Infectious Pharmacology Flashcards
A 72-year-old woman is admitted to hospital with severe cellulitis of her right leg. She has no allergies.
What is the most appropriate treatment?
A. Amoxicillin and clarithromycin
B. Benzylpenicillin and flucloxacillin
C. Cefotaxime and aciclovir
D. Co-amoxiclav and metronidazole
E. Co-amoxiclav and gentamicin
B. Benzylpenicillin and flucloxacillin
In the clinical setting, antibiotics are chosen based on a ‘best guess’ as to the likely causative organism and antibiotic sensitivities. When infection is severe, being wrong with this guess and prescribing inadequate antibiotic treatment can be life threatening, so combination antibiotics are often prescribed to cover all likely eventualities.
Skin and soft tissue infections are most commonly caused by Staphylococcus aureus and Group A Streptococci (e.g. Streptococcus pyogenes). These bacteria are usually sensitive to flucloxacillin (a penicillinase-resistant penicillin) and benzylpenicillin (a ‘standard’ penicillin), respectively. As such, this combination is appropriate for severe cellulitis.
Amoxicillin (a broad-spectrum penicillin) and clarithromycin (a macrolide) are used in severe pneumonia to cover typical and atypical organisms, respectively. Cefotaxime (a cephalosporin) and aciclovir (an antiviral drug) are used in suspected intracranial infection to cover bacterial meningitis and viral encephalitis, pending a diagnosis from lumbar puncture. Co-amoxiclav (amoxicillin with clavulanic acid) and metronidazole are used in intra-abdominal sepsis to cover Gram-negative aerobic and anaerobic gut organisms. Co-amoxiclav and gentamicin (an aminoglycoside) are used in complicated urinary tract infections to cover Gram-negative organisms.
An 83-year-old woman is admitted to the acute medical unit with a diagnosis of mild community-acquired pneumonia (CURB-65 score 1). Her mobility is poor, but she has no active co-morbidities, does not usually take any medications, and has no allergies.
What would be the most appropriate antibiotic to treat her infection?
A.Cefotaxime
B. Ciprofloxacin
C. Doxycycline
D. Ertapenem
E. Flucloxacillin
C. Doxycycline (tetracycline) is used first line for pneumonia because they treat gram-ve and gram +ve bacteria.
A wide spectrum of organisms can cause community-acquired pneumonia, including Streptococcus pneumoniae (Gram positive), Haemophilus influenzae (Gram negative) and ‘atypical’ organisms such as Mycoplasma pneumoniae and Legionella pneumophila. The ‘best guess’ antibiotic for pneumonia therefore should ideally have a broad spectrum of activity to cover all these possibilities. Doxycycline (a tetracycline) is suitable because it covers Gram-positive, Gram-negative and atypical organisms.
Flucloxacillin is incorrect because it is a penicillinase-resistant penicillin with a narrow spectrum of activity, principally focused against Staphylococcus aureus.
The quinolone antibiotics, including ciprofloxacin, are generally reserved for second- or third-line therapy to preserve their usefulness, as bacteria easily acquire resistance to them. Ciprofloxacin is mostly effective against Gram-negative organisms, including Pseudomonas aeruginosa. Moxifloxacin and levofloxacin have greater activity against Gram-positive organisms and are therefore preferred for pneumonia.
Ertapenem (a carbapenem) and cefotaxime (a cephalosporin) are broad-spectrum antibiotics which have to be given by injection. They are reserved for severe infections and those associated with resistant organisms, such as hospital-acquired pneumonia in people with underlying chronic lung disease.
A 44-year-old man needs antibiotic treatment for infection with a penicillinase-producing strain of Staphylococcus aureus.
What antibiotic is this organism most likely to be resistant to?
A.Benzylpenicillin
B.Co-amoxiclav
C. Flucloxacillin
D. Tazocin®
E. Vancomycin
A.Benzylpenicillin-> penicillinase break down beta-lactam ring in penicillins
A 56-year-old man notices tinnitus and dizziness after discharge from hospital where he was treated for severe pneumonia. During this admission (which included a spell in the intensive care unit), his antibiotic treatment included courses of doxycycline, co-amoxiclav, clarithromycin, piperacillin with tazobactam, and gentamicin.
Which antibiotic is most likely to have caused this adverse effect?
