Antibiotics

Question 1

1) Name the main uses of penicillins.
2) What are the main uses of cephalosporins?
3) What are the main uses of macrolides?
4) What are the main uses of aminoglycosides?
5) Name the main uses of tetracyclines.

Answer 1

1) Antimicrobial chemotherapy of sensitive bacterial infections (e.g. community acquired pneumonia, bacterial endocarditis)
2) Antimicrobial chemotherapy of sensitive bacterial infections (e.g. community acquired pneumonia)
3) Antimicrobial chemotherapy of sensitive bacterial infections (e.g. community acquired pneumonia, atypical pneumonia)
4) Antimicrobial chemotherapy of sensitive bacterial infections (e.g. bacterial endocarditis, pyelonephritis, intra-abdominal infection)
5) Antimicrobial chemotherapy of sensitive bacterial infections (e.g. community acquired pneumonia, atypical pneumonia)

Question 2

Name the 5 penicillin P-drugs.

Answer 2

Amoxicillin 
Benzylpenicillin 
Co-amoxiclav 
Flucloxacillin (staphylococci) 
Piperacillin-tazobactam

Question 3

Name the 4 cephalosporin P drugs.

Answer 3

Cefaclor
Cefuroxime
Cefotaxime
Ceftriaxone

Question 4

Name the 3 macrolide P drugs.

Answer 4

Azithromycin
Clarithromycin
Erythromycin

Question 5

Name the 3 aminoglycoside P drugs.

Answer 5

Gentamicin
Streptomycin (TB)
Tobramycin

Question 6

Name the 4 tetracycline P drugs.

Answer 6

Doxycycline
Tetracycline
Minocycline (acne)
Lymecycline (acne)

Question 7

Give the 2 common clinical indications for the use of cephalosporins and carbapenems.

Answer 7

1) Oral cephalosporins are second and third line treatment for UTIs and RTIs.
2) IV cephalosporins and carbapenems are reserved for severe and complicated infections or antibiotic resistant organisms. They can be used for most indications due to their broad spectrum.

Question 8

1) What are cephalosporins and carbapenems derived from?
2) What is their antimicrobial effect due to?
3) Describe the basic mechanism of action of cephalosporins and carbapenems.

Answer 8

1) Naturally occurring antimicrobials produced by fungi and bacteria.
2) Their beta lactic ring.
3) They inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell-wall synthesis during bacterial cell growth. This weakens the wall, preventing them from maintaining an osmotic gradient, resulting in bacterial cell swelling, lysis and death.

Question 9

1) Describe the spectrum of action of cephalosporins and carbapenems.
2) What has progressive structural modification led to in cephalosporins?
3) Why are cephalosporins and carbapenems naturally more resistant to beta-lactamases?

Answer 9

1) They both have a broad spectrum of action.
2) Successive generations being created (1st to 5th) with increasing activity against gram negative bacteria and less oral activity.
3) Due to the fusion of the beta lactam ring with a dihydrothiazine ring (cephalosporins) or a unique hydroxyethyl side chain (carbapenems).

Question 10

1) Give 2 common adverse effects of cephalosporins and carbapenems.
2) When might antibiotic-related colitis occur with use of cephalosporins/ carbapenems?
3) Why might cross-reactivity causing anaphylaxis occur in penicillin allergic patients when cephalosporins/ carbapenems are used?
4) When is there a particular risk of central nervous system activity using carbapanems and what might this cause?

Answer 10

1) GI upset: N+V.
2) When broad spectrum antibiotics kill gut flora, allowing overgrowth of toxin-producing C.Diff. Can be complicated by colonic perforation and death.
3) Because they share structural similarities with penicillins.
4) Particularly when carbapenems are used in higher doses or in patients with renal impairment, and this could cause seizures.

Question 11

1) Who should cephalosporins and carbapenems be used with caution in?
2) What is the main contraindication for cephalosporins and carbapenems?
3) In which patients should a dose reduction of cephalosporins/ carbapenems be used?

Answer 11

1) People at risk of C.Diff infection (inpatients and the elderly).
2) Patients that have allergies to penicillins, cephalosporins or carbapenems, particularly with Hx of anaphylaxis.
3) In those with renal impairment.

