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Suggested answers to exercises in the text

Thank you for downloading our suggested answers for the exercises in the Antibiotics open learning programme. Before you go any further, we’d just like to offer a few pointers to help you get the most from these answers. We’ve written them to help you to learn. We refer to this approach as ‘formative assessment’. For this to work well, you need to have tried all of the exercises first. We’d advise you to have actually written down your answers in the open learning programme. People are often tempted to get hold of the suggested answers so that they can confirm what they were ‘about to write’. In practice this results in you simply using our suggested answers as a text book. And this isn’t the best approach. For any exercise that we give you, we would recommend that you check the right reference first time, not our answers. You can then have a look at the answers that we offer. If they are the same, then you know the route that you used to find the answer is one that is likely to work well for you in practice. If they are different, then consider why that might be. Has the evidence base changed since we wrote our learning programme? Have you used the right resource? Have you answered the question? Whichever the reason for your answer differing, it will probably give you the chance to write a new CPD entry about that question. Thank you for taking the time to read these brief notes. If you’ve written all your answers down, then please turn over and read on.

Suggested answers to exercises in the text Quiz: How much do you know? 1. List five patient factors that could affect your choice of antimicrobial. We expect that you would have thought of the following:

• Allergies • Age of patient • Renal impairment • Hepatic impairment • Route available and suitability • Disease severity • Pregnant or breast feeding • Interactions • Immune status of patient

If you picked things like Nature of the infection or Organism involved, then consider whether these are patient factors.

2. Name three antimicrobial agents that can be used to treat Pseudomonas aeruginosa We expect you will have selected from this list.

• Ciprofloxacin • Ceftazidime • Ticarcillin • Azlocillin • Piperacillin • Aminoglycosides • Colistin • Carbopenems

Do you know which would be used first line where you practice?

3. What are the common organisms that cause skin and soft tissue infections and what is the first line therapy for these?

Most common First line therapy Staph. aureus Flucloxacillin Strep. pyogenes Benzylpenicillin

4. What patient factors must be considered when switching patients from intravenous to

oral therapy?

We expect you would include: Review all IV antibiotics after no more than 48 hours. Consider oral alternatives. Base the decision to switch on clinical indicators such as

• Normal temperature for at least 24 hours • Low CRP • Clinically improving • Able to take oral medications

• Not suffering from high risk infections

Patients with some infections may meet these criteria after only a few days but you still need to delay the oral switch for 2 weeks or more. These infections include:

• Septic arthritis • Osteomyelitis • Liver abscesses • Adequately drained abscesses and empyemas

5. Which organisms are most likely to cause urinary tract infections?

Organism Domicilary Hospital Escherichia Coli 70‐80% 50% Proteus mirabilis 10% 1‐5% Klebsiella spp 1‐5% 5‐10% Staphylococcus saprophyticus

10‐15% 0

Enterococci 1‐5% 10‐20% Other coliforms <1% 5‐10% Staph. epidermidis 1‐5% 10‐20% Ps aeruginosa 1‐2% 5‐10%

6. List three points you would make when counselling a patient who has just been started

on rifampicin for pulmonary tuberculosis?

• Continue taking the prescribed doses, even when you feel better. • Rifampicin can colour body fluids orange‐red (urine, sweat, tears). Permanent

discolouration of soft contact lenses will occur. • Look out for signs of liver disease (loss of appetite, jaundice, fatigue, nausea,

vomiting and abdominal pain). Seek medical attention immediately if liver disease is suspected.

• If you take the contraceptive pill you must use alternative contraception during and for eight weeks after rifampicin treatment

Remember that those patients prescribed ethambutol should be told see their Doctor if they experience any visual changes.

7. Which antibiotic is most commonly prescribed for anaerobic infections in the UK? Metronidazole

8. What would you recommend as first choice antimicrobial for a pregnant woman with a

urinary tract infection?

Trimethoprim and nitrofurantoin are used first line in urinary tract infections. Trimethoprim can cause folate deficiency in the first trimester, and nitrofurantoin may produce neonatal haemolysis if used at term. Either amoxicillin or cefalexin are usually chosen first line empirical treatment. Asymtomatic bacteriurea would be treated according to culture and sensitivities. Refer to local guidelines as some guidelines recommend trimethoprim or nitrofurantion, as short‐term use is unlikely to cause problems to the foetus.

