HCAI - Prevalence and Trends Flashcards
How is the HSE dealing with HCAI infections at the moment
HSE following the Antimicobial Resistance Infection Control (AMRIC) Action Plan 2022-2025
What are the five aims of the AMRIC action plan?
Improved patient outcomes
Improved patient safety
Staff education and training
Improved staff safety
Awareness and deeper understanding
Give some recent examples of why we need infection control
Major outbreaks of CPE prior to covid in tallagha and limerick
What is a HCAI
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
Comment on the global prevalence of HCAIs
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
Why does rate of HCAI differ from hospital to hospital?
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
What is the prevalence of HCAIs in Ireland
According to the latest point prevalence study its approximately 7.4%
Who categorises HCAI
The ECDC has categorised HCAI into 13 broad categories
What are the 13 ECDC categories
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
What are our most common causes of HCAI in ireland
Multi- drug resistant organisms
device related infections
Surgical site infections
Pneumonia
C. diff
norovirus
other infetions such as TB, influenza, VZV, Sars, Cov2 etc
Give some examples of device related infections
Catheter associated UTI
Central line associated BSI
Ventillator associated pneumoniae
What are the three main direct impacts of HCAIs
- patient suffering:
- direct cause of 5,000 deaths per year in Ireland and 37,000 deaths/year in EU - Extended length of stay
- Delays discharge by an average of 11 days - 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
Comment on the morbidity of HCAIs
- direct cause of 5,000 deaths per year in Ireland and 37,000 deaths/year in EU
A HCAI can increase your hospital stay by how many days?
11 days on average
Comment on the financial cost of a HCAI
- 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
What are the indirect impacts of HCAIs
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
Are all HCAIs preventable
No HCAIs can be classified as inevitable or preventable
Talk about inevitable HCAIs
Not all HCAIs can be avoided:
- the young/old
- thos undergoin invasive procedures
- immunosuppressed
Thes are all more susceptible
Talk about preventable HCAIs, how many could be prevented
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
How common are HCAIs in the USA?
Incidence of 4.5%
1.7 million HCAI per year
How common are HCAIs in Europe
Prevlalence of 7.1 between 2022 and 2023
20.5% in ICU patients
4.5 million HCAI per year
How common are HCAIs in Ireland
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
What are the five main reasons for high incidence of HCAIs
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
What % of rooms in hospitals are single bed rooms
34% of beds
What hospital factors affect HCAIs
space
ventilation
cleanliness
What procedural factors affect HCAIs
Diagnostics
Therapy
Care
Rehabiblitation
What microorganism factors affect HCAIs
MDROs
virulence factors of orgnaism
What host factors affect HCAIs
Old age
Dehibilitation
Immunosuppression
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
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
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
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
Give some examples of device related infections
Catheter associated UTI
Ventilator associated pneumonia
Central venous catheter or periphperal venous cannula -> central line associated bsi
How do we assess the burden of HCAI
Through point prevalence studies done every few years:
- determining the incidence and prevalence
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
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)
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
What were the 5 aims of the last point prevalence study carried out by EARS-NET
- measure the overall prevalence of HAI, types of HAI, HAI causative pathogens and key antimicrobial resistance profiles
- measure the overall prevalence of antimicrobial use, types of antimicrobial prescribed, as well as compliance with local guidelines
- 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
- 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
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
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
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
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
How has our Antimicrobial usage changes according to the three pps
2012 = 34% AMU
2017 = 39.7% AMU
2023 = 40.4% AMU
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
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%
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
List the top 7 HCAI in Ireland
Penumonia
Surgical site infections
UTIs
BSIs
systemic infection
C. difficile infection
Skin and soft tissue infection
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
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
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
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
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%
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
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
What organisms are most commonly associcated with UTI HCAIs
32% E. Coli
15% Klebsiella
15% Enterococcus
9% Pseudomonas
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
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
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?
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
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
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%
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
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%
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
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
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
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%
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
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
Compare MRSA in 2023 to 2017 and 2012
23.4% in 2023
28% in 2017
3% in 2012
NB: rate decreasing year on year
Compare VRE in 2023 to 2017 and 2012
18.4% in 2023
39% in 2017
26% in 2012
trending downwards
Compare Pseudomonas resstance in 2023 to 2017 and 2012
5% of Pseudomonas were carbapenem resistant in 2023
15% were resistant in 2017
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%
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
What are the two sources of HCAI
Endogenous
Exogenous
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
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
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
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
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
What organisms are most likely to contaminate water
P. aeruginosa and S. marcescens
These can survive for over 250 days on sink surfaces
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
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
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
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
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
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
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
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
What environmentl factor puts you at much greater risk for HCAI
Prior room occupacy
Increased risk if prior occupant of room had an infection
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%
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
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%
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
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
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)
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
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
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%
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
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
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
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
Talk about C. diff outbreak strains
Some outbreak strains have increased sporulation
Ribotype o27 could sporulate much more readily than other strains
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
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
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
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
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
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
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
What are c, diff toxins a and b?
Theyre both glycosyltransferass
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
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
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
Talk about the prevalnce of CDI over the past three PPSs
2023 = 4.8%
2017 = 4.4%
2012 = 5.7%
relatively stable
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
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
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
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
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
What does NAP1 stand for?
North America Pulse Type 1
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
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
Give some other ribotypes other than 027
078
017
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
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
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
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
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
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
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)
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
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
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
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
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
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
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
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
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
what are the clinical features of MRSA
Nasal carriage
Old age
Male
Admission to ICU
Surgery
Exposure to MRSA-colonised patient
What infections are most commonly associated with MRSA
Underlying chronic disease
Repeated hospital admissions
Prolonged/repeated antibiotics especially the B-lactams
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
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
What are the most common HA MRSA clones in Ireland
ST22
ST8
ST5
ST1
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
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
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
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
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
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
What resistance are we concerned with in VRE
We have had our first linezolid resistant E. faecium in 2014
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
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
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
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
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
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
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
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
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
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
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
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
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
