAIs include:
- infections which first appear48 hours or more after hospital admission
- infections contracted by hospital staff as a consequence of their work e.g. hepatitis B

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5
Q

Comment on the global prevalence of HCAIs

A

5-15% of all in-patient in high income countries
9-30% of ICU patients
Rates varyin in different types of hospitals due to diferent patient populations
Large and referral hospitals generally have higher rates than smaller or community hospitals
Rates of infection vary according to the specialty service
Surgical and medical services typically have the highest rates of infection

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6
Q

Why does rate of HCAI differ from hospital to hospital?

A

Varying types of procedures and treatments used e.g. a surgical day ward will see a lot more than a gynae ward etc
Variations in the effectiveness of hospital infection prevention and control programmes

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7
Q

What is the prevalence of HCAIs in Ireland

A

According to the latest point prevalence study its approximately 7.4%

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8
Q

Who categorises HCAI

A

The ECDC has categorised HCAI into 13 broad categories

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9
Q

What are the 13 ECDC categories

A

More serious infections associated with morbidity:
- Bloodstream infections
- clinical sepsis
- pneumoniae

More common but less significant infections:
- Surgical site infections
- urinary tract infections

Others:
- Bone and joint infections
- cardiovascular system infections
- central nervous system infections
- eye, ear, nose, throat and mouth infections
- gastrointestinal infections
- lower respiratory tract infections other than pneumonia
- reproductive system infections
- skin and soft tissue infections

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10
Q

What are our most common causes of HCAI in ireland

A

Multi- drug resistant organisms
device related infections
Surgical site infections
Pneumonia
C. diff
norovirus
other infetions such as TB, influenza, VZV, Sars, Cov2 etc

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11
Q

Give some examples of device related infections

A

Catheter associated UTI
Central line associated BSI
Ventillator associated pneumoniae

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12
Q

What are the three main direct impacts of HCAIs

A
  1. patient suffering:
    - direct cause of 5,000 deaths per year in Ireland and 37,000 deaths/year in EU
  2. Extended length of stay
    - Delays discharge by an average of 11 days
  3. Financial cost
    - Cost of 3000 euro/episode on average but can be up to 9000
    - estimated cost of 234 million/year in Ireland and 1,000 million/year in the UK
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13
Q

Comment on the morbidity of HCAIs

A
  • direct cause of 5,000 deaths per year in Ireland and 37,000 deaths/year in EU
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14
Q

A HCAI can increase your hospital stay by how many days?

A

11 days on average

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15
Q

Comment on the financial cost of a HCAI

A
  • Cost of 3000 euro/episode on average but can be up to 9000
  • estimated cost of 234 million/year in Ireland and 1,000 million/year in the UK
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16
Q

What are the indirect impacts of HCAIs

A

Additional antimicrobial therapy - tend to be resistant organisms so less common treatments used, thus:
- increasing costs
- toxicity
- selective pressure for resistance

Lack of confidence in the Health Care system and its professionals

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17
Q

Are all HCAIs preventable

A

No HCAIs can be classified as inevitable or preventable

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18
Q

Talk about inevitable HCAIs

A

Not all HCAIs can be avoided:
- the young/old
- thos undergoin invasive procedures
- immunosuppressed

Thes are all more susceptible

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19
Q

Talk about preventable HCAIs, how many could be prevented

A

Up to 40% of HCAI are preventable through bettwer application of infection prevention and control procedures

Its estimated that up to 70% of vacular-catheter related BSIs are preventable
Up to 55% of VAP and SSIs could be prevented

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20
Q

How common are HCAIs in the USA?

A

Incidence of 4.5%
1.7 million HCAI per year

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21
Q

How common are HCAIs in Europe

A

Prevlalence of 7.1 between 2022 and 2023
20.5% in ICU patients
4.5 million HCAI per year

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22
Q

How common are HCAIs in Ireland

A

Prevalence is increasing, mosty due to change in definition
2012 = 5.2%
2017 = 6.1%
2023 = 7.4%
Approximately 670 inpatients have a HAI on any given day
30,000 patients in Ireland are affected by HAI annually

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23
Q

What are the five main reasons for high incidence of HCAIs

A

Hospitals house large numbers of sick people whose immune systems are often in a weakened state

Increased use of outpatient treatment means that people who are in the hospital are sicker on average

Many medical procedures bypass the body’s natural protective barriers

Routine use of antimicrobial agents in hospitals create selection pressure for the emergence of resistant strains

Insufficient facilities resulting in overcrowding and high bed occupancy, understaffing, under financed medical service etc

