🦠 Infectious Diseases and Antimicrobials

1. Which antibiotic is the usual first choice for uncomplicated streptococcal pharyngitis in a patient with no allergy?

1. Ciprofloxacin, because it achieves the highest tonsillar tissue concentrations of any agent
2. Penicillin V or amoxicillin, given for the full course recommended by the guideline
3. Vancomycin given orally, because it is not absorbed and acts directly on the throat tissue
4. Azithromycin, which is preferred first-line because of its very short treatment course

Group A streptococcus remains uniformly susceptible to penicillin, so penicillin V or amoxicillin is first-line, with a macrolide or first-generation cephalosporin reserved for allergy. Fluoroquinolones are inappropriate and oral vancomycin acts only in the gut lumen. Source: CPhA Therapeutic Choices, pharyngitis chapter.

2. A patient reports that penicillin gave him a rash aged five, with no swelling or breathing difficulty. What is the most appropriate approach?

1. Take a structured allergy history, since most such labels do not represent true allergy
2. Record a lifelong absolute contraindication to all beta-lactam antibiotics without further enquiry
3. Give a full dose of penicillin at once without any assessment of the history at all
4. Substitute a fluoroquinolone permanently for every future infection of any kind

Most childhood rashes attributed to penicillin were viral or benign, and carrying an inaccurate label leads to broader, less effective and more toxic therapy, so a structured history and, where appropriate, referral for assessment are recommended. Blanket avoidance and reflex fluoroquinolone use are both harmful. Source: CPhA Therapeutic Choices, antimicrobial allergy chapter.

3. Why is amoxicillin-clavulanate more likely than amoxicillin alone to cause diarrhoea?

1. Amoxicillin is not absorbed at all when it is combined with clavulanate in one tablet
2. The clavulanate component itself has a direct effect on gastrointestinal motility and flora
3. Clavulanate is an antibiotic with a very broad spectrum that eradicates all gut organisms
4. The combination is always given at four times the dose of amoxicillin used alone in adults and in children

Clavulanate contributes independently to gastrointestinal upset, which is why the combination is reserved for situations where beta-lactamase production is likely and why taking it with food is advised. Clavulanate is a beta-lactamase inhibitor with little antibacterial activity of its own. Source: Health Canada product monograph for amoxicillin-clavulanate.

4. A patient with a documented anaphylactic reaction to penicillin needs treatment for cellulitis. Which option is most appropriate?

1. A carbapenem, which shares no structural features with the penicillin molecule at all
2. A first-generation cephalosporin at full dose, since cross-reactivity is impossible
3. A non-beta-lactam agent with activity against streptococci and staphylococci
4. Amoxicillin given with an antihistamine, which prevents any anaphylactic reaction

After true anaphylaxis, a non-beta-lactam such as clindamycin or a suitable alternative is used unless formal allergy assessment has been performed, because premedication does not prevent anaphylaxis. Cross-reactivity with modern cephalosporins is low but is not zero. Source: CPhA Therapeutic Choices, skin and soft tissue infections chapter.

5. Which macrolide is the most potent inhibitor of CYP3A4 and therefore the most interaction-prone?

1. Clarithromycin, which raises exposure to statins, calcium channel blockers and many others
2. Azithromycin, which is the strongest CYP3A4 inhibitor of the currently marketed macrolides
3. Erythromycin ophthalmic ointment, which produces high systemic concentrations after use
4. Fidaxomicin, which is absorbed completely and inhibits CYP3A4 throughout the body within a few hours of dosing

Clarithromycin is a strong CYP3A4 inhibitor and causes clinically important interactions with simvastatin, some calcium channel blockers, colchicine and several immunosuppressants, whereas azithromycin has little effect. Topical erythromycin and oral fidaxomicin have minimal systemic exposure. Source: Health Canada product monograph for clarithromycin.

