Antibiotics Flashcards

1
Q

Name two penicillin antibiotics? - actual penicillin e.g. not amoxicillin

A
  1. Benzylpenicillin (Penicillin G)

2. Phenoxymethylpenicillin (Penicillin V)

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2
Q

What is the mechanism of action of penicillins?

A

Penicillins inhibit the enzymes responsible for cross-linking peptidoglycans in bacterial cell walls. This weakens cell walls, preventing them from maintaining an osmotic gradient. Uncontrolled entry of water into bacteria causes cell swelling, lysis and death.

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3
Q

What is the significance of the beta-lactam ring in penicillins?

A

Beta-lactam rings are responsible for antimicrobial activity. Side chains attached to the beta-lactam ring can be modified to make semi-synthetic penicillins. The nature of the side chain determines the antimicrobial spectrum and other properties of the drug.

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4
Q

How does bacterial resistance to beta-lactams occur?

A

Bacteria resist the actions of penicillins by making beta-lactamase, an enzyme which breaks the beta-lactam ring and prevents antimicrobial activity. Other mechanisms of resistance include limiting the intracellular concentration of penicillin (reduced bacterial permeability or increased extrusion) or changes in the target enzyme to prevent penicillin binding.

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5
Q

What percentage of people have a penicillin allergy?

A

1-10%

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6
Q

On first exposure, how does a penicillin allergy present?

A

Skin rash, 7-10 days after first exposure

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7
Q

What are the indications for use of penicillin V / penicillin G?

A

Streptococcal infections;
1. Tonsillitis
2. Pneumonia (in combination with a macrolide if severe)
3. Endocarditis
4. In combination with flucloxacillin for severe skin and soft tissue infections
Clostridium perfringens infections e.g. gas gangrene
Meningococcal infections:
1. Meningitis
2. Septicaemia

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8
Q

Which immunoglobulin is involved in the more common, less severe penicillin reaction, which can appear 1-2 days on repeat exposure?

A

IgG

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9
Q

In more severe penicillin allergies, which immunoglobulin is involved, and what kind of reaction is it? (this applies to all penicillins)

A

IgE-mediated anaphylactic reaction- this can be life threatening, occurring within minutes to hours, with hypotension, bronchial and laryngeal spasm/oedema and angioedema.

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10
Q

What can occur with high doses of penicillin or when severe renal impairment may delay excretion of penicillin?

A

Central nervous system toxicity (including convulsions and coma)

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11
Q

What is the obvious contraindication for use of penicillin?

A

Penicillin allergy

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12
Q

When should a reduced dose of penicillin be used? (this applies to all penicillins)

A

In someone with renal impairment

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13
Q

Penicillins reduce the excretion of which drug (often used to treat RA), increasing the risk of toxicity?

A

Methotrexate

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14
Q

Benzylpenicillin can only be administered via which routes?

A

IV or IM (as gastric acid prevents GI absorption)

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15
Q

Name the antipseudomonal penicillin?

A

Piperacillin with tazobactam = Tazocin

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16
Q

What are antipseudomonal penicillins reserved for (1) and in what conditions are they used? (3)

A

Antipseudomonal penicillins are reserved for severe infections, particularly where there is:

  • a broad spectrum of potential pathogens (including Pseudomonas aeruginosa) OR
  • antibiotic resistance is likely OR
  • patients are immunocompromised
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17
Q

Which clinical infections are treated by piperacillin with tazobactam (Tazocin)? (4 - broad areas of infection)

A
  1. Lower respiratory tract infection
  2. Urinary tract infection
  3. Intra-abdominal sepsis
  4. Skin and soft tissue infection
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18
Q

How has the beta-lactam side chain been modified to form piperacillin?

A

The side chain of broad-spectrum penicillins has been converted to a form of urea. This longer side chain may improve affinity to penicillin binding proteins, increasing the spectrum of antimicrobial activity to include Pseudomonas aeruginosa.

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19
Q

Why is tazobactam combined with piperacillin?

A

Tazobactam is a beta-lactamase inhibitor, so confers antimicrobial activity against beta-lactamase-producing bacteria e.g. staph aureus, and gram-negative anaerobes.