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24
Q

What % of rooms in hospitals are single bed rooms

A

34% of beds

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25
What hospital factors affect HCAIs
space ventilation cleanliness
26
What procedural factors affect HCAIs
Diagnostics Therapy Care Rehabiblitation
27
What microorganism factors affect HCAIs
MDROs virulence factors of orgnaism
28
What host factors affect HCAIs
Old age Dehibilitation Immunosuppression
29
What are the three main risk factors in HCAIs
A persons susceptibiliity to the infection The nature of the persons exposure to the microbe The virulence of the microbe causing the infection
30
What certain people might be at further risk of HCAI
Immunocompromised people such a transplant patients The very young due to immaturity of their immune system The elderly because of predisposing underlying disease, impaired blood supply and immobility
31
Give some specific examples of mortality associated with resistance
CPE BSIs have a mortality of 50% You are twice as likely to die with MRSA BSI then MSSA You are twice as likely to die with VRE BSI then VSE Patients with C. diff are twice as likely to die as those without C. diff
32
What are some non specific host factors that contribute to HCAI
Underlying disease in any age group and the treatment of that disease e.g. cytotoxic drugs or steroids can predispose to infection Invasive procedures allowing organisms easier access to previously protected tissues such as instrumentation procedures e.g. catherisation and those on drips of those receiving nasogastric feeds etc
33
Give some examples of device related infections
Catheter associated UTI Ventilator associated pneumonia Central venous catheter or periphperal venous cannula -> central line associated bsi
34
How do we assess the burden of HCAI
Through point prevalence studies done every few years: - determining the incidence and prevalence
35
what is incidence and how do we report it for HCAIs
Incidence is the rate of new cases of the disease Its reported as the number of new cases occurring within a period of time
36
What is prevalence and how is it reported
Prevalence is the actual number of cases with the disease - during a period of time (period prevalence) - at a particular date in time (point prevalence)
37
How do we calculate the rate of HCAI
By knowing how many people have the HAI and by knowing the number of people in the population at risk: Rate = number of infections/population at risk (x10,000) NB: can also be done for each month
38
What were the 5 aims of the last point prevalence study carried out by EARS-NET
1. measure the overall prevalence of HAI, types of HAI, HAI causative pathogens and key antimicrobial resistance profiles 2. measure the overall prevalence of antimicrobial use, types of antimicrobial prescribed, as well as compliance with local guidelines 3. identify priority areas for future interventions to prevenet and control HAI for antimicrobial stewardship and for future targeted incidence surveillance f HAI 4, Contribute data from Ireland and N. Ireland to the European report 5. Disseminate the PPS results to those who need to know at local, regional, national and EU level to identify problems and set up priorities accordingly
39
How many major point prevalence studies have been done, why did Denise call them disappointing?
3 mjor studies have been done Disappointing as very limited information on organisms in infection - just provided a big list of organisms not related to each infection etc
40
Who and where was the last point prevalence study of HAI taken place
Co ordinated by ECDC throughout EU/EEA countries Took place in Ireland in May 2023 65 hospitals from 50 pubic and 15 private hospitals 12,650 patients on 707 wards ad 14, 695 beds 34% single rooms The irish pps was done as part of a larger european pps
41
What were some of the findings from the last PPS done in Ireland
Pneumoniae and lower respiratory tract infections including covid accounted for 29.3% of HCAI UTIs accounted for 19.2% BSIs accounted for 11.9% NB: remember you can have more than one HAI at a time
42
Why did HAI increase in ireland so much between 2017 and 2023, how did this affect our standing in europe
Mostly due to a change int he defiition of pneumoniae: - removed the need for chest xray t diagnose - led to an increase in HCAI pneumoniae we also include sars cov2 as a HCAI in 2023 We also now included nursing home cases in 2023 We were below the EU average prio to these changes but now were above it
43
How has our Antimicrobial usage changes according to the three pps
2012 = 34% AMU 2017 = 39.7% AMU 2023 = 40.4% AMU
44
What were some of our results from the last PPS
901 patients had at least one HCAI HCAI prevalence of 7.4% 966 HCAIs were reported: 31 patients had>1 HCAI 19.7% had at les one invasive device, compared to: - 18.7% in 2017 - 16.3% in 2012
45
What did our pps reveal about HCAI prevalence in ICU vs non-ICU patients, what was the reasoning for this
There was significantly more in IU than outside ICU which was attributed to more devices and catheters: - 55.3% had CVCs compared to 6.8% outside - 34.8% had intubation compared to 0.4% - 60.2% had urinary catheters compared to 12.8%
46
Wha did our PPS reveal about HCAI by patient speciality?
There was lower prevalence in certain specialities: - 7.8% prevalence in general surgery compared to: - 2.0% in obstetrics/maternity - 2.3% in paediatrics - 2.8% in cardiology
47
List the top 7 HCAI in Ireland
Penumonia Surgical site infections UTIs BSIs systemic infection C. difficile infection Skin and soft tissue infection
48
Comment on changes in the rate of HCAI prevalence for our top 7 infections between 2017 and 2023
