HCAI and C.DIFF Flashcards
what is healthcare-associated infections (HCAI)
Often referred to as nosocomial infections
HCAIs can include e.g. surgical site infection, UTIs (and other catheter-related infection), pneumonia (including ventilator-related) and a range of others such as gastrointestinal and soft tissue infection
Include those caused by well-known HCAI-related pathogens such as MRSA, ESBL- and CRE, VRE (PM2A2), C. diff (this lecture) and norovirus (Lecture 5). Also ESKAPE pathogens (Lecture 1)
Pose risk not only to patients but also staff and visitors
AMR: Often involve drug-resistant (including MDR) organisms, difficult to treat and higher risk of morbidity and mortality
what is clostridium difficile
A Gram positive, anaerobic, spore-forming rod. It was named difficile because it grows slowly and is difficult to culture
Responsible for the development of antibiotic-associated diarrhoea (AAD) and colitis
Now named Clostridioides difficile
how is CDI transmitted?
Fecal-oral transmission
Leading cause of nosocomial diarrhoea associated with antibiotics
C. difficile implicated in:
20-30% of antibiotic-associated diarrhoea (AAD)
Significant % of antibiotic-associated colitis and
more severe pseudomembraneous colitis
Increased mortality with CDI
what infection is difficult to contain?
Spores spread infection and are difficult to contain and decontaminate. Require specific control measures. SIGHT
what are the symptoms of CDI?
Depends on severity:
Commonly mild-to-moderate diarrhoea (can be severe)
From mild abdominal cramping to severe pain
If severe, pseudomembranes, adherent yellowish-white plaques on the intestinal mucosa
In rare cases: fulminant life-threatening colitis
Fever, low grade to severe
Dehydration
how can you assess the severity of CDI
Adapted from NICE / PHE:
Mild:normal white cell count (WCC). Usually <3 episodes of loose stools (type 5-7 on Bristol Stool Chart).
Moderate:associated with increased WCC (but <15x109/L) and typically associated with 3–5loose stools/day.
Severe:associated with a WCC >15x109/L, or acutely increased serum creatinine (>50% increase above baseline), or temperature >38.5°C, or evidence of severe colitis. Number stools may be less reliable indicator of severity.
Life-threatening:signs & symptoms include hypotension, partial or complete ileus, toxic megacolon, or computerised tomography (CT) evidence of severe disease.
bristol stool chart
Type 1: Separate hard lumps
Type 2: Sausage-shaped, lumpy
Type 3: Sausage-like, cracks on surface
Type 4: Sausage-like, smooth/soft
Type 5: Soft blobs but with clear edges
Type 6: Fluffy pieces, ragged edges, mushy
Type 7: Watery, no solid pieces, liquid
what are the risk factors for CDI?
Increasing age
Proximity to infected patients
Nasogastric tube
Non-surgical GI conditions
Anti-ulcer medication (PPI)
Long duration of hospital stay
Presence of underlying disease (e.g. IBD)
Undergoing surgery
Receiving chemotherapy
ICU stay
Long duration of antimicrobial therapy
Courses of multiple antimicrobials
what is the diagnosis of CDI
Usually depends on:
Clinical symptoms and risk factors (e.g. diarrhoea, ABx exposure) including history
Cytotoxic assay and toxigenic culture
ELISA/EIA for toxins A/B presence of C. difficile toxins in stool*
ELISA/EIA for GDH
PCR/NAAT for toxin genes
- TcdA, TcdB and can include binary
what is the general management of CDI?
Stopping the offending antibiotic (if possible)
Spontaneous resolution may occur
15-23% of patients within 48-72h of stopping
Continuing therapy
Associated with refractory disease
Symptomatic treatment
Fluid & electrolyte replacement
But not anti-diarrhoeals
But specific treatment is nearly always indicated, typically antibiotics (see later)
Guidance for management and treatment of CDI was PHE 2013 (here) but
Replaced by NICE guidance ng199 in July 2021
Diagnosis and reporting still follow previous PHE guidance 2012
what antibiotic treatments are used for CDI?
- vancomycin
-metronidazole
-fidaxomicin
what is the dose of vancomycin used?
Usual initial dose
125mg four times a day, given enterally, for 10 days
IV vancomycin is ineffective
From July 2021, used first line for mild, moderate and severe CDI
Also can be used in recurrent and life-threatening cases (see later)
Shown to give 86-100% response rate
what is the MoA of vancomycin
cell wall synthesis inhibition
what is the doses of metronidazole used?