9. Which organism causes vaginal thrush? What would you recommend as first line treatment?

Candida albicans Treatment with topical azoles such as Clotrimazole or oral fluconazole are both effective.

10. Name three common healthcare associated infections (HCAI). Your list would include: Methicillin Resistant Stapphylococcus aureus Vancomycin intermediate Stapphylococcus aureus Vancomycin Resistant Stapphylococcus aureus Clostridium difficile Pseudomonas Glycopeptide resistant enterococci Acinetobacter Extended‐spectrum beta‐lactamase producing organisms

Part Two.

1. If you are allergic to penicillin you have a 25% chance of also being allergic to

cephalosporins. False 2. Gentamicin given once a day is less toxic than traditional regimens that are given more

frequently. True At least 30 controlled clinical trials have compared once vs multiple daily dosing. Toxicity was usually determined using non‐sensitive end points such as measurements of creatinine for nephrotoxicity and clinically detectable hearing loss for ototoxicity. In most of these trials it was concluded that gentamicin once daily resulted in less nephrotoxicity although any reduction in ototoxicity was not clinically significant. 3. You must be cautious when giving ciprofloxacin to people with epilepsy. True 4. You must advise people to take ketoconazole with food or just after eating. True 5. The correct dose of aciclovir to treat herpes simplex is 400mg four times a day. False. The correct dose is five times each day. 6. You must administer 1g of vancomycin in a 500mL infusion of 0.9 percent sodium

chloride over 60 minutes. False. We’d expect it to be in an infusion of 200mL 0.9 percent sodium chloride and administered over at least 100 minutes. 7. The first line therapy for Clostridium difficile is vancomycin 500mg capsules. False. Metronidazole is usually used first line. 8. Co‐amoxiclav is the first line antimicrobial following a dog bite. True

9. Ciprofloxacin has an oral bioavailability of about 75%. True 10. Cefuroxime has activity against Pseudomonas aeruginosa. False Exercise 1 With this table we suggest the antibiotic of choice. However, we can’t tell you what your local guidelines would say. Infection Likely causative

organisms Antibiotic choice for empirical therapy

Gastrointestinal infections

Campylobacter spp Salmonella spp Shigella spp Escherichia coli 0157 Giardia lamblia Clostridium difficile

Antibiotic therapy is seldom indicated in acute infective gastroenteritis. Antimicrobial therapy only reduces diarrhoea by 1‐2 days and cause antibiotic resistance. Antibiotic therapy is usually reserved for people with positive stool cultures, particularly if symptoms are severe or not settling. In many people the symptoms of gastroenteritis may be resolved by the time a report is received. 1st line: Oral Metronidazole for 10 days 2nd line: Vancomcycin

Endocarditis

Viridans group streptococci Streptococcus bovis Enterococcus faecalis Enterococcus faecium Staphylococcus aureus

Initial therapy should be benzylpenicillin and gentamicin as for viridans streptococci unless there is a strong suspicion of other organisms. Staphylococcus aureus endocarditis is particularly common in IV drug abusers and patients on haemodialysis, in which case flucloxacillin and gentamicin should be prescribed.

Upper respiratory tract infections: •pharyngitis •tonsillitis •sinusitis

Streptococcus pyogenes (group A) Streptococcus pneumoniae Haemophilus influenzae Moraxella catharrhalis

Phenoxymethylpenicillin. The majority of sore throats are viral and do not require antimicrobials.

Lower respiratory tract infections: •community‐ acquired pneumonia (non severe) •hospital‐acquired pneumonia

Streptococcus pneumoniae Haemophilus influenzae ‘Atypical organisms’ Pseudomonas aeruginosa Escherichia coli 0157 Staphylococcus aureus

Amoxicillin or Erythromycin Initially broad spectrum antimicrobials until sensitivities. Treatment may include tazocin or ciprofloxacin or vancomycin.

Meningitis

Neisseria meningitidis Streptococcus pneumoniae

Cefotaxime or ceftriaxone have adequate cover and penetration into CNS. May be fungal, viral or mycobacterial in which case alternative therapy is required.

Urinary tract infections/ pyelonephritis

Escherichia coli 0157 Enterococcus spp Proteus spp Klebsiella spp

First choice for uncomplicated UTI is usually trimethoprim or nitrofurantoin. Pyelonephritis is usually treated with co‐amoxiclav or ciprofloxacin.