Penumonia: - 28.9% in 2017 - 27.4% in 2023 Surgical site infections: - 18.0% in 2017 - 13.6% in 2023 - fell to third most common in 2023 vs 2nd in 2017 UTIs: - 14.5% in 2017 - 14.6% in 2023 - now the 2nd most common vs 3rd in 2017 BSIs: - 9.9% in 2017 - 8.6% in 2023 systemic infection: - 6.2% in 2017 - 8.5% in 2023 - was the 5th most common but now the 6th in 2023 C. difficile infection: - 4.4% in 2017 - now grouped in with GI infections at 8.5% in 2023 - has rose to 5th most common vs 6th in 2017 Skin and soft tissue infection: - 3.8% in 2017 - 3.7% in 2023 - fell from 7th to 8th in 2023
49
What were some of the diiference betwen public and private hospitals as noted by the pps
SSI was the top HCAI in private hospitals vs PN in public hospitals Private hospitals had smaller numbers of infections but a higher frequency of HCAI e.g. - public had 0.9% SSIs in 205 patients while public had 1.9% SSIs in 26 patients
50
Talk about HCAI Pneumonia according to PPS
Pneumonia is the commonest HAI at n=265 cases 27.4% of all HAI 2.1% of study population 23 (8.7%) were associated with intubation of the respiratory tract: - compared to 16% in 2017) VAP is the most common ICU-acquired infection
51
How is prevalence of pneumonia HAI changing across the pps
Prevalence is increasing but proportion is decreasing i.e. amount of PN increasing but other HAI increasing more: - 2017 PN accounted for 29% of HAI and 1.9% prevalence - 2023 PN accounted for 27.4% of HAI but had a 2.1% prevalence NB: remember there was a change in definition that lead to PN going from second most frequet to most fequent - rates are stable when you take this into account
52
What organisms are most common in VAP in ICU HAI
GNB such as: K. pneumonia: 11% Enterobacter: 3% Pseudomonas: 11% Staphylococcus 7% Covid 19: 20%
53
How is prevalence of UTI HAI occording to the 2023 ppv
there were 141 UTIs which accounted for 14.6% total HAI 1.1% of UTIs were inpatients Only 56% were microbiologically confirmed 38.3% were associated with the presence of a catheter - was 29% in 2017
54
How is prevalence of UTI HAI changing across the pps
Proportion of 14.5% remains the same from 2017 to 2023 Prevalence of 1.1% in 2023 and 1.2% in 2017 However its ranking has increased from 3rd in 2017 to 2nd in 2023
55
What organisms are most commonly associcated with UTI HCAIs
32% E. Coli 15% Klebsiella 15% Enterococcus 9% Pseudomonas
56
Comment on the prevalence of surgical site infections according to the pps of 2023
Common HAI with n=131, accounts for 13.6% of all HAI 1% of inpatients 33% were classified as superficial incisional 42% were deep surgical site infections
57
How is prevalence of SSI HAI changing across the pps
accounted for 18% of SSIs in 2017 but now 13.6% in 2017 Prevalence of 1.2% in 2017 and now 1% in 2023 Proportion nad prevalence both decreasing its rank fell from 2nd in 2017 to 3rd in 2023, it had been 1st in 2012
58
What organisms were most associated with SSIs
It depended on the location and type of surgery but: - S. aureus accounted for 15% - E. Coli 10% - Klebsiella, GNBs in GI and GUT surgeries - MDRO?
59
Comment on the prevalence of BSIs in ireland according to the last pps
83 cases accounting for 8.6% of BSIs 0.7% of inpatients 45.8% primary vs 45.8% secondary 26 cases or 31.3% had an invasive device
60
How is prevalence of BSI HAI changing across the pps
9.9% of HAI in 2017 with a prevalence of 0.6% Fell to 8.6% of HAI in 2023 with a prevalence of 0.7% Rank remains same at 4th most common
61
What organisms are most common in BSIs according to 2023 pps
S, aureus at 15% CNS at 16% S. pneumonia at 2.2% Enterobacterales at 33% (significant) E. Coli at 12% Klebsiella at 12% P. aeruginosa at 7% Enterococcus species at 11% Anaerobes Candida at 7,2%
62
What four factors did the pps discover put patients at higher risk of HCAI
Surgery since hospital admission increased prevalence to 10.9 from 6.8% in non surgery CVS presence increased HAI prevalence to 17.7% vs 6.4% in those without Intubation presen increased HAI prevalence to 23.1% vs 7.1% in those without Urinary catheter present increased HAI prevalence to 15.5% vs 6.0% in those without
63
Comment on the prevalence of Gastrointestinal infections according to the most recent pps
The 5th commonest HAI with 82 cases (8.5%) Prevalence of 0.6%
64
How is prevalence of gastrointestinal HAI changing across the pps
Was 8% in 2017 vs 9.8% in 2012 Figures not really available for 2023 as C. diff was grouped in with GI infections Prevalence of 0.5% in 2017 vs 0.54% in 2012 Ranking 5th remains same
65
Comment on trends in C. diff according to pps
4.8% in 2023 Accounts for 4.4% of HAI in 2017 vs 5.7% in 2012
66
Talk about the microbiology results from the pps of 2023
Results are only available for 616 HAIs Only 62.7% of these had a pahogen detected No microbiology data provided on 12.5% Specimens not sent on 12.1% Results not available or missing for 6.7% Pathogen not isolated in 6% All in all really poor microbiology results
67
Give a general on the distribution of microorganisms found in the 2023 pps
E. Coli accounted for 15.1% of HAI S. aureus accounted for 14.7% of HAIs SARS Cov 2 accounted for 9.3% C. difficile accounted for 8.9% E. faecium accounted for 6.0% K. pneumoniae accounted for 5.6%
68
Talk aout the AST that was carried out on GNs int he last PPS
105/126 Enterobacterales were tested for susceptibility to 3GC - 7 of these of 6.7% were resistant 108 were tested for susceptibility to carbapenems, one or 1% was determined to be a CRE - but this was susceptible to 3GC 1/12 P. aeruinosa wer carbapenemase resistant
69
Talk about AST carried out on GPs during the las pps
15/69 s. aureus were tested for susceptibility to oxacillin and 15 or 23.4% were determined to be MRSA 49/52 Enterococcus species were tested for susceptibility to vancomycin of which nine (18.4%) were determined to be VREs
70
Compare MRSA in 2023 to 2017 and 2012
23.4% in 2023 28% in 2017 3% in 2012 NB: rate decreasing year on year
71
Compare VRE in 2023 to 2017 and 2012
