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M201 > W8 Overview of Antibiotics > Flashcards

W8 Overview of Antibiotics Flashcards

1
Q

Bacteria:

A

Single-celled, prokaryotic organisms
Groups are called colonies
No nucleus
Stain= Gram +/-ve
Anaerobic
Atypical shape

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2
Q

Why doesn’t gram -ve cell wall get stained?

A

In Gram positive- THICK peptidoglycan layer that is exposed! whereas gram -ve has THINNER peptidoglycan layer sandwiched between outer membrane and inner

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3
Q

What are the types of gram positive and negative bacteria?

A

Gram-positive:
- Streptococcus
- Staphylococcus
- Clostridium
- Botulinum

Gram-negative:
- Cholera
- Gonorrhea
- E. Coli
- Pseudomonas
- Aeruginosa

coccus- round
spirillum- spiral

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4
Q

Overview of bacterial infections (for info)

A

Fill in when you have time!
- need to learn 1/2 of each example

STI
GI
Otitis media

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5
Q

What causes most bacterial infections?

A
  • Most bacterial infections are caused by bacteria that are part of natural body flora
  • A change in habitat for those organisms can result in infection
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6
Q

Clostridium Difficile
Gram +/-ve?
What are the risk factors?

A
  • Gram +ve anaerobe
  • Minor part of normal gut flora

Risk factors:
* Exposure to broad spectrum antibiotics
* Multiple antibiotic exposures
* Proton pump inhibitor (PPI) use
* Co-morbidities

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7
Q

Pseudomonas Aeruginosa
Gram +/-ve?
What are the risk factors?

A
  • Gram –ve bacillus
  • Not part of our natural flora
  • Able to live in various environments
  • Opportunistic pathogen
  • Immunocompromised hosts are susceptible
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8
Q

What are the different targets of antibiotics?
(MoA)

A
  • Cell wall synthesis
  • DNA gyrase
  • RNA elongation
  • DNA-directed RNA polymerase
  • Protein synthesis (30s ans 50s inhibitors)
  • Protein synthesis (RNA)
  • Cytoplasmic membrane structure
  • Folic acid metabolism
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9
Q

Mechanisms of action of antibiotics:

A

Cell wall synthesis
* Penicillins
* Cephalosporins
* Vancomycin
* Cycloserine
DNA gyrase
* Quinalones e.g. Ciprofloxacin
RNA elongation
* Actinomycin
DNA-directed RNA polymerase
* Rifamparin
Protein synthesis (30s and 50s inhibitors)
50s
* Erythromycin (macrolides)
* Chloramphenicol
30s
* Tetracyclines
* Nitrofuans
* Streptomycin
- Protein synthesis (RNA)
* Mupirocin
Cytoplasmic membrane structure
* Polymyxins
* Daptomycin
Folic acid metabolism
* Trimethoprim
* Sulfonamides

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10
Q

What are some systemic infection markers?

A
  • Fever
  • Rigor
  • Chills
  • Myalgia
  • Headache
  • Anorexia
  • Delirium
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11
Q

What are peripheral/local infection markers?

A
  • Erythema
  • Pain
  • Heat
  • Swelling
  • Pus
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12
Q

What are vital signs infection markers?

A
  • Change in body temperature ( <36.1 or >38°C)
  • Tachycardia
  • Hypotension
  • Tachypnoea
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13
Q

What are infection markers?
of Haematology?
Biochemistry?
Microbiology tests?
Urinalysis?

A
  • Inc white blood cell count
  • Changes to neutrophils ( gen inc but low in neutropenic sepsis)
  • Inc platelets
  • Inc C reactive protein
  • Inc erythrocyte sedimentation rate
  • Inc serum creatinine
  • Inc liver function test
  • Changes to procalcitonin level
  • Presence of organism
  • Microscopy
  • Culture
  • Serology
  • Polymerase chain reaction
  • Presence of leucocyte esterase
  • Presence of nitrates (only if symptomatic)
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14
Q

What is the aim of an antibiotic?

A
  • Kill pathogenic bacteria, whilst causing no harm to human tissue
  • The Abx targets the physiology or biochemistry that are unique to bacteria and then:
    -Bind to target site
    -Occupy an adequate number of binding sites
    -Remain at the binding site for sufficient time period

So major determinants for efficacy are the CONCENTRATION of the drug and TIME at the binding sites.

