Management of uncomplicated urinary tract infection Robert Townsend MSc, MB ChB, DTM&H, MRCPath

Drug review UTI Management of uncomplicated urinary tract infection Robert Townsend MSc, MB ChB, DTM&H, MRCPath Skyline Imaging Ltd Urinary tract infections account for a significant proportion of GP consultations and prescribing of antibiotics. Our Drug review describes the properties and side-effects of the antibiotics used in the treatment of uncomplicated UTI, followed by sources of further information and the Datafile. Every year, around 5 per cent of women present to their GP with symptoms of dysuria and frequency, and approximately half of this number have confirmed urinary tract infection (UTI) upon laboratory investigation. This makes UTI one of the most common reasons for both presentation to primary care (especially in otherwise well women) and for antibiotic prescription. 1 Acute uncomplicated UTI is defined as UTI in a person with a structurally and functionally normal urinary tract. In contrast, a UTI can be considered complicated if there are functional or anatomical abnormalities within the urinary tract or underlying diseases that predispose to UTI, eg diabetes mellitus. 2 Acute uncomplicated UTI is predominantly observed in women, and recurrent cystitis is seen mostly in young, healthy women with normal urinary tracts (though the shorter female urethra is a predisposing factor to UTI). Complicated UTI may occur in anyone with predisposing illness or underlying abnor- 28 Prescriber 19 July 2007 www.escriber.com

Antibiotic Contraindications Common side-effects Rare but serious side-effects Trimethoprim trimethoprim hypersensitivity, nausea, vomiting, hypersensitivity, severe blood dyscrasias, severe renal pruritus, rash skin rash, blood dyscrasias impairment, pregnancy, porphyria Nitrofurantoin nitrofurantoin hypersensitivity, anorexia, nausea hypersensitivity, acute and chronic renal impairment, G6PD pulmonary reactions, hepatitis, deficiency, <3 months of age, peripheral neuropathy, severe skin porphyria rashes, pancreatitis, blood dyscrasias, neurological disturbance Amoxicillin and penicillin hypersensitivity, nausea, vomiting, hypersensitivity, severe skin rash, co-amoxiclav penicillin-associated hepatic diarrhoea, rash pseudomembranous colitis, dysfunction hepatitis, blood dyscrasias Cephalosporins cephalosporin hypersensitivity, nausea, vomiting, hypersensitivity, severe skin rash, porphyria diarrhoea, rash pseudomembranous colitis, blood dyscrasias Quinolones quinolone hypersensitivity, nausea, diarrhoea, neurological disturbance children, pregnant or vomiting, abdominal (including hallucinations and lactating women pain, headache, rest- psychosis), hypersensitivity, photolessness, rash, pruritus sensitivity, tendon inflammation and damage, hepatic necrosis, severe skin rash, blood dyscrasias Pivmecillinam penicillin hypersensitivity, nausea, vomiting, hypersensitivity, severe skin rash, carnitine deficiency, oesoph- dyspepsia blood dyscrasias ageal strictures, gastrointestinal obstruction, infants <3 months Table 1. Contraindications and common and rare side-effects of antibiotics prescribed in UTIs malities and treatment options may be more problematic, having to take into account the underlying condition. We will therefore restrict our discussion to the management of uncomplicated UTI. Bacterial spectrum The majority of UTIs are caused by Escherichia coli (over 70 per cent generally), with approximately 10-15 per cent caused by other enterobacteriaceae (such as Proteus and Klebsiella) and faecal streptococci (Enterococcus). Faecal flora account for most of the uropathogens encountered, probably utilising a mechanism of initial colonisation of the perineum, followed by passage up the female urethra (a process often aided by sexual intercourse). The skin commensal Staphylococcus saprophyticus accounts for around 5-10 per cent of UTI cases in young women. Treatment options There is evidence that untreated, uncomplicated cystitis in nonpregnant women appears not to be associated with any long-term sequelae, ie impaired renal function or increased