18.4% in 2023 39% in 2017 26% in 2012 trending downwards
72
Compare Pseudomonas resstance in 2023 to 2017 and 2012
5% of Pseudomonas were carbapenem resistant in 2023 15% were resistant in 2017
73
Comment on AMU according to the 2023 pps
Overall AMU orevalence at 40.2% Prevalence higher in private hospitals (48.1%) compared to 39.3% in public Prevalence highest in adults in ICU (70.4%) followed by surgical specialities at 51.0% The lowest prevalence was in rehabilitation at 13.0%
74
What does the ECDC have to say about HCAI in Ireland
European centre for disease prevention and control On any given day there are 670 inpatients with a HAI in irish hospitals 30,000 patients in Ireland are affected annually
75
What are the two sources of HCAI
Endogenous Exogenous
76
What are the endogenous and exogenous sources of HCAI
Endogenous are from the patients own inestinal, skin, oral or microflora Exogenous are from ieither another person in the hospital - cross infection or a contamination item of equipment or building service - environmental infection
77
What kind of bacteria tend to be exogenous
It depends upon the nature of the source: - moist areas tend to be colonised with GNBS such as E. Coli, Klebsiella and Pseudomonas Air and dustborne organisms are those that can withstand drying, e.g. streptococci, staphylococci, mycobacteria and acinetobacter
78
What are the main exogenous sources of HAI
Cross infection or contact tranmission - S. aureus Environmental infection through contaminated sources such as water, sinks, air, dust, medications e.g. IV fluids, medical devices, catheters, endoscopes, food etc
79
Give some examples of the main contaminated sources resulting in environmental infection of a HAI and the pathogens associated with them
Catheters - S. aureus or CNS Dust - S. aureus of CNS Medical equipment - Endoscopes, enterobacterales, pseudomonas, c. difficile Fluids - p. aeruginosa from disinfectants food - salmonella or campylobacter
80
Talk about water contamination in HAIs
Many citations of water as a souce of HAI Many reports have identified the presence of GNBs in hospital sinks CRE outbreak in Limerick Patients exposed by hand-washing, bedpans, enteral feeding, respiratory equipment, drinking, showering, bed bathing etc
81
What organisms are most likely to contaminate water
P. aeruginosa and S. marcescens These can survive for over 250 days on sink surfaces
82
Why is there such as issue with sinks and HAIs
The sink splash zone -> study looked at how far water spread from sink from doing normal hand hygiene -> theres often lots of medical equipment near the sink which has potential to be contaminated etc
83
What are some suggestions of transission methods of waterborne infections?
Direct contact with water - hydrotherapy Ingestion of water through contaminaed ice Indirect contact transmission through improperly repossessed medical devices Inhalation of aerosols dispoersed from water sources Aspiration of contaminated ater Contamination of splash zones
84
Talk about hospital water systems as a reservoir for CPOss
A systenatic review has shown the following: 32 reports of CROs in the hospital water environement These are associated with clinical outbreaks in the ICU setting Drainks, sinks and faucets were most frequently colonised Pseudomonas aeruinosa was the predominant orgnism Imipenemase (IMP), Klebsiella pneumonia carbapenemase (KPC) and Verona integron metallo B lactamase (VIM) were the most common carbapenemase s found Replacement of colonised water reservoirs maybe required for long term clearance - there is also debate on wheterh or not ICU should go sink free
85
What were the commonmost organisms found to colonise water environments in hospitals
Pseudomonas aeruinosa was the predominant orgnism Imipenemase (IMP), Klebsiella pneumonia carbapenemase (KPC) and Verona integron metallo B lactamase (VIM) were the most common carbapenemase s found
86
Talk about air as an exogenous source of HCAI transmission
airborne spread as seen with staphylococci and c. difficile Some diseases such as pulmonary TB and Legionnaires can also spread through airborne outes Other airborne agents include sars CoV2, apergillus, varicella zoster, influenza and RSV
87
How can contact transmission occur
Direct contact with infected or colonised patient or health care staff (also through their hand transmission) Also through infected droplets including coughing and sneezing
88
Give some examples of routes of transmission
Infected patient contaminates surfaces, next patient in that room infected Sinks contaminated - splash zone contaminates nearby equipment then used on patient - infected patient
89
Just how long can pathogens survive in the healthcare environment
MRSA: 7 das up to 12 months VRE: 5 days up to 46 months P. aeruginosa: 6 hours up to 16 months C. difficile: >5monhs due to spores Acinetobacter baumannii: 3 days to 11 months CRE only 19 days Norovirus 8 hours to 7 days Rotavirus 6-60days
90
What environmentl factor puts you at much greater risk for HCAI
Prior room occupacy Increased risk if prior occupant of room had an infection
91
Talk about prior occupancy risk for HCAI
if MRSA then risk increased by 1.5% If VRE then risk increased by 2.25% If P, aeruginosa then increased by 1.75% I C. diff then 2.5% I A.baumannii then 3.5%
92
What are the changing trends in HCAI
Pattern of HCAI has changed over the years due to advancements in medicine and the development of antimicrobials Initially majority of infections were caused by gram-positive organisms particularly S. aureus With the advent of antimicrobials active against staphylococci, GN organisms such as E. Coli, K. pneumoniae and P. aeruginosa have emerged as important pathogens e.g. MRSA shows great decline More recently the development of invasive medical techniques has had further impact
93
Currently what are the trends in HCAI organisms
