Clinical Practice Guideline

Uncomplicated Bacterial Community- acquired Urinary Tract Infection in Adults

Epidemiology, Diagnosis, Treatment, and Prevention

Dtsch Arztebl Int 2017; 114(50): 866-73; DOI: 10.3238/arztebl.2017.0866

Kranz, J; Schmidt, S; Lebert, C; Schneidewind, L; Schmiemann, G; Wagenlehner, F

Background: Uncomplicated bacterial community-acquired urinary tract infection is among the more common infections in outpatient practice. The resistance level of pathogens has risen markedly. This S3 guideline contains recommendations based on current evidence for the rational use of antimicrobial agents and for the prevention of inappropriate use of certain classes of antibiotics and thus of the resulting drug resistance. The prevention of recurrent urinary tract infection is considered in this guideline for the first time.

Methods: The guideline was updated under the aegis of the German Urological Society (Deutsche Gesellschaft für Urologie). A systematic literature search (period: 2008–2015) concerning the diagnosis, treatment, and prevention of uncomplicated urinary tract infections was carried out in the Cochrane Library, MEDLINE, and Embase databases. Randomized, controlled trials and systemic reviews were included. Relevant guidelines were identified in a guideline synopsis.

Results: Symptom-oriented diagnostic evaluation is highly valued. For the treatment of cystitis, fosfomycin-trometamol, nitrofurantoin, nitroxolin, pivmecillinam and trimethoprim are all equally recommended. Fluorquinolones and cephalosporins are not recommended. Uncomplicated pyelonephritis with a mild to moderate clinical course ought to be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For acute, uncomplicated cystitis, with mild to moderate symptoms, symptomatic treatment alone may be considered instead of antibiotics after discussion of the options with the patient. Mainly non-antibiotic measures are recommended for prophylaxis against recurrent urinary tract infection.

Conclusion: Physicians who treat uncomplicated urinary tract infections should familiarize themselves with the newly revised guideline’s recommendations on the selection and dosage of antibiotic treatment so that they can responsibly evaluate and plan antibiotic treatment for their affected patients.

Uncomplicated bacterial urinary tract infection is one of the most commonly occurring community-acquired infections. In 2013, 7.32% of the female members of the German health insurance fund Barmer GEK were diagnosed with uncomplicated urinary tract infection (uUTI; ICD-10 code N39.0), 1.73% with acute uncomplicated cystitis (AUC; N30.0), and 0.16% with acute uncomplicated pyelonephritis (AUP: N10) (1). The estimated incidence of UTI in women over 18 years of age in the USA is 12.6% (2). On the basis of the Barmer GEK data, German prescription practice for diagnosed cystitis runs contrary to the recommendations of the guideline issued in 2010. For example, the drug class most commonly prescribed for the treatment of UTI in 2012 was a fluoroquinolone, given in 48% of cases (1). Antibiotic resistance is a growing global problem that is leading to considerably increased costs and daunting challenges in health care (1, 35). According to the data of the ARMIN resistance-monitoring project in the German federal state of Lower Saxony, for instance, resistance of Escherichia coli to ciprofloxacin has increased from 10.3% to 14.7% in the past 10 years (6). Growing resistance to cotrimoxazole and ampicillin has also been noted (7, 8). It is known that different antibiotics exert a varying amount of selection pressure not only on the pathogens responsible for the infection, but also on the uninvolved local flora. This is termed collateral damage, and the substances used in the treatment of uncomplicated UTI with the greatest effect in this respect are the cephalosporins and fluoroquinolones.

The goal of updating the guideline is to provide clinical practice recommendations for the diagnosis, treatment, and prevention of uncomplicated bacterial community-acquired UTI in adults. The recommendations and statements are intended to help members of all professions concerned with the diagnosis, treatment, and prophylaxis of acute uUTI: primary-care physicians, gynecologists, infectious disease specialists, internists working in primary care, clinical pathologists, microbiologists, urologists, and pharmacists.

Method

The revised S3 guideline was compiled according to the regulations of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) (9) under the aegis of the German Urology Society (Deutsche Gesellschaft für Urologie, DGU). It was decided not to solicit or accept funding from the pharmaceutical industry. All authors’ conflicts of interests were publicized. The content of the central statements and recommendations was voted on separately by experts with and without conflicts of interest. A complete list of the authors of the updated S3 guideline and the professional societies they represent is provided in the eBox.