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15
Q

What are the types of abx? (4)

A
  1. Narrow spectrum
  2. Bactericidal
  3. Broad spectrum
  4. Bacteriostatic
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16
Q

What are the mechanisms of resistance?

A
  • Penetration resistance
  • Efflux pump
  • Hydrolysis
  • Mutation of the binding site
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17
Q

What are the principles of therapy?

A
  1. Antibacterial drug choice
  2. Antibacterials, considerations before starting therapy
  3. Advice to be given to patients and their family and/or carers
  4. Antibacterials, considerations during therapy
  5. Superinfection
  6. Notifiable diseases
  7. Sepsis and early management
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18
Q

Choice of antibiotic: What must be considered? (4)

A
  1. Patient factors
    - History of allergy
    - Renal/Hepatic function
    - Susceptibility to infection
    - Ability to tolerate drugs by mouth
    - Severity of illness
    - Risk of complications
    - Ethnic origin
    - Age
    - Female?
    - Previous antibiotics
    - Previous microbiology results
  2. Likely causative organism:
    - Site
    - Likely pathogen
    - Antibacterial sensitivity
  3. Risk of bacterial resistance
  4. Treatment Failure:
    * Repeated antibacterial courses
    * A previous or current culture with resistant
    bacteria
    * At higher risk of developing complications
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19
Q

Antibacterials, considerations before starting therapy? (6)

A
  • Viral infections?
  • Samples should be taken for culture
  • Knowledge of prevalent organisms
  • Dose
  • Route of administration
  • Duration
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20
Q

Antibacterials, considerations during therapy? (4)

A
  • Review the choice of antibacterial
  • In the absence of culture, review and stop on clinical grounds
  • Review IV antibacterial within 48 hours
  • Consider stepping down to oral antibacterials where possible
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21
Q

Prophylaxis

A

Patient has no infection but there is a risk of infection after surgery

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22
Q

Selection of appropriate antimicrobial:
What abx are used in:
eye infections?
dental infections?
ear infections?

A

Chloramphenicol
Amoxicillin or metronidazole

Otitis externa- flucloxacillin/ clarithromycin
Otitis media- amoxicillin, co-amoxiclav or clarithromycin/erythromycin

chap 5 bnf notifiable diseases

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23
Q

Selection of appropriate antimicrobials:
GI infections?
Cardiovascular: endocarditis
COPD?
Nose?

A

GI- Clarithromycin/erythromycin

CVS- Amoxicillin, Low-dose Gentamicin, Vancomycin, Flucloxacillin,

COPD-

24
Q

Who would you report a notifiable disease to?

A

The local heath protection team

25
Q

Penicillins
What are some examples?

A
  • Beta-lactamase sensitive:
    benzylpenicillin (penicillin G- injectable)
  • phenoxymethylpenicillin (penicillin V- oral)
  • Broad-spectrum (but inactivated by beta-lactamases): amoxicillin and ampicillin
  • Penicillinase-resistant penicillin:
26
Q

Penicillins
What are the SE?

What are the cautions and contraindications?

A

Hypersensitivity, diarrhoea, antibiotic-associated colitis, encephalopathy, thrombocytopenia

  • Hypersensitivity (1-10%) and anaphylaxis
    (<0.05%).
    A minor rash that occurs after 72hrs is not a
    true allergy.
  • Maculopapular rashes common with ampicillin and amoxicillin (in renal impairment).
  • Flucloxacillin: hepatic disorder, cholestatic
    jaundice and hepatitis may occur even up to 2 months after treatment (more prevalent in men over 65 and patients who have recieved long courses =2 weeks+)
  • Co-amoxiclav contra-indicated in penicillin-associated jaundice or hepatic disfunction
27
Q

Co-amoxiclav contains which?

A

Amoxicillin + Clauvulanic acid- stops bacteria from breaking down clauvanic acid, allowing the abx to work better.

28
Q

How do Flucloxacillin and Penicillin V need to be taken- directions?

A

Flucloxacillin, Penicillin V: to be taken on
an empty stomach, an hour before food or
2 hours after food. Maintain adequate
hydration.

29
Q

Cephalosporins:
What are the generations used?