6. Which cardiac risk is shared across the macrolide class?

1. Complete atrioventricular block occurring within minutes of the first oral dose
2. Prolongation of the QT interval with a risk of torsades de pointes in susceptible patients
3. Irreversible dilated cardiomyopathy developing after a single five-day course in previously healthy adults
4. Acute coronary artery spasm that produces myocardial infarction in most patients

Macrolides prolong the QT interval, and the risk of torsades rises with electrolyte disturbance, bradycardia, other QT-prolonging drugs and existing conduction disease. The other cardiac events are not features of the class. Source: Health Canada product monographs for the macrolides.

7. How should a patient take ciprofloxacin in relation to dairy products, antacids and mineral supplements?

1. Take the antibiotic together with an antacid to prevent the gastric irritation it causes
2. Take the antibiotic with a large glass of milk, which improves its absorption markedly
3. Separate the antibiotic from these products by the interval stated in the monograph
4. Take the antibiotic with an iron supplement so that both are absorbed at the same time

Fluoroquinolones chelate calcium, magnesium, aluminium, iron and zinc, and simultaneous administration can reduce absorption enough to cause treatment failure, so the doses are separated by the stated interval. All three alternatives would impair absorption. Source: Health Canada product monograph for ciprofloxacin.

8. Which adverse effects led to restrictions on fluoroquinolone use for uncomplicated infections?

1. Isolated transient elevation of the serum amylase without any clinical consequence
2. Reversible hair loss and mild nail discolouration seen in most treated patients within the first two weeks
3. Tendinitis and tendon rupture, peripheral neuropathy and central nervous system effects
4. A predictable fall in blood pressure requiring hospital admission in every patient

Disabling and potentially irreversible musculoskeletal, neurological and psychiatric reactions, together with aortic aneurysm and dissection signals, led regulators to restrict fluoroquinolones to infections without safer alternatives. The other effects are not the basis of the restriction. Source: Health Canada safety review of the systemic fluoroquinolones.

9. Which instruction reduces the risk of oesophageal irritation from doxycycline?

1. Take it with a full glass of water and remain upright for a period after the dose
2. Take it lying down immediately before sleep so that the tablet passes slowly down the oesophagus overnight
3. Take it with a very small sip of water to reduce the contact time in the throat
4. Crush the tablet and take it dry so that it does not adhere to the oesophagus

Doxycycline can cause pill oesophagitis, so it is taken with a full glass of water while sitting or standing and is not taken immediately before lying down. Small sips, recumbency and dry administration all increase mucosal contact. Source: Health Canada product monograph for doxycycline.

10. Which patient should generally not receive doxycycline?

1. An adult with well controlled asthma who uses an inhaled corticosteroid twice daily
2. A pregnant woman in the second half of pregnancy, because of effects on developing teeth
3. An adult with treated hypothyroidism who takes a stable dose of levothyroxine daily
4. An adult with seasonal allergic rhinitis controlled by an intranasal corticosteroid through the pollen season

Tetracyclines bind to calcium in developing teeth and bone, so they are avoided in the later part of pregnancy and in young children except when the benefit clearly outweighs the risk, as in some tick-borne infections. The other conditions are not contraindications. Source: Health Canada product monograph for doxycycline.

11. Which agent is inappropriate for pyelonephritis despite being useful for cystitis?

1. Trimethoprim-sulfamethoxazole, because it is inactive against all urinary pathogens
2. Ciprofloxacin, because it does not achieve adequate concentrations in kidney tissue
3. Nitrofurantoin, because it concentrates in urine but does not reach renal tissue
4. Amoxicillin-clavulanate, because it is destroyed by beta-lactamase in the kidney

Nitrofurantoin achieves therapeutic concentrations only in urine, so it is effective in uncomplicated cystitis and inadequate for tissue infection such as pyelonephritis or prostatitis. The other agents do reach renal tissue and are used according to susceptibility. Source: Health Canada product monograph for nitrofurantoin.

