GIS28 Antibacterial Treatment Of Enteric Infections Flashcards

1
Q

Enteric infections

A
  • acute diarrhoea caused by microbial enteropathogens
    —> often self-limiting
    —> fluid / electrolyte replacement
    —> antimicrobial therapy: reduce severity and duration

Time of onset:
- acute: <2 weeks
- persistent: 2-4 weeks
- chronic: >4 weeks

Types of stool:
- watery diarrhoea
- dysentery (invasive diarrhoea)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Severity of diarrhoea

A

Mild:
- <=3 unformed stool/day
- minimal associated symptoms

Moderate:
- >=4 unformed stool/day
- systemic symptoms

Severe:
- >=6 unformed stool/day
- fever
- systemic symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Mechanisms of diarrhoea

A
  1. ***Secretory: H2O secretion > H2O absorption due to toxins
  2. ***Osmotic: excessive solute in the gut lumen —> H2O can’t be absorbed e.g. lactose intolerance
  3. ***Infectious / inflammatory: epithelial destruction, loss of absorptive capacity
    —> bacterial: do not use anti-motility drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Bacteria that cause diarrhoea

A
  1. Vibrio cholera
  2. Shigella
  3. Escherichia coli
  4. Salmonella
  5. Campylobacter jejuni
  6. Staphylococcus aureus
  7. Bacillus cereus (food poisoning)
  8. Clostridium difficile (food poisoning)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Subtypes of E. coli

A
  1. Enterotoxigenic (ETEC)
    —> 2 toxins —> watery diarrhoea
    - traveller’s diarrhoea
  2. Enteropathogenic (EPEC)
    —> watery diarrhoea
    - infantile diarrhoea (in nurseries)
  3. Enterohaemorrhagic / verocytotoxigenic / Shiga toxin-producing (EHEC / VTEC / STEC)
    —> person-to-person transmission in day care setting
    - haemorrhagic colitis (bloody diarrhoea)
    - haemolytic uraemic syndrome
    - thrombotic thrombocytopenic purpura
  4. Enteroinvasive (EIEC)
    —> developing world
    - dysentery
  5. Enteroaggregative (EAggEC)
    - diarrhoea in adults and children
  6. Diffusely adherent (DAEC)
    - diarrhoea in children
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Medically important diarrhoea

A
  • ***community outbreaks
  • ***inflammatory, blood diarrhoea
  • severe volume depletion
  • ***high fever
  • severe abdominal pain
  • duration > 4-5 days
  • impaired host (e.g. HIV)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cholera

A

Life-threatening watery diarrhoea
- due to cholera toxin by vibrio cholerae
- in faecally contaminated food / water

Treatment:
1. Oral Rehydration Salts (ORS fluid replacement)

  1. Short course ***broad spectrum antibiotics for severe cases
    - Fluoroquinolones (ciprofloxacin)
    - Co-trimoxazole (trimethoprim + sulfamethoxazole)
    - Tetracycline (doxycycline)
    - Macrolide (azithromycin)
  2. Vaccination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Salmonella infection / Salmonellosis

A

Contaminated food / drink

Symptoms:
- within 12-72 hours: N+V, fever, diarrhoea, abdominal cramps
- 4-7 days: mild to severe symptoms, most recover without treatment
- severe case: break through intestinal wall to bloodstream

Typhoid fever:
***Broad-spectrum antibiotics (depend on resistance pattern)
- Fluoroquinolones (Ciprofloxacin)
- Co-trimoxazole
- 3rd gen Cephalosporin (Ceftriaxone)
- Penicillins (amoxicillin, ampicillin)

Non-typhoid salmonella gastroenteritis
- antibiotics NOT required unless severe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Shigellosis

A

Self-limiting

Treatment:
1. Oral rehydration / IV fluid replacement
2. Antibiotic required ONLY in dysentery
- Fluoroquinolones
- 3rd gen Cephalosporin
- ampicillin / co-trimoxazole (few bacteria still sensitive because of resistance)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Campylobacter gastroenteritis

A
  • diarrhoea / dysentery mild and self-limiting
  • abdominal pain and fever

Treatment:
- Macrolide (used in severe)
- Fluoroquinolones (increasing frequencies of resistance) / other broad-spectrum antibiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Traveller’s diarrhoea

A
  • change in climate, social conditions, sanitation standards and facilities
  • diarrhoea likely within 2-10 days
  • usually due to ETEC

Treatment:
1. Oral rehydration
2. Broad spectrum antibiotics for 3-5 days (↓ severity and duration)
—> Co-trimoxazole (1st choice)
—> Fluoroquinolone
—> 3rd gen Cephalosporin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Antibiotic-associated diarrhoea

A
  • Majority due to overgrowth of C. difficile in the gut
  • Clostridium difficile toxin produces
    —> water diarrhoea
    —> pseudomembranous colitis

Treatment:
1. Metronidazole
2. Oral vancomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Drugs used in the treatment of enteric infections

A
  1. β-lactam (penicillins, cephalosporins)
  2. Fluoroquinolones (ciprofloxacin)
  3. Co-trimoxazole
  4. Macrolides (erythromycin, azithromycin)
  5. Tetracycline (doxycycline)
  6. Metronidazole
  7. Vancomycin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Vancomycin