mortality, and that untreated recurrent cystitis rarely progresses to an upper UTI. 3 The treatment of uncomplicated UTI is therefore aimed at the morbidity associated with potentially distressing (and disrupting) symptoms. Empirical therapeutic decisions should be guided by local knowledge of resistance patterns of the likely uropathogens. The trend away from sending uncomplicated UTI urine samples for culture and sensitivity means that these data may be lacking or incomplete. So, for example, if only urine from treatment failures is examined, then a skewed population of more resistant organisms may be seen (the more sensitive organisms would be less likely to fail treatment). www.escriber.com Prescriber 19 July 2007 29

VM adverse events, they are not recommended as first-line agents for empirical therapy. 2 Supportive treatments General measures shown to be of benefit include increased fluid intake (to increase urinary output) and an analgesic (to control pain and/or fever). Oral agents that alkalinise the urine may also be of benefit and may help to alleviate symptoms. Antibiotics Antibiotics commonly used in uncomplicated UTI include trimethoprim, nitrofurantoin, beta-lactam antibiotics and quinolones. Their contraindications and side-effects are shown in Table 1, and their drug interactions in Table 2. Figure 1. Dipstick showing positive for blood and nitrates, suggestive of infection; a short (three-day) course of empirical treatment is recommended in uncomplicated UTI One approach is to send urine for culture and at the same time prescribe a first-line urinary antibiotic: this not only provides good sensitivity data on which to base future resistance trends, but also a prepared result if the patient fails treatment. Short courses of antibiotic appear to be highly effective in the treatment of uncomplicated UTI and are desirable as they improve compliance, cost less and are associated with fewer adverse reactions. 4 A study of 75 clinical trials by the Infectious Diseases Society of America produced guidelines that were later reviewed by the American Urological Association and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). 5 In summary, they concluded: trimethoprim, co-trimoxazole and quinolones given for three days was as effective as treatment for a longer duration single-dose regimens appear to be less effective than the same antibiotic given for longer and should not be recommended longer duration of treatment usually causes higher rates of adverse events although co-trimoxazole was the most commonly studied drug, it was found that trimethoprim alone was equivalent to co-trimoxazole in eradication and, given the side-effect profile of sulphonamides, trimethoprim alone may be considered the preferred drug fluoroquinolones showed a similar three-day efficacy to co-trimoxazole/trimethoprim; however, given the greater expense and possibility of higher incidence of Trimethoprim Trimethoprim is a dihydrofolate reductase inhibitor first introduced to augment the activity of sulphonamides by sequential inhibition of folic acid synthesis, and is the commonest first-line therapy. Sensitivity of enterobacteriaceae to this antibiotic varies according to location and whether primary- or secondary-care populations are examined. Trimethoprim has no activity against Pseudomonas and variable activity against enterococci. Clinically, the most important method of resistance is by the use of plasmid-mediated dihydrofolate reductases that are resistant to the effects of this antibiotic. Antibiotic resistance to trimethoprim is increasing among uropathogens, with local data showing that approximately 30 per cent of isolates of E. coli are now resistant. Trimethoprim is absorbed readily from the GI tract and reaches peak serum levels one to four hours after ingestion. About 60-80 per cent of the dose is excreted in the urine, achieving an excess of the minimum inhibitory concentration (MIC) for most of the urinary pathogens. Trimethoprim monotherapy at a dose of 100-200mg twice daily is effective first-line therapy for uncomplicated UTI in women, but should be avoided in pregnancy especially during the first trimester due to its antifolate mode of action (see Table 1). Nitrofurantoin Another commonly used first-line agent, nitrofurantoin has a poorly understood mode of action but appears to require intracellular reduction via nitrofuran reductase. The active components are capable of blocking inducible enzymes and also damaging bac- 30 Prescriber 19 July 2007 www.escriber.com