ESKAPE pathogens Enterobacteriacea predominate with 37% (includes E. Coli) S. aureus at 15% Enterococci at 9% CNS at 9% Candida species at 6% Pseudomonas at 4%
94
What organisms are the CDCs current threats
Carbapenemase resistant acinetobacter: pneumonia, wound, bsi, utis, 700 deaths in 2017 and 8,500 cases Drug resistant candida auris: emerging MDR, severe infections and spread, 323 cases in 2018 Clostidioides difficile: life-threatening diarrhea and colitis, 223,900 infections per year, 12,800 deaths per year Carbapenem resistant enterobacterales: MDR and PDR, 1,100 deaths and 13,100 cases in 2017 Drug-resistant gonorrhea: life threateneing ectopic pregnancy and infertility as well as increased HIV risk, 550,000 MDR infections per year
95
Talk about viral HCAI
Very significant in last 2 years affecting both healthcare and patients Viruses acquired by respiratory route: SARS, Cov2, Inluenza and RSV Viruses acquired by contact with vesicular lesions such as VZV and Herpes simplex virus Viruses acquired by contact with contaminated fomites such as norovirus and rotavirus Viruses acquired by contact with blood-contaminated fomites, needle
96
What are some common HCAI orgniams
Gram negatives: - enterobacterales such as E. Coli, K. oneumonia and enterobacter spp - non fermenters such as pseudomonas spp, acinetobacer spp and stenotrophomas spp Gram positives: - C. difficile - Enterococcus species VRE - staph auerus (MRSA/VISA/VRSA)
97
Talk about the significance of C. difficile
Leading cause of HCAI in the US: - 453,000 per year and 29,600 deaths 126,000 cases per year in Europe - 3% attributable to mortality In Ireland 4.4% of HAI in 2017 vs 5.7% in 2012 A major pathogen in the community despite substantial under-diagnosis Changing epidemiology
98
What are the reservoirs for C.diff?
Endogenous: - colonised human gastrointestinal tract Exogenous: - Asymptomatic carriers: very high carriage rate in babies as theyre born sterile but in a hospital environemnt where c, diff is present - symptomatic patients - contaminated equipment - the hands of health care works Animal reservoirs: - pigs -> potential for zoonotic transmission but not food contamination
99
Talk about carriage rates of C. diff
0-3% of European adults carry C. diff 15% of Japanese population 20-35% hospitilised patients following antibiotic exposure (asymptomatic) Neonates 15-70% Infants 1 to 2 years old - 30-65%
100
Talk about C. diff transmission in HC
Person-to-person via oral faecal route Contact with spores left behind in the environment Either by patients who have CDI or who are colonised with CDI asymptomatically
101
Provide estimations on asymptomatic colonisation of patients in healthcare settings vs community
3-26% of patients in acute care hospitals 5-7% of patients in long term care facilities <2% of normal adults with no exposure to the healthcare setting Rates go up with age and lenngth of hospital stay
102
Talk about C. difficile spores
Spores are highly resistant to desiccation, chemicals and extreme temperatures Spores frequently contaminate the environment around patients with CDI, potentially persistin for months and even years Transmitted by direct spread from an infected surface Epidemic strains greater sporulation capacity Sub inhibitory concentrations of non chlorine based cleaning agents significanly increased sporulation capacity Increasing evidence of airborne dissemination Germination not extensively studied
103
What could be a possible future treatment of c diff
If we could stop spore germination then c diff would never be able to get to the gut
104
Talk about C. diff outbreak strains
Some outbreak strains have increased sporulation Ribotype o27 could sporulate much more readily than other strains
105
What are some drug factors affecting risk of C. diff
Broad spectrum antibiotics such as ampicillin or amoxycillin, 2nd or 3rd GC such as clindamycin and since 2000 fluoroquinolones have been associated with C. diff Duration of antibiotics - prolongred treatment and repeated treatments etc Combintion therapies Antibiotics with high biliary excretion
106
What are some host factorsaffecting C. diff risk
Age Underlying pathologes Previous AAD Severe underying disease Chronic disease of the digestive system Hospitilisation: - length of hospital stay - gastro - intestinal surgery - major surgery - gastric catheter etc
107
What are some bacterial factors associated with C. diff risk?
Mutations within toxin genes and regulators that can make some strains more likely to casue serious infection or persist in the environment
108
What are the three ways a C. diff infection can progress
Non toxigenic C. diff = asymptomatic colonisation Toxigenic C. diff but IgG response to ToxA = asymptomat colonisation Toxigenic C. diff but no IgG response to ToxA = symptomatic CDI
109
Talk about C. diff recurrence
Elderly generally get an infection which is treated with broad spectrum antibiotics resulting in C. diff More antibiotics are then given to treat the ifection Patient recovers but more C. diff comes back again etc Cycle repeats This is associatd with pseudomembraneous colitits and toxic megacolon -> end of life
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What is the main C. difficile cirulence factor
The c diff pathogenicity locus which encodes the large clostridial toxins e.g. tcdA and tcdB The CDT locus (c. difficile toxin) locus -> which encodes the binary toxins CdtA and CdtB without this pathogenicity locus strains are rarely toxic, there are maybe one or two strains that have just the binary toxin Therefore we say the pathogenicity locus is required for pathogenicity
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Desribe the general organisation of the pathogenicity locus
TcdR = positive regulator a factor TcdB = toxin B TcdE = extracellular release of toxins out of bacterial cell TcdA = toxin A TcdC = negative regulator -> it swithes off transcription and translation of tcdb