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20
Q

What is the common possible side effect caused by Tazocin?

A

GI upset; nausea and diarrhoea are common

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21
Q

Less frequently, what side effects an occur from using Tazocin?

A

Antibiotic-associated colitis can occur (when broad-spectrum antibiotics kill normal GI flora, allowing overgrowth of toxin-producing C.diff).

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22
Q

What are the warnings (2)/contraindications (1) associated with using Tazocin?

A
  1. Use in caution with people at risk of C.diff infection
  2. Use in caution/reduced dose in patients with moderate/severe renal impairment
  3. Contraindicated in penicillin allergy
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23
Q

As with other penicillins, which drug do they reduce the renal excretion of?

A

Methotrexate

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24
Q

Antipseudomonal penicillins enhance the anticoagulant effect of which drug, and how?

A

Warfarin, by killing normal GI flora that synthesises vitamin K.

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25
Q

What is the only route of administration of piperacillin and tazobactam?

A

IV infusion

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26
Q

Name two commonly prescribed, broad spectrum penicillin based antibiotics?

A
  1. Amoxicillin

2. Co-amoxiclav

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27
Q

Name the 4 indications for use of amoxicillin or co-amoxiclav?

A
  1. Pneumonia (which may be caused by gram positive e.g. strep pneumoniae, or gram negative e.g. haemophilus influenzae pathogens)
  2. UTI (most commonly caused by E.coli) (Trimethoprim and nitrofurantoin are alternatives).
  3. Hospital acquired infection/intra abdominal sepsis: co-amoxiclav (e.g. co-amoxiclav and clarithromycin)
  4. H.pylori associated peptic ulcers - combination therapy
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28
Q

For amoxicillin, what is added to the beta-lactam ring side chain?

A

An amino group is added to the side chain, this increases activity against aerobic Gram-negative bacteria, making this a broad spectrum antibiotic.

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29
Q

What is combined with amoxicillin to make co-amoxiclav?

A

Clavulanic acid

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30
Q

Why is clavulanic acid a useful addition to amoxicillin?

A

Clavulanic acid is a beta-lactamase inhibitor, therefore increasing the spectrum of antimicrobial activity further, to include beta-lactamase-producing bacteria (staph aureus and gram-negative anaerobes).

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31
Q

Which antibiotic does MRSA resist the action of?

A

Flucloxacillin

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32
Q

What are the indications for use of flucloxacillin, and which bacteria is it effective against? (3)

A

Staphylococcal infection:

  1. Skin and soft tissue infections e.g. cellulitis
  2. Osteomyelitis and septic arthritis
  3. Endocarditis
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33
Q

Which drug can flucloxacillin be used in combination with in severe skin and soft tissue infections?

A

Benzylpenicillin

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34
Q

What is added to the beta-lactam ring side chain in production of flucloxacillin?

A

An acyl side chain. It protects the beta-lactam ring from beta-lactamases.

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35
Q

How does methicillin-resistant staph. aureus resist the actions of flucloxacillin?

A

It reduces the penicillin binding affinity

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36
Q

Why is it important to check what symptoms a patient experienced when they say they are allergic to penicillin?

A

Patients may say they are allergic to penicillin when they may have experienced side effects including nausea and vomiting. This isn’t a true allergy, as opposed to symptoms including skin rash, bronchospasm or anaphylaxis.

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37
Q

Name two cephalosporins?

A
  1. Cefalexin
  2. Cefotaxime
  3. Cefadroxil
  4. Cefradine
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38
Q

Name two carbapenems?

A
  1. Meropenem
  2. Ertapenem
  3. Imipenem
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39
Q

What is the mechanism of action of cephalosporins and carbapenems?

A

Cephalosporins and carbapenems are derived from naturally occurring antimicrobials produced by fungi and bacteria. Like penicillins, their antimicrobial effect is due to their beta-lactam ring. During bacterial cell growth, cephalosporins and carbapenems inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell walls. This weakens cell walls –> cell swelling, lysis and death.

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40
Q

Are cephalosporins and carbapenems broad or narrow spectrum antibiotics?