Question 12

1) How can cephalosporins enhance the anticoagulant effect of Warfarin?
2) Describe the interaction between cephalosporins and aminoglycosides.
3) Describe the interaction between carbapenems and Valproate.

Answer 12

1) By killing normal gut flora that synthesise vitamin K.
2) Cephalosporins may increase nephrotoxicity of aminoglycosides.
3) Carbapenems reduce plasma concentration and efficacy of valproate.

Question 13

1) Name an orally active cephalosporin.
2) How are cephalosporins usually prescribed?
3) Describe how IV cephalosporins are used.
4) Describe how carbapenems are available.

Answer 13

1) Cefalexin.
2) For 6-12 hourly administration.
3) At high doses for severe infections (e.g. Cefotaxime 2g IV 6 hourly for bacterial meningitis).
4) They are only available for IV administration.

Question 14

1) Describe the ways that cephalosporins can be administered.
2) Describe the ways that carbapenems can be administered.
3) Which carbapenem can facilitate the outpatient administration of antibiotics?

Answer 14

1) orally, IV by infusion or bolus and IM.
2) IV injection or infusion.
3) Ertapenem as it is administered OD.

Question 15

1) In many hospitals, when/ who can prescribe cephalosporins/ carbapenems and why?
2) Why is use of second and third generation cephalosporins particularly restricted?

Answer 15

1) They can only be prescribed with the approval of a microbiologist in order to reduce the risk of the development of resistance.
2) Because antibiotic associated colitis seems to occur more commonly with these.

Question 16

Give the 4 common clinical indications for the use of Tetracyclines.

Answer 16

1) Acne vulgaris, particularly where there are inflamed papule, pustules and/ or cysts (Proprionibacterium acnes).
2) LRTIs (infective exacerbations COPD/ atypical pneumonia - mycoplasma/ chlamydia psittaci).
3) Chlamydial infection including pelvic inflammatory disease.
4) Other infections such as anthrax, typhoid, malaria and Lyme disease (Borrelia Burgdoferi).

Question 17

Name the 3 main clinical indications for the use of macrolides.

Answer 17

1) Treatment of respiratory and skin and soft tissue reactions as an alternative to penicillins when they are contraindicated by allergy.
2) In severe pneumonia added to a penicillin to cover atypical organisms including Legionella and mycoplasma pneumonia.
3) Eradication of H. Pylori in combination with a PPI and either amoxicillin/ metronidazole.

Question 18

1) What do macrolides do?
2) Describe why inhibition of protein synthesis is useful.
3) Describe the spectrum of activity of erythromycin.

Answer 18

1) Inhibit bacterial protein synthesis by binding to ribosome 50S subunit of bacterial ribosomes to block translocation.
2) Because it is bacteriostatic, assisting the immune system in killing and removing bacteria from the body.
3) Relatively broad spectrum of action against Gr+ and some Gr- organisms.

Question 19

1) Describe the spectrum of activity of synthetic macrolides (clarithromycin and azithromycin).
2) Why is bacterial resistance to macrolides common?
3) Adverse effects are most common and severe with which macrolide?

Answer 19

1) Increased activity against Gr- bacteria, particularly haemophilia influenzae.
2) Mainly due to ribosomal mutations preventing macrolide binding.
3) Erythromycin, although they can occur with any macrolide.

Question 20

1) Describe the adverse effects of macrolides when taken orally.
2) Describe the main adverse effect of macrolides when given intravenously.
3) When should macrolides not be prescribed?

Answer 20

1) They are irritant when taken orally, causing nausea, vomiting, abdominal pain and diarrhoea.
2) Thrombophlebitis.
3) If there is a Hx of macrolide sensitivity

Question 21

Aside from the specific oral and IV side effects of macrolides, name 5 other adverse effects.

Answer 21

1) Allergy
2) Antibiotic-associated colitis.
3) Liver abnormalities including cholestatic jaundice.
4) Prolongation of the QT interval (predisposing to arrhythmias)
5) Ototoxicity at high doses.

Question 22

1) Why are macrolides useful when penicillins are contraindicated by allergy?
2) Describe macrolide elimination by the body and describe where caution might be needed.
3) Which macrolides inhibit cytochrome P450 enzymes?
4) Describe the effect of CYP450 enzyme inhibition.