terial DNA. Susceptible organisms vary somewhat, with E. coli, Citrobacter, enterococci and Staph. saprophyticus being generally sensitive, but members of the Proteus, Providencia, Morganella and Pseudomonas groups being resistant. GI absorption is enhanced when the drug is taken with food. Although serum concentrations are low with a serum half-life estimated at only about 30 minutes, the drug concentration in the urine is substantial and easily able to exceed the MIC of susceptible organisms. Nitrofurantoin should not be used in patients with renal insufficiency as they may achieve subtherapeutic levels in the urine and raised serum levels. This antibiotic should only be used for its antibacterial action in the bladder and lower urinary tract, and not if there is any evidence or suggestion of upper urinary symptoms. Beta-lactam antibiotics Beta-lactams are a large group of broad-spectrum antibiotics that target cell wall synthesis in a range of Gram-positive and Gram-negative organisms. They act by attaching to penicillin-binding proteins that, aside from binding to beta-lactam antibiotics, are responsible for the final cross-linking of the bacterial cell wall, thus conferring strength, rigidity and the ability to withstand osmotic pressures. This large group of antibiotics is comprised of penicillins, aminopenicillins, cephalosporins, monobactams and carbapenems. Although many betalactams are used in the treatment of UTI, we shall restrict ourselves to the oral agents commonly used in primary care for simple uncomplicated UTI. The three main ones are therefore amoxicillin, co-amoxiclav and cefalexin. As always, before commencing on a course of betalactam antibiotics, penicillin allergy should be enquired about and borne in mind. Amoxicillin Initially introduced as a development of penicillin that demonstrated a broader spectrum of activity both for Gram positives and negatives, its usefulness is, however, now limited by bacterial resistance. Amoxicillin is thus no longer recommended as empirical therapy for uncomplicated UTI given the level of beta-lactamase-mediated resistance, which locally and nationally is around 50 per cent (see Figure 2). It may be used as a second-line agent when the results of culture are known. Amoxicillin is safe to use in pregnancy but only when antibiotic sensitivities are known (as discussed above). It demonstrates good bioavailability from oral dosing and is visibly excreted in the urine. Antibiotic Trimethoprim Nitrofurantoin Amoxicillin and co-amoxiclav Quinolones Pivmecillinam Interactions warfarin, phenytoin, digoxin, antimalarials, ciclosporin, cytotoxics antacids warfarin, oral contraceptives NSAIDs, antacids, warfarin, phenytoin, ciclosporin, iron, theophylline warfarin, oral contraceptives Table 2. Drug interactions with antibiotics used to treat UTIs Co-amoxiclav Co-amoxiclav is a combination drug comprising amoxicillin and clavulanic acid. Clavulanic acid is an inhibitor of a range of bacterial beta-lactamase enzymes and thus restores some of the lost spectrum of activity to amoxicillin. It is thus suitable for empirical therapy. This combination drug is often expressed as a ratio of amoxicillin:clavulanate and demonstrates absorption and bioavailability similar to that of amoxicillin. However, the addition of clavulanate means caution should be exercised in pregnancy, and where possible an alternative should be chosen. Cefalexin This is a first-generation cephalosporin antibiotic that is stable to some of the beta-lactamase enzymes that have so limited the use of amoxicillin. While retaining much of its Gram-negative activity, it does not have the drawback of co-amoxiclav in that it is not combined with a