A

1, 2, 3, 5
1st Generation

  • Cefalexin
  • Cefradine
  • Cefadroxil
    2nd/3rd generation cephalosporins)
  • Cefaclor
  • Cefuroxime
  • Cefixime - orally active
  • Ceftriaxone
  • Cefotaxime
  • Ceftazidine
  • Ceftaroline

Side-effects: Antibiotic-associated colitis (mostly with

30
Q

Cephalosporins:

A

Cross sensitivity with other beta-lactam antibacterials:
Patients with history of immediate hypersensitivity to
penicillin and other beta-lactams should not receive
cephalosporins.
1st Generation
Side-effects: Antibiotic-associated colitis (mostly with
2nd/3rd generation cephalosporins)
* Cefalexin
* Cefradine
* Cefadroxil
* Cefaclor
* Cefuroxime
* Cefixime - orally active
* Ceftriaxone
* Cefotaxime
* Ceftazidine
* Ceftaroline
If no suitable alternative is available, then cefixime,
cefotaxime, ceftazidime, ceftriaxone, or cefuroxime can be
used in caution.
2nd Generation
3rd Generation
5th Generation

31
Q

Aminoglycosides:
What are some examples?

A

Amikacin, Gentamicin, Neomycin,
Streptomycin, Tobramycin

32
Q

Aminoglycosides:
Gentamicin?

When should the once-daily doses be avoided? How should the dose be adjusted?

A

Gentamicin serum concentration:
* 1 hour Peak concentration:
5-10 mg/L (3-5 in endocarditis)
* Pre-dose trough concentration:
<2 mg/L (<1 in endocarditis)
(narrow therapeutic index)

Once-daily dose should be avoided in CrCl <20 mL/min
Dose adjustment: interval between doses must be increased, if renal impairment is severe, the dose itself should be reduced as well.

33
Q

Aminoglycosides:

Cautions and contraindications?
SE?
MHRA/CHM advice?

A

Cautions & contraindications:
Auditory disorders: (ototoxicity)
Nephrotoxicity
Muscular weakness (Myasthenia gravis)
Dehydration corrected prior to administration

Side-effects: may impair neuromuscular
transmission, irreversible ototoxicity,
nephrotoxicity, N+V, antibiotic-associated colitis, peripheral neuropathy

MHRA/CHM advice: Aminoglycosides
(gentamicin, amikacin, tobramycin, and
neomycin): increased risk of deafness in
patients with mitochondrial mutations.

34
Q

Glycopeptides
What are some examples?

A

Vancomycin, teicoplanin, telavancin

35
Q

Glycopeptides
Cautions & contraindications?
SE?

A

Cautions & contraindications:
Avoid in history of deafness, elderly
caution: systemic absorption enhanced
in patients with inflammatory disorders
of the intestinal mucosa or with
C.difficile

Agranulocytosis, neutropenia,
nephrotoxicity, ototoxicity, blood disorders,
fever, rashes, SCAR reaction,
photosensitivity, ‘red-man- syndrome’
flushing, thrombophlebitis, tinnitus
(discontinue)

36
Q

Glycopeptides
Monitoring?
Interactions?

A

Monitoring: TROUGH LEVEL 10-20 mg/L (LEARN)
- All patients require monitoring of serum
vancomycin, more regularly if renally impaired.
- Monitor auditory function, blood counts,
urinalysis, hepatic + renal function, monitor
leucocyte count

Avoid with ototoxic drugs: ciclosporins aminoglycosides, loop diuretics

37
Q

Peak level and trough levels definition?

A

Peak and trough levels indicate drug levels in an individual’s body. A peak is the highest level of a medication in the blood, while a trough level indicates the lowest concentration. Troughs of medication concentration occur after the drug has been broken down and metabolized by the body

38
Q

Macrolides
What are examples?

Side effects?

A

Azithromycin - once daily dose
Clarithromycin - BD (avoid in pregnancy)
Erythromycin - BD/QDS (used in pregnancy)

Side-effects: GI side-effects (mostly with
erythromycin), hepatotoxicity, rash,
ototoxicity (with high doses), skin reactions, vision issues.

39
Q

Directions of Macrolides?

