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Barts year 3 semester 1 > Antimicrobial agents > Flashcards

Antimicrobial agents Flashcards

1
Q

What is the difference between bactericidal and bacteriostatic?

A
  • Bactericidal actively kills bacteria whereas bacteriostatic prevents bacteria multiplying
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2
Q

What is the difference between an antimicrobial and an antibiotic?

A

An antimicrobial is any substance that is active against microbes whereas an antibiotic is a naturally occuring product active against bacteria

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3
Q

What do broad-spectrum bacteria kill?

A

Gram positives, negatives and/or negative anaerobes

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4
Q

What do bacteriostatic antibiotics require in order to be effective?

A

A functioning host immune system

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5
Q

What antibiotics effect the folic acid metabolism of bacteria?

A
  • Trimethoprim

- Sulfonamides

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6
Q

What antibiotics effect the cell wall synthesis of bacteria?

A
  • Beta lactams

- Glycopeptides

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7
Q

What do Quinolones inhibit?

A

DNA gyrase

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8
Q

What does Metronidazole inhibit?

A

DNA replication

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9
Q

What does rifampicin inhibit?

A

DNA-directed RNA polymerase

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10
Q

What antibiotics inhibit protein synthesis?

- Which ones inhibit 50S and which ones inhibit 30S

A 
50S inhibitors
- Chloramphenicol 
- Macrolides 
- Clindamycin 
30S inhibitors 
- Aminoglycosides 
- Tetracycline
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11
Q

What do polymyxins inhibit?

A

Cytoplasmic membrane structure (gram negatives)

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12
Q

Name some mostly anti-gram-positive antimicrobials?

A
  • Penicillins
  • Fusidic acid
  • Macrolides
  • Clindamycin
  • Glycopeptides
  • Oxazolidinones
  • Daptomycin
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13
Q

Name some mostly anti-gram-negative antimicrobials?

A
  • Polymyxin
  • Trimethoprim
  • Aminoglycosides
  • Monobactams (Aztreonam)
  • Temocillin
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14
Q

Name types of broad spectrum antimicrobials?

A
  • Beta lactams (e.g carbapenems, amoxicillin/clavulanate, piperacillin/tazobactam, cephalosporins)
  • Chloramphenicol (gram positives, negatives, atypicals, anaerobes)
  • Tetracycline (gram positives, negatives, atypicals and anearobes, spirochetes)
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15
Q

Describe the concept of the magic bullet?

A

A compound which would harm only the pathogen and not the host - refers to selective toxicity

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16
Q

What infections are difficult to treat due to inadequete penetration of antimicrobials into the target site?

A
  • Endocarditis
  • Meningitis
  • Osteomyelitis
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17
Q

Give an example of synergistic antimicrobials?

A

Beta-lactams with aminoglycosides (often used to treat endocarditis)

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18
Q

Give examples of antagonistic antimicrobials?

A
  • Tetracycline or chloramphenicol with Beta lactams (or 2 beta lactams together, like flucloxacillin with amoxicillin)
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19
Q

Give an example of drugs with high therapeutic indexes?

A

Beta lactams

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20
Q

Give an example of drugs with low/narrow therapeutic indexes?

A

Aminoglycosides

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21
Q

What type of gram negative antimicrobials are intrinsically resistant to polymyxin (colistin)?

A

Proteus

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22
Q

What can chloramphenicol be toxic to?

A

Bone marrow (can cause aplastic anaemia)

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23
Q

What is chloramphenicol mainly used for

A
  • Eye drops

- Meningitis in those with penicillin allergy

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24
Q

Describe the difference between eukaryote and prokaryote ribosomes?

A
  • Prokaryotes contain a 70S ribosome with a 50S and 30S subunit
  • Eukaryotes contain an 80S ribsome with a 60S and 40S subunit
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25
Q

Name 2 Beta-lactamase susceptible narrow spectrum penicillins?

A
  • Penicillin V and G
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26
Q

Name 2 Beta-lactamase resistant penicillins?

A
  • Flucloxacillin
  • Nafcillin
    (Also Methicillin and Oxacillin, but these are not used clinically)
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27
Q

Name 2 Beta-lactamase susceptible broad spectrum penicillins?