A. Clarithromycin
B. Co-amoxiclav
C. Doxycycline
D. Gentamicin
E. Piperacillin with tazobactam
D. gentamicin-> ototoxic and affects vestibulocochlear nerve-> hearing loss and tinnitus
Aminoglycosides (e.g. gentamicin) accumulate in cochlear and vestibular hair cells where they trigger apoptosis and cell death. This can cause deafness, tinnitus and vertigo. Macrolides (e.g. clarithromycin) can also cause tinnitus and hearing loss, but this is rare and usually associated with long-term therapy. Other drugs that cause ototoxicity include vancomycin and loop diuretics.
A 4-year-old boy is found to have pneumonia.
What antibiotic is contraindicated at this age?
A. Amoxicillin
B. Cefotaxime
C. Co-amoxiclav
D.Clarithromycin
E.Doxycycline
E. doxycycline (tetracycline) can bind to Ca2+-> cause rickets
Tetracyclines (e.g. doxycycline) bind to calcium in developing teeth and bone. This can cause discolouration and/or hypoplasia of tooth enamel and theoretically could affect the developing skeleton. They should not be prescribed for women who are pregnant or breastfeeding or to children who have not yet formed their secondary dentition (under 12 years of age). The other antibiotics can be used in children if clinically indicated.
A 68-year-old woman is found to have cellulitis. She has a past medical history of hypertension, leg cramps and urge incontinence. Her medication comprises bendroflumethiazide, oxybutynin and quinine sulfate. She is allergic to penicillin, which causes a rash. The doctor begins to prescribe clarithromycin, but is alerted to a possible interaction by the electronic prescribing system.
What is the main risk of prescribing clarithromycin in this case?
A.Hyperkalaemia
B.QT-interval prolongation
C.Renal impairment
D.Myopathy
E.Seizures
B.QT-interval prolongation (amiodarone, sotalol, TCAs and SSRIs), erythromycin and clarithromycin, antipsychotics (e.g haloperidol)
B. QT-interval prolongation. The QT interval is the time between the beginning of the QRS complex and the end of the T-wave. It mostly reflects the time taken for the ventricles to repolarise. The QT interval is said to be prolonged if, after correction for heart rate (by dividing it by the square root of the RR interval), it exceeds 0.44 seconds in men or 0.46 seconds in women. This is associated with an increased risk of a life-threatening arrhythmia called torsade de pointes, a form of ventricular tachycardia.
There are several causes of a prolonged QT interval. Drug causes include antiarrhythmics (e.g. amiodarone), antipsychotics (e.g. haloperidol), macrolide antibiotics (e.g. clarithromycin), and quinine. Combining drugs with QT-prolonging effects can be dangerous (clarithromycin with quinine sulfate for this patient) and should be avoided. A useful database of drugs that prolong the QT interval is maintained by the University of Arizona Center for Education and Research on Therapeutics at www.qtdrugs.org (accessed 24/2/14).
This patient is not taking any drugs that increase the potassium concentration, and is not at risk of seizures. Had she been taking a statin, there would have been a risk that clarithromycin could precipitate myopathy.
A 72-year-old woman is advised to take doxycycline 100 mg daily and prednisolone 30 mg daily for an exacerbation of chronic obstructive pulmonary disease. Her usual medication is aspirin 75 mg daily, ferrous sulfate 200 mg twice daily, furosemide 40 mg daily, lansoprazole 30 mg daily, and ramipril 5 mg daily.
What medicine should she be advised to separate from doxycycline by at least 2 hours?
A.Aspirin
B.Ferrous sulfate
C.Furosemide
D.Lansoprazole
E. Ramipril
B. Ferrous sulfate.
B. Ferrous sulfate. Tetracyclines bind to divalent cations. They should therefore be separated by at least 2 hours from doses of calcium, antacids or iron (e.g. ferrous sulfate). The interaction reduces absorption of both drugs, although the risk of subtherapeutic antibiotic concentrations is generally the greatest concern.
A 92-year-old man with severe fluid overload requires treatment with intravenous antibiotics. The cardiologist has recommended that these be given as low volume bolus injections rather than by infusion if possible.
Which antibiotic can be administered as an intravenous bolus injection?
