• Consider offering a prescription for a 'stand-by' antibiotic to be used for future episodes of cystitis before prescribing prophylactic drug treatment.
• When deciding to offer prophylactic drug treatment, consider the frequency, severity, and impact of recurrent cystitis, and whether referral for urological investigation would be appropriate.
• For recurrent cystitis associated with sexual intercourse:
• Offer trimethoprim 100 mg to be taken within 2 hours of intercourse (off-label use).
• For recurrent cystitis not associated with sexual intercourse:
• Offer a 6-month trial of low-dose continuous antibiotic treatment.
• Suitable antibiotics are:
• Trimethoprim 100 mg every night.
• Nitrofurantoin (immediate-release) 50 mg to 100 mg every night (modified-release nitrofurantoin is not licensed for prophylaxis).
• Treatments that are not recommended include:
• Methenamine hippurate.
• Oestrogen products (for post-menopausal women).

'Stand-by' antibiotics as an alternative to preventive antibiotics

• The recommendation to consider 'stand-by' antibiotics is based on expert opinion [Harris et al, 2008].

Post-coital antibiotics

• There is limited evidence from a Cochrane systematic review that post-coital antibiotics may be more effective than placebo and as effective as continuous antibiotic treatment in preventing urinary tract infection (UTI) associated with sexual intercourse.
• The recommendation to offer trimethoprim 100 mg is extrapolated from evidence provided by a small, double-blind, randomized controlled trial that co-trimoxazole 240 mg (containing trimethoprim 40 mg and sulfamethoxazole 200 mg) given within 2 hours of intercourse was more effective than a post-coital placebo [Stapleton et al, 1990]. Trimethoprim (a narrow spectrum antibiotic) has been found to be as effective as co-trimoxazole in treating UTI and produces fewer adverse effects [SIGN, 2006; BNF 57, 2009; European Association of Urology, 2009]. The European Association of Urology also recommend that it is reasonable to offer the doses of antibiotics used for nightly prophylaxis for post-coital use [European Association of Urology, 2009].
• Although another study supported the post-coital use of ciprofloxacin (a quinolone) [Melekos et al, 1997], broad spectrum antibiotics are less preferred. This is in line with guidance issued by the Health Protection Agency which recommended avoiding the use of broad spectrum antibiotics when narrow spectrum antibiotics remain effective [HPA, 2009]. There are concerns that broad spectrum antibiotics increase the risk of Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA), and resistant UTIs.

Referral before starting continuous antibiotic prophylaxis

• Seeking specialist advice before starting continuous antibiotic prophylaxis is recommended pragmatically to decide whether the woman needs investigation to exclude an underlying cause.

Continuous antibiotic prophylaxis

• Effectiveness
• There is weak evidence from a Cochrane systematic review that continuous antibiotics reduce recurrence of urinary tract infections more than placebo but are associated with more adverse effects [Albert et al, 2004]. There are limited data showing that antibiotics do not continue to prevent bacteriuria after treatment is stopped.
• Continuous antibiotics have not been directly compared with cranberry products [SIGN, 2006].
• Choice of antibiotic
• There is insufficient direct evidence to prefer any particular antibiotic over another. Trimethoprim and nitrofurantoin are recommended options for prophylaxis of recurrent UTI because:
• Narrow spectrum antibiotics, such as trimethoprim and nitrofurantoin, are generally preferred over broad spectrum antibiotics due to concerns over increasing the risk of Clostridium difficile, MRSA, and resistant UTIs [HPA, 2009].
• Both trimethoprim and immediate-release nitrofurantoin are licensed for the prophylaxis of recurrent UTI [Goldshield Pharmaceuticals, 2002b; Goldshield Pharmaceuticals, 2002c; Actavis, 2007]. The modified-release formulation of nitrofurantoin is not licensed [Goldshield Pharmaceuticals, 2007].
• Dosage and duration of treatment
• The dosages are based on those recommended by manufacturers of these antibiotics and in line with the dosages used in trials investigating prophylaxis of recurrent UTIs [Goldshield Pharmaceuticals, 2002c; Goldshield Pharmaceuticals, 2002b; Albert et al, 2004; Actavis, 2007].
• A 6-month trial is recommended, as this reflects the duration of most trials on prophylactic antibiotics. Information on long-term follow up is lacking.
• Bacterial resistance
• There are concerns that resistance to trimethoprim and nitrofurantoin is increasing, but there is little current published evidence on resistance patterns for trimethoprim and nitrofurantoin (see the evidence section on Prevalence).
• Consequently, CKS recommends that local antibiotic guidelines should be followed, taking into account local resistance pattern.

Treatments not recommended

• Methenamine hippurate
• Methenamine hippurate is not recommended for preventing UTI because there is only weak evidence from a Cochrane systematic review that treatment may be effective for up to 7 days [Lee et al, 2007].
• Oestrogen products (for postmenopausal women)
• Oestrogen products are not recommended for use as preventive treatment in primary care because there is evidence from a Cochrane systematic review that oral oestrogens are no more effective than placebo in reducing recurrent UTIs in postmenopausal women, and there is conflicting evidence from two small trials on intravaginal oestrogen [Perrotta et al, 2008].