A
  • ***Glycopeptide
  • almost completely excreted in urine
  • renal failure: dosage adjustment

Mechanism of action:
- bacteriCIDAL
- ***block bacterial cell wall synthesis —> susceptible to osmotic pressure (cell lysis)
- effective vs many drug-resistant bacteria
- lower incidence of bacterial resistance (VRE, VISA superbugs are emerging)

Administration:
- **Slow IV for systemic therapy —> high incidence of pain and thrombophlebitis
- Rapid IV infusion —> **
“red man syndrome”
- Reserved for
—> serious infection in penicillin-allergic patients
—> resistant organisms (MRSA, MRSE infection)

  • Oral route: useful for treatment of Enterocolitis (Clostridium difficile colitis)

Adverse effects:
- **Nephrotoxicity
- **
Ototoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Co-trimoxazole

A
  • Trimethoprim + Sulfamethoxazole (1:5)
  • Synergistic antibacterial effect against Gram +ve and Gram -ve bacteria
    —> except P. aeruginosa, Enterococcus, Gram -ve anaerobes

Adverse effects:
- GI discomfort
- Hypersensitivity
- Low incidence of serious adverse effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

MOA of Co-trimoxazole

A

BacteriCIDAL

Sulfamethoxazole (sulfonamides):
- inhibit **Dihydropteroate synthetase
- Para-aminobenzoic acid —X—> Dihydrofolic acid
- interferes with bacterial **
folic acid synthesis and growth

Trimethoprim:
- inhibit **Dihydrofolate reductase
- blocks production of **
Tetrahydrofolic acid

  • Caution in patients with severe ***G6PD
17
Q

Mechanisms of resistance to co-trimoxazole

A
  1. Alteration of different substrate enzymes / their overproduction
  2. Loss of bacterial drug-binding capacity
  3. Decreased cell permeability
18
Q

Metronidazole

A
  • Synthetic Nitroimidazole derivative
  • important agent in anaerobic infections (intra-abdominal infections)
  • BacteriCIDAL vs Bacteroides fragilis

Spectrum:
- **Anaerobic bacteria (Bacteroides, Clotridium)
- **
Protozoa (Entamoeba, Giardia)

Resistance:
- Rare
- Decreased activation (↓ redox reaction) of drug

SE:
- N/V
- headache
- ***Metallic taste
- alcohol intolerance, seizures, peripheral neuropathy (rare)

19
Q

MOA of metronidazole

A
  • Enter bacteria via diffusion
  • Nitro group of metronidazole is chemically reduced by redox enzyme pyruvate-ferredoxin oxidoreductase (PFOR)
    —> forms highly reactive ***Nitro radical anion
    —> disrupts the DNA helical structure
    —> inhibit DNA synthesis
    —> cell death
20
Q

Pharmacokinetics of metronidazole

A
  • very well absorbed
  • excellent penetration
  • metabolised in Liver
  • Urine excreted
21
Q

Viral gastroenteritis

A

Acute infection, self-limiting
- Rotavirus
- Norovirus
- Adenovirus

Treatment:
- Fluid and electrolyte replacement with ORS
- NO antiviral drugs available

22
Q

Summary

A

Mild:
- fluids only (ORS)
- lactose free diet
- avoid caffeine

Moderate:
- anti-motility agent (loperamide)

Severe:
- Fluoroquinolones
- Co-trimoxazole
- Macrolides

23
Q

β-lactam (penicillins, cephalosporins) (transpeptidase / PBP)
Macrolides (50s —> block A site to P site) (bacteriostatic)
Tetracycline (30S —> block A site) (bacteriostatic)
Fluoroquinolones (Topoisomerase IV, II —> DNA cleavage)

A

More information see CPRS L71

β-lactam:
Mimics structure of D-Ala-D-Ala link
—> covalently bind to and inhibit ***transpeptidase/penicillin binding protein (PBP)
—> inhibit pentapeptide cross linking between NAM subunits
—> bacterial cell wall weakens
—> autolysin activated to destroy existing cell wall / osmotic lysis

Macrolide:
Irreversible binding to 50S subunit
—> Inhibit ***translocation of polypeptide chain from A to P site by peptidyltransferase
—> block movement of peptidyl tRNA from A to P site
—> incoming tRNA cannot bind to A site
—> stop protein synthesis

Tetracycline:
Bind to 30S
—> prevent **access of amino acid tRNA to A site on mRNA-ribosome complex
—> block addition of amino acid to existing peptide chain
—> stop protein synthesis
- **
Teeth discolouration
- **Reduced bone growth (children <8)
- **
Photosensitivity

Fluoroquinolones:
1. Inhibit DNA gyrase (topoisomerase II)
—> quinolone-DNA-gyrase complex
—> induced cleavage of DNA
2. Inhibit DNA topoisomerase IV
- GI symptoms
- CNS symptoms (dizziness, confusion, insomnia)
- **Photosensitivity
- **
Ruptured tendons / Arthropathy (CI in children, pregnant and nursing women)