beta-lactamase inhibitor (clavulanate), which means that it has the advantage of being safe to use in pregnancy. Caution must be exercised in patients with known penicillin allergy, especially since the reported crosshypersensitivity between penicillins and cephalosporins is around the 10 per cent mark. Cefalexin is the most commonly used oral cephalosporin for the management of UTI, showing reasonable bioavailability and excretion into the urinary tract. Cephalosporins have no activity against the uropathogen Enterococcus and often poor activity against Staph. saprophyticus. Increasing numbers of so-called extended-spectrum beta-lactamase (ESBL)-producing Gram negatives may prove a future limiting factor to the use of www.escriber.com Prescriber 19 July 2007 31

Resistance (%) 60 50 40 30 20 10 0 Ampicillin/amoxicillin Trimethoprim 1989 1991 1993 1995 1997 1999 2001 Figure 2. Percentage resistance of urinary E. coli to ampicillin/ amoxicillin and trimethoprim, 1989-2001 such cephalosporins in the community. Indeed, ESBLproducing bacteria have frequently been isolated from many sites, including urinary, in both hospital and community settings, and is another reason for continuing vigilance in how we use antibiotics and the importance of knowing your local microbial resistance patterns. Quinolones These are a large family of synthetic bactericidal agents that do not act on the cell wall as beta-lactams do, but instead at the level of the bacterial chromosome. They inhibit the activity of DNA gyrase and topoisomerase, enzymes essential for the correct packaging and managing of cellular DNA. These enzymes have no effect on their mammalian counterparts. Quinolones can be divided into generations like cephalosporins, with the first-generation quinolone being nalidixic acid (Uriben), a drug used as a urinary antibiotic due to its good Gram-negative spectrum of activity and good oral absorption and urinary levels. Its use has largely been superseded by the newer, second-generation fluoroquinolones such as ciprofloxacin. Although both nalidixic acid and ciprofloxacin have good Gram-negative activity, they have very limited Gram-positive action, especially against Gram-positive uropathogens. Quinolone antibiotics should be avoided in children, pregnancy and breastfeeding due to concerns regarding arthropathy in animal studies. Gram-negative resistance of uropathogens in the community to ciprofloxacin is currently only about 5 per cent, which is a valuable reason for this important antibiotic not to be a first-line choice. 6 Quinolone antibiotics are known to select for and encourage MRSA (methicillin-resistant Staph. aureus) and should be used cautiously in patients known (or suspected) to be MRSA positive. 7 Likewise in numerous recent publications quinolone usage has also been implicated in Clostridium difficile infection, particularly with reference to the newly described O27 hypervirulent strain. 8,9,10 Quinolone antibiotics are not recommended for first-line management of uncomplicated UTI partly for the reasons already expressed: to attempt to limit resistance occurring to this potent group of antibiotics, because they are more expensive than some of the alternatives already mentioned and because of some of the issues concerning MRSA and C. difficile. Taking MSUs While nearly all primary care physicians would request an MSU be sent in more complex cases such as cases of UTI in children, pregnancy and in diabetic men, it has been shown that in otherwise well women there can a wide variation in sample requesting. 