Answer 22

1) Because there is no cross-sensitivity between the drug classes.
2) Mostly hepatic with renal contribution so caution is required in hepatic impairment and dose reduction may be required in severe renal impairment.
3) Erythromycin and Clarithromycin.
4) Increases plasma concentrations and risk of adverse effects in drugs metabolised by CYP450 enzymes.

Question 23

1) Which other drugs should macrolides be prescribed with caution in?
2) Describe the interaction between macrolides and warfarin.
3) Describe the interaction between macrolides and statins.

Answer 23

1) Drugs that can prolong the QT interval or cause arrhythmias (amiodarone, antipsychotics, quinine, quinolones, SSRIs).
2) Increased risk of bleeding.
3) Increased risk of myopathy.

Question 24

1) What is the most commonly prescribed macrolide in the UK and why?
2) How is clarithromycin usually prescribed?
3) When would clarithromycin be administered intravenously?
4) What is the usual dosage for clarithromycin?

Answer 24

1) Clarithromycin as it is more stable and causes fewer side effects than erythromycin and is cheaper than azithromycin.
2) For oral administration as it is absorbed readily in the intestine and has good bioavailability.
3) Where patients are unable to take or absorb drugs via the GI tract (e.g. due to vomiting).
4) 250-500mg BD for 7-24 days.

Question 25

1) How do you reduce the risk of thrombophlebitis when administering clarithromycin IV? 2) If there is evidence of pneumonia, how should macrolides be prescribed? 3) In which situations might macrolides be required to treat LRTIs?

Answer 25

1) Dilute IV clarithromycin withNaCl then infused into a large proximal vein over at least 60 minutes to reduce the risk. 2) They should generally be added to penicillin treatment 3) They may be required to cover penicillin-resistant atypical organisms that cause pneumonia but do not cause other LRTIs (Legionella/ mycoplasma pneumoniae).

Question 26

Give the 4 common clinical indications for the use of metronidazole.

Answer 26

Treatment of infections caused by anaerobic bacteria in: 1) Antibiotic associated colitis caused by C. Diff which is a gram positive anaerobe. 2) Oral infections or aspiration pneumonia caused by gram negative anaerobes from the mouth. 3) Surgical and gynaecological infections caused by gram negative anaerobes from the colon. 4) Effective treatment of protozoal infections including trichomonal vaginal infection, amoebic dysentery and giardiasis.

Question 27

1) How does metronidazole enter bacterial cells? 2) Describe how metronidazole works in anaerobic bacteria. 3) Why does metronidazole not work in aerobic bacteria?

Answer 27

1) By passive diffusion. 2) Reduction of metronidazole generates a intros free radical > this binds to DNA, reducing synthesis and causing widespread damage, DNA degradation and cell death. 3) Because aerobic bacteria are not able to reduce metronidazole in this way.

Question 28

Describe 2 mechanisms of bacterial resistance to metronidazole.

Answer 28

1) Reduced uptake of metronidazole. | 2) Reduced generation of intros free radicals.

Question 29

State the 2 main adverse effects which can occur with metronidazole that can occur with most antibiotics.

Answer 29

1) GI upset (N+V) | 2) Immediate and delayed hypersensitivity reactions.

Question 30

Describe 4 neurological adverse effects that can occur when metronidazole is used at high doses.

Answer 30

1) Peripheral neuropathy 2) Optic neuropathy 3) Seizures 4) Encephalopathy

Question 31

1) How is metronidazole metabolised? 2) In whom should the dose of metronidazole used be reduced? 3) Why should alcohol not be drunk whilst taking Metronidazole?

Answer 31

1) By hepatic CYP450 enzymes 2) Those with severe liver disease. 3) Because it inhibits the enzyme acetaldehyde dehydrogenase so can cause a Disulfiram-like reaction (the flush reaction).

Question 32

1) Why does metronidazole reduce metabolism of Warfarin and Phenytoin? 1a) What are the effects of this? 2) Describe the interaction between metronidazole and lithium. 3) Describe the interaction between CYP450 inducers and Metronidazole.