Chlamydia Chlamydia trachomatis Doxycycline or azithromycin

Osteomyelitis

Staphylococcus aureus beta‐haemolytic streptococci

Flucloxacillin plus fusidic acid

Septic arthritis

Staphylococcus aureus beta‐haemolytic streptococci

Flucloxacillin plus fusidic acid

Otitis externa

Pseudomonas aeruginosa Staphylococcus aureus

Topical neomycin for no longer than one week.

Otitis media

Streptococcus pneumoniae Haemophilus influenzae Moraxella catarrhalis

Many cases are viral. It is usually a self limiting illness with approximately 80% of cases resolving without antibiotic therapy. If antibiotics appropriate amoxicillin is usually first line.

Cellulitis Staphylococcus aureus Streptococcus pyogenes (group A)

Benzypenicillin and flucloxacilln

Exercise 2 We think that the ideal properties for a new antimicrobial would be: Broad spectrum No development of resistance by bacteria Safe, non‐toxic Stable, long shelf life Non‐allergenic Low cost High therapeutic index Nice taste And if you were a patient you’d probably want: Easy dose regimen – just once or twice a day Don’t need to take it for long No side effects Doesn’t affect any other medicines. Case Study 1 ‐ Tom Billingham What advice would you give Tom? We expect you would have referred Tom to his local general practice. Tom returns from the GP with a prescription for itraconazole 200mg twice daily for 7 days (3 courses) 21 days apart. Is this prescription appropriate for Tom’s athlete’s foot and fungal nail infection? Itraconazole can be used for the treatment of dermatophyte infections. This dose is correct for a toenail infection and would also clear his athlete’s foot. From Tom’s PMR you find he is taking the following prescribed drugs: Simvastatin tablets, 40mg at night Aspirin tablets, 75mg each day Verapamil MR tablets, 240mg each day Salbutamol inhaler 100 micrograms, two puffs as needed Beclometasone inhaler 250 micrograms, two puffs twice each day What would you do now? Itraconazole can increase the negative inotropic effect of verapamil. CSM has advised prescribing itraconazole to paients at risk of heart failure should be undertaken with caution. Due to the possible interactions and the fact that there are more suitable alternatives, we expect you decided to suggest an alternative to the GP. What recommendation would you make to the prescriber? Terbinafine is the first line antifungal in the treatment of fungal nail infections. It would be an appropriate recommendation for Tom.

What advice would you give Tom? You should advise Tom to Dry his feet properly before putting socks on ‐ fungi love damp environments. Leave his shoes and socks off where possible Avoid synthetic shoes ‐ these will give him sweaty feet Change and wash his socks frequently. If he goes swimming he should wear flip‐flops in the changing room to prevent re‐infection. Case Study 2 ‐ Jack Spencer Jack Spencer is a 27 year old accountant who has been admitted to the respiratory ward due to an increasing shortness of breath and coughing over the last week. Upon admission he had difficulty in speaking more than a few words at a time. An examination revealed that Jack was tachycardic (142 beats/min) and had a respiratory rate of 25 breaths per minute. His blood pressure was 147/85. Jack’s temperature was normal and his white cell count was 5.6 X 109/L (4‐10 X 109/L). He was hypoxic on admission. Jack was started on

• 60% oxygen therapy • hydrocortisone 100mg intravenously, four times a day • Combivent nebulas, inhale one four times a day • Aminophyline intravenous infusion 500mg in 500mL sodium chloride 0.9%, at a rate of

35mL/hour • Ceftazidime 1g intravenously, three times a day

Is this antimicrobial therapy indicated for this patient? No Jack is more likely to be suffering from an acute asthma attack. There are no clinical signs of infection. If upon admission Jack had a temperature of 39.5oC and a white cell count of 15 X 109/L on admission, what difference would this have made to your thoughts on infection and use of antimicrobial therapy? In this case Jack could be suffering from community acquired pneumonia. The most likely pathogens would be Str pneumoniae or H influenza. Assessment of the severity of the pneumonia is paramount in deciding on empirical antimicrobial therapy. Clinical adverse prognostic features (CURB‐65) are:

• Confusion ‐ new mental confusion (defined as an abbreviated mental score of 8 or less, or new disorientation in person, place or time)