12. Why is nitrofurantoin avoided when creatinine clearance is substantially reduced?

1. Reduced urinary concentration means the drug may not reach an effective level in urine
2. It accumulates in the kidney and causes an immediate irreversible tubular necrosis
3. It is contraindicated because it raises serum potassium in every patient with impairment
4. It cannot be given with any other drug when renal function falls below the normal range

Nitrofurantoin depends on renal excretion to reach therapeutic urinary concentrations, so efficacy falls as clearance declines, and there is also concern about systemic accumulation and pulmonary and hepatic toxicity with long-term use. The other statements are inaccurate. Source: Health Canada product monograph for nitrofurantoin.

13. An otherwise healthy non-pregnant woman has asymptomatic bacteriuria found on a routine urine culture. What is the correct action?

1. No antibiotic treatment, because treating it does not improve outcomes and drives resistance
2. A seven-day course of an oral antibiotic to prevent progression to pyelonephritis and of later renal scarring
3. A single dose of an intravenous antibiotic to eradicate the organism definitively
4. A three-month course of low-dose prophylaxis to prevent recurrence of the bacteriuria over the following winter

Asymptomatic bacteriuria is treated only in pregnancy and before certain urological procedures, because treatment in other groups produces no benefit and increases resistance and adverse effects. Prolonged prophylaxis is not indicated for this finding. Source: CPhA Therapeutic Choices, urinary tract infection chapter.

14. Which laboratory change should be anticipated when trimethoprim-sulfamethoxazole is given to a patient on an ACE inhibitor?

1. A fall in serum sodium caused by direct stimulation of antidiuretic hormone release
2. A fall in serum potassium, because sulfamethoxazole acts as a potent loop diuretic at the usual treatment dose
3. A rise in serum calcium, because trimethoprim increases intestinal calcium absorption from the diet each day
4. A rise in serum potassium, because trimethoprim blocks the distal epithelial sodium channel

Trimethoprim acts like amiloride at the distal nephron, and combined with renin-angiotensin blockade it can produce dangerous hyperkalaemia, especially in older patients or with reduced renal function. The other electrolyte changes are not features of this combination. Source: Health Canada product monograph for trimethoprim-sulfamethoxazole.

15. Which patient factor makes trimethoprim-sulfamethoxazole particularly hazardous?

1. Well controlled essential hypertension treated with a single agent for many years
2. Glucose-6-phosphate dehydrogenase deficiency, because of the risk of haemolysis
3. A previous uncomplicated cholecystectomy performed several years before the illness
4. A history of childhood asthma that has been completely quiescent for two decades

Sulfonamides can precipitate haemolysis in glucose-6-phosphate dehydrogenase deficiency, and the combination also causes severe cutaneous reactions, hyperkalaemia and marrow suppression. The other histories do not alter the risk. Source: Health Canada product monograph for trimethoprim-sulfamethoxazole.

16. A patient develops flushing of the face and upper body during a vancomycin infusion. What is the correct interpretation?

1. A true immunoglobulin E mediated allergy that permanently contraindicates the drug and all related glycopeptides
2. An infusion-rate-related histamine reaction, managed by slowing the rate of administration
3. An expected sign that the target concentration has been reached in the bloodstream
4. A sign of bacterial endotoxin release requiring the infusion to be stopped permanently and never restarted afterwards

Vancomycin infusion reaction is a direct, rate-dependent histamine release rather than an allergy, and it is managed by slowing the infusion and pretreating with an antihistamine when necessary. Labelling it as an allergy denies the patient a useful antibiotic. Source: Health Canada product monograph for vancomycin.

17. How is intravenous vancomycin therapy most appropriately monitored in current practice?

1. By clinical response only, since concentration monitoring has been shown to be useless in randomised comparisons
2. By measuring the peak concentration alone, since the trough gives no useful information about the risk of toxicity
3. Against a pharmacokinetic target of exposure relative to the minimum inhibitory concentration
4. By measuring the concentration in the urine collected over a twenty-four hour period

Contemporary practice targets an area under the curve relative to the minimum inhibitory concentration, estimated from concentrations, rather than a trough alone, in order to balance efficacy against nephrotoxicity. Clinical response alone and urinary measurement are not adequate. Source: CPhA Therapeutic Choices, antimicrobial dosing chapter.