A

Broad spectrum

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41
Q

What is the configuration of a cephalosporin in related to the beta-lactam ring?

A

Cephalosporins have a dihydrothiazine ring fused to the beta-lactam ring

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42
Q

What is the side chain attached to the beta-lactam ring in carbapenems?

A

Hydroxyethyl side chain

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43
Q

What are the indications for use of cephalosporins and carbapenems?

A
  1. Oral cephalosporins are second- and third- line treatment options for urinary and respiratory tract infections
  2. IV cephalosporins and carbapenems are reserved for the treatment of infections that are very severe or complicated, or caused by antibiotic resistance organisms. Due to their broad antimicrobial spectrum, they can be used for most indications.
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44
Q

What are the adverse effects associated with cephalosporin and carbapenem use? (4)

A
  1. GI upset
  2. Antibiotic associated colitis (C.diff)
  3. Hypersensitivity - as they share structural similarities to penicillins, reactivity can occur in penicillin-allergic patients
  4. Risk of CNS toxicity including seizures when carbapenems are prescribed at a high dose
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45
Q

What is the contraindication for use of carbapenems/cephalosporins?

A

Allergy to penicillin, cephalosporin or carbapenem, particularly if it was an anaphylactic reaction.

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46
Q

When should carbapenems be used with caution (related to the risk to CNS including seizures)?

A

In patients with epilepsy

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47
Q

When is a dose reduction required when using either carbapenems/cephalosporins?

A

In patients with renal impairment

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48
Q

Which drug do carbapenems reduce the efficacy of (related to the caution for use)?

A

Valproate

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49
Q

Trimethoprim is a first choice antibiotic for treatment of which infection?

A

Uncomplicated UTI

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50
Q

Trimethoprim can be combined with which drug to form co-trimoxazole?

A

Sulfamethoxazole

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51
Q

What is the indication for use of co-trimoxazole? (1)

A

Pneumocystis pneumonia: for treatment and prevention in people with immunosuppression e.g. due to HIV infection

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52
Q

What are the alternatives to trimethoprim for treating a UTI?

A
  1. Nitrofurantoin

2. Amoxicillin

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53
Q

What is the mechanism of action of trimethoprim?

A

Bacteria have to make their own folate for functions including DNA synthesis, trimethoprim inhibits bacterial folate synthesis, which in turn slows bacterial growth (bacteriostatic).

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54
Q

Is trimethoprim broad or narrow spectrum?

A

Broad spectrum against both Gram - positive and -negative bacteria, including enterobacteria e.g. E.coli.

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55
Q

What is the action of sulfamethoxazole, and why is it useful when combined with trimethoprim?

A

Sulfamethoxazole also inhibits bacterial folate synthesis, but works on a different step in the pathway, therefore used together as co-trimoxazole, there is a more complete inhibition of bacterial folate synthesis, making them bactericidal.

56
Q

When is trimethoprim contraindication?

A

In the first trimester of pregnancy –> it is a folate antagonist so there is an increased risk of fetal abnormalities.

57
Q

What are the cautions for use of trimethoprim? (5)

A
  1. Anyone with a folate deficiency
  2. In people with renal impairment
  3. Neonates
  4. Elderly
  5. People with HIV infection
58
Q

What is the indication for use of nitrofurantoin?

A

Uncomplicated lower urinary tract infection (UTI).

59
Q

What are the other antibiotic options for treating a lower UTI? (2)

A
  1. Amoxicillin

2. Trimethoprim

60
Q

Why is nitrofurantoin suited to treating uncomplicated lower UTIs?

A

Nitrofurantoin is effective against the common causative microorganisms, it reaches therapeutic concentrations in urine through renal excretion, and is most bactericidal in acidic environments such as urine.

61
Q

What is the mechanism of action of nitrofurantoin?

A

Nitrofurantoin is metabolised in bacterial cells by nitrofuran reductase. Its active metabolite damages bacterial DNA and causes cell death. Nitrofurantoin is active against gram-negative (e.g. E.coli) and gram-positive (e.g. staph. saprophyticus) organisms that commonly cause UTIs.

62
Q

When is nitrofurantoin not so effective in treating UTIs?