Answer 32

1) Because it has some inhibitory effect on CYP450. 1a) Increased risk of bleeding with Warfarin and increased risk of toxicity, including impaired cerebellar function with Phenytoin. 2) Metronidazole increases the risk of toxicity with lithium. 3) They can cause reduced plasma concentrations of Metronidazole, which can cause impaired antimicrobial efficacy.

Question 33

1) When is oral administration of metronidazole used? 2) When is Metronidazole used via IV administration? 3) Describe another administration route that can be used for nil by mouth patients. 4) When might Metronidazole be used as a gel for topical administration?

Answer 33

1) For GI infection or where the patient is not systemically unwell. 2) For severe infections where patients cannot take treatment by mouth. 3) Rectal metronidazole is another administration route. 4) To treat vaginal infection (bacterial vaginosis) or to reduce the odour from an infected skin ulcer.

Question 34

1) What must you warn the patient not to drink when they are taking Metronidazole? 2) Why are anaerobic bacteria often resistant to penicillins? 3) Which type of penicillin is useful for anaerobic bacterial infections?

Answer 34

1) Alcohol during or for 48 hours after treatment. 2) Due to the production of beta lactamases. 3) Co-amoxiclav has good efficacy against anaerobes.

Question 35

Name the 3 main indications for the use of penicillins.

Answer 35

1) Streptococcal infections - tonsillitis, pneumonia, endocarditis and skin and soft tissue infections. 2) Clostridial infection (e.g. tetanus) 3) Meningococcal infection.

Question 36

1) What do penicillins inhibit? 2) What does inhibition of this enzyme do? 3) What is responsible for the antibacterial activity of penicillins?

Answer 36

1) The enzymes responsible for cross-linking peptidoglycans in bacterial cell walls. 2) Weakens the bacterial cell wall, preventing maintenance of an osmotic gradient leading to cell swelling, lysis and death. 3) The beta lactic ring.

Question 37

1) What does the nature of the side chain attached to the beta lactic ring in penicillins determine? 2) How can bacteria resist the actions of penicillins? 3) Describe 2 other ways that bacteria can become resistant to penicillins.

Answer 37

1) The antimicrobial spectrum and other properties of the drug. 2) By releasing beta lactamase which breaks down the beta lactic ring and prevents antibacterial activity. 3) Limiting the intracellular concentration of penicillin (reduced bacterial permeability or increased extrusion) and changes in the target enzyme to prevent penicillin binding.

Question 38

1) What percentage of people are affected by penicillin allergies? 2) How does the common form of penicillin allergy usually present? 3) Describe the less common form of penicillin allergy.

Answer 38

1) 1-10% 2) A skin rash 7-10 days after first exposure or 1-2 days after repeated exposure (subacute (delayed) IgG reaction). 3) Immediate, life threatening IgE mediated anaphylactic reaction.

Question 39

1) What adverse effect of penicillins can occur with high doses or where severe renal impairment delays excretion? 2) What is the main contraindication of penicillin? 3) What is the main contraindication of penicillin use?

Answer 39

1) Those with renal impairment. | 2) Hx of penicillin allergy.

Question 40

1) What can penicillins reduce the renal excretion of and what does this increase the risk of?

Answer 40

Penicillins can reduce the renal excretion of methotrexate, increasing the risk of toxicity.

Question 41

1) Why can benzylpenicillin only be administered by injection? 2) Why can penicillin V be taken orally? 3) What can be caused if amoxicillin is used to treat a sore throat due to EBV and what antibiotic should you choose instead?

Answer 41

1) Because hydrolysis by gastric acid prevents absorption in the GI tract. 2) Because it is stable in the presence of gastric acid. 3) A skin rash can be caused and so you should use phenoxymethylpenicillin (penicillin V) in young people requiring antibiotics to treat a sore throat.

Question 42

What circumstances are antipseudomonal penicillins reserved for?

Answer 42

1) Severe infections, particularly where there are broad spectrums of potential pathogens (including pseudomonas aeruginosa). 2) When antibiotic resistance is likely. 3) When patients are immunocompromised (neutropenia).

Question 43

Name the 4 main clinical indications for the use of antipseudomonal penicillins.

Answer 43

1) LRTI 2) UTI 3) Intra-abdominal sepsis 4) Skin and soft tissue infections.