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What are c, diff toxins a and b?
Theyre both glycosyltransferass
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Talk about the different C. diff toxins
There is 63% similarity bettween TcdA and TcdB TcdB027 is much more cytotoxic on several cell line than TcdB(historical strain), due to variations within the C-terminal binding domain
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What is the CROPs and what is special about this
CROPs = binding domain The region prone to repeats - much more likely to get mutations here Binding region Strains can have deletions and insertions in this regions - could result in strains expressing only one toxin etc
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Talk about C. difficile surveilanc
Notifiable disease since 2008. Mandatory Surveillance Prior to 2012 only new cases were notifiable New and Recurrent cases now reported Enhanced voluntary surveillance
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Talk about the prevalnce of CDI over the past three PPSs
2023 = 4.8% 2017 = 4.4% 2012 = 5.7% relatively stable
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Where is C. diff ribotyping done
Theres no C. diff reference lab where ibotyping is done atm Cherry orchard is our acting reference lab and has started doing whole genome sequencing for c. dif However this lab is operating on a schedule i.e. you can only send strains for typing during certain periods etc
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Talk about all the different C. diff strains
There are 45 different squence types There is significant heterogeneity 6 STs predominate in >17 isolates There is broad correlation between ribotypes (RT) and WGS derived ST
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List some of he C. diff sequence types
ST11 (16%) to Ribotype 078 ST8 (13%) to RT O02 ST2 (12%) to RTs O14, o20, 076, 220 ST6 (7%) to RT O05 ST10 (6%) to RT O15 ST3 (4.5%) to RT O01, O09,O72, 115
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Comment on the changing epidemiology of CDI
Rates are increasing Higher mortality rates Higher colectomy rates - more severe diseas More recurrences Outbreaks were difficult to control Association with fluoroquinolone use -> especialy newer fluoros such as moxifloxacin Effectiveness of metronidazole questioned NB: Increased community acquired without historical risk factors -> used to be a HCAI in elderly on antibiotics -> theres even been reports of young patients dieing from the disease
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Talk about C. difficile epidemic strains, what strain is it?
Since 2004 there has been the emergence of a hypervirulent epidemic strain NAP1/027 which has been associated with a changing pattern of disease severity
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What does NAP1 stand for?
North America Pulse Type 1
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Why was ribotype 027 so important
This epidemic strain produced 16 times more toxin A and 23 times more toxin B than control strains These enterotoxic and proinflammatory proteins are the primary virulence factors of C. difficile NAP1/027 has been found to have spread from hospitals into communities and is increasingly resistant to all fluoroquinolones
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Why was toxin expression different in 027
tcdc = toxin regulator gene responsible for turning toxin a and b production off was truncated leading to increased production
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Give some other ribotypes other than 027
078 017
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Whats different about 078
increase in toxin production and fluoroquinolone resistance different mutation in the tcdc regulator gene Definitely an association with this type and animals - potential zoonotic transmision -> humans to animals and animals to humans but not food borne
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When could we potentially miss C. diff strains
A couple strains which usually have large deletions in the tcdc gene resulting in a truncated gene These can be missed when using EIAs for toxin A only
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What were the results of C. difficile ribotyping between 2014 and 2018?
Ribotyping reported for 395 (19% of cases): 22% 002 11% 014 11% 078 7% 015 5% 005
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Talk about the C. difficile epidemiology study in Europe
All inpatient diarrhoeal samples Two sampling days 482 participating hospitals across 19 countries Both C, diff culture and for free toxin were carried out looking for infection and carriage 027 predominated in both infection and carriage both 001/072 and 014/020 rates were higher in carriage group In general infection and carriage tended to be caused by the same strains
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Wha are the current and future antimicrobial methods of treating CDI
Currently: - Metronidazole - used to be our firt line - Vancomycin - Nitazoxanide - Teicoplanin - Fidaxomicin Future: - Ramplanin
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What are the non-antimicrobial agents used to treat C. diff
Toxin-Neutralising agents: - Cholestyramine Biotherapeutic agents: - Saccharomyces boulardii - faecal transplants Immune-mediated agents: - Intravenous Immunoglobulin IVIG
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What are some non-antimicrobial agents under development
Bovine whey protein 'mucomilk' Tolevamer Human monoclonal antibodies (HuMabs) Toxoid vaccines (toxinis A and B) Active vaccines (SLP, flagella antigens)
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Talk about C. diff vaccines