18. Which toxicity of aminoglycosides may be irreversible?

1. Ototoxicity, affecting hearing and vestibular function, which may be permanent
2. Nephrotoxicity, which invariably progresses to permanent dialysis dependence once the drug has been given
3. Hepatotoxicity, which always leaves a fixed cholestatic pattern after therapy that persists for many years
4. Photosensitivity, which persists for the remainder of the patient's lifetime

Aminoglycoside ototoxicity can be permanent, whereas the nephrotoxicity is usually reversible when the drug is stopped, which is why monitoring of renal function and attention to duration and cumulative dose matter so much. Hepatotoxicity and photosensitivity are not features. Source: Health Canada product monographs for the aminoglycosides.

19. What is the rationale for extended-interval aminoglycoside dosing?

1. Concentration-dependent killing with a post-antibiotic effect allows high peaks and low troughs
2. The drug is absorbed more completely when it is given only once in each twenty-four hours than when it is divided
3. Extended intervals are used only because they reduce the cost of preparing the infusion and the nursing time required
4. The drug requires a long trough period to be converted into its active metabolite

Aminoglycosides kill in proportion to peak concentration and retain a post-antibiotic effect, so a high peak with a prolonged low trough maximises efficacy while reducing the time-dependent uptake into renal and cochlear cells. The other explanations are not correct. Source: CPhA Therapeutic Choices, antimicrobial dosing chapter.

20. Which counselling point is traditionally given with metronidazole?

1. Avoid all dairy products for a month after the last dose has been taken because of a calcium interaction
2. Take each dose with a glass of wine, which improves the absorption of the drug from the intestinal tract
3. Expect the stool to become bright green for the duration of the treatment course and for a week afterwards
4. Avoid alcohol during and shortly after the course because of a reported reaction

A disulfiram-like reaction with flushing, nausea and vomiting has been reported with metronidazole and alcohol, so avoidance during and for a short period after therapy is the conventional advice, although the evidence is debated. The drug can darken urine rather than the stool. Source: Health Canada product monograph for metronidazole.

21. Which agents are used for an initial episode of Clostridioides difficile infection?

1. Intramuscular benzathine penicillin given as a single dose at presentation
2. Intravenous vancomycin, because it achieves the highest concentration in the colon
3. Oral ciprofloxacin, which is the preferred first-line therapy for this infection
4. Oral vancomycin or fidaxomicin, given for the duration stated in the guideline

Oral vancomycin and fidaxomicin achieve high intraluminal colonic concentrations and are the preferred agents, whereas intravenous vancomycin does not reach the colonic lumen. Fluoroquinolones are a leading precipitant rather than a treatment. Source: CPhA Therapeutic Choices, Clostridioides difficile chapter.

22. Which antibiotic classes are most strongly associated with precipitating Clostridioides difficile infection?

1. Inhaled tobramycin used long term in patients with cystic fibrosis lung disease
2. Topical antibacterial ointments applied to small superficial skin wounds
3. Ophthalmic antibiotic drops used for a few days for bacterial conjunctivitis
4. Fluoroquinolones, clindamycin, cephalosporins and broad-spectrum penicillins

Agents that disrupt colonic flora most profoundly carry the greatest risk, and stewardship to reduce their use is the principal preventive measure alongside hand hygiene and environmental cleaning. Topical, ophthalmic and inhaled routes carry little colonic exposure. Source: CPhA Therapeutic Choices, Clostridioides difficile chapter.

23. Why do azole antifungals cause so many drug interactions?

1. They induce every cytochrome P450 isoenzyme, which accelerates elimination of other drugs and of their active metabolites
2. They inhibit cytochrome P450 isoenzymes, particularly CYP3A4, and some inhibit transporters
3. They bind irreversibly to plasma albumin and displace all other protein-bound drugs from their binding sites
4. They alter gastric pH so profoundly that no other oral drug can be absorbed at all during the treatment course

Azoles work by inhibiting a fungal cytochrome enzyme and also inhibit human isoenzymes, particularly CYP3A4, raising concentrations of statins, immunosuppressants, some anticoagulants and many other substrates. They are inhibitors rather than inducers. Source: Health Canada product monographs for the azole antifungals.