Was first-line therapy mild to moderate, first episode until July 2021, 400mg three times a day orally for 10-14 days
Now only recommended in certain cases and in combination with vancomycin, 500mg three times a day IV 10 days
Shown to be equally effective to vancomycin
how is oral metronidazole absorbed?
Completely absorbed from GI tract
Usually undetectable in faeces
Concentrations higher when stools are watery or semi-formed
Due to increased GI transit time
Incomplete absorption; seepage of drug across inflamed mucosa
Concentrations lower in semi-formed stool
No correlation between concentrations & outcome however
may be relevant if MIC high, especially when diarrhoea begins to subside
when is IV metronidazole used and concentration in stool?
Appears useful in treatment, recommended in more severe cases
Gives good concentrations in stools during acute illness
Small scale studies show clinical improvement
But case reports do show some failures
No evidence to support superior
what is the MoA of metronidazole
Metronidazole diffuses into the organism, inhibits protein synthesis by interacting with DNA, and causes a loss of helical DNA structure and strand breakage. Therefore, it causes cell death in susceptible organisms.
DNA damage/ free radical
what is the MoA if fidaxomicin?
Macrocyclic antimicrobial, targeted, narrow spectrum
(inhibits RNA polymerase)
From clinical trials – shown to be non-inferior to vancomycin and superior for preventing recurrence and for global cure
Expensive (£1350/10-day course, 200mg tablet, twice/day)
not first line - can be used as relapse or recurrence
what are other treatment options?
Rifamixin: non-absorbed antibiotic
Toxin-binding: cholestyramin
Immunological: e.g. Enteral immunoglobulin (limited evidence), monoclonal antibodies against toxins e.g. bezlotoxumab (see next slide)
Microbiological: Fecal microbiota transplants (see next slide)
Probiotics: Have an increasing profile: useful or not?
why does recurrence happen?
Failure to fully clear initial infection? Re-infection with new strain?
what is relapse and its first-line treatment?
reccurence within 12 weeks
now give Fidaxomicin first line
what is recurrence and its firstline treatment?
If recurrence (after 12 weeks),
first-line is vancomycin or fidaxomicin
how is CDI reported?
Reportssubmitted via same web-enabled system used to collect MRSA bacteraemia data: www.hpa.org.uk
Trusts now sets C. difficile targets each year (maximum permitted number of cases) with sanctions applied for excess cases
how can you prevent outbreaks and reduce cases
Requires good infection control
Hand washing (not with alcohol rubs)
Cohorting/isolation of patients
Barrier nursing / PPE
Increased surveillance
Improved control of antimicrobial use
(antimicrobial stewardship, Lecture 3)
Education
which antimicrobials are assoiciated with CDI ?
Traditionally
Clindamycin
More recent studies
-2nd and 3rd Generation cephalosporins
-Penicillins (e.g. piperacillin/tazobactam), carbapenems
-Aminoglycosides, fluoroquinolones
In fact any antimicrobial can cause CDI
Antimicrobial use may be most important risk factor for transition from colonisation to toxin production
pathogenicity of CDI?
Complex, not fully understood
Pre-existing illness & antibiotic therapy
Alters healthy bacterial flora of the colon
Toxicogenic strains of C. difficile produce toxins that are responsible for pathogenicity – main toxins are Toxin A and Toxin B (encoded by TcdA and TcdB genes). Main virulence factors.
Some strains also produce binary toxin (CDT).
Toxins cause diarrhoea (below)
Immune status is important determinant
Toxin A, toxin B & binary toxin contribute to CDI
Toxin A causes fluid secretion & intestinal inflammation
Toxins A & B both activate cytokine release
Trend towards more severe disease with binary toxin
Hypervirulent strain ribotype 027/NAP1 leads to more severe infection (TcdB027 version)
progression of CDI
Uncolonised asymptomatic colonisation toxin production CDI
1)Assymptomatic carrier: risj factors - underlying disorder, exposure to health
2) progression to CDI
3) Due to progression risk factors (age over 65, abx exposure, distruption to normal gut flora, colonised toxigenic c.difficile, PPI)
4) recuurent/relapse can occur due to age, abx, more virulent strain, PPI/acid supression –> causing CDI
Non carrier - no progession to CDO
-age less than 65
no abx exposute
high serum antibody response to toxins (a and b)