Toxoid vaccines tha have been developed Dont induce enough of a response in the elderly as humeral response declines with age -> vaccine just dont work on the old Hence why no point in vaccination as these are the most at rism
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Talk about intravenous immunoglobulin as a treatment method of C. diff
Pooled human sera that contains antibodies - as most people have antibodies Limited evidence Case reports Case seried for sever or refractory One single group evaluation: - response in 10/17 cases (59%) - single dose of 400mg/kg may be considered
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Talk about faecal microbiota transplantation
Not recommended for the treatment of a first episode of CDI No significant difference in clinical effectiveness when compared to vancomycin FMT is recommended in patients who have had 2 or more episodes of CDI Works by replacing the microbiome and stopping C. diff from growing No difference compared to treatment with vancomycin
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What study was done on C. diff treatment via FMT, what were the results?
A randomised, double-blind placebo controlled trial was carried out in septemebt 2022 42 prs, 21 got placebo, 21 got treatment 19/21 (90%) in the FMT group and 7/21 (33%) in the placebo group had resolution of CDAD at week 8 The aboslute risk reduction was 57% Found to be highly effective and superior to the standard of care vancomycin alone in achieving sustained resolution from C. difficile
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What were the results of a systematic review and meta-analysis of FMT
13 trials and 610 patients FMT found to be associated with lower clinical cure rates in RCTs than in open-label or observational studies (67% vs 82%) Delivery of FMT by colonoscopy or oral tubes e.g. nasojejunal tubes was more effective than by enema Cost and safety are important considerations Each treatment costs 3000 euro Serious associated advense events including deaths due to the transmission of pathogenic and or MDRO
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Why are FMT deemed cost effective even though they cost 3000 euros
3,000 is nothing compared to the ongoing cost of keeping a patient in hospital and treating them for weeks
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Talk about monoclonal antibody treatment for C. diff
Bezlotoxumab is a human monoclonal antibody against toxin B Used adjunct to antibiotics to prevent recurrence of CDI Significantly lower rate of recurrence (17% recurrence compared to 28% with placebo) Not recommended due to cost but can be used along side other antibiotics with specialist input
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Talk about MRSA emergence
It emerged in the 1960s In 2017 PPS s. aureus was responsible for 15% of all HCAI and 37% of these were MRSA In 2023 were down to 9.7% MRSA - a huge drop 2 strains of MRSa Spread between hospitals is a major problem -> epidemic MRSA
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What are the two different strains of MRSA
Sporadic MRSA: - encountered only sporadically and are rarely a cause of infection - epidemic MRSA - strains that have a propensity to spread in the hospital environment
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what are the clinical features of MRSA
Nasal carriage Old age Male Admission to ICU Surgery Exposure to MRSA-colonised patient
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What infections are most commonly associated with MRSA
Underlying chronic disease Repeated hospital admissions Prolonged/repeated antibiotics especially the B-lactams
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How is MRSA transmissed?
Occurs primarily from colonise or infected patients via the hands of healthcare workers Contact transmission to other patients or staff very common Airborne transmission important in the acquisition of nasal carriage
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Comment on HA MRsA epidemiology
HA-MRSA has been limited to five predominant lineages worldwide The previously predominant HA-MRSA clone has been displaced Now ST22-MRSA-IV predominates in Irish hospitals: - caused 80% of BSIs Isolates from non BSIs are more diverse: - ST8, ST5, ST1
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What are the most common HA MRSA clones in Ireland
ST22 ST8 ST5 ST1
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why do we have no information on colonisation rates o MRSA in Ireland
Currently Irish MRSA guidelines are only recommended testing HCws for S. aureus carriage during infection outbreaks and in high-risk units
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Talk about VRE emergence
First isolated in enterococci in UK and France in 1986 - 11% of all HCAI are ents and 26% of these are VRE in 2012 pps - 9% of all HCAI and 39% of these were VRE in 2017 i.e. proportion of VRE increasing
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what is the mechanism of resistance in VRE
Alteration of cell wall precursors 8 acquired resistance phenotypes VanA and VanB phenotypes most clinically significant VanA: High level, inducible resistance to vancomycin and teicoplanin VanB: moderate to high level resistance to vancomycin but susceptible to teicoplanin
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What are the risk factors for VRE
Close physical proximity to VRE i.e patient in the room Long period of hospitalisation Hospitilisation in long term care facilities, surgical units or ICUs Presence of urinary catheter/feeding tubes Multiple course of antibiotics - increases the density of VRE in the GI tract
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How is VRE spread