A
  • Ampicillin and Amoxicillin
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28
Q

Name penicillins with Beta-lactamase inhibitors?

A
  • Amoxicillin and clavulanic acid

- Piperacillin and tazobactam (anti-pseudomonal), this is even broader spectrum

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29
Q

What are examples of carbapenems? (type of Beta lactams that are active against gram negatives)

A
  • Meropenem and imipenem
  • Etapenam (not anti-pseudonomal)
  • Doripenam
  • Faropenem
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30
Q

What penicillins are used at Barts Trust?

A
  • Penicillin (oral) G (IV)
  • Benzylpenicillin (IV)
  • Flucloxacillin (oral and IV)
  • Amoxicillin +/- clavulanic acid (a Beta lactamase inhibitor)
  • Temocillin (IV)
  • Pivmecillinam (oral)
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31
Q

What percentage of people have a penicillin allergy (immediate IgE mediated anaphylaxis)

A

0.05% of patients

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32
Q

What are side effects of penicillin?

A
  • Jarisch Herxheimer reaction (spirochetes)
  • Coombs positive haemolytic anaemia
  • Interstitial nephritis
  • Serum sickness
  • Hepatitis
  • Drug fever
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33
Q

Penicillins penetration into tissues?

A

penetrates most including meninges

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34
Q

What are the mechanisms of microbial resistance to penicillin?

A
  • Beta-lactamase

- Alteration of PBPs

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35
Q

What can penicillin interact with?

A
  • Allopurinol

- Methotrexate

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36
Q

How many times a day should penicillin be taken?

A

4 - 6 times a day

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37
Q

How often is amoxicillin given?

A

3 times a day

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38
Q

What are possible side-effects of amoxicillin?

A
  • Rash with mononucleosis
  • Increased PT
  • Kounis syndrome
  • Neutropenia
  • Antibiotic associated diarrhoea
  • Fever
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39
Q

What can amoxicillin interact with?

A

Allopurinol (rash)

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40
Q

What is amoxicillin given for?

A

Streptococcal disease except when empirically for a sore throat; listeria

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41
Q

What organisms are resistant to amoxicillin?

A
  • > 80% of staphylococcus
  • S pneumoniae (mainly in Spain and the USA)
  • Gonococcal resistance worldwide
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42
Q

How often is flucloxacilin given?

A

4 times a day

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43
Q

What are the side-effects of flucloxacilin?

A
  • Cholestasis
  • Hepatitis
  • Rash
  • D and V
  • Leukopenia
  • Anemia
  • Thrombocytopenia
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44
Q

What is flucloxacillin used to treat?

A

All S aureus infections except MRSA

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45
Q

Describe the mechanism of microbial resistance against flucloxacilin?

A

Alteration of penicillin binding proteins

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46
Q

What organisms are resistant to flucloxacilin?

A
  • > 80% of staphylococci
  • S pneumoniae in USA, Spain
  • Gonococcal resistance worldwide
47
Q

What is the purpose of clavulanic acid in co-amoxiclav?

A

Acts as a Beta-lactamase inhibitor

48
Q

What is co-amoxiclav used to treat?

A
  • Gram positive and negative

- Anti-anaerobic action also

49
Q

How often is co-amoxiclav to be taken?

A

3 times daily

50
Q

What specifically can co-amoxiclav cause as a side-effect?

A

Drug induced liver injury in 13-23% (mild)

- positive blood test for 1,3 beta D-gucan with IV drug

51
Q

What are resistant to co-amoxiclav?

A
  • MRSA

- Nosocomial gram negatives (including pseudomonas)

52
Q

What are the clinical uses of co-amoxiclav?

A
  • Polymicrobial infections

- Beta-lactamase producing gram positives and negatives

53
Q

What is the mechanism of co-amoxiclav resistance?

A
  • ESBLS
  • Impermeability
  • Efflux
  • Altered PBPs
54
Q

What is piptazobactam made of?

A
  • Piperacillin

- Tazobactam

55
Q

How is piptazobactam administered?

A

IV

56
Q

How often is piptazobactam administered?

A

3 - 4 times a day

57
Q

What are side-effects of piptazobactam use?

A
  • Hypernatremia
  • Neutropenia
  • Diarrhoea
58
Q

What drug can piptazobactam interact with?