Question 44

1) What might the longer side chain of piperacillin improve and what is the benefit? 2) What is the benefit of adding tazobactam to piperacillin?

Answer 44

1) May improve the affinity to penicillin binding proteins, increasing the spectrum of activity including to pseudomonas aeruginosa. 2) Tazobactam is a beta lactamase inhibitor so confers activity against beta lactamase producing bacteria (staph aureus and gram-negative anaerobes).

Question 45

1) What is a common adverse effect of antipseudomonal penicillins? 2) Name 2 less frequent adverse effects of antipseudomonal penicillins.

Answer 45

1) GI upset including nausea and diarrhoea. | 2) Anti-biotic associated colitis and delayed or immediate hypersensitivity.

Question 46

1) Who should antipseudomonal penicillins be used with caution in? 2) What is the main contraindication of antipseudomonal penicillins? 3) In whom should the dose of aentispeudomonal penicillins be reduced?

Answer 46

1) People at risk of C. Diff infection (particularly those in hospital and the elderly) 2) Hx of penicillin allergy. 3) Those with moderate/ severe renal impairment.

Question 47

Describe the interaction between antipseudomonal penicillins and Warfarin.

Answer 47

Antipseudomonal penicillins can enhance the anticoagulant effect of warfarin by killing normal GI flora that synthesise vitamin K.

Question 48

1) How is piperacillin with tazobactam administered? 2) What does addition of an amino acid group to the side chain in amoxicillin do? 3) What does the addition of clavulanic acid to amoxicillin do?

Answer 48

1) Only by IV infusion. 2) Increases activity against Gr- bacteria, making it more broad spectrum. 3) Increases the spectrum of antimicrobial activity further to include beta-lactamase producing bacteria (staph aureus and Gr- anaerobes).

Question 49

Give the 4 common clinical indications for the use of broad-spectrum penicillins.

Answer 49

1) Empirical treatment of pneumonia which can be caused by Gr- or Gr+ pathogens. 2) Empirical treatment of UTI (most commonly caused by E.Coli). Trimethoprim/ nitrofurantoin are alternatives. 3) As part of combination treatment (co-amoxiclav) for hospital acquired infection or intra-abdominal sepsis. 4) Combination treatment for H. Pylori associated peptic ulcers.

Question 50

1) What is a common adverse reaction of broad spectrum penicillins? 2) Name 2 less common adverse effects of broad spectrum antibiotics. 3) What is a rare side effect of co-amoxiclav?

Answer 50

1) GI upset (N+D) 2) Antibiotic associated colitis and hypersensitivity reactions. 3) Cholestatic jaundice.

Question 51

1) Who should broad spectrum antibiotics be used with caution in? 2) What is the only absolute contraindication to broad spectrum antibiotics? 3) Who should a dose reduction of broad spectrum antibiotics be used in?

Answer 51

1) Those at risk of C. Diff infection (those in hospital and the elderly). 2) Hx of penicillin allergy. 3) Those with severe renal impairment (risk of crystalluria).

Question 52

Give 2 interactions of broad spectrum penicillins.

Answer 52

1) reduced renal excretion of methotrexate. | 2) enhanced anticoagulant effect of warfarin.

Question 53

1) Why are quinolone generally reserved for 2nd and 3rd line treatment? 2) How do quinolones kill bacteria? 3) What are quinolones particularly active against? 4) Name 2 newer quinolones with enhanced activity against Gr+ organisms, and state why this is beneficial.

Answer 53

1) Due to the potential for rapid emergence of resistance and an association with C. Diff infection. 2) By inhibiting DNA synthesis. 3) Aerobic Gr- bacteria (explains their utility in UTIs and GI infections) 4) Moxifloxacin and Levofloxacin

Question 54

Give the 4 common clinical indications for the use of Quinolones.

Answer 54

1) UTI 2) Severe GI infection (Shigella/ campylobacter) 3) LRTI (Moxifloxacin/ Levofloxacin) 4) Ciprofloxacin for action against Pseudomonas aeruginosa.

Question 55

Name the 2 main ways that resistance is developed to Quinolones.