A

Some organisms that less commonly cause UTIs e.g. klebsiella and proteus species, have intrinsic resistance to nitrofurantoin. It is relatively rare for E.coli to acquire nitrofurantoin resistance.

63
Q

What common potential side effects can nitrofurantoin cause? (3)

A
  1. GI upset - nausea and diarrhoea
  2. Immediate or delayed hypersensitivity reactions
  3. Turn urine dark yellow or brown
64
Q

What are the rare side effects nitrofurantoin can cause?

A
  1. Chronic pulmonary reactions e.g. pneumonitis and fibrosis
  2. Hepatitis
  3. Peripheral neuropathy
    all of which are more likely with prolonged use
65
Q

What side effect can occur in neonates whose mothers have used nitrofurantoin?

A

Haemolytic anaemia - as immature red blood cells are unable to mop up nitrofurantoin-stimulated superoxides, which damage red blood cells.

66
Q

Due to the side effects occurring in neonates with the use of nitrofurantoin, when is this antibiotic contraindicated?

A
  1. Pregnant women towards term

2. Babies in the first 3 months of life

67
Q

Other than in pregnant women and babies, when else is nitrofurantoin contraindicated? (1)

A
  1. In people with renal impairment
68
Q

Are there any drug interactions to be aware of when using nitrofurantoin?

A

No

69
Q

Why is nitrofurantoin not useful in complicated UTIs?

A

Its tissue concentrations are very low, so won’t treat pyelonephritis or complicated UTIs. A more suitable treatment would be co-amoxiclav or gentamicin.

70
Q

Name two common tetracyclines?

A
  1. Doxycycline
  2. Lymecycline
    (others as well as tetracycline, include: minocycline and tigecycline)
71
Q

What are the indications for use of tetracylines? (4)

A
  1. Acne vulgaris - particularly where there are inflamed papillose, pustules and/or cysts (Propionibacterium acnes)
  2. Lower respiratory tract infections including exacerbations of COPD (e.g. Haemophilus influenzae), pneumonia and atypical pneumonia (mycoplasma, Chlamydia psittaci, Coxiella burnetii (Q fever)).
  3. Pelvic inflammatory disease - chlamydia infection
  4. Other infections such as typhoid, anthrax, malaria and Lyme disease.
72
Q

What is the mechanism of action of tetracyclines?

A

Tetracyclines inhibit bacterial protein synthesis. They bind to the ribosomal 30S sub-unit found specifically in bacteria. This prevents binding of tRNA to mRNA, which prevents addition of new amino acids to growing polypeptide chains. This action is bacteriostatic, which assists the immune system in killing and removing bacteria from the body.

73
Q

Tetracyclines were discovered in 1945 and have been widely used, what is the negative consequence of this?

A

Some bacteria have acquired resistance to tetracyclines. A common mechanism of this is through acquisition of an efflux pump, which allows bacteria to pump out tetracyclines, preventing cytoplasmic accumulation.

74
Q

What are the common side effects associated with tetracyclines (as with all antibiotics)?

A

GI upset - nausea, vomiting and diarrhoea

75
Q

Although they cause GI upset, Tetracyclines are considered to be among the lowest risk of antibiotics for which bacterial infection?

A

C.diff infection

76
Q

In what percentage of people taking tetracyclines experience a hypersensitivity reaction?

A

1%

77
Q

What are the specific side effects tetracyclines can cause? (4)

A
  1. Oesophageal irritation, ulceration and dysphagia
  2. Photosensitivity
  3. Discolouration of teeth enamel if prescribed for children
  4. Intracranial hypertension (rare- causes headache and visual disturbance)
78
Q

What are the contraindications for using tetracyclines?

A
  1. Pregnancy
  2. Breastfeeding
  3. Children <13
79
Q

When should tetracylines be avoided?

A

In people with renal impairment

80
Q

What are the important drug interactions in relation to tetracyclines? (2)

A
  1. Tetracyclines bind to divalent cations. Therefore, they should not be given within 2 hours of calcium, antacids or iron, which will prevent antibiotic absorption.
  2. Tetracyclines can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesis vitamin K.
81
Q

Although tetracyclines should be taken with food to reduce the chance of nausea and vomiting, what kind of foods should be avoided as they prevent absorption of the antibiotic?

