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Flashcards in Antibiotics Part 2 Deck (66):
1

What are the four possible targets of antibiotics?

Cell wall biosynthesis
Protein biosynthesis
DNA and RNA replication
Folate metabolism

2

What do protein synthesis inhibitors actually inhibit?

Either the 50S or the 30s ribosomal subunits, so that protein transplation can't occur

3

Which antibiotics inhibit the 50S ribosomal subunit?

Macrolides (erythromycin, clarithromycin and azithromycin)
Clindamycin
Chloramphenicol

4

Which antibiotics inhibit the 30S ribosomal subunit?

Aminoglycosides (gentamicin)
Tetracyclines (doxycycline)

5

What bacteria are macrolides active against?

Good spectrum against gram positives and respiraotry gram negatives.
Active against 'atypicals'
- legionella
- mycoplasma
- chlamydia

6

How are macrolides administered?

Orally - excellent oral absorption even in severe infection

7

What are 'atypical' bacteria?

Bacteria that don't colour with gram staining (remain colourless). They are neither gram positive or gram negative

8

List some of the possible complications of Macrolides.

Diarrhoea and vomiting
QT prolongation - can lead to arrhythmias
Hearing loss with long term treatment (not a problem for short courses)

9

What are some of the importance drug interactions of Clarithromycin (a macrolide)?

Simvastatin - avoid co-prescription by temporarily stopping Simvastatin
Atorvastatin - similar to above
Warfarin - only an issue if the patient isn't being regularly monitored

10

Is resistance to macrolides common?

Resistance among typical pathogens is relatively common (can be used in non-severe infections)
Resistance among atypical pathogens is relatively rare (included in treatment for severe infections to cover these organisms)

11

What are the similarities between Clindamycin and macrolides?

Same mechanism of action
Excellent oral absorption
Principle action is against gram positives

12

What are the key differences between Clindamycin and macrolides?

No action against aerobic gram negatives or atypical bacteria
Excellent activity against anaerobes

13

What antibiotic would be added to patients with a gram positive toxin mediated disease, and why?

Clindamycin beause it is highly effective at stopping exotoxin production

14

Give some examples of gram positive mediated disease?

Toxic shock syndrome
Necrotising fasciitis

15

What is the main side effect of Clindamycin?

Because it is very active against anaerobes, it effectively disrupts the colonic flora.
- this leads more easily to a C.diff infection
(all antibiotics cause CDI to a small extent)

16

Why does C.diff commonly colonise the gut after antibiotic use?

Antibiotics dramatically after the colonic flora
C.diff easily colonises and forms spores which are difficult to eradicate as they can remain inactive until put under stress.
C.diff has developed resistance against common antibiotic classes

17

Which antibodies most commonly cause C.diff infections?

4 C's
- Clindamycin
- Co-amoxiclav (broad)
- Cephalosporins
- Ciprofloxacin

18

How can the disruptive properties of antibiotics on colonic flora be minimised?

Keep antibitoics as narrow spectrum as possible
Use a faecal transplant to re-balance gut flora

19

Chloramphenicol is broad spectrum, which means its very toxic, causing....

Bone marrow suppression (aplastic anaemia)
Optic neuritis

20

What are the modern uses of chloramphenicol?

Topical therapy to eyes
- doesn't cause BM suppression (not administered systemically)
Bacterial meningitis with beta-lactam allergy

21

Why has use of aminoglycosides increased more in the last 5 years?

Improved dosing regimens
Restriction of other broad spectrum antibiotics

22

Which bacteria is Gentamicin (an aminoglycoside) active against?

Excellent gram negative coverage (some gram positive effects), so a different class is needed to treat gram positive as well

23

Describe the action of Gentamicin when it binds to the 30S ribsome

Reversibly binds to the 30S ribosome
- bacteriostatic action (stops bacterial growing)
- results in prolonged post-antibiotic effect

24

Does Gentamicin have a bacteriostatic or bactericidal action?

Both
- bacteriostatic action by binding to the 30S ribosome
- bactericidal actionon the cell membrane, resulting in rapid killing early in the dosing interval

25

What are the possible toxic effects of aminoglycosides (including gentamicin)

Nephrotoxicity
Ototoxicity (hearing loss, loss of balance and oscillopsia)
Neuromuscular blockade (only significant in myaesthenia gravis)

26

Why are aminoglycosides given as once-daily dosing?

Risk of toxicity
- given a high initial dose to take advantage of rapid killing
- leave long dosing interval
- measure tough level to ensure drug isn't accumulating

27

Which bacteria are tetracyclines active against?

Gram positives and respiratory gram negatives
Atypical organisms

28

What are the possible toxic effects of tetracyclines?

Almost none
- avoid in children (under 12) and in pregnancy
- causes bone abnormalities and tooth discoloration

29

Name some of the atypical organisms Doxycycline is active against

Rickettisia
Mycoplasma
Coxiella
Chlamydia
Chlamyodophila

30

Which antibiotics act against DNA repair and replication by acting on DNA gyrase?

Quinolones
-Ciprofloxacin
- Levofloxacin

31

What antibiotic acts against DNA repair and replication by acting on RNA polymerase?

Rifampin

32

Are quinolones broad or narrow spectrum, and are they bacteriostatic or bactericidal?

Broad spectrum
Bactericidal

33

How should quinolones be administered?