11 The optimum management of uncomplicated UTIs should ideally include the taking of an MSU just prior to starting the course of antibiotics for several reasons: this would reassure the physician that the empirical choice was correct when the report is duly available it would provide accurate epidemiological and antibiotic resistance data essential for guiding future strategy (rather than just sending in complex, relapse or recurrent cases) if the empirical therapy fails due to resistance, then a second antibiotic with known sensitivity can be selected without having to wait for an MSU to be sent in for someone who has now been symptomatic for at least three days. Sending an MSU will also be useful if it demonstrates pyuria, ie white cells but no growth, in which case it may point to another pathology/diagnosis. However in the majority of otherwise well women the cost of routinely sending MSUs to the lab for culture and sensitivity may be the most expensive part of the treatment, and in a recent study data suggested that 23 urine cultures would need to be performed to predict one infection in which resistance would cause clinical failure in their cohort. 12 Therefore requesting an MSU in all straightforward cases may be impractical and expensive, in which case restricting sample sending for only complex cases, treatment failures and those at risk of resistant 32 Prescriber 19 July 2007 www.escriber.com

history and examination suggest a urinary tract infection positive result dipstick urinalysis negative result 3-day course of empirical treatment reassure, consider alternative diagnosis, eg STIs, candidosis, pelvic pathology (treat and investigate as appropriate) failure of treatment or recurrence of symptoms send urine to laboratory for culture and sensitivity no resolution or recurrence of symptoms positive result negative result 7-day course of treatment as per sensitivity report failure of treatment or recurrence of symptoms, if more than 3 episodes of recurrence, refer for investigation and consider prophylaxis consider alternative diagnosis, eg STIs, candidosis, pelvic pathology (treat and investigate as appropriate) Figure 2. Recommended management of women with an uncomplicated UTI; in patients who test positive to dipstick urinalysis, optimal management would include taking a urine sample, although this may be impractical in all straightforward cases isolates (previous antibiotics, hospitalisation or known resistant organisms) may represent the most optimal use of resources, while acknowledging that this may skew local resistance data. Structured surveillance of local resistance patterns will provide essential data for drawing up local guidelines. For example, knowing the resistance to agents such as amoxicillin and cefalexin may change the first- and second-line agents. As such, microbiological input should be sought for drawing up and altering such guidelines, and will be essential in the forward monitoring of antibiotic resistance patterns. Conclusions Uncomplicated UTI in an otherwise well woman is a common problem for primary care and accounts for a considerable amount of morbidity, antibiotic prescribing, laboratory time and NHS cost. It has been demonstrated that, generally speaking, the majority of well women should need no more than three days antibiotic therapy with a first-line agent. Short courses, where possible, to minimise antibiotic exposure are essential if we are to maintain the effectiveness of the currently available antibiotic classes in an era of increasing resistance (including ESBL-producing Escherichia coli and www.escriber.com Prescriber 19 July 2007 33

Klebsiella species) while still providing effective treatment. References 1. Hamilton-Miller JM. The urethral syndrome and its management. J Antimicrob Chemother 1994;33:63-73. 2. Naber KG. Treatment options for acute uncomplicated cystitis in adults. J Antimicrob Chemother 2000;46(S1):23-7. 3. Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am 1997;11(3):551-81. 4. Naber KG. Short-term therapy of acute uncomplicated cystitis. Current Opinion in Urology 1999;9:57-64. 5. Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women Infectious Diseases Society of America (IDSA). Clin Infect Dis 1999;29 (4):745-58. 6. Drug & Therapeutics Bulletin 1998;36(4). 7. Weber SG, Gold HS, Hooper DC, et al. Fluoroquinolones and the risk of methicillin-resistant Staphylococcus aureus in hospitalised patients. Emerg Infect Dis 2003;9(11):1415-22. 8. Kazakova SV, Ware K, Baughman B, et al. A hospital outbreak of diarrhea due to an emerging epidemic strain of Clostridium difficile. Arch Intern Med 2006;166(22):2518-24. 