A

Methotrexate

59
Q

What organisms are resistant to piptazobactam?

A
  • MRSA

- Hospital acquired Gram negative organisms including pseudomonas

60
Q

What can Vancomycin together with piptazobactam cause?

A

AKI

61
Q

When are first generation cephalosporins usually used and what are they?

A

Surgical prophylaxis

  • Cephalexin
  • Cephalothin
  • Cefazolin
  • Cefadroxil
62
Q

When are second generation cephalosporins usually used and what are they?

A

Obstetrics and gynaecology

  • Cefuroxime
  • Cefotetan
  • Cefomandole
  • Cefoxitin (CF)
63
Q

When are third generation cephalosporins usually used and what are they?

A

Meningitis, streptococcal infections

  • Cefotaxime
  • Ceftriaxone
  • Ceftazidime (P. aeruginosa)
64
Q

What is a fourth generation cephalosporin and what organism is it usually used against?

A

Cefipime

- P. aeruginosa

65
Q

What organism is cefuroxime not active against? (2nd generation cephalosporin)

A

Pseudomonas spp

66
Q

What percent of patients with penicillin allergy also have cefuroxime allergy?

A

~ 10%

67
Q

What can cefuroxime cause as a side-effect?

A
  • C difficile
  • Diarrhoea
  • Gall bladder issues, RUQ pain
68
Q

What is cefuroxime not active against?

A
  • MRSA

- Certain gram negatives

69
Q

What is cefuroxime used to treat?

A
  • Meningitis

- Pneumonia

70
Q

What is ceftazidime (3rd gen) used mostly for?

A
  • Intra-abdominal infections together with metronidazole
  • UTIs - especially when pseudonomas involved
  • Do not use in community acquired (S pneumoniae) pneumonia
71
Q

What does ceftazidine cover?

A

Gram positive and negative, including pseudomonas spp

72
Q

What is the route of adminstration of ceftazidine?

A

IV

73
Q

Give an example of a carbapenem

A

Meropenem

74
Q

What is the spectrum of action of carbapenems (such as meropenem)?

A
  • Gram positive, negative
  • Anti-anaerobic
  • Anti-pseudomonal
75
Q

What are possible side-effects of carbapenems (such as meropenem)?

A
  • Rule out penicillin and cephalosporin allergy (cross allergy around 1 - 9%)
  • Rash
  • Seizure
76
Q

When are carbapenems (such as meropenem) usually used?

A
  • Not typically used in hospital

- ICU, polymicrobial infections

77
Q

Give 2 examples of glycopeptides

A
  • Vancomycin

- Teicoplanin

78
Q

What are glycopeptides (such as Vancomycin/Teicoplanin) used to treat?

A
  • Problem gram positive infections - such as MRSA and C. difficile
79
Q

How often are glycopeptides given and by what route?

A

1 - 2 times per day and by IV

80
Q

What organism is resistant to glycopeptides?

A

VRE (Vancomycin-resistant enterococcus)

81
Q

Describe how VRE develops resistance to glycpeptides?

A

Through alteration of its binding site

82
Q

Describe the penetration into tissues of glycopeptides

A

They are large molecules so have poor penetration, none into CSF

83
Q

What class of antibiotic is inhibits protein synthesis and is bactericidal?

A

Aminoglycosides (e.g gentamicin and Amikacin)

84
Q

What is the route of administration of aminoglycosides (such as gentamicin and amikacin)

A

IV

85
Q

What are the clinical uses of aminoglycosides (such as gentamicin and amikacin)?

A
  • Used against gram negatives
  • Used adjunct to serious systemic sepsis including pseudomonas
  • Gram negative urosepsis
  • Used with B-lactams for infective endocarditis
  • Group B and enterococcal sepsis
86
Q

Describe aminoglycoside penetration

A
  • 100% water soluble

- Poor lung and CNS penetration

87
Q

What are side-effects of aminoglycosides (such as gentamicin and amikacin)?

A
  • Nephrotoxicity

- Ototoxicity

88
Q

How often are aminoglycosides given?

A

Usually once daily

89
Q

Describe the mechanism of microbial resistance of aminoglycosides

A
  • Impermeability

- Efflux

90
Q

What are macrolides given for?