directly from patients Contaminated fomites Contaminated hands of staff or equipment Study revealed that your just as likely to have contaminated gloves after touching environment as touchin a positive patient Increased risk if previous room occupant was positive
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Talk about VRE epedmiology, what study was carried out
Really sharp increase in BSI with VRE - a noted problem in liver unit in st. vincents Study was done to investigate this using gel electrophoresis ran from january 1s 2009 to june 30th 2012 50 isolates were typed, 20 were from outside of st. vincents to get a representative of ireland as well as control strains a polyclonal outbreak with 8 clusters were identified 40% of non SVUH isolates were clustered
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What resistance are we concerned with in VRE
We have had our first linezolid resistant E. faecium in 2014
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Talk about the study on VRE carriage
Done to investigat VRE carriage in an acute irish hospital - gut colonisation cohort of patients in 2014 cross-sectioooooonal study at Cork University hosp 350 faecal specimens submitted to the microbiology laboratory for routine investigation hospital inpatients and community-based patients Overall prevalence of 19.1%, 31.4% in CUH 0% in non hospitilisated patients 22.2% in external hospital samples 86.6% were vanA only, remainder were vanA and vanB2/3
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What were the key findings of a study on an ICU setting in a nonoutbreak setting to identify potential reservoirs
39.4% recovery of VRE from 157 patients and their bed spaces pt and bed space 29.8% recovery of vre Envionmental sits 6.5% Most frequent sites were drip stands, bed control panel and chart holders - 61% We were able to detect far more vre when looking in the environment but we couldnt prove the link between patients
156
Why has ireland such a high rate of VRE
NB: rates are coming down but still wok to do however theyre not really a priority Not an isolation priority Lack of local and national VRE data to inform Infection prevention and control: - emerging locally from VSE - antimicrobial pressure Poor ineffective evironmental decontamination HCW and patients Hand hygiene, shared toilets etc
157
Talk about the emergence of MDR GNBs
Important and increasing threat to healthcare worldwide Reservoirs of GN bacteria in healthcare facilities - they account for about 28% of total HCAI isolates Implicated in the most common HAIs BSIs, UTIs, VAPs and SSI Acinetobacter, pseudomonas and enterobacterales
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Talk about Acinetobacter baumannii
An opportunistic pathogen - can persist in the environment - acquisition of antimicrobial resistance especially carbapenems - can dessicate - can readilt form bibofilm Emerged as important healthcare associated pathogens 1st WHO critial priority pathogen ICU and Burns units A triple threat: opportunistic pathogen, biofilm, environmenta reservoir of mobile genetic elements
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Talk about carbapenem resistant acinetobacter baumanii
Its highly resistant through mobile genetic elements Were limited in terms of treatment options, possibly tetracycline and colistin but were kind of out of options It frequently cause persistent outbreaks within and across healthcare facilities 8 genetically well distinguishable clonal complexes Multi resistant strains are particularly problematic CRAB
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What are some risks of CRAB?
increased mortality - recent caase studies report mortality rates of up to 70% Longer hospital stays Higher hospital costs Frequency and severity of infections have increased Growing numbers of epidemic outbreaks
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A. baumanii are associated with what kinds of infections?
BSI central lines Pneumoniae - ventilator UTIs - cathetor associated HCAI are associated with larger hospitals, ICU admission and prolonged hospital stays
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What are some risk factors for CRAB infections
Recent exposure to antibiotics, especially carbapenems and 3GC Presence of CVC or urinary catheter Severity of illness largre hospita size >500 Prolonged ICU stays
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What are the environmental reservoirs for CRAB
Aqueous reservoirs Drains Sinks Toilets 5-30% of surfaces can remain contaminate Existing detergent and disinfectant formulations cannot disrupt biofilms Enhanced focus on cleaning practices ID of environmental contamination early in outbreaks is critical to limiting their spread
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How does resistance develop in CRAB
B-lactamases, the most prevalent being AmpC cephalosporinases and OXA-carbapenemases porin alterations Multi drug effluc pumps Aminoglycoside modifying enzymes mutations within the fluoroqunolone target sites
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Talk about A. baumanii in Ireland
MDR is a growing threat in Europe No data from pps 2017 or 2023 Recent outbreak in conolly hospital of oxa-48 rates increasing: Acinetobacter outbreaks: - 0 in 2022 - 1 in 2023 - 3 in 2024 Acinetobacter resistant: - 5 in 2022 - 16 in 2023 - including 2 clusters (5 isolates each) both OXA-23 in 2023
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What are the current projects/initiatives on CRAB
CRAB surveillance initiated by the ECDC - three labs have been recruited - going to collect information on the first 10 infections submitted -started across EU/EEA in October 2024 -one lab recruited from each NUT2 l3vel (3 in Ireland) - if no CRAB infections then colonisation - if no CRAB then CSAB infections - if no CSAB infections then colonisations Survey in OI will run until 30th of pril 2025