A.Amoxicillin
B.Clarithromycin
C. Doxycycline
D. Gentamicin
E. Vancomycin
A.Amoxicillin
A. Amoxicillin. Amoxicillin (a broad-spectrum penicillin) is formulated for intravenous administration and can be given safely as a slow bolus injection or intravenous infusion (providing the patient is not allergic to penicillin). Clarithromycin (a macrolide), gentamicin (an aminoglycoside) and vancomycin all require slow intravenous infusion rather than bolus injection to minimise toxicity. As bolus injections, clarithromycin can cause phlebitis and arrhythmias; gentamicin can cause ototoxicity; and vancomycin can cause anaphylactoid reactions. Doxycycline (a tetracycline) is only available for oral administration.
In practice, antibiotic choice will be determined principally by the diagnosis (and therefore likely organisms and their sensitivities) and the severity of infection. The fluid volume associated with its administration would be an additional but secondary consideration.
A 29-year-old man who has been advised to take antibiotics asks his doctor if he can drink alcohol while on treatment.
What antibiotic should not be taken with alcohol?
A.Amoxicillin
B.Clarithromycin
C.Doxycycline
D.Metronidazole
E. Trimethoprim
D.Metronidazole.
People taking metronidazole who drink alcohol may experience an unpleasant reaction, including flushing, headache, nausea and vomiting. This reaction is thought to be due to inhibition of the enzyme acetaldehyde dehydrogenase, preventing clearance of the intermediate alcohol metabolite – acetaldehyde – from the body. Alcohol should be avoided during and for 48 hours after metronidazole treatment.
Chronic excessive alcohol consumption can reduce absorption of doxycycline (a tetracycline), but this is less likely and less severe than the interaction with metronidazole. The other antibiotics listed here do not interact with alcohol. Nevertheless, this might be a good opportunity to discuss ‘safe’ alcohol consumption (maximum of 21–28 units per week for a man).
A 47-year-old woman is being treated with once daily gentamicin for pyelonephritis. She received her first dose 21 hours ago. Her next dose is due in 3 hours and the nurse has called you to ask if any tests need to be performed before it is given.
What test should be performed 18–24 hours after the first dose of gentamicin?
A.Audiometry
B.C-reactive protein concentration
C.Estimated glomerular filtration rate
D.Serum creatinine concentration
E. Serum gentamicin concentration
E. Serum gentamicin concentration. Gentamicin, an aminoglycoside, is a potentially dangerous drug. Its dosing should be guided by measurement of the serum gentamicin concentration. There are several approaches to monitoring once daily gentamicin therapy and you should consult local policies. However, the most common method is to measure the ‘trough’ concentration; that is, the lowest concentration expected during the dosage interval. This is taken 18–24 hours after the last dose, and should be <1 mg/L to minimise the risk of toxicity.
The other tests are less time-critical and, generally, measurement so soon after the start of treatment is unlikely to be particularly informative. Audiometry may be used in prolonged aminoglycoside therapy to monitor its effects on hearing, since aminoglycosides are ototoxic. C-reactive protein is an inflammatory marker which can be used to monitor for resolution of infection. Impaired renal function is common in severe infections and influences gentamicin dosing regimens. It is assessed using the estimated glomerular filtration rate (GFR) and the serum creatinine concentration, from which estimated GFR is derived. Estimated GFR may be more informative than serum creatinine concentration, but it can be misleading when the renal function is unstable.
A 31-year-old man presents 7 hours after a paracetamol overdose. His only symptoms are nausea and epigastric discomfort. He has no relevant past medical history and takes no regular medication. The serum paracetamol concentration is above the treatment line on the paracetamol poisoning treatment graph.
What is the most appropriate treatment?
A.Acetylcysteine
B.Activated charcoal
C.Cyclizine
D.Omeprazole
E.Naloxone
A.Acetylcysteine
A 24-year-old woman is receiving an intravenous infusion of acetylcysteine for paracetamol poisoning. Thirty minutes into the infusion, she develops a rash. On examination, her heart rate is 95 beats/min and her blood pressure is 117/78 mmHg. She has a widespread urticarial rash.
What is the most appropriate immediate management?