A

Dairy products - calcium in the GI tract binds to tetracycline and prevents them being absorbed.

82
Q

Name two aminoglycosides?

A
  1. Gentamicin
  2. Amikacin
    (others include; streptomycin, tobramycin)
83
Q

Which bacteria (Gram-positive or Gram-negative) are aminoglycosides particularly useful in treating?

A

Gram-negative aerobes e.g. pseudomonas aeruginosa

84
Q

What are the common indications for use of aminoglycosides?

A
  1. Severe sepsis (including where the source is unidentified)
  2. Pyelonephritis and complicated UTI
  3. Biliary and intra-abdominal sepsis
  4. Endocarditis
85
Q

As aminoglycosides lack activity against streptococci and anaerobes, which drugs should they be combined with when the organism causing infection is unknown?

A

Either metronidazole or penicillin

86
Q

What is the mechanism of action of aminoglycosides?

A

Aminoglycosides bind irreversibly to bacterial ribosomes - the 30S subunit and inhibit protein synthesis (much like tetracyclines). They are bactericidal.

87
Q

Streptomycin was one of the first effective drugs against which bacterial infection? (due to it targeting Gram-negative aerobes, staphylococci and mycobacteria)

A

TB

88
Q

How do aminoglycosides enter a bacteria? and why is this relevant to them not being effective against anaerobes and streptococci?

A

Aminoglycosides enter bacterial cells via an oxygen dependent transport system, hence anaerobes and streptococci don’t have this system, so have innate resistance to aminoglycosides.

89
Q

How do bacterial cells adapt to become resistance to aminoglycosides if they do have the oxygen-dependent transport system?

A

They can reduce their cell membrane permeability, or acquire enzymes that modify aminoglycosides to prevent them from reaching the ribosomes.

90
Q

How can penicillins boost the effectiveness of aminoglycosides?

A

Penicillins weaken bacterial cell walls, so they can enhance aminoglycoside activity by increasing bacterial uptake.

91
Q

What are the two most important side effects that aminoglycosides can cause?

A
  1. Nephrotoxicity

2. Ototoxicity

92
Q

Why do aminoglycosides cause nephrotoxicity and what clinical signs may occur?

A

They accumulate in the renal tubular epithelial cells where they trigger apoptosis and cell death. It can lead to reduced urine output and rising serum creatinine and urea.

93
Q

How do aminoglycosides cause ototoxicity?

A

They accumulate in the cochlear and vestibular hair cells where they trigger apoptosis and cell death.

94
Q

What may the patient complain of with ototoxicity?

A

Hearing loss, tinnitus (cochlear damage) and/or vertigo (vestibular damage). …it may be irreversible.

95
Q

Ototoxicity is more likely to occur if aminoglycosides are used in combination with which others drugs? (2)

A
  1. Loop diuretics e.g. furosemide

2. Vancomycin

96
Q

Nephrotoxicity is more likely to occur if aminoglycosides are prescribed alongside which other drugs? (4)

A
  1. Ciclosporin
  2. Platinum chemotherapy
  3. Cephalosporins
  4. Vancomycin
97
Q

What is the only route of administration possible for aminoglycosides and why?

A

IV administration - as they are highly polarised, so cannot cross the lipid membranes, so cannot be given orally.

98
Q

There are no major contraindications for using aminoglycosides, however they should be avoided in certain situations unless absolutely necessary. In which patients should they be avoided?

A
  1. People with myasthenia gravis
  2. People with renal impairment
  3. Elderly
  4. Neonates
99
Q

Name 3 commonly prescribed macrolides?

A
  1. Clarithromycin
  2. Erythromycin
  3. Azithromycin
100
Q

What are the common indications for use of macrolides?

A
  1. Skin and soft tissue infections - as an alternative to penicillins e.g. flucloxacillin
  2. Respiratory infections - as an alternative to penicillins
  3. Severe pneumonia - added to a penicillin to cover atypical organisms including Legionella pneumophila and Mycoplasma pneumoniae
  4. H.pylori causing peptic ulcer (in combination with either amoxicillin or metronidazole and a PPI)
101
Q

What is the mechanism of action of macrolides?