• Urea: new raised >7mmol/l • Respiratory rate raised >30breaths/min • Blood pressure: Low blood pressure (systolic < 90mm/Hg and/or diastolic <60mm/Hg) • Age>65 years

Patients with a score of 0‐2 adverse prognostic factors are treated as non‐severe. Patients with a score of 3 or more adverse prognostic factors are treated as severe. Jack would be treated as non‐severe and oral amoxicillin 500mg tds and oral erythromycin 500mg qds should be recommended. Case Study 3 ‐ Martin Cross Martin Cross is a 21year old intravenous drug user. He has been admitted via his GP after feeling unwell with pain in his knee, which he could not move. He was flushed, in pain and slightly agitated. From his notes you see that upon admission Martin had a temperature of 39oC, his pulse was 125 and his BP was 110/70. His respiratory rate was 26 breaths/min. His knee is red and swollen and the doctors have diagnosed septic arthritis. Before antimicrobials were prescribed Martin had his knee aspirated and a sample was sent to microbiology along with blood samples for culture and sensitivities. The following was prescribed on his drug card. Methadone 1mg/mL, 50mL oral daily Flucloxacillin 500mg intravenously, four times a day Is this prescription appropriate for him? Staphylococcus aureus is the most common pathogen in septic arthritis. In IV drug users, gram‐negative bacteria including P. aeruginosa, Enterobacter, and Serratia species are also important pathogens. Appropriate empirical therapy would consist of flucloxacillin and fusidic acid to cover Staphylococci and either a quinolone or gentamicin to cover the gram negative bacteria or a second generation cephalosporin. The dose of 500mg qds iv is not sufficient. The minimum required dose would be 1gram qds to get sufficient concentrations at the site of infection. You contact the doctor and the treatment is changed to Flucloxacillin 2g qds iv and Ciprofloxacin 750mg bd po. Two days later you visit the ward. Martin is feeling better. His temperature has come down and the culture and sensitivities have come back from the laboratory. Pseudomonas aeruginosa was isolated from the knee aspirate. The sensitivities were: S=Sensitive R=Resistant Ciprofloxacin S Ceftazidime S Gentamicin S Meropenem S

Which drug therapy would you recommend for Martin now and why? As Pseudomonas aeruginosa was isolated and flucloxacillin has no activity against Pseudomonas, it should be stopped. As the isolate is sensitive to ciprofloxacin this should be continued. It has the advantage of oral administration so can be continued at home as treatment will need to be continued for 4‐6 weeks. If Martin doesn’t improve then flucloxacillin should be restarted as sometimes patients get mixed infections. Case Study 4 ‐ Edna Green Edna Green is 78 years old and normally lives in a nursing home. She has been admitted to the hospital’s care of the elderly ward by her GP. She is currently on day 7 of a 10 day course of cephalexin 500mg three times daily, which was prescribed by her GP for a urinary tract infection. Edna has become dehydrated after developing diarrhoea and fever. The medical team suspect she has Clostridium difficile associated diarrhoea. A stool sample has been sent to microbiology and Edna is being given intravenous fluids. Consider the following: What risk factors does Edna have for developing C. difficile associated diarrhoea? Antibiotic therapy with broad spectrum agent Elderly patients are at greater risk of developing C. difficile. What other measures should be taken in Edna’s management? The cephalexin should be stopped. Electrolytes should be corrected if needed. Edna should be isolated in a side room and barrier nursed. Isolating the patient and implementing barrier nursing protect the hospital environment from contamination. Personnel attending the infectious patient wear special protective clothing, masks and gloves. Hand washing is very important before leaving the room even though gloves must be worn by all staff. Edna is prescribed loperamide 2mg ‘when required’. Is this appropriate in suspected C. dfficile diarrhoea? No. Loperamide has been associated with toxic megacolon when given to patients with C. difficile colitis. C. difficile toxin was isolated from the stool sample. What further treatment should Edna be given? Metronidazole and vancomycin oral are both effective in treating C. difficile. Metronidazole is used first line as it is as effective as vancomycin but is cheaper. Edna is prescribed metronidazole 400mg tds for a ten day course. After five days there has been no clinical improvement in Edna. What would you suggest to the medical team at this point? Clinical improvement is usually seen within 2‐4 days. Edna should have her treatment changed to vancomycin 125mg capsules four times a day.. What support would you provide for the nursing home, or advice in general on preventing and managing C. difficile infection? Check out your local protocol.