Answer 55

1) Prevention of intracellular accumulation of the drug by reducing permeability. 2) Increasing efflux. 3) Development of protective mutations in target enzymes.

Question 56

1) How are quinolone resistance genes spread? 2) Name 2 general adverse effects of quinolones. 3) What can use of quinolones promote?

Answer 56

1) Horizontally between bacteria plasmids, accelerating acquisition of resistance. 2) GI upset (N+D) and immediate and delayed hypersensitivity reactions. 3) Clostridium difficile colitis, particularly with the hypervirulent 027 strain.

Question 57

Give 3 class specific adverse effects of quinolones.

Answer 57

1) Neurological effects (lowering of the seizure threshold and hallucinations) 2) inflammation and rupture of muscle tendons. 3) prolongation of the QT interval and increase the risk of arrhythmias.

Question 58

Name 3 groups of people that quinolones should be used with caution in due to an increased risk of adverse effects.

Answer 58

1) patients at risk of seizures 2) patients who are growing (potential risk of arthropathy) 3) risk factors of QT prolongation (cardiac disease or electrolyte disturbance).

Question 59

1) What types of drugs reduce absorption and efficacy of quinolones? 2) Describe the interaction between ciprofloxacin and theophylline. 3) Co-prescription of quinolones and what increases the risk of seizures?

Answer 59

1) Drugs containing divalent cations (e.g. calcium and antacids). 2) Ciprofloxacin inhibits certain CYP450 enzymes, increasing risk of toxicity with some drugs, notably theophylline. 3) NSAIDs.

Question 60

1) What does co-prescription of quinolones and prednisolone increase the risk of? 2) Name another group of drugs that quinolones should be prescribed with caution in.

Answer 60

1) Increased risk of tendon rupture. 2) Drugs that prolong the QT interval or cause arrhythmias (amiodarone, antipsychotics, quinine, macrolide antibiotics and SSRIs).

Question 61

1) Why can high concentrations of quinolones be achieved by oral administration? 2) What does ciprofloxacin have particularly good antibacterial activity against?

Answer 61

1) Because they are rapidly and extensively absorbed in the intestine. 2) Organisms causing severe traveller's diarrhoea (shigella, salmonella and campylobacter).

Question 62

Name the 4 common indications for the use of Tetracyclines.

Answer 62

1) Acne vulgaris 2) LRTIs (infective exacerbations COPD, pneumonia/atypical pneumonia 3) Chlamydial infection including PID 4) Other infections such as typhoid, anthrax, malaria and Lyme disease.

Question 63

1) What do tetracyclines do? 2) What do tetracyclines bind to? 3) What does this binding prevent? 4) What does inhibition of protein synthesis do?

Answer 63

1) Inhibit bacterial synthesis 2) Ribosomal 30S subunit found specifically in bacteria. 3) binding of tRNA to mRNA, which prevents addition of new amino acids to growing peptide chains. 4) Stops bacterial growth (inhibition of protein synthesis is bacteriostatic) which assists the immune system in killing and removing bacteria from the body.

Question 64

1) What is the spectrum of tetracycline activity? | 2) Describe a common mechanism of resistance to tetracyclines.

Answer 64

1) Relatively broad spectrum | 2) Efflux pump which allows bacteria to pump out tetracyclines, preventing cytoplasmic accumulation.

Question 65

1) What adverse effects do tetracyclines commonly cause? 2) Tetracyclines are among the lowest risk antibiotics for what? 3) In what percentage of people do hypersensitivity reactions to tetracyclines occur? 4) Why is there no cross reactivity between tetracyclines and penicillins?

Answer 65

1) N+V+D 2) C. Diff infection 3) ~1% 4) Because the antibiotic structures are different - tetracyclines have no beta lactic ring.

Question 66

Name 3 tetracycline specific side effects.

Answer 66

1) Oesophageal irritation, ulceration and dysphagia. 2) Photosensitivity 3) Discolouration and/or hypoplasia of tooth enamel if prescribed for children.

Question 67

1) What is a rare adverse effect of tetracyclines that causes headaches and visual disturbance. 2) Give the 3 contraindications of tetracyclines. 3) Why are these conditions contraindicated?