A

Take with or just after food.
Label 5 - do not take indigestion remedies 2
hours before or after you take this medicine:
Azithromycin + Erythromycin

Azithromycin can be sold to the public for
treatment of confirmed asymptomatic
chlamydia in those over 16 years of age, and
for the treatment of their partners - max 1g

40
Q

Macrolides:
Cautions & contraindications
MHRA/CHM warning for Erythromycin (2020

A

Patients with a predisposition to QT interval
prolongation. May aggravate myasthenia gravis

Warning:
* Patients should not be given erythromycin with a history of QT interval prolongation or ventricular arrhythmia, or those with electrolyte disturbances.
* 2-3-fold increase in the risk of infantile
hypertonic pyloric stenosis during infancy
monitor for vomiting or irritability with feeding.

A potential drug interaction between
rivaroxaban and erythromycin resulting in an increased risk of bleeding

41
Q

Quinolones:
Examples?

SE?

A

Ciprofloxacin, Levofloxacin, Moxifloxacin,
Norfloxacin, Olfoxacin

prolongs QT interval, seizures, GI side-effects, dizziness, headache, eye disorders, decreased appetite

42
Q

Quinolones:
Patients advised to seek immediate medical attention if:

A

If they experience a rapid onset of SOB especially when lying down flat in bed, swelling of ankles, feet, or abdomen or new onset heart palpitations.

  • Avoid administration of dairy products due to reduced exposure. Do not take milk, indigestion remedies, iron or zinc 2 hours before or after taking this medicine.
  • Discontinue if psychiatric, neurological and
    hypersensitivity reactions occur.
43
Q

Quinolones:
P + BF?
Cautions & contraindications?

A

Cautions & contraindications:
* CSM: may induce convulsions (e.g. when taking with NSAIDs)
* Tendon damage: within 48 hours, some cases several months after stopping, do not give to patients with a history of tendon disorders or those taking corticosteroids (increases risk of tendinitis) -discontinue if tendon damage is suspected.
* Small risk of aortic aneurysm and heart valve regurgitation: sudden onset severe abdominal, chest, or back pain develops
* Caution: exposure to sunlight and UV radiations should be avoided up to 48 hours after treatment stopped. G6PD deficiency, history of epilepsy, myasthenia gravis, psychiatric disorders, children or
adolescents (Arthropathy)

44
Q

Tetracyclines:
What are the examples?

A

Tetracycline, Doxycycline, Minocycline

45
Q

Tetracyclines:
What are the SE?
Cautions & contraindications?

A

N+V, diarrhoea, antibiotic-
associated colitis, dysphagia,
oesophageal irritation, hepatotoxicity,
blood disorders, photosensitivity,
hypersensitivity, hepatotoxicity

Cautions & contraindications:
* Headache and visual disturbances indicate benign intracranial hypertension (discontinue)
* Contra-indicated in children <12 years old
(deposition in growing bone and teeth, by binding to calcium causing staining and occasionally dental hypoplasia)
Should not be given to pregnant or breast-feeding women, effects on skeletal development, may cause
discolouration of child’s teeth, and maternal
hepatotoxicity has been reported.
* Myasthenia gravis, systemic lupus erythematosus

46
Q

Tetracyclines:
Indications?

A

Tetracyclines should not be given within 2 hours of calcium, antacids or iron, which will prevent antibiotic absorption.
Tablets should be swallowed whole with plenty of fluid while sitting or standing.
Patients should be advised to avoid exposure to sunlight or sun lamps.

47
Q

Trimethoprim:

A

Antifolate antibiotic.
- when fetus is forming

Cautions & contraindications:
Blood dyscrasias
acute prophylaxis, elderly, neonates,
those at risk of folate deficiency
Avoid in first-trimester of pregnancy due
to antifolate effect

Side-effects: allergic reactions,
anaphylaxis, drug fever, electrolyte
imbalances, GI disturbances, photosensitivity, fungal overgrowth

48
Q

Trimethoprim:
Monitoring?
Interactions?

A

Monitoring:
Hyperkalaemia, increased creatinine concentration,
renal function, plasma-trimethoprim if used for long-
term treatment.
Monitor and advise patients to look out for blood
dyscrasias symptoms: sore throat, rash, mouth
ulcers, bruising, bleeding, purpura, fever.

Interactions:
- Not to be used with potassium-elevating drugs
(aldosterone antagonist, ACEI, ARBs)
- Not to be used with other folate antagonists
(methotrexate) or drugs that increase folate
metabolism (phenytoin)

49
Q

Nitrofurantoin Vs Trimethoprim in Pregnancy, when cant they be given?