Exercise 3 We aren’t going through each of these in depth. Here are our suggestions. We expect that you would have considered drug interactions, concomitant illnesses, length of treatment courses and specific advice needs of each patient. Sangeeta Shah’s PMR Calcichew 2 tds with meals Alfacalcidol 0.25mcg daily Darbopoetin 50mcg weekly Atenolol 50mg od From this prescription it looks as if Sangeeta has some renal impairment. The degree of renal impairment will distinguish what dosage reduction will be required. The following recommendations are from the BNF Appendix 3 and the renal drug handbook which should also be consulted for specific dose recommendations and dose adjustments. The renal drug handbook also gives recommended dose adjustments for patients having dialysis.

1. Erythromycin 500mg qds 7/7 ‐ In severe renal impairment max dose 1.5g daily 2. Amoxicillin 500mg TDS 7/7 – In severe renal impairment dose reduction required. If

glomerular filtration rate (GFR) <10ml/minute 250mg every eight hours. 3. Ciprofloxacin 500mg bd 5/7‐ moderate and severe renal impairment dose reduction required.

GFR <20ml/minute half normal dose. 4. Doxycycline 200mg stat then od 6/7 – no dose change needed 5. Nitrofurantoin 50mg qds 7/7 – avoid use. Ineffective as inadequate urine concentrations 6. Trimethoprim 200mg bd 3/7 – BNF recommendations are: If creatinine clearance 15‐30ml/minute: a normal dose for 3 days and then reduce to half this dose for the remaining course. If creatinine clearance less than 15ml/min: half the normal dose should be prescribed. The renal drug handbook recommends:

• If GFR less than 15ml/min half the normal dose should be prescribed. • If GFR >25 as in normal renal function. • If GFR 15‐25 Dose as normal for 3/7 then 50% of dose every 18 hours. • If GFR <15 50% of dose every 24 hours.

In this case and with all the male prescriptions treatment should be for 7 days. The dose would then need adjusting according to his degree of renal impairment.

7. Oxytetracycline 500mg bd 3/12 – avoid use Calcium salts reduce the absorption of tetracyclines and ciprofloxacin so Sangeeta would need to be counselled on the appropriate timing of his antimicrobials.

Jessica Rosenthal PMR Microgynon ‘as directed’ With all these prescriptions there is a risk of a reduced effect of the combined oral contraceptive pill and Jessica should be advised to take extra precautions during and for 7 days after treatment. With prescription number 7, Jessica can be advised that after 3 weeks additional precautions are not necessary. Nitrofurantoin for 3 days would be sufficient in treating an uncomplicated UTI. Moses Obgekoko PMR Phenytoin 100mg three times daily Warfarin 3mg as directed by the anticoagulation clinic Warfarin’s effect is increased by many antibacterials. Erythromycin, ciprofloxacin, amoxicillin, doxycycline, trimethoprim and oxytetracycline can all cause an increase in INR. The British Committee for Standards in Haematology (BCSH) guideline on oral anticoagulation (3rd edition; 1998) contains a section on drug interactions, located through the NLH Guidelines Database, which states: ‘For short courses of new drug therapy, oral anticoagulant dose adjustment is not essential but a slight dose reduction or omission of one dose could be recommended if a known potentiator is prescribed (grade C). If medication is for >5 days the INR should be checked 1 week after commencement and oral anticoagulant dose adjusted accordingly, returning to normal maintenance dose after stopping the new drug.’ Antibiotics are not specifically mentioned in this guidance. You could find out from Moses if the GP mentioned the interaction. You could find out when his next appointment is at the anticoagulation clinic. If it is not for some time you could suggest he brings it forward. Reassure Moses that there are very few case reports of significant interactions, but he needs to look for signs of increasing INR such as bruising and bleeding gums. Erythromycin and ciprofloxacin have the most established interaction and in patients who are at higher risk of the interaction (elderly) it would be advisable to use an alternative antibacterial or closely monitor them. In hospital when warfarin is prescribed with anticoagulants you can recommend closer monitoring and make the team aware of the interaction. Phenytoin levels are increased by trimethoprim and also an increased antifolate effect occurs with this combination. Ciprofloxacin can either increase or decrease plasma phenytoin levels. Ciprofloxacin also lowers the seizure threshold and should be used in caution in patients with epilepsy. Alan Doherty PMR Simvastatin40mg nocte Aspirin 75mg daily Ramipril 5mg daily Lansoprazole 30mg daily Erythromycin causes an increased risk of myopathy when administered with simvastatin and the CSM advises to avoid concomitant use. All other prescriptions would be suitable for Alan.