9. Cookson B. Hypervirulent strains of Clostridium difficile. Postgrad Med J 2007;83(979):291-5. 10. Delaney JA. Antimicrobial drugs and communityacquired Clostridium difficile-associated disease (CDAD), UK. Emerg Infect Dis 2007;13(5):761-3. 11. Hillier S, Bell J, Heginbothom M, et al. When do general Resources Further reading BMJ Collected Resources. All articles published in the BMJ since 1998. http://bmj.bmjjournals.com/ collections. British national formulary. March, 2007. Coping with cystitis. Clayton C. London: Sheldon, 1995. Medical microbiology. 3rd ed. Mims C, et al. Edinburgh, New York: Elsevier Mosby, 2005. Medical microbiology: a guide to microbial infections: pathogenesis, immunity, laboratory diagnosis and control. 17th ed. Greenwood D, Slack, RCB, Peutherer JF. Edinburgh, New York: Churchill Livingstone/ Elsevier, 2007. PRODIGY guidance. http://www.cks.library.nhs.uk/ uti_lower_women. Key points uncomplicated UTI is a very common complaint and one of the most common reasons for GP referral one of the commonest reasons for the prescribing of antibiotics the majority (>70 per cent) are caused by E. coli, with coliforms, enterococci and staphylococci making up most of the remainder three days of a first-line empirical antibiotic is usually sufficient treatment ideally, urine samples should be sent for analysis to provide local epidemiology and antibiotic resistance data and to guide subsequent management should first-line treatment fail practitioners request urine samples for microbiology analysis? The applicability of antibiotic resistance surveillance based on routinely collected data. J Antimicrob Chemother 2006;58:1303-6 12. McNulty CA, Richards J, Livermore DM, et al. Clinical relevance of laboratory-reported antibiotic resistance in acute uncomplicated urinary tract infection in primary care. J Antimicrob Chemother 2006;58:1000-8. Dr Townsend is a consultant microbiologist at Sheffield Teaching Hospitals, an honorary clinical lecturer at the University of Sheffield and honorary clinical fellow at Sheffield Hallam University SIGN guidance no. 88. Management of suspected bacterial urinary tract infection in adults. www.sign.ac.uk/ pdf/sign88.pdf. Websites EdRenINFO. Information provided by the Royal Infirmary of Edinburgh Renal Unit for patients and for doctors who are not renal specialists. This site includes information about many kidney problems including urinary tract infections. http://renux.dmed.ed.ac.uk/ EdREN/EdRenRUnithome.html. www.patient.co.uk. Information leaflets for patients: Cystitis in women, Cystitis recurrent infections in women, Urine infection in men, Urine infection in pregnancy, and Urine infection in children. Information and support for people with any kind of cystitis including interstitial cystitis: www.cob foundation.org/. 34 Prescriber 19 July 2007 www.escriber.com

Datafile Antibiotics used in the treatment of UTIs Drug Available as Strength/form Typical adult dosage Cost 1 Antibacterial methenamine Hiprex 1g tabs 1g twice daily 22p hippurate patients with catheters: up to 33p 1g 3 times daily Cephalosporins cefaclor Distaclor 500mg caps 250mg every 8 hours, max 4g 2.50 2 125mg, 250mg per 5ml susp daily 1.24 Distaclor MR 375mg sust-rel tabs 375mg twice daily 99p cefaclor 250mg, 500mg caps 250-500mg every 8 hours, 1.35-2.48 125mg, 250mg per 5 ml susp max 4g daily 1.40-2.80 125mg, 250mg per 5 ml sugar- 1.48-2.95 free susp cefadroxil Baxan 500mg caps 500mg-1g twice daily 53p- 1.05 125mg, 250mg, 500mg per 81p- 1.62 5ml susp (as powder for reconstitution) cefalexin Ceporex 250mg, 500mg tabs 1g twice daily 1.08 250mg, 500mg caps 1.08 125mg, 250mg, 500mg per 1.14 5ml syrup (as granules) Keflex 250mg, 500mg caps 1-4g daily in divided doses 24-94p 250mg, 500mg tabs 24-94p 125mg, 250mg per 5ml susp 31p- 1.26 cefalexin 250mg, 500mg caps 26p- 1.02 250mg, 500mg tabs 22-90p 125mg, 250mg per 5ml oral susp 1.04-4.15 cefixime Suprax 200mg tabs 200-400mg daily in single or 1.89-3.78 100mg per 5ml paed susp divided doses cefpodoxime Orelox 100mg tabs 100-200mg twice daily 2.04-4.07 proxetil 40mg per 5ml paed susp cefradine Velosef 250mg, 500mg caps 1-2g daily in 2 or 4 divided 67p- 1.35 250mg per 5ml syrup (as doses 84p- 1.69 powder for reconstitution) cefradine 250mg, 500mg caps 1-2g daily in 2 or 4 divided 97p- 1.93 doses cefuroxime Zinnat 125mg, 250mg tabs 125mg twice daily 69p- 1.38 axetil 125mg per 5ml susp pyelonephritis 250mg twice 79p- 1.58 daily 1 Cost of 1 day s treatment; prices MIMS June 2007, Drug Tariff May 2007 2 3 caps www.escriber.com Prescriber 19 July 2007 35