24. Which monitoring accompanies oral terbinafine for onychomycosis?

1. Serum lithium concentration measured every two weeks throughout the treatment course
2. Liver enzymes and a complete blood count, as directed for prolonged courses
3. Thyroid function tested weekly because of a high risk of thyroiditis with this drug
4. Bone mineral density measured before and after the treatment course is completed

Terbinafine can cause hepatotoxicity and, uncommonly, haematological effects, so baseline and periodic liver enzyme testing is recommended for the prolonged courses used in nail infection, and taste disturbance is also discussed. The other tests are unrelated. Source: Health Canada product monograph for terbinafine.

25. Within what period must an antiviral for influenza normally be started to give the greatest benefit?

1. Only once a laboratory-confirmed result has returned, whatever the delay involved
2. At any time during the illness, since benefit is identical whenever therapy starts
3. Only after the fever has settled, so that the drug is not wasted on a viral peak
4. As soon as possible after symptom onset, within the window stated in the guidance

Neuraminidase inhibitors shorten illness and reduce complications most when started early after symptom onset, so treatment of high-risk patients is often begun on clinical grounds without waiting for confirmation. Delaying until fever settles or until testing returns removes most of the benefit. Source: CPhA Therapeutic Choices, influenza chapter.

26. Which adjustment is required for valacyclovir in a patient with reduced renal function?

1. The drug is replaced by an intravenous formulation at twice the usual daily dose
2. No adjustment is ever required, because the drug is eliminated entirely by the liver
3. The dose is increased, because renal impairment reduces conversion to acyclovir
4. Dose reduction or interval extension, since accumulation causes neurotoxicity

Valacyclovir is converted to acyclovir, which is renally cleared, so accumulation in renal impairment can cause confusion, hallucinations and crystalluria; dose and interval are adjusted and hydration is maintained. Increasing the dose would be dangerous. Source: Health Canada product monograph for valacyclovir.

27. Why is pyridoxine given alongside isoniazid?

1. To increase the antimicrobial activity of isoniazid against the tubercle bacillus within the infected tissue
2. To prevent the peripheral neuropathy caused by isoniazid-induced pyridoxine depletion
3. To prevent the orange discolouration of body fluids caused by isoniazid therapy during the first month
4. To protect the optic nerve from the specific toxicity of isoniazid on vision at the doses normally used

Isoniazid interferes with pyridoxine metabolism and can cause a dose-related peripheral neuropathy, which supplementation prevents, particularly in patients with diabetes, alcohol use disorder, malnutrition, pregnancy or renal failure. Orange fluids are a rifampin effect and optic neuritis belongs to ethambutol. Source: Canadian Tuberculosis Standards.

28. Which effect of rifampin creates the largest number of clinically important interactions?

1. Complete blockade of intestinal absorption of every drug taken at the same time
2. Potent inhibition of CYP3A4, which raises the concentration of many substrates
3. Irreversible binding to plasma albumin, which displaces all other bound drugs
4. Potent induction of multiple cytochrome P450 isoenzymes and of P-glycoprotein

Rifampin is one of the most powerful enzyme inducers in clinical use, lowering concentrations of hormonal contraceptives, warfarin, many antiretrovirals, immunosuppressants and numerous other drugs, and the effect persists for a period after it is stopped. It is an inducer, not an inhibitor. Source: Health Canada product monograph for rifampin.

29. Which specific monitoring accompanies ethambutol therapy?

1. Bone marrow aspiration every three months to detect aplastic anaemia early during prolonged therapy
2. Audiometry every month, because the drug causes irreversible hearing loss in a substantial minority
3. Renal biopsy at the start and end of therapy to detect interstitial nephritis caused by the drug itself
4. Visual acuity and colour discrimination, because of the risk of optic neuritis

Ethambutol can cause dose-related optic neuritis with loss of acuity and of red-green discrimination, so baseline and periodic visual assessment is standard and patients are told to report any visual change immediately. The other investigations are not required. Source: Canadian Tuberculosis Standards.