Orally
- has excellent oral bioavailability
- even in sever infections

34

What infections should Ciprofloxacin be used to treat?

UTI/abdominal infections
- good gram negative action and weaker gram positive action

35

What infections should Levofloxacin be used to treat?

Respiratory tract infections
- good gram negative action and some gram positive action

36

Describe the toxicity associated with Quinolones?

GI toxicity - nausea, vomiting and C.diff infections
QT prolongation
Tendonitis

37

Which bacteria are Ciprofloxacin active against?

Excellent gram negative action
Weaker gram positive action
Atypical pathogens

38

Which bacteria are Levofloxacin active against?

Good gram negative action Some gram positive action
Atypical pathogens

39

What indicators suggest the use of Rifampicin?

TB - in combination therapy
In addition to another antibiotic in serious gram positive infections (especially S.aurerus)

40

Why are the drug interactions with Rifampicin so important?

Rifampicin is a potent CYP450 enzyme inducer, so most drugs that undergo hepatic metabolism are affected.

41

Why is treating TB a problem?

Its slow growing, has a high bacterial burden and there is limited access of drugs to the granuloma (No vascular supply)

42

What is the solution when treating TB (a granuloma with no vascular supply)?

Prolonged course of therapy (6 months)
Combination therapy to prevent resistance and kill growing and resting organisms

43

What are the four antibiotics commonly used to treat TB, and why.

Isoniazid - bactericidal to fast growing mycobacteria
Rifampicin - bactericidal against slowly replicating organisms in necrotic foci
Pyrazinamide - bactericidal even against slow growing mycobacteria intracellularly
Ethambutol - bacteriostatic against slow gorwing mycobacteria

44

What are the second line agents of TB treatment?

Quinolones and aminoglycosides

45

Why is folate inhibition a method of antibacterial action?

Inhibition of folate metabolism pathway leads to impaired nucleotide synthesis and therefore impaired DNA replication

46

Name two folate inhibitor antibiotics.

Trimethoprim
Sulfamethoxaole

47

What is Trimethoprim used to treat and why?

Limited to uncomplicated urinary tract infections due to major problem with resistant bacteria

48

What is the range of action of Trimethoprim against bacteria?

Good range of action against gram positives and gram negatives.

49

How is Trimethoprim administered?

Orally

50

What are the possible toxic effects of Trimethoprim?

Elevation of serum creatinine
- doesn't reflect fall in GFR
- related to action on the proximal tubules
Elevated serum potassium
- problematic in chronic renal impairment
- hyperkalaemia is dangerous
Rash and GI disturbance
- nausea

51

What is co-trimoxazole?

Combination antibiotic with Trimethoprim and Sulphamethoxazole

52

What are the pros and cons of co-trimpxazole over Trimethoprim?

Cons
- bone marrow suppression
- SJS - ulcertaion
Pros
- used in certain uncommon infections

53

What bacteria are metronidazole active against and why?

Most anaerobic bacteria (not actinomyces)
- enters by passive diffusion and produces free radicals

54

When would metronidazole be used?

Its often added to therapy in intra-abdominal infections (especially in abscess)

55

What are the possible toxic effects of Metronidazole?

Causes an unpleasant reaction when in contact with alcohol
Peripheral neuropathy can occur in long term cases

56

Are uncomplicated UTIs treated with antibiotics immediately in clinic?

As this is a low risk infection, it can wait for culture results and is treated with targeted therapy. Often dealt with in primary care.

57

What are the treatments for an uncomplicated UTI infected?

Trimethoprim - penetrates well into tissues (including the prostate), so is a very good choice for men
Nitrofuratoin - broad spectrum (So not ideal). Concentrated in the urine, so it has no effect on other tissues

58

What are the most common causes of UTI?

Can be a gram positive
- Enterococcus
- Staphylococcus
Most likely to be a gram negative
- E.Coli or other coliforms
- Pseudomonas

59

With what antibiotics would you treat a complicated UTI?

Ciprofloxacin - very active against wider range of gram negatives

60

With what antibiotics would you treat a severely unwell patient (sepsis)?

In sepsis you would be concerned about gram neagtive and enterococcal bacteria
- Amoxicillin - active against enterococci
- Gentamicin - gram negative coverage
Together they have a good covering of gram negative and enterococcal bacteria

61

Which antibiotics are considered to be safe during pregnancy?

Most beta-lactams (broad spectrum may cause NEC in premature infants)
Macrolides
Anti-tuberculants

62

Which antibiotics are not considered safe during pregnancy?

Tetracylcines (bone/tooth abnormalities)
Trimethoprim (neural tube defects in 1st trimester)
Nitrofurantoin (haemolytic anemia)
Aminoglycosides (ototoxicity in 2nd/3rd trimester)
Quinolones (bone and joint abnormalities)

63

What is the treatment for community acquired pneumonia?

Oral amoxicillin

64

If amoxicillin isn't working for pneumonia treatment (when it's more severe), what is the treatment?

Co-amoxiclav and clarithromycin
- these cover the staphylococci and atypical causes of pneumonia, which are more serious and deadly
- also cover again beta-lactamase

65

Which organisms normally cause urinary tract infections?

Coli forms (E.Coli, proteus species)

66

Why aren't penicillins used for urinary tract infections?

50% of E.Colis are resistant to penicillin - and this is the most common organism for a UTI