A

Don’t give in 3rd trimester
Dont give in first trimester

50
Q

Nitrofurantoin

A

Cautions & contraindications:
* Acute porphyrias, G6PD deficiency , infants less
than 3 months old.
* Caution in anaemia, diabetes, electrolyte
imbalances, folate deficiency, susceptibility to
peripheral neuropathy, Vit B deficiency
* Pregnancy: avoid at term - may produce
haemolysis
* BF: avoid, small amounts enough to produce
haemolysis in G6PD - deficient infants.
Side-effects: pulmonary reactions,
nausea and anorexia, hypersensitivity
reactions, peripheral neuropathy, blood
disorders.
Taken with or just after food, may
discolour urine but this is harmless
Monitoring:
* Renal function: avoid if eGFR <45 mL/
min; may be used in caution if eGFR
30-44 mL/min as a short course of 3-7
days to treat lower UTI
* On long-term therapy, monitor liver
function and monitor for pulmonary
symptoms, especially in the elderly
(discontinue if deterioration in lung
function)

51
Q

Clindamycin

A

Clindamycin
Cautions & contraindications:
Should not be used with existing
diarrhoea (colitis more common in
middle-aged and elderly women
especially after an operation)
Avoid injections containing benzyl
alcohol in neonates
Avoid in acute prophyrias
Monitoring:
- Monitor liver and renal function if treatment exceeds
10 days and in infants
- Not harmful in 2nd and 3rd trimester
- Present in breast milk and so child needs to be
monitored for side-effects and diarrhoea.
Side-effects: antibiotic-associated colitis,
GI side-effects, oesophageal disorders,
taste disturbances, jaundice, blood
disorders, rash, Steven-Johnson syndrome,
skin reactions.
Counselling:
Patients should be advised to discontinue
immediately and contact a doctor if diarrhoea
develops.
- Dalacin 2% cream can damage latex condoms
and diaphragms
- Advise patients to take with a full glass of water

52
Q

Metronidazole
Cautions & contraindications?

A

Metronidazole

Cautions & contraindications:
Clinical and laboratory monitoring if treatment > 10 days
Vaginal gel is not licensed for use in children under 18 years
With topical use: avoid exposure to strong sunlight or UV light
With vaginal use: avoid intravaginal preparations in
young girls who are not sexually active, unless there is
no alternative; not recommended during menstruation;
some systemic absorption may occur with vaginal gel.
P+BF: avoid high-dose regimens, use only if
potential benefit outweighs risk.
Side-effects: gastro-intestinal side-
effects, taste disturbances, furred
tongue, oral mucositis, anorexia,
vulvovaginal candidiasis, pelvic
discomfort (with vaginal use)
Do not drink alcohol or use any alcohol hand sanitisers, avoid it!- disulfiram-like
reaction
Take with or just after food, or a meal
Swallow whole do not chew or crush
Take with full glass of water Interactions:

Interactions:
- Metronidazole is an enzyme inhibitor, so
may enhance the effect of warfarin, and phenytoin
- CYP450 inducers can also decrease the function of metronidazole

53
Q

Linezolid

A

Cautions & contraindications:
CHM advice: optic neuropathy; if used for >28 days
Patients advised to report symptoms of visual impairment or new visual symptoms even if not given for long-term
Blood disorders: thrombocytopenia, anaemia, leucopoenia – it’s recommended that patients receive a full blood count weekly.
P+BF: not recommended unless
necessary with close monitoring
Side-effects: anaemia, constipation,
diarrhoea, eosinophilia, headache,
nausea, vomiting, taste disturbances,
severe optic neuropathy, blood
disorders.
Avoid consuming large amounts of
tyramine-rich foods (mature cheese, salami,
marmite, oxo, Bovril, pickled herring, or any
similar meat or yeast extract or fermented
soya bean extract and some beers, lagers or
wines) and other MAOIs
Caution: unless close observation and BP monitoring possible, linezolid should be avoided in uncontrolled hypertension, pheochromocytoma, carcinoid tumour,
thyrotoxicosis, bipolar depression, schizophrenia or acute confusional states.

