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Fine-tuning vs. destroying guidelines
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In the specialty of infectious diseases, we frequently fine-tune guidelines or recommendations. For example, there are changes in immunization policies based on the availability of new vaccines and results of studies in subpopulations. All too often, however, we see papers confirming what we already know, sometimes (purposefully or innocently) overlooking the fact that the information has been published before. It is very difficult to review old literature where frequently no abstracts are available electronically. Another repetitive phenomenon is meta-analyses of the same data with the addition or subtraction of a small number of papers.
Rarely there are occasions when we destroy a guideline by totally voiding previous recommendations. This happens most frequently with antibiotic therapy because a pathogen’s spectrum of antimicrobial susceptibility is constantly changing as pathogens evolve. An example is recommendations for treatment of gonococcal infections.
In the area regarding treatment of urinary tract infections (UTI), there have been a number of recommendation-destroying occurrences over the years. One example was the adoption of short-course therapy for uncomplicated lower UTI in women after years of recommendations of longer therapies. Another example was the recognition that treatment of asymptomatic bacteriuria is not indicated and should not be undertaken in patients with diabetes or in the elderly. Recently, it was demonstrated that treatment of asymptomatic bacteriuria in adult nonpregnant women is actually harmful, resulting in increased numbers of symptomatic infections and causing more antibiotic resistance of infecting organisms.
For many years, screening for bacteriuria in pregnancy and treating it has been recommended in the United States. These recommendations were based on numerous studies performed over many years, demonstrating that a significant proportion of women with bacteriuria during pregnancy developed acute pyelonephritis, a very unpleasant infection and in many studies a cause of adverse effects on the fetus. The usual incidence of pyelonephritis among bacteriuric pregnant women was generally reported as 20% or more. Furthermore, eradication of the bacteriuria was shown to greatly decrease the incidence of pyelonephritis in the bacteriuric population. Less clear was the relationship between asymptomatic bacteriuria in pregnancy and adverse effects on the fetus. The Infectious Diseases Society of America’s guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults state that “Pregnant women should be screened for bacteriuria by urine culture at least once in early pregnancy, and they should be treated if the results are positive. ... Periodic screening for recurrent bacteriuria should be undertaken following therapy.”
Periodically, studies challenging guidelines are published, and we have to be cautious to not just accept such papers on face value. A recent study by Kazemier and colleagues from the Netherlands in The Lancet Infectious Diseases called into question “a routine policy of midtrimester screening and subsequent treatment for asymptomatic bacteriuria in low-risk women with a singleton pregnancy.” This potentially attacks a guideline that has been constructed over many years and supported by many studies from multiple countries showing that bacteriuria in pregnancy was related to an increased occurrence of acute pyelonephritis later in the pregnancy and that eradication of the bacteriuria dramatically decreased the incidence of pyelonephritis. The overwhelming message was that bacteriuria in pregnancy had significance for the health of the mother, and in many studies, probably the well-being of the fetus. Of course, few if any of these studies would stand up to the rigorous demands of evidence-based medicine using randomized controlled trials; by the same token, neither would the use of antibiotics for the treatment of pneumococcal pneumonia.
In the same study, “The proportion of women with pyelonephritis, preterm birth, or both did not differ between untreated or placebo-treated asymptomatic bacteriuria-positive women and asymptomatic bacteriuria-negative women (6 [2.9%] of 208 vs. 77 [1.9%] of 4,035; adjusted OR = 1.5; 95% CI, 0.6-3.5) nor between asymptomatic bacteriuria-positive women treated with nitrofurantoin vs. those who were untreated or received placebo (1 [2.5%] of 40 vs. 6 [2.9%] of 208; risk difference, 0.4; 95% CI, 3.6 to 9.4). Untreated or placebo-treated asymptomatic bacteriuria-positive women developed pyelonephritis in five [2.4%] of 208 cases, compared with 24 [0.6%] of 4,035 asymptomatic bacteriuria-negative women (adjusted OR = 3.9; 95% CI, 1.4-11.4).” While 2.4% is significantly higher than 0.6%, it was stated to be of questionable importance in terms of screening the entire pregnant population and treating those with bacteriuria to prevent so few cases of pyelonephritis.
The most striking result reported was the extremely low frequency of pyelonephritis in the untreated or placebo-treated bacteriuric populations (2.4% compared with the 10-fold higher rates in the older literature). The lower incidence of pyelonephritis observed in more recent studies in pregnant women in general probably reflects treatment of bacteriuria during the pregnancy. The low number of women with untreated bacteriuria and pyelonephritis in this study precludes any meaningful comparison of risk to the fetus. The authors, along with Lindsey E. Nicolle, MD, who wrote a related editorial in the same issue of the journal, point out possible limitations of the study. However, none of the limitations seems adequate to explain the discrepancy in the very low occurrence of pyelonephritis in a pregnant population not treated for asymptomatic bacteriuria unless the population or medical care system in the Netherlands differs sufficiently from those of other countries that have studied bacteriuria in pregnancy. Even if the delivery of health care has evolved to a vastly superior level in the Netherlands, it probably has not in many parts of the world, so the results cannot be generalized. Of course the results of this study beg the replication of controlled studies in other populations, especially in this age of antibiotic stewardship. However, it is doubtful that such studies will occur in countries with institutional review boards and guidelines for detecting and treating bacteriuria in pregnancy, as well as a legal system such as ours. Until and unless such studies are reported, the current recommendations for treatment of bacteriuria in pregnancy should stay in place.
- References:
- Cai T, et al. Clin Infect Dis. 2012;doi:10.1093/cid/cis534.
- Cai T, et al. Clin Infect Dis. 2015;doi:10.1093/cid/civ696.
- Nicolle LE, et al. Clin Infect Dis. 2005;doi:10.1086/427507.
- Nicolle LE. Lancet Infect Dis. 2015;doi:10.1016/S1473-3099(15)00145-0.
- Kazemier BM, et al. Lancet Infect Dis. 2015;doi:10.1016/S1473-3099(15)00070-5.
- For more information:
- 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 an Infectious Disease News Editorial Board member.
Disclosure: Kaye reports no relevant financial disclosures.