Peter Hanson PMR Theophylline 200mg twice daily Salbutamol when required Salmeterol two puffs twice a day Beclometasone 250 two puffs twice a day Erythromycin and Ciprofloxacin both increase plasma concentrations of theophylline. It would be advisable to contact the GP and recommend a reduced dose of theophylline whilst taking these antibacterials. Ciprofloxacin and theophylline when administered together may have an increased risk of convulsions, this is something to be aware of. Case Study 5 ‐ Peter Grainger In a few months’ time Peter Grainger is taking his wife on safari in Kenya. His wife is epileptic and takes phenytoin 300mg daily. He is aware that they need to get yellow fever, Hepatitis A and Typhoid vaccinations. He asks your advice on what antimalarial prophylaxis they should consider. What would you recommend? Kenya is a very high risk area for malaria. The recommended chemoprophylaxis is either mefloquine, doxycycline or Malarone. Mefloquine prophylaxis should be avoided in patients with epilepsy as it can cause seizures. Doxycycline’s metabolism is increased when given with phenytoin so if doxycycline was to be considered a higher dose might be more appropriate. As there is no guidance on the ideal dose of doxycycline for prophylaxis and the risk of photosensitivity with doxycycline, we would recommend Malarone as the treatment of choice. We would recommend they both took Malarone as then they could take it at the same time and remind each other. What other advice would you offer Peter? We expect that you would offer Peter advice on avoiding mosquito bites. Case Study 6 – Jean Roberts Mrs Jean Roberts brings a prescription to the pharmacy for her 2 year old son Jamie. The prescription is for trimethoprim 50mg daily. Jamie weighs 13kg. From his PMR you see that Jamie has just completed a 5 day course of trimethoprim 50mg twice daily. Is the prescription appropriate for Jamie? No the normal prophylactic dose for a child is 1‐2mg/kg at night. For Jamie this would be a dose of 13‐26mg at night. The doctor changes the prescription to 25mg at night. When you give Jean the prescription she says she doesn’t understand why it is needed as Jamie is feeling better now, and she has read in the newspaper that the overuse of antibiotics is causing resistant bacteria to develop. How would you respond? The prophylaxis of UTIs in children is important to prevent further infections whilst awaiting investigations. The long term use of prophylactic trimethoprim for UTIs is not normally associated

with resistance and needs to be given to prevent any damage to Jamie’s kidney which could result from further infections. Jean can be reassured that it is normal and that the treatment will be reviewed once the results of the investigations are known, although some children do need to continue on long term antibiotics if abnormalities are found. Jean should be advised to give Jamie his trimethoprim at night as it will be concentrated in the urine for the longest period of time and will be more beneficial. Also she should try and give it every night and not to adjust the dose if she thinks he has another infection. If she misses one night’s dose she shouldn’t double up the following night. Case Study 7 ‐ Likely indications Amoxicillin 3g one hour before procedure Prevention of endocarditis in a patient with heart‐valve lesion, septal defect, patent ductus, prosthetic valve, or history of endocarditis Penicillin V 500mg, twice daily for two months and to continue Prevention of pneumococcal infection in asplenia or in patients with sickle cell disease Rifampicin 600mg, every 12 hours for two days Prevention of secondary case of meningococcal meningitis Clindamycin 600mg, one hour before procedure Prevention of endocarditis in a patient with heart‐valve lesion, septal defect, patent ductus, prosthetic valve, or history of endocarditis in a patient with penicillin allergy, or who has received more than single dose of penicillin in the previous month Nitrofurantoin 100mg, at night Prophylaxis against recurrent urinary tract infections Erythromycin 500mg, twice daily for three months and to continue Management of Acne rosacea Case Study 8 ‐ Norman Holden Mr Norman Holden has been admitted for an emergency appendectomy. You visit him when he returns from theatre. He is prescribed intravenous cefuroxime 750mg three times daily and intravenous metronidazole 500mg three times daily but there is no duration stated on the drug chart. He received a dose of each antimicrobial prior to going to theatre. Was Mr Holden given appropriate antimicrobial prophylaxis? The organisms most frequently isolated from the wound after appendectomy are Bacteroides and Escherichia coli. So the combination Mr Holden received was appropriate. Is it necessary for Mr Holden to continue on these antimicrobials? This depends on whether Mr Holden’s appendix was gangrenous or perforated or just acutely inflamed. If Mr Holdens appendix was acutely inflamed then there is no need for antimicrobial therapy to be continued, the stat doses should be sufficient. If Mr Holden had a perforated appendix and especially if there had been evidence of local or general peritonitis or intraabdominal abscess the therapy should be considered therapeutic and continued for 5 days.