54
Q

Ms A, a 30 year old female patient presents with a sore throat and fever (T=38°C). She is otherwise healthy and has no known drug allergies. Her FeverPain score is 1. You establish she has an acute sore throat
1. Advice on management in primary care.
2. Would Ms A need a follow up?
3. Would you give an antibiotic?
4. If yes, what is the first line antibiotic?

A

Maximum FEVERPAIN score=5

Infection markers:
Temp, pus on tonsils, pain, swelling

Using NICE CKS
Sore throat due to a viral or bacterial cause is a self-limiting condition which generally resolves within two weeks- no treatment

First-line- phenoxymethylpenicillin 500mg QDS for 5-10 days OR 1g BD (QDS when severe)
Second line (allergic to above)- Clarithromycin 250-500mg BD for 5 days

lifestyle advice- paracetamol/ibuprofen. keep hydrated. BUT no NSAIDS in asthma. Salt water gargling to relieve pain. Don’t have hot drinks- can exacerbate pain. Children- go back to school after fever.

55
Q

What is the FEVERPAIN criteria? (5)

A
  • Fever
  • Purulence
  • Attend rapidly
  • Severely inflamed tonsils
  • No cough or coryza (inflammation of mucus membranes in the nose)

Each of the FeverPAIN criteria score 1 point (maximum score of 5). Higher scores suggest more severe symptoms and likely bacterial (streptococcal) cause. A score of 0 or 1 is thought to be associated with a 13 to 18% likelihood of isolating streptococcus. A score of 2 or 3 is thought to be associated with a 34 to 40% likelihood of isolating streptococcus. A score of 4 or 5 is thought to be associated with a 62 to 65% likelihood of isolating streptococcus

56
Q

Mr B, a 27-year-old male patient presents with pain in his left ear. He reported it was itchy and tender on moving the jaw. On examination, the ear canal appears red and swollen with some discharge being present. A diagnosis of acute otitis externa was made.
1. Advice on management in primary care.
2. Would you give an antibiotic?
3. If yes, what is the first line antibiotic?

A

Otitis externa- flucloxacillin/ clarithromycin

  1. Manage aggravating factors, cleaning the external auditory canal. Analgesia and counselling on drug administration.
  2. Possibly
  3. Acetic acid 2% 1 spray TDS or Ear drops for 7 days
    Topical antibiotics with or without a topical corticosteroids (7-14 days)

Lifestyle advice- CKS
- Avoid damage to the external ear canal:
Troublesome ear wax should be removed safely to avoid damaging the ear canal. Cotton buds or other objects should not be used to clean the ear canal.
Keep the ears clean and dry.
Avoid swimming and water sports for at least 7–10 days during treatment.
Use ear plugs and/or a tight-fighting cap when swimming.
Keep shampoo, soap, and water out of the ear when bathing and showering, for example by inserting ear plugs or cotton wool (with petroleum jelly).
Consider using a hair dryer (at the lowest heat setting) to dry the ear canal after hair washing, bathing, or swimming

57
Q

Summary - Principles of antibiotic prescribing
(for info)

A
  • Initiate antibiotics as soon as possible in severe infection.
  • A dose and duration of treatment for adults is usually suggested, but adjust for age, weight and renal function.
  • In severe or recurrent cases, consider a larger dose or longer course.
  • Confirm dosing and interaction information
  • Check for allergy.
  • Consider lower threshold for antibiotics in patients with multiple morbidities; consider culture and seek advice.
  • Suspect neutropenic sepsis if patients having cancer treatment become unexpectedly or seriously unwell. Refer immediately!! for assessment at their appropriate local hospital.
  • Prescribe an antibiotic ONLY when there is likely to be a clear clinical benefit.
  • Consider a no, or delayed, antibiotic strategy for acute self-limiting upper respiratory tract infections.
  • Use simple generic antibiotics if possible- not brand
  • Avoid broad-spectrum antibiotics when narrow-spectrum antibiotics remain effective, as they increase risk of Clostridium difficile, MRSA and resistant UTIs.
  • Avoid widespread use of topical antibiotics- small amounts should be used but patients use like creams
  • Where a ‘best guess’ therapy has failed or special circumstances exist,
    microbiological advice can be obtained from your local microbiology team.
  • Monitor renal function, and biochemical results as appropriate.
  • Monitor response to treatment, safety and adverse reactions.
  • Counsel patients on administration and the importance of completing the course

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