In Reply

The clinical S3 guideline for uncomplicated urinary tract infections (UTIs) deals with the therapy of uncomplicated UTIs, not their prophylaxis. Professor Wenderlein’s comment that in postmenopausal patients, local vaginal prophylactic administration of estradiol can prevent recurring UTIs is correct; however, it does not relate to acute treatment but to prophylaxis.

Wefer points out the S3 guideline’s similarity to the current guideline of the European Association of Urology. Since all quality guidelines can be developed according to the same rules of evidence based medicine, similar recommendations in international publications (1) are a quality indicator rather than a problem. The important pillars that this S3 guideline is based on (development of resistance, collateral damage, study data, side effects, dosages) are near-identical in the comparable, international, high-quality guidelines.

No consensus was reached with regard to assessing trimethoprim. This is primarily because of the different assessments of existing resistance limits. In Germany, the resistance rate of E coli to cotrimoxazole/trimethoprim is 30% (2).

The S3 guideline applies to all German speaking countries, which is why we included pivmecillinam into the therapy, which is available in Austria, for example, and constitutes a suitable substance for treating uncomplicated cystitis, for the reasons set out in the guideline.

With regard to Liebendörfer’s comment that nitrofurantoin is not therapeutic alternative, we might say: the resistance rate for nitrofurantoin has not risen in recent years and has been reported as below 10% in all studies. Liebendörfer probably means that in break-through infections during long-term therapy with nitrofurantoin, resistance rates above 20% have been observed. This is possible, and we would not argue with this. For this reason, in every patient requiring antibiotic therapy, previous antibiotic therapy needs to be considered; this is also the case for previous therapy with cotrimoxazole and fluoroquinolones. The possible side effects of nitrofurantoin and the restricted indication in the product information are openly dealt with in the S3 guideline. However, cotrimoxazole can occasionally have severe adverse effects (Hopf et al., 1981), as can trimethoprim, albeit more rarely (Bijl et al., 1998).

Grundmann compares the current guideline with a 1989 book on antibiotic therapy by Simon and Stille. However, much has changed in the intervening 22 years. In 1989, resistance to fluoroquinolones did not exist in uncomplicated UTIs and was thus not perceived as a problem. This has changed fundamentally in the meantime. For this reason, fluoroquinolones are not recommended as first-line therapy in acute cystitis but only in acute uncomplicated pyelonephritis. Fosfomycin trometamol, by contrast, is recommended as first-line treatment for uncomplicated UTIs because of its currently favorable resistance profile, its low potential for inducing collateral damage, and the high quality evidence from studies (meta-analysis). Swalve-Bordeaux points out the possible rise in resistance if fosfomycin trometamol is given more often. But the development of resistance is an unavoidable problem associated with antibiotic treatment, which we can try to reduce as much as possible while remaining aware that it cannot be prevented altogether. For this reason, every prescription for an antibiotic substance needs to be analyzed critically with regard to indication and sequelae, as we have to make the most of the substances that are currently at our disposal.

In response to our much mentioned ties to pharmaceutical companies: these include primarily activities such as studies and lectures, without preference for any particular company. This is reflected in the fact that almost all manufacturers that deal with antibiotic substances were listed, which ultimately shows the lack of bias among the scientists involved in the guideline. All vital recommendations for antibiotic treatment are carried by all participants in the guideline team, independently of any existing potential competing interests.

DOI: 10.3238/arztebl.2012.0081b

Prof. Dr. med. Florian M.E. Wagenlehner

Klinik und Poliklinik für Urologie, Kinderurologie und Andrologie Universitätsklinikum Gießen und Marburg GmbH, Standort Gießen

Wagenlehner@aol.com

Conflict of interest statement
Professor Wagenlehner has received travel and hotel expenses and lecture honoraria from the following companies: Astellas, Bayer-Vital, Calixa, Cerexa, Cernelle, Cubist, GSK, MerLion, OM-Pharma, Janssen-Cilag, Johnson and Johnson, Lilly, Pharmacia, Pierre-Fabre, Rosen-Pharma, Sanofi-Aventis, Strathmann, Zambon, and Serag Wiessner.