Case Study 9 ‐ About vancomycin The senior house officer from the admissions ward telephones to ask your advice. He has a patient with MRSA cellulitis who is at high risk of bacteraemia. The microbiologist has recommended vancomycin and the SHO wants you to recommend the dose. The patient has a creatinine clearance of 69mL/min and weighs 68kg . What advice would you offer? From the table in the medicine compendium for vancomycin, an initial dose of 1g every 24 hours can be recommended10. How should the dose be administered? Each vancomycin vial must first be diluted with 10 mL water for injections and then further diluted to a concentration no greater than 5mg/mL. Therefore the smallest volume of fluid required is 200mL, for practical reasons I would recommend that it was given in 250mL sodium chloride and then administered over 100 minutes (rate no greater than 10mg/min) What monitoring is required for this patient? Vancomycin needs to be monitored to prevent toxicities. A trough level prior to the 3rd dose is needed and the ideal level for this is between 5‐10mg/L. Before the 3rd dose a trough level of 3.4mg/L was obtained. What advice on dosing this patient would you offer now? Decrease the dosing interval to twelve hourly so the concentration of vancomycin in the serum is kept above 5mg/L. What monitoring would you advise? A further trough level is required prior to the third dose of the new 12 hourly dosing schedule. Case Study 10 ‐ Munaf Patel Munaf Patel, who weighs 56kg, has been admitted to the oncology ward. He has been prescribed Timentin 3.2g four times a day and gentamicin 400mg daily in accordance with your antimicrobial guidance for febrile neutropenic patients. He has no renal impairment. Munaf has told the nursing staff that he had a severe rash when prescribed penicillin as a child. Are these antibiotics appropriate? Timentin is a combination of ticarcillin (a penicillin) and clavulanic acid so is not an appropriate choice for Munaf. The Timentin was changed to ceftazidime in accordance with the guidelines. Ten hours after the start of his gentamicin infusion a serum sample was taken and sent for gentamicin drug monitoring. The level was 5mg/L. What recommendations would you make about Munaf’s gentamicin regimen? The dose of gentamicin should remain the same but given at 36 hour intervals instead of 24, in accordance with Hartford nomogram.

Case Study 11 ‐ Mr Hale Mr Hale a 67 year old regular patient has been diagnosed with exacerbation of chronic obstructive pulmonary disease. He is prescribed doxycycline 200mg stat then 100mg daily for 7 days. Whilst he is waiting for his prescription he waits outside so as he can have a cigarette. Mr Hale also takes the following: Ferrous sulphate tablets 200mg bd Ranitidine tablets 300mg nocte Salbutamol inhaler two puffs four times daily Ipratropium bromide inhaler two puffs four times a day Aminophylline mr tablets 225mg twice daily What advice would you give Mr Hale regarding his antimicrobial treatment? We expect you’d advise him to take them with a full glass of water at about the same time each day with food. You’d tell him to take them at a different time of day to his iron tablets. You’d stress that he needs to finish his course of tablets. You’d probably tell him that he might get a skin reaction to strong sunlight and that they could irritate his stomach – but that will stop when he finishes the course. What other advice would you offer Mr Hale? We’re sure you’d advise him to stop smoking! When you did this, you’d be wanting to keep an eye on his aminophylline dose as this can be affected by smoking. Case Study 12 ‐ Sue Harding

Sue Harding asks your advice regarding her 12 year old daughter. Sue treated her daughter with lyclear creme rinse two weeks ago for head lice. Sue has checked her daughters’ hair today and found more live lice. What would you recommend?

