When should cystitis be treated?

General practitioners are in an extremely difficult position because women with cystitis require immediate treatment. However, half of all non-pregnant women with the symptoms of urgency, dysuria, and frequency will have no detectable bacterial infection (but see: What is significant bacteriuria?). In about 50% of cases with a proven bacteriuria, symptoms may resolve through natural host defences without drug treatment in 3 days. It could, therefore, be argued that no woman should be treated for a lower urinary tract infection until they have had 3 days of symptoms. However, this is putting a large number of women potentially at risk from ascending infection, and the misery of 3 days of illness. Many women try to avoid taking antibiotics for recurrent urinary tract infections since they know from bitter experience that the eradication of pathogenic bacteria from their urinary tract has an effect on their commensal flora of bowel and vagina. The broad-spectrum penicillins in particular destroy the commensal flora, including the lactobacilli, so facilitating the colonization of the urethral introitus with resistant Gram-negative organisms, and also allowing Candida albicans to gain dominance in the vagina. Many women know that they get thrush after antibiotics, but still 75% of women do not realize the link. Trimethoprim and nitrofurantoin do not usually select resistant bowel organisms and leave the urethral flora undisturbed, protecting the patient against Gram-negative colonization.

It would seem reasonable to treat only those symptomatic women who are dipstick positive for leucocytes and/or nitrites. It is also reassuring to know that the weight of evidence favours the conclusion that although urinary tract infections can produce severe impairment of renal function, this is rare in the absence of major predisposing factors such as obstruction, stones, reflux, abnormalities of the voiding mechanisms, pregnancy, or diabetes mellitus.

What is significant bacteriuria?

The whole topic of urinary tract infections is fraught with problems of definition. The work by H.E. Kass defining significant bacteriuria as >105 colony-forming units (c.f.u.) per ml of voided urine was based on two groups of women, with asymptomatic bacteriuria and acute pyelonephritis. This has been widely generalized to all patient populations with urinary tract infections but has never been evaluated for cystitis. The only reliable urine specimen is obtained by bladder aspiration or sterile catheterization; but these are invasive, uncomfortable, and not feasible in general practice. Voided urine is easy to collect, but inevitably contaminated with periurethral flora.

A general practitioner needs a test that reliably distinguishes true bladder bacteriuria from contaminated specimens. On the Kass definition of 105 c.f.u./ml, many women with the symptoms of dysuria and frequency are told “there’s nothing wrong”. Stamm and Hooton argue that a new significant bacteriuria threshold should be agreed of >102 uropathogens per ml for symptomatic patients. This proves to be far more sensitive for E. coli (0.95), and only slightly less specific (0.85). This threshold of 102 c.f.u. coliforms is a very sensitive indicator of infections since if these women are followed they will invariably reach a count of 105 over the succeeding days. At present, laboratories have not taken up this revised >102 c.f.u. suggestion: in the UK laboratories report in the range of 105 to >105 c.f.u./ml.

Should I screen women for asymptomatic bacteriuria?

The first problem is what is true asymptomatic bacteriuria, and what is contamination. Of true asymptomatic bacteriuria, 30% will become symptomatic in time and the women will then seek treatment. However, most women with true asymptomatic bacteriuria appear to experience it as a transient phenomenon. Women therefore get intermittent asymptomatic bacteriuria, which can resolve without treatment. Since women with asymptomatic bacteriuria either present sooner or later with an acute urinary tract infection, or self-cure, there seems at present no good argument for routine screening of the whole sexually active population of women. However, there are a few subgroups that should be considered: antenatal women, women with known abnormalities of their urinary tract, and diabetics.

When should an mid-stream sample of urine be sent?

Given that voided urine in the general practice setting is almost inevitably contaminated, is there any point in sending one at all? The other major problem with sending urine for culture and sensitivity is one has to make an immediate therapeutic decision when seeing the patient about treatment, and the results from the laboratory will come back 3 days later when 80 – 90% of the patients seen and treated should be completely better.

In a survey of Danish general practitioners, microbiologists, and urologists, 48% of general practitioners, but only 24% of microbiologists said they would routinely send a urine sample for culture on a previously fit 30-year-old woman. In Oxfordshire, the implementation of guidelines on the use of the laboratory for urine culture, has led to better patient management and more efficient use of the laboratory.

What length antibiotic course?

The literature is full of studies varying from single-dose antibiotics to a full 6-week course for acute urinary tract infections. The advocates of a single-dose therapy argue that this is the treatment of choice for uncomplicated urinary tract infections in general practice since a single dose ensures compliance and cures simple cystitis. There will be an immediate relapse in the 30% who have an occult upper urinary tract infection. This can be looked on as a useful clinical guide to those patients who need further investigation, intensive treatment, and supervision. Other workers in the field are concerned that the single-dose regimen is less effective; further validation with large, controlled trials are still needed.

The 3-day course is now in vogue. It has the advantage of fewer side effects over the previously favoured 7 – 14-day treatment schedules, and a lower relapse rate than a single dose. However, some bacteriologists argue that although a 3-day course of trimethoprim is effective, if nitrofurantoin is used 5 – 7 days is better.

If an upper renal tract infection is suspected, there is evidence that a 14-day course of antibiotics is as effective as a 6-week course with fewer side effects (concomitant thrush, drug reactions such as rashes and diarrhoea, and patient compliance). There is also less likelihood of reinfection with resistant organisms.

In all uncomplicated non-pregnant female patients with lower urinary tract infections, a 3-day course of trimethoprim or nitrofurantoin seems reasonable. There is still controversy as to whether complicated urinary tract infections (including those of pregnant women) should be treated with a 7-, 10- or 14-day course.

Does the urethral syndrome need treatment?

Should the woman be advised to drink a large quantity?

One of the few things everyone seems to know about cystitis is that the sufferer should increase their fluid intake. The normal range of urine osmolarity is 300 – 1200 mosmol/l; if urine becomes very dilute (<200 mosmol/l) growth of bacteria is reduced. A diuresis also helps bladder emptying, theoretically allowing the pathogenic E. coli to be flushed out of the system (although this ignores the E. coli’s ability to attach on to the bladder wall epithelium).

Women also drink substances to change the pH of their urine, to create a less favourable environment for the pathogenic E. coli, which further confuses the picture. However, some people argue that an excessive diuresis may actually enhance vesicouretheral reflux and in some cases actually facilitate bacteria reaching the kidneys. It also dilutes antibacterial substances in the urine, which may decrease their therapeutic efficacy. There is no prospective trial on the beneficial or detrimental use of drinking fluids in women with uncomplicated urinary tract infections. This is distinct from the beneficial effects of drinking cranberry juice, which has been found to inhibit pathogenic E. coli fimbrial adherence.

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