Answer 67

1) Intracranial hypertension. 2) Pregnancy, breastfeeding and children <12 years. 3) because tetracyclines bind to teeth and bones during foetal development, infancy and early childhood.

Question 68

Why should tetracyclines be avoided in patients with renal disease?

Answer 68

As their anti-anabolic effects can raise plasma urea and reduced excretion can increase the risk of adverser effects.

Question 69

1) Why should tetracyclines not be given within 2 hours of calcium, antacids or iron? 2) Describe the interaction between tetracyclines and warfarin.

Answer 69

1) As tetracyclines bind to divalent cations and these will prevent antibiotic absorption. 2) Tetracyclines can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesise vitamin K.

Question 70

1) What is the main common indication for the use of Nitrofurantoin? 2) Why is Nitrofurantoin particularly suited to the treatment of UTIs?

Answer 70

1) Uncomplicated lower UTI, as a first-line antibiotic. 2) because it is effective against the most common causative organisms, reaches therapeutic concentrations in urine through renal excretion and is most bactericidal in acidic environments such as urine.

Question 71

1) How is nitrofurantoin metabolised? 2) What does the active metabolite of Nitrofurantoin do? 3) What types of organisms is Nitrofurantoin active against?

Answer 71

1) It is reduced in bacterial cells by nitrofuran reductase. 2) damages bacterial DNA and causes cell death (bactericidal effect). 3) Gr- (e.g. E. coli), Gr+ (staph. saprophyticus) bacteria which commonly cause UTIs.

Question 72

1) Which types of bacteria are resistant to nitrofurantoin? 2) Which bacteria is it rare for to develop nitrofurantoin resistance? 3) Which 2 types of bacteria are less common causes of UTIs which have intrinsic resistance to nitrofurantoin.

Answer 72

1) Bacteria with reduced nitrofuran reductase activity are resistant to nitrofurantoin. Some organisms that are less common causes of UTIs have this intrinsic resistance. 2) It is relatively rare for E. coli to acquire nitrofurantoin resistance. 3) Klebsiella and proteus species.

Question 73

1) Name two side effects of nitrofurantoin which are common with other antibiotics as well. 2) What colour can nitrofurantoin turn urine? 3) Name 3 side effects of Nitrofurantoin which usually occur with prolonged administration. 4) What side effect of nitrofurantoin might happen, specifically in neonates?

Answer 73

1) GI upset (N+V) and immediate and delayed hypersensitivity reactions. 2) Dark yellow or brown. 3) Chronic pulmonary reactions (pneumonitis and fibrosis), hepatitis and peripheral neuropathy - all more likely with prolonged administration. 4) Haemolytic anaemia may occur because immature red blood cells are unable to mop up nitrofurantoin-stimulated superoxides, which damage red blood cells.

Question 74

1) Give 3 contraindications to the use of nitrofurantoin. 2) Why is nitrofurantoin contraindicated in renal impairment? 3) When is caution required when using nitrofurantoin and why?

Answer 74

1) Pregnancy towards term, babies in the first 3 months of life and renal impairment. 2) Because impaired excretion increases toxicity and reduces efficacy due to lower urinary drug concentrations. 3) Caution required when using nitrofurantoin for long term prevention of UTIs as chronic use increases the risk of adverse effects, particularly in elderly patients.

Question 75

Describe important interactions of Nitrofurantoin.

Answer 75

There are no significant interactions between nitrofurantoin and other commonly prescribed drugs.

Question 76

1) How is nitrofurantoin available for administration? 2) For a typical UTI, what is the dosage regimen for Nitrofurantoin? 3) What is the treatment regimen using Nitrofurantoin for the prevention of recurrent UTIs?

Answer 76

1) Only available for oral administration. 2) 50-100mg 6 hourly (3/7 for uncomplicated, 7/7 for complicated and in men). 3) single 50-100mg ON dose. Only longer than 6/12 if strongly indicated, and this requires monitoring.

Question 77

1) Why should you not prescribe nitrofurantoin for pyelonephritis or other complicated UTIs? 2) What is a suitable alternative regimen?

Answer 77

1) Because tissue concentrations of nitrofurantoin are very low. 2) Co-amoxiclav with gentamicin.

Question 78

Name the 2 common clinical indications for the use of Trimethoprim.