We expect that you wanted to know how Sue had used the crème rinse and whether she had checked or treated anyone else in the family. You would have asked about the live lice that she found – were they of the same size, babies, adults or a mixture. That would help you decide whether this was resistance, treatment failure or a new infection. You probably decided to recommend malathion in an isopropanol base, or dimeticone. Case Study 13 ‐ Gary Downing

Gary Downing, a regular customer, requests some Brolene eye drops. You remember he has previously been sold three bottles in recent months. What questions would you ask?

You probably wanted to double check the symptoms that Gary is displaying. Perhaps he has an allergic conjunctivitis, or viral conjunctivitis. Since it seems likely that Gary has an ongoing problem with his eyes, we expect you would have referred him either to his GP or ophthalmologist.

Case Study 14 ‐ John Chilton

John Chilton a local teenager has been buying benzoyl peroxide 10% gel treatment from your pharmacy for the last five months. When he visits to purchase a further supply you notice his acne is looking very inflamed and red. What questions would you ask?

We’d expect that you’d have asked John more about how he uses the cream, how often and how much being particular areas to check. Does he use it every day? Or just when he feels that his acne is bad? Most people would have seen an improvement in their acne within two months of starting treatment. If John hasn’t, then it would be sensible to refer him to his GP. If John is just using it now and again, and seems to be using the cream in accordance with the dose instructions, then you’d probably want to recommend a lower strength cream. You’d also be wanting to check whether there could be any other cause. Case Study 15 ‐ Suleman Khan Suleman Khan who is 65 years old came into your pharmacy last week complaining of a cough and was sold a bottle of mixture. He returns to your pharmacy today for his regular prescription of bendroflumethiazide 2.5mg daily. Upon questioning him you find that he has had this cough for four weeks and that he returned from a two month holiday in Pakistan eight weeks before that. Mr Khan is a regular patient at your pharmacy. He has high blood pressure and diet controlled type 2 diabetes. Today he looks like he has lost weight, and he is breathless. He now weighs 55kg. What would you do? We expect you’d refer him to his GP. The following day Mr Khan visits his GP. Upon examination, he is found to be mildly pyrexial (37.8oC) but there is no evidence of anaemia or clubbing. Crepitations are audible over the lung apices. There were no other physical signs. Suspecting that Mr Khan may have tuberculosis, the GP refers him to the respiratory outpatients’ clinic at the local hospital. Mr Khan’s chest X‐ray shows bilateral upper and middle‐lobe shadowing. His sputum is found to contain acid fast bacilli. Mycobacterium tuberculosis is subsequently cultured, and a Mantoux test is strongly positive. Mr Khan is diagnosed with pulmonary tuberculosis. What drug treatment would you expect Mr Khan to be initiated on? As Suleman is likely to have pulmonary TB we would expect a combination of isoniazid, rifampicin, pyrizinamide and ethambutol. Mr Khan brings the following prescription to the hospital outpatients

isoniazid 300mg daily rifampicin 600mg daily pyrazinamide 2g daily ethambutol 900mg daily

Is this prescription correct? The doses on this prescription are correct as his weight is 55kg

Is there anything missing? Pyridoxime is usually added to treatment to prevent isoniazid induced peripheral neuropathy. Suleman is at a higher risk of this as he is diabetic. What counselling would you give Mr Khan? Continue taking the prescribed doses, even when you feel better Rifampicin can colour body fluids orange‐red (urine, sweat, tears). Permanent discolouration of soft contact lenses will occur. Look out for these signs of liver disease ‐ loss of appetite, jaundice, fatigue, nausea, vomiting and abdominal pain). Get medical attention at once if liver disease is suspected. See your doctor straightaway if you experience any visual changes The pharmacist contacts the prescriber and requests pyridoxime 25mg daily is added to this prescription to prevent peripheral neuropathy (patient with diabetes, so at increased risk) which is then added to the prescription. What are the common side effects of each of the drugs? Isoniazid, ethambutol and rifampicin are all associated with liver disease. Liver function should be checked before treatment begins, those with pre‐existing liver disease and alcoholics should have their liver function monitored throughout treatment. Ethambutol can affect vision and patients should have their visual activity checked before treatment.

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