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The journey from fact to fiction
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Recently, I reviewed the subject of urinary tract infection, and the current status reminded me of the enormous changes in thinking that have occurred over the years.
In the mid-1960s when I first became involved with studies on UTI, one of the important areas of research was based on the importance/necessity of quantitation of bacteria in the urine for diagnosis of UTI. The emphasis on quantitation led to studies of the epidemiology of asymptomatic bacteriuria, which was determined to have great significance.
The magic number of the requirement of ≥105 bacteria/mL urine for diagnosis was widely applied, not only to asymptomatic bacteriuria but also to symptomatic infection.
Donald Kaye
Over the years, lectures to medical students required the understanding of the importance of quantitative urine cultures and the magic number for diagnosis of UTI. In addition, UTI in general was viewed as a serious disease that, especially in children, and particularly if recurrent, could lead to renal insufficiency if they were not kept bacteriuria-free.
Fast forward to 2013
With the realization that about one-third of young women with cystitis do not have “significant bacteriuria” (false negatives on urine culture), urine cultures have become relatively unimportant in the management of most women with lower tract infection. Asymptomatic bacteriuria that over the years was viewed as deleterious to the health of diabetics and the elderly is now accepted to have no such effects. The approach of treating asymptomatic bacteriuria in women with frequent recurrences of symptomatic cystitis to prevent recurrences has been shown to be ineffective and may even increase symptomatic recurrences. In fact, with the exception of a dwindling number of indications, the current approach is: Don’t look for asymptomatic bacteriuria and don’t treat it. The two exceptions in adults in which asymptomatic bacteriuria is considered significant and should be eradicated are in pregnant women and in those who are to have surgical procedures that traumatize the mucosa of the urinary tract. Another possible controversial indication is in renal transplant patients in the post-transplant period. At one time, management of infants and young children with recurrent UTI included screening for asymptomatic bacteriuria and keeping them free of asymptomatic infection. Those with vesicoureteral reflux often had surgical repair. The current literature indicates that screening for and treating asymptomatic bacteriuria is not indicated in young children, not even infants. Even the approach to vesicoureteral reflux has become more conservative with much less surgery recommended and reserved only for high grades of reflux. For a succinct authoritative example of how far the pendulum has swung in children, see “‘Do not do’ recommendation details” (www.nice.org.uk/usingguidance/donotdorecommendations/detail.jsp?action=details&dndid=9).
The current and logical view is that the great majority of symptomatic UTIs in women, although annoying, is benign and self-limited. This realization took years to develop. Although complicated, UTI in the presence of anatomic or functional abnormalities, immunosuppression, renal failure and renal transplantation, and UTI in pregnancy are exceptions and require more attention; the major reason for treating most patients is to relieve symptoms. The one clear cut benefit of treating the great majority of lower UTI is relief of symptoms.
Sensability of developments
There are much more recent developments that to me make little sense. For example, the recently published international clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women (Gupta K. Clin Infect Dis. 2011;52: e103-e120) list trimethoprim-sulfamethoxazole, nitrofurantoin and fosfomycin (Monurol, Forest Laboratories) as first-line drugs for cystitis but do not list fluoroquinolones as first-line drugs. The reason stated is to reserve the drugs for other uses because of “collateral damage” (ecological adverse effects of antimicrobial therapy). At the risk of committing intellectual heresy, I question this recommendation, and I suspect it will be largely ignored by physicians treating UTIs. Fluoroquinolones, and ciprofloxacin in particular, have been among the most widely used and reliable drugs for UTIs and have less bacterial resistance than TMP-SMX and are probably associated with fewer reinfections than fosfomycin. Generic ciprofloxacin also is considerably cheaper than fosfomycin in the United States. Furthermore, the 3-day use of fluoroquinolones for cystitis probably adds little pressure to spread of resistance compared with the widespread, misuse (including treatment of asymptomatic bacteriuria and other non-indicated uses) and the probable spread of fluoroquinolone-resistant organisms from food in some countries.
As far as the future, the increasing resistance of community-acquired Escherichia coli (CTX-M-15 ESBL E. coli O25:H4 sequence type ST131) coupled with the lack of new promising antibiotics should speed the development of new approaches to management of UTI by means other than antibiotic therapy. Some of the studies that show promise for prevention of reinfections in women are use of probiotics (demonstrated in women) and animal research with vaccines, colonization with “non-virulent” strains of E. coli and immunostimulents.
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Donald Kaye, MD, is a professor of Medicine at Drexel University College of Medicine, Associate Editor of ProMED-mail, Section Editor of News for Clinical Infectious Diseases and is an Infectious Disease News Editorial Board member.Disclosure: Kaye reports no relevant financial disclosures.