A

Macrolides inhibit bacterial protein synthesis. They bind to the 50S subunit of the bacterial ribosome and block translocation. This inhibition of protein synthesis is bacteriostatic, which assists the body’s immune system in killing the bacteria.

102
Q

Which are the synthetic macrolides? (2)

A

Clarithromycin and azithromycin

103
Q

What do synthetic macrolides have an increased activity against?

A

Gram-negative bacteria; particularly Haemophilus influenzae

104
Q

Is bacterial resistance to macrolides common?

A

Yes - usually due to ribosomal mutations preventing macrolide binding

105
Q

What are the side effects associated with macrolide use? (8)

A

The most common and severe side effects are in relation to erythromycin use, but can occur with any macrolide. They are an irritant, causing:

  1. Nausea/vomiting
  2. Abdominal pain/diarrhoea
  3. Thrombophlebitis - when given IV
  4. Allergy
  5. Antibiotic associated colitis
  6. Cholestatic jaundice
  7. Prolongation of the QT interval
  8. Ototoxicity (at high doses)
106
Q

When should macrolides not be prescribed, or prescribed with caution?

A

People with:

  1. Macrolide hypersensitivity (contraindication)
  2. Severe hepatic impairment
  3. Severe renal impairment
107
Q

What effect do erythromycin and clarithromycin (but not azithromycin) has on cytochrome P450 enzymes?

A

They inhibit cytochrome P450 enzymes. This therefore increases plasma concentrations and risk of adverse effects with drugs metabolised by the P450 enzymes.

108
Q

Macrolides should be prescribed with caution when patients are taking which other types of drugs? (5)

A
  1. Amiodarone
  2. Antipsychotics
  3. Quinine
  4. Quinolone antibiotics
  5. SSRIs
109
Q

Name some commonly prescribed quinolones?

A
  1. Ciprofloxacin
  2. Levofloxacin
  3. Ofloxacin
110
Q

What are the indications for use of ciprofloxacin? (10)

A
  1. Bacterial eye infection
  2. Corneal ulcer
  3. Fistulating Crohn’s disease
  4. Respiratory tract infections
  5. UTIs
  6. Uncomplicated acute cystitis in women
  7. Prostatitis
  8. Gonorrhoea
  9. Surgical prophylaxis
  10. Prevent of secondary case of meningococcal meningitis
111
Q

What are the indications for use of levofloxacin?

A
  1. Eye infections
  2. Sinusitis
  3. Acute exacerbation of bronchitis
  4. CAP
  5. UTI
  6. Prostatitis
  7. Complicated skin and soft tissue infections
  8. Inhalation of anthrax
  9. Pseudomonas aeruginosa causing infection
112
Q

What side effects can quinolones cause?

A
  1. Convulsions (in patients with or without a history of convulsions)
  2. Tendon damage/rupture - rare
113
Q

What is the contraindication associated with quinolone use?

A

Not be to be prescribed in patients with a history of tendon damage caused by quinolones

114
Q

What are the cautions for use of quinolones? (4)

A

People who have:

  1. Diabetes
  2. Epilepsy
  3. G6PD deficiency
  4. Myasthenia gravis
115
Q

What is the mechanism of action of quinolones?

A

Quinolones exert their antibacterial effect by preventing bacterial DNA from unwinding and duplicating, thus interfering with DNA replication. They are therefore bactericidal.

116
Q

Name some anaerobic antimicrobials?

A
  1. Metronidazole

2. Beta lactams (though there is a lot of resistance)

117
Q

What is the mechanism of action of metronidazole?

A

Metronidazole enters the bacterial cells by passive diffusion. In anaerobic bacteria, reduction of metronidazole generates a nitroso free radical. This binds to DNA, reducing synthesis and causing widespread damage, DNA degradation and cell death.

118
Q

Why is metronidazole only effective at treating anaerobic bacteria?

