Not all women presenting with the symptoms of acute dysuria and frequency have cystitis. It is reasonable to offer antibiotics to those women who have a positive leucocyte esterase and/or nitrite dipstick test. There has been one recent RCT of nitrofurantoin versus placebo for treating uncomplicated urinary tract infections in adult women. It showed that 77% of the group treated with nitrofurantoin showed a symptomatic improvement in 3 days, whereas there was spontaneous improvement in 54% of the placebo group. One of the placebo group developed pyelonephritis, none of the treated group did. The withdrawal rates in the two groups for “side effects” was 9 – 10%. This study would not be allowed now, as no written information or signed informed consent was required by Ghent University Hospital ethics committee. However, it is reassuring for general practitioners to read that we have been right to treat uncomplicated urinary tract infections with antibiotics!
There has been a great recent interest in cranberry juice. Some women have been taking this as an “alternative therapy” for years, believing it to sterilize the urine. Recent work has shown that components in the juice may prevent urinary tract infection by inhibiting fimbrial adherence of pathogenic E. coli. Uropathogenic E. coli adhere to mucosal lining of the urinary bladder with adhesins designated MS and MR on their fimbriae. Plant juices from cranberry, blueberry, or bearberry (Vaccinium ericaceae) contained a high molecular weight inhibitor of MR. Attempts to isolate the active agent from cranberry and blueberry juices are being made. Women may prefer this natural remedy, which has fewer side effects, to taking courses of antibiotics. There is also evidence that continuous prophylactic cranberry juice, as little as 30 ml twice daily, may reduce the rate of urinary tract infections (see continuous treatment section).
Angela Kilmartin set up the “U and I” clubs in the 1970s to help fellow sufferers gain support, knowledge, and understanding. She also wrote Understanding cystitis and Cystitis: a complete self-help guide. Although the national self-help group is no longer in existence, there are still local groups. There are also a number of free information leaflets, which give basic information about the causes of cystitis and preventive measures, which should be available in surgery waiting rooms.
Which antibiotics work?
As a general practitioner, the primary aim is to choose the most effective antibiotic. Other considerations are: side effects, safety in potentially pregnant women, and cost. The prevalence of resistance to antibiotics in bacteria changes with time and geographical area: practitioners need to be aware of local patterns of sensitivity.
From the data published from 240 centres in 17 countries (the UK was one of those participating, but the USA was not), urine samples from women with uncomplicated urinary tract infections were analysed for urinary pathogen and sensitivity. E. coli accounted for 80% of uropathogens in all 17 countries. The rates of resistance among E. coli were 30% to ampicillin and sulphamethoxazole, 15% to trimethoprim, 6% to nalidixic acid, 3% to ciprofloxacin, and >2% resistant to amoxicillin-clavulanic acid, mecillinam, cefadroxil, nitrofurantoin and fosfomycin. There is cause for concern that there is a rapid increase in quinolone resistance among community-acquired E. coli in Portugal (36%) and Spain (20%). From US data, looking at changes in the prevalence of resistance from 1992 to 1996, there was a 20% prevalence of resistance to ampicillin, cephalothin, and sulphamethoxazole in the E. coli isolates. Resistance to trimethoprim changed from 9% in 1992 to 18% in 1996. Professor Stamm concludes with the ominous statement that in the USA “trimethoprim may not be an acceptable choice for empirical first-line therapy for much longer”. By contrast, resistance to nitrofurantoin and ciprofloxacin did not change (0 – 2%). It is important to maintain a dialogue with your local medical microbiologist to develop local protocols for the empirical treatment, taking into account changes in local resistance patterns.
Most women do not like taking drugs continuously. They may only get three attacks of cystitis a year and resent having to take daily medication for this unlikely event. From their symptoms, 92% of women can correctly self-diagnose a urinary tract infection. This is because acute cystitis usually presents with the same symptoms each time. When giving women antibiotics to start treatment on their own, they should be told that if the symptoms have not completely resolved within 48 hours they should seek medical attention. Women prefer this method as they feel more in control of their body and their medication.
A low-dose nightly antibiotic, or even twice weekly, can reduce the recurrence of urinary tract infections by 95%. If the woman relapses on prophylaxis the uropathogen is inevitably a reinfection with a different organism that is resistant to the antibiotic being used. Urinary cultures must be made to identify the uropathogen and define its sensitivity to antimicrobial agents. It seems reasonable to plan a year of treatment, and then 6 months off.
Brumfitt and Hamilton-Miller looked at 219 females aged 9 – 89 with recurrent urinary tract infections, and gave them a year’s prophylaxis with nitrofurantoin. They chose three different regimens: 50 mg microcrystalline nitrofurantoin twice a day, 100 mg macrocrystalline nitrofurantoin once a day, or 50 mg macrodantin daily at bedtime. In all groups there was a 5.4-fold decrease in symptomatic episodes. Women with proven abnormalities of their urinary tract responded just as well as those without a structural abnormality. In 16%, prophylaxis was not helpful, for no clear reason as they still had nitrofurantoin-sensitive urinary tract infections: in their paper they do not mention how they tested compliance with treatment. The macrodantin group had the lowest dropout rate for adverse reactions, which were mainly nausea. Clinical improvement in all groups was maintained for 6 months after the end of prophylaxis, which was also found from the Melekos group (see post-intercourse). The conclusion was that macrocrystalline nitrofurantoin 50 mg at bedtime is an effective, safe, and appropriate choice for long-term (12 months), prophylaxis for urinary tract infections.