Datafile Antibiotics used in the treatment of UTIs (cont.) Drug Available as Strength/form Typical adult dosage Cost 1 Sulphonamides and folic acid inhibitors trimethoprim Trimopan 100mg, 200mg tabs 200mg twice daily 13p trimethoprim 100mg, 200mg tabs 19p 50mg per 5ml sugar-free oral 68p susp co-trimoxazole Septrin 80mg/400mg tabs 2 tabs or 10ml every 12 62p (trimethoprim/ 80mg/400mg per 5ml susp hours 88p sulfameth- 40mg/200mg per 5ml paed susp oxazole) Septrin Forte 160mg/800mg tabs 1 tab every 12 hours 47p co-trimoxazole 80mg/400mg tabs 2 tabs every 12 hours 1.76 Nitrofuran nitrofurantoin Furadantin 50mg, 100mg tabs 50-100mg 4 times daily 39-72p Macrobid 100mg mod-rel caps 100mg twice daily with 70p food Macrodantin 50mg, 100mg caps 50-100mg 4 times daily 41-77p nitrofurantoin 50mg, 100mg tabs 32-60p Penicillins amoxicillin Amoxil 250mg, 500mg caps 250-500mg 3 times daily 51p- 1.03 Amoxil Syrup 125, 250mg per 5ml syrup 9-18p (as powder) Amoxil paediatric 125mg per 1.25ml powder suspension for suspension Amoxil Sachet 3g per sachet powder 3g then 3g 10-12 hours later 5.85 amoxicillin 250mg, 500mg caps 250-500mg 3 times daily 16-26p 125mg, 250mg per 5ml oral susp 32-64p 125mg, 250mg per 5ml sugar- 41-83p free oral susp 3g per sachet powder 3g then 3g 10-12 hours later 5.67 ampicillin Penbritin 250mg, 500mg caps 500mg every 3 times daily 44p ampicillin 250mg, 500mg caps 49p 125mg, 250mg per 5ml susp 2.22 Penicillin/beta-lactamase inhibitor co-amoxiclav Augmentin 250mg/125mg, 500mg/125mg 375-625mg 3 times daily 52p- 1.04 (amoxicillin/ tabs before meals clavulanic acid) 125mg/31mg, 400mg/57mg, 250mg/62mg sucrose-free paed susp Augmentin 250mg/125mg disp tabs 375-625mg 3 times daily 1.46-2.92 Dispersible before meals co-amoxiclav 250mg/125mg, 500mg/125mg 250mg 3 times daily 79p tabs before meals 1 Cost of 1 day s treatment; prices MIMS June 2007, Drug Tariff May 2007 2 3 caps 36 Prescriber 19 July 2007 www.escriber.com

Datafile Antibiotics used in the treatment of UTIs (cont.) Drug Available as Strength/form Typical adult dosage Cost 1 co-amoxiclav co-amoxiclav 125mg/31mg, 250mg/62mg 250mg 3 times daily 76p (cont.) oral susp before meals Amidino penicillin pivmecillinam Selexid 200mg tabs acute cystitis: 400mg initially, 1.35 hydrochloride then 200mg 3 times daily to total of 10 tabs recurrent bacteriuria: 400mg 3 2.70-3.60 or 4 times daily Quinolones ciprofloxacin Ciproxin 100mg, 250mg, acute, uncomplicated 93p 500mg, 750mg tabs cystitis: 100mg twice daily other UTIs: 250-750mg 1.50-4.00 twice daily 250mg per 5ml susp acute, uncomplicated 1.65 cystitis: 250mg twice daily other UTIs: 250-500mg 1.65-3.30 twice daily ciprofloxacin 100mg, 250mg, 500mg, acute, uncomplicated 58p 750mg tabs cystitis: 100mg twice daily other UTIs: 250-750mg 41p-78p twice daily levofloxacin Tavanic 250mg, 500mg tabs 250mg once daily 1.45 nalidixic acid Uriben 300mg per 5ml susp 10-15ml 4 times daily 3.04-4.57 norfloxacin Utinor 400mg tabs 400mg twice daily 73p norfloxacin 400mg tabs 75p ofloxacin Tarivid 200mg, 400mg tabs 200-400mg daily, increasing 78p- 3.12 ofloxacin 200mg, 400mg tabs if necessary to 400mg twice 69p- 2.49 daily Tetracyclines doxycycline Vibramycin-D 100mg disp tabs 200mg on the first day, then 61p- 1.23 doxycycline 50mg, 100mg caps 100-200mg daily 23-46p minocycline Aknemin 50mg, 100mg caps 200mg daily in divided doses 1.05 minocycline 50mg, 100mg tabs 95p oxytetracycline oxytetracycline 250mg tabs 250-500mg 4 times daily 22-43p chlortetracycline/ Deteclo 115.4mg/115.4mg/69.2mg 1 tab every 12 hours 26p tetracycline/ tabs demeclocycline 1 Cost of 1 day s treatment; prices MIMS June 2007, Drug Tariff May 2007 2 3 caps www.escriber.com Prescriber 19 July 2007 37