A.Continue acetylcysteine and give chlorphenamine
B.Continue acetylcysteine and give ranitidine
C.Temporarily stop acetylcysteine and give adrenaline
D.Temporarily stop acetylcysteine and give chlorphenamine
E.Temporarily stop acetylcysteine and give ranitidine
D. Temporarily stop acetylcysteine and give chlorphenamine. When administered intravenously at high doses (such as in paracetamol poisoning), acetylcysteine can cause an anaphylactoid reaction. Like anaphylaxis, anaphylactoid reactions are mediated by histamine and involve symptoms such as urticaria, angioedema and bronchospasm. However, in contrast to anaphylaxis they do not involve IgE antibodies. This means that the reactions tend to build up more gradually, such that they can usually be identified and treated before they become too severe.
At this stage, the management would be to stop the acetylcysteine and administer an intravenous antihistamine (H1-receptor antagonist), such as chlorphenamine. Once the reaction has subsided, it is usually safe to restart the infusion at a lower rate. Adrenaline, administered by intramuscular injection, is the key treatment for anaphylaxis, but it is not required for anaphylactoid reactions unless they are very severe or the diagnosis is in doubt. Ranitidine is an H2-receptor antagonist used to suppress gastric acid production. It has little, if any, role in the treatment of anaphylactic and anaphylactoid reactions.
A 75-year-old man is admitted 1 hour after an acute ischaemic stroke. He is aphasic and his swallow is judged to be unsafe. It has not been possible to insert a nasogastric tube. You are asked to prescribe intravenous fluid to cover the next 24–36 hours.
He weighs 80 kg. He is not dehydrated. His serum potassium concentration and renal function are normal.
What is the most appropriate fluid regimen to prescribe at this stage?
A
500 mL glucose 5% over 12 h
500 mL sodium chloride 0.9% over 12 h
B
1 L glucose 5% over 12 h
1 L sodium chloride 0.9% over 12 h
C
1 L sodium chloride 0.9% over 10 h
1 L sodium chloride 0.9% over 10 h
1 L glucose 5% with potassium chloride 40 mmol over 10 h
D
1 L glucose 5% with potassium chloride 40 mmol over 8 h
1 L glucose 5% with potassium chloride 40 mmol over 8 h
500 mL sodium chloride 0.9% over 8 h
E
1 L glucose 5% with potassium chloride 20 mmol over 8 h
1 L glucose 5% with potassium chloride 20 mmol over 8 h
1 L glucose 5% with potassium chloride 20 mmol over 8 h
Show Answer
D. 1 L glucose 5% with potassium chloride 40 mmol over 8 h; 1 L glucose 5% with potassium chloride 40 mmol over 8 h; 500 mL sodium chloride 0.9% over 8 h. The patient described in this scenario requires intravenous fluid therapy to cover his normal daily fluid and electrolyte requirements (often referred to as ‘maintenance requirements’). For stable adult patients these are, roughly:
Water 30 mL/kg/day
Sodium 1 mmol/kg/day
Potassium 1 mmol/kg/day
These can be met using a combination of glucose 5% (which effectively just provides water), sodium chloride 0.9% (which provides water and sodium), and potassium chloride (which is given as an ‘additive’ in the other fluids). There are numerous ways of arriving at the appropriate amounts, but option D is a reasonable one. This will provide 2.5 L/day of water, 77 mmol/day of sodium and 80 mmol/day of potassium.
The other options are less satisfactory: option A provides only 1 L of water and no potassium; option B provides too much sodium and no potassium; option C provides too much sodium; and option E does not provide any sodium at all.
Different approaches need to be taken if the patient has already built up a fluid deficit (i.e. they are dehydrated); if they have additional ongoing fluid losses (e.g. due to diarrhoea); or they have an electrolyte abnormality, oliguria or renal impairment.
A 35-year-old woman is found to be hypotensive. She was admitted 6 hours ago with acute pancreatitis. Analgesia and intravenous fluids were administered and she was transferred to the ward. Over the past hour, her heart rate has been 100–110 beats/min and her blood pressure around 85/50 mmHg. She has not passed any urine since admission. Her serum potassium concentration is 5.1 mmol/L (normal 3.5–4.7).
What is the most appropriate option for initial fluid resuscitation?
A.Compound sodium lactate (Hartmann’s solution) 500 mL IV over 10 minutes
B.Glucose 5% 500 mL IV over 10 minutes
C.Human albumin solution 5% 250 mL IV over 10 minutes
D.Sodium chloride 0.9% 500 mL IV over 10 minutes
E. Sterile water 500 mL IV over 10 minutes
D. Sodium chloride 0.9% 500 mL IV over 10 minutes.