A

As aerobic bacteria are not able to reduce metronidazole to form the nitroso free radical, widespread damage to the bacterial cell does not occur. Therefore the spectrum of action of metronidazole is restricted to anaerobic bacteria (and protozoa).

119
Q

What are the more common side effects that metronidazole can cause? (2)

A
  1. GI upset - nausea and vomiting

2. Immediate or delayed hypersensitivity

120
Q

If metronidazole is prescribed at high doses or for prolonged used, what side effects can occur?

A

Neurological adverse effects including peripheral and optic neuropathy, seizures and encephalopathy.

121
Q

When should metronidazole be prescribed with caution and why? (1)

A

In people with severe liver disease because it is metabolised by hepatic cytochrome P450 enzymes.

122
Q

Why is it important not to consume alcohol while taking metronidazole?

A

Metronidazole inhibits the enzyme acetaldehyde dehydrogenase, which is responsible for clearing the immediate alcohol metabolite acetaldehyde from the body. The combination of the two can cause flushing, headache, nausea and vomiting.

123
Q

What are the common indications for use of metronidazole? (5)

A
  1. Antibiotic associated colitis caused by C.diff (which is a Gram-positive anaerobe)
  2. Oral infections (such as a dental abscess)
  3. Aspiration pneumonia (caused by Gram-negative anaerobes in the mouth)
  4. Surgical and gynaecological infections - caused by Gram-negative anaerobes from the colon, e.g. Bacteroides fragilis
  5. Protozoal infections - including trichomonal vaginal infection, amoebic dysentery, giardiasis.
124
Q

What are the important drug interactions to note with metronidazole?

A

Metronidazole has some inhibitory effects on cytochrome P450 enzymes, reducing metabolism of warfarin (increasing the risk of bleeding) and phenytoin (increasing the risk of toxicity, including impaired cerebellar function).

125
Q

Name the 2 common indications for use of vancomycin?

A
  1. Treatment of Gram-positive infection, e.g. endocarditis, where infection is severe and/or penicillins cannot be used to due resistance (e.g. MRSA or allergy).
  2. Antibiotic-associated colitis caused by C.diff infection (usually second-line where metronidazole is ineffective or poorly tolerated).
126
Q

What has vancomycin more recently been replaced with in hospitals in LTHT?

A
  1. Teicoplanin

2. Linezolid

127
Q

Name two glycopeptide antibiotics?

A
  1. Vancomycin

2. Teicoplanin

128
Q

What is the mechanism of action of vancomycin?

A

Vancomycin inhibits growth and cross-linking of peptidoglycan chains, inhibiting synthesis of the cell wall of Gram-positive bacteria. It therefore has specific activity against Gram-positive aerobic and anaerobic bacteria and is inactive against most Gram-negative bacteria.

129
Q

How are some bacteria becoming resistant to vancomycin?

A

They can modify their cell wall structure to prevent vancomycin binding.

130
Q

What is the most common side effect caused by IV vancomycin?

A

Thrombophlebitis (pain and inflammation of the vein at the site of infusion).

131
Q

What adverse reactions can occur if vancomycin is infused rapidly?

A

Anaphylactoid reactions classically described as ‘red man syndrome’. This refers to the generalised erythema and may be associated with; bronchospasm and hypertension.

132
Q

Why are anaphylactoid reactions not a true allergy?

A

Because they are not antigen-mediated, but are rather due to non-specific degranulation of mast cells.

133
Q

What other side effects can IV vancomycin cause? (4)

A
  1. True allergy - immediate or delayed hypersensitivity (any route of administration)
  2. Nephrotoxicity (renal failure and interstitial nephritis)
  3. Ototoxicity (tinnitus and hearing loss)
  4. Blood disorders (neutropenia and thrombocytopenia)
134
Q

In which patients should caution be taken when prescribing vancomycin - in regards to avoiding toxicity?

A
  1. People with renal impairment

2. Elderly (increased risk of hearing impairment)

135
Q

Which drugs when co-prescribed with vancomycin may increase the risk of ototoxicity and nephrotoxicity? (3)

A
  1. Aminoglycosides
  2. Loop diuretics
  3. Ciclosporin (an immunosuppressant drug)