30. What is the best response to a patient requesting an antibiotic for a common cold?

1. Explain that the illness is viral, offer symptomatic measures and describe warning signs
2. Supply an antibiotic to maintain the therapeutic relationship with the patient who has come to expect one
3. Advise the patient to use a leftover antibiotic from a previous prescription at home for the next few days
4. Recommend a delayed prescription in all cases without any clinical assessment of the presenting illness

Antibiotics do not shorten a viral upper respiratory illness and cause harm and resistance, so the pharmacist explains the natural history, recommends symptomatic care and describes the features that would warrant reassessment. Supplying antibiotics or reusing leftovers is inappropriate. Source: CPhA Therapeutic Choices, upper respiratory infections chapter.

31. Which principle underlies the shorter antibiotic courses now recommended for many infections?

1. Shorter courses are chosen only to reduce the cost of the medicine to the patient
2. Longer courses are always safer because they guarantee eradication of every organism
3. Course length has no effect on resistance, so duration is a matter of preference only
4. Shorter courses are as effective for many infections and reduce resistance and adverse effects

Trial evidence supports shorter durations for many common infections, and reducing exposure lowers the selection pressure for resistance and the risk of adverse effects and Clostridioides difficile infection. Longer is not automatically safer. Source: CPhA Therapeutic Choices, antimicrobial stewardship chapter.

32. Which approach is appropriate for a well child over two years with mild acute otitis media?

1. A ten-day course of a fluoroquinolone as the preferred first-line oral treatment
2. Immediate intravenous antibiotics for every child presenting with any ear pain
3. Analgesia with a period of watchful waiting and a plan for review if symptoms persist
4. No analgesia at all, so that any deterioration can be detected by the parents

Watchful waiting with adequate analgesia is appropriate for selected older children with mild illness, with amoxicillin used if symptoms persist or worsen, or immediately in younger or more unwell children. Fluoroquinolones are not used and analgesia is always provided. Source: CPhA Therapeutic Choices, otitis media chapter.

33. A patient has a purulent skin abscess. What is the most important element of management?

1. Incision and drainage, with antibiotics added according to severity and risk factors
2. A prolonged oral antibiotic course alone, since drainage delays healing of the skin
3. Topical antibiotic ointment alone, which reliably resolves a collection of pus
4. Complete avoidance of any intervention until the abscess discharges spontaneously

Drainage is the definitive treatment for an abscess, and antibiotics are added when there is surrounding cellulitis, systemic features, immunosuppression or other risk factors, with coverage for methicillin-resistant organisms when indicated. Antibiotics alone do not treat a collection. Source: CPhA Therapeutic Choices, skin and soft tissue infections chapter.

34. Which factor determines the choice of malaria chemoprophylaxis for a traveller?

1. The price of the product alone, since all regimens are equally effective everywhere
2. The destination and its resistance pattern, together with the traveller's own characteristics
3. The traveller's preferred tablet size and colour, which determine adherence entirely
4. The season of the year in Canada rather than conditions at the destination

Prophylaxis is selected on destination-specific resistance patterns, duration and style of travel, pregnancy, comorbidity, interactions and tolerability, with counselling on bite prevention and on the need for medical assessment of any fever after travel. Price and appearance are secondary considerations. Source: Canadian recommendations for the prevention and treatment of malaria.

35. What must a traveller be told about stopping malaria chemoprophylaxis after returning home?

1. Continue for the full period stated after leaving the risk area, which differs by agent
2. Stop on the day of departure from the risk area, whichever agent has been used
3. Stop as soon as the traveller feels well, regardless of the regimen prescribed
4. Continue for exactly one year after return, whichever agent has been prescribed

The post-travel duration depends on whether the agent acts on liver stages, so atovaquone-proguanil is continued for a short period after leaving while mefloquine and doxycycline are continued for several weeks. Stopping early is a common cause of breakthrough infection. Source: Canadian recommendations for the prevention and treatment of malaria.