A
  • Pediatric infections in those who have allergy to penicillin
  • Atypical pneumonias
  • STIs
  • Legionella (although usually quinolones given)
91
Q

What are examples of Macrolides?

A
  • Erythromycin
  • Clrithromycin
  • Azithromycin
92
Q

What drugs affect nucleic acid metabolism?

A
  • Quinolones
  • Rifampicin
  • Metronidazole
93
Q

Why do drugs which affect nucleic acid metabolism have poor selective toxicity?

A
  • Nucleotide synthesis and polymerisation is generally similar in bacteria and mammals, hence selective toxicity is poor
94
Q

What are the only oral anti-pseudomonal agents?

A

Quinolones (ciprofloxacin, moxifloxacin, levofloxacin)

95
Q

What are the clinical uses of rifampicin?

A
  • TB

- Staphylococcal infections

96
Q

What is metronidazole active against / used against?

A
  • Anaerobes

- Bacteriodes fragilis

97
Q

Give examples of quinolones

A
  • Ciprofloxacin (mainly GI)
  • Levofloxacin (mainly respiratory)
  • Moxifloxacin (mainly respiratory)
98
Q

In what patients are levo and moxifloxacin mainly used?

A
  • Patients with Beta-lactam allergy and pneumonia
  • Pseudomonal infection
  • Atypical microbacterial respiratory infection
99
Q

What are the clinical uses of fluoroquinolones

A
  • Respiratory infections (TB, inhaled anthrax)
  • Opthalmic infection
  • Prostatitis
  • Prophylaxis if exposed to meningococcal disease
100
Q

What are possible side-effects of fluoroquinolones?

A
  • Not used in pregnancy
  • Photosensitivity
  • Seizures
  • Prolonged QT
  • Tendon rupture
101
Q

What patients do not tolerate antifolates?

A

Sulphur allergy

102
Q

When are antifolates used clinically?

A
  • Soft tissue infections
  • Osteomyelitis
  • PCP (Pneumocystis pneumonia)
103
Q

What specifically do antifolates target?

A

Sulphonamides target Dihydopteroate synthase

  • Human cells instead contain dihydrofolate reductase
  • Trimethoprim targets dihydrofolate reductase
104
Q

What are examples of antifolates?

A
  • Sulphonamides

- Trimethoprim (inhibits dihydrofolate reductase, although inhibits the bacterial enzyme far more)

105
Q

Why do membrane disorganising agents show poor slective toxicity?

A

Bacterial and mammilian membranes are very similar

106
Q

What are examples of membrane disorganising agents?

A
  • Amphotericin (an antifungal agent)
  • Colistin (a polymixin)
  • Daptomycin
107
Q

Desribe the ideal antibiotic (magic bullet)

A
  • Selectively kills pathogen
  • Does not destroy microbiome
  • Reaches and concentrates itself in the target organ
  • Reach good levels in body fluids that are infected
  • Minimally toxic
  • Does not select resistance
  • Inexpensive
108
Q

What does linezolid kill?

A

All gram positives (including VRE and MRSA)

109
Q

Name some bacteria that have developed a large amount of resistance to antibiotics

A
  • Neisseria gonorrhea
  • M TB
  • Pneumococci
  • H. influenzae
  • Salmonella and shigella spp
  • Beta-lactamase producing coliforms
  • Many UTIs, resp diseases, diarrhoeal diseases
110
Q

Name some resistant nosocomial infections?

A
  • MRSA
  • coagulase negative staphylcococci
  • Multi-resistant enterococci
  • Multi-resistant gram negative rods including pseudomonas spp, Klebsiella spp, enterobacter spp, Acinetobacter spp
111
Q

What percentage of ED patients receive an antibiotic?

A

25 - 33%

112
Q

What other than an antibiotic is given in meningococcal or pneumococcal meningitis?

A

Steroid

113
Q

What is an example of a point-of-care test which can tell whether a patient has a viral or bacterial infection?

A

Pro-calcitonin - can be used in chest infections

- More bio-markers needed in the ED!!!

114
Q

What drug is sulphonamide and trimethoprim combined?

A

Cotrimoxazole

Barts year 3 semester 1 (7 decks)

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