HCAI and C.DIFF Flashcards

1
Q

what is healthcare-associated infections (HCAI)

A

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

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2
Q

what is clostridium difficile

A

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

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3
Q

how is CDI transmitted?

A

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

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4
Q

what infection is difficult to contain?

A

Spores spread infection and are difficult to contain and decontaminate. Require specific control measures. SIGHT

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5
Q

what are the symptoms of CDI?

A

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

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6
Q

how can you assess the severity of CDI

A

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.

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7
Q

bristol stool chart

A

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

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8
Q

what are the risk factors for CDI?

A

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

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9
Q

what is the diagnosis of CDI

A

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

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10
Q

what is the general management of CDI?

A

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

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11
Q

what antibiotic treatments are used for CDI?

A
  • vancomycin
    -metronidazole
    -fidaxomicin
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12
Q

what is the dose of vancomycin used?

A

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

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13
Q

what is the MoA of vancomycin

A

cell wall synthesis inhibition

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14
Q

what is the doses of metronidazole used?

A

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

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15
Q

how is oral metronidazole absorbed?

A

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

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16
Q

when is IV metronidazole used and concentration in stool?

A

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

17
Q

what is the MoA of metronidazole

A

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

18
Q

what is the MoA if fidaxomicin?

A

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

19
Q

what are other treatment options?

A

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?

20
Q

why does recurrence happen?

A

Failure to fully clear initial infection? Re-infection with new strain?

21
Q

what is relapse and its first-line treatment?

A

reccurence within 12 weeks
now give Fidaxomicin first line

22
Q

what is recurrence and its firstline treatment?

A

If recurrence (after 12 weeks),
first-line is vancomycin or fidaxomicin

23
Q

how is CDI reported?

A

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

24
Q

how can you prevent outbreaks and reduce cases

A

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

25
Q

which antimicrobials are assoiciated with CDI ?

A

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

26
Q

pathogenicity of CDI?

A

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)

27
Q

progression of CDI

A

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)