Answer 78

1) 1st line uncomplicated UTIs (alternatives = nitrofurantoin and amoxicillin) 2) Co-trimoxazole for treatment and prevention of pneumocystis pneumonia in people with immunosuppression (e.g. due to HIV).

Question 79

1) Why do bacteria need to make their own sources of folate and what do they need this for? 2) Describe the bacteriostatic action of trimethoprim. 3) Describe the spectrum of action of trimethoprim.

Answer 79

1) Because they are unable to use external sources of folate so need to make their own for essential functions, including DNA synthesis. 2) Inhibits bacterial folate synthesis, slowing bacterial growth (bacteriostatic). 3) Broad spectrum of action against Gr+ and Gr- bacteria, particularly enterobacteria. However, clinical utility is reduced by widespread bacterial resistance.

Question 80

Give 2 mechanisms of resistance against trimethoprim.

Answer 80

1) Reduced intracellular antibiotic accumulation. | 2) Reduced sensitivity of target enzymes

Question 81

1) Name another drug which inhibits bacterial folate synthesis. 2) Why might trimethoprim and sulfamethoxazole be used together.

Answer 81

1) Sulfonamides also inhibit bacterial folate synthesis. | 2) Together they cause a more complete inhibition of folate synthesis, making them bactericidal.

Question 82

1) Name the 2 side effects that trimethoprim most commonly causes. 2) Which types of reactions occur rarely with trimethoprim, but more commonly with sulfonamides? 3) Which haematological disorders might trimethoprim cause and why? 4) What electrolyte abnormalities might Trimethoprim cause?

Answer 82

1) GI upset (N + V and a sore mouth) and a skin rash. 2) Severe hypersensitivity reactions, including anaphylaxis, drug fever and erythema multiforme. 3) Megaloblastic anaemia, leucopenia and thrombocytopenia - because as a folate antagonist, trimethoprim can impair haematopoiesis. 4) It can also cause hyperkalaemia and elevation of plasma creatinine levels

Question 83

1) Why should trimethoprim not be used with other potassium-elevating drugs? 2) What increases the risk of adverse haematological events when using trimethoprim? 3) Describe the interaction between trimethoprim and warfarin.

Answer 83

1) Because it predisposes to hyperkalaemia (e.g. when used with aldosterone antagonists, ACEi's, ARBs). 2) Use with other folate antagonists (methotrexate) and drugs that increase folate metabolism (e.g. phenytoin) increases the risk of adverse haematological effects. 3) Trimethoprim can enhance the anticoagulant effect of Warfarin by killing normal gut flora that synthesise vitamin K.

Question 84

1) How is trimethoprim available for administration? 2) How is trimethoprim prescribed for an acute UTI? 3) How is trimethoprim prescribed for prophylaxis of a recurrent UTI?

Answer 84

1) Oral administration. 2) 200mg 12 hourly (duration determined by severity). 3) 100mg OD ON.

Question 85

1) How is co-trimoxazole available for administration? | 2) Why must co-trimoxazole be diluted immediately before intravenous use?

Answer 85

1) Orally or intravenously. | 2) in order to prevent crystallisation.

Question 86

1) Trimethoprim can cause a small, reversible rise in serum creatinine concentration without a reduction in GFR - why is this? 2) And so why is Trimethoprim less effective for UTI treatment in patients with renal impairment?

Answer 86

1) Because trimethoprim competitively inhibits creatinine secretion by the renal tubules 2) Because it is out-competed by creatinine for secretion into the urinary tract.

Question 87

1) Why is trimethoprim contraindicated in the first trimester of pregnancy? 2) Who should trimethoprim be used with caution in and why? 3) Why is dose reduction of trimethoprim required in patients with renal impairment?

Answer 87

1) Because it is a folate antagonist and so is associated with an increased risk of foetal abnormalities (CV defects and oral clefts). 2) Use with caution in people with folate deficiency as they are more susceptible to adverse haematological effects. 3) Trimethoprim is mostly excreted into the urine, so is less suited to people with renal impairment.

Question 88

Which 3 groups of people are particularly susceptible to the adverse effects of trimethoprim?

Answer 88

1) Neonates 2) The elderly 3) Patients with HIV