For the first time, the guideline was supported by UroEvidence@Deutsche Gesellschaft für Urologie, the knowledge transfer center of the DGU. UroEvidence was responsible for sifting of the identified publications by two experts working independently (JK, SS), literature management (JK, SS), and assessment of the level of evidence and risk of bias in the treatment studies (JK, SS, LS). Evidence assessment was based on the results of a systematic survey of the literature on the topics diagnosis and treatment of uUTI and prevention of recurring UTI (rUTI). Details of the search strategy can be found (in German) in the long version of the guideline (10). The databases Cochrane Library, MEDLINE, and Embase were searched for publications in the period 1 January 2008 (continuing from the systematic survey carried out for the first edition of the guideline published in 2010) to 31 December 2015. Furthermore, the data of all currently available relevant studies were incorporated in the interests of a “living guideline.” The publications identified by the literature search were sorted according to topic and divided accordingly among the working groups. To be included, studies not only had to have a patient population as defined below, but also had to fulfill the requirements for study design: randomized controlled trial (RCT) or systematic review with or without meta-analysis. A flow chart of the literature survey according to the PRISMA statement (11) is shown in eFigure 1. The risk of bias was assessed for all studies included: for RCTs using the Cochrane Risk of Bias Tool, for systematic reviews and meta-analyses using the Scottish Intercollegiate Guideline Network (SIGN) system (12, 13). Assessment of the level of evidence followed the 2009 criteria of the Oxford Centre for Evidence-based Medicine (14). The evidence tables (effect sizes) of the recommended antibiotics are shown in eTable 1.

eFigure 1

A guideline synopsis was carried out to identify existing relevant guidelines. The guidelines selected for inclusion (n = 19) were evaluated independently by two authors of the present guideline according to the AGREE criteria (15).

The recommendation grades were decided by the members of the guideline group (see classification in eFigure 2). Evidence-based statements and recommendations were formulated over the course of 17 consensus/telephone conferences. Formal consensus finding took the form of a nominal group process under the leadership of an external moderator from the AWMF (Prof. Kopp). The version of the guideline for consultation was published via the professional societies and on the homepage of the AWMF (10). Comments were discussed by the guideline group and taken into consideration in the final version. The methods, the comments made during the consultation process, and the steps taken to determine conflicts of interest are described in detail in the guideline report (10).

eFigure 2

The different categories of patients with uUTI ought to be considered separately for purposes of diagnosis, treatment, and prevention:

  • Non-pregnant women in the premenopause with no relevant comorbidity (standard group)
  • Pregnant women with no relevant comorbidity
  • Women in the postmenopause with no relevant comorbidity
  • Young men with no relevant comorbidity
  • Patients with diabetes mellitus and stable metabolism with no relevant comorbidity

Results

On the basis of the systematic literature survey, 75 recommendations and 68 statements were agreed upon without discord both by participants with and those without conflicts of interest. The definitions can be found in the Box.

In the following, we present selected recommendations on diagnosis (eTable 2, eFigures 3 and 4), treatment (Table 1, Table 2, eFigure 4), and prevention (Table 3) for the largest groups of patients (nonpregnant women in the premenopause and pregnant women with no relevant comorbidity). For the other groups of patients defined above, the reader is referred to the long version of the guideline (10).

eFigure 3
eFigure 4
eTable 2

Diagnosis

The diagnostic techniques are intended to establish whether a UTI is present and, in some cases, to identify the pathogen responsible for the infection and to determine how it can be treated.

Confirmation of acute uncomplicated cystitis (AUC) on clinical criteria alone is afflicted by an error rate of up to one third (16, 17). The only way of reducing diagnostic inaccuracy would be always to perform a urine culture with determination of all pathogens, even those present in low counts (gold standard). However, pursuing this maximal strategy in nonselected patients is neither economically reasonable (18) nor practicable in daily routine, because the delay before the results of a urine culture are known means that they would have no essential influence on the empirical short-term treatment.

Diagnosis in the standard group: nonpregnant women in the premenopause

Acute uncomplicated cystitis (AUC)—There is a probability of almost 80% that women who have no risk factors for complicated UTI, complain of typical symptoms (pain on passing water, pollakisuria, severe urgency), have no vaginal symptoms (itchiness, altered secretions), and deny fever and flank pain will have AUC (e1, e2) (evidence level IIa). A urine culture is unnecessary in women with clear-cut clinical symptoms of uncomplicated, nonrecurrent or non-treatment-resistant cystitis. In a first manifestation of AUC, or if the patient is unknown to the physician, the medical history ought to be taken and a symptom-related medical examination carried out (evidence level V-B). With the validated Acute Cystitis Symptom Score (ACSS) questionnaire (eFigure 5), AUC can be diagnosed with a high degree of certainty based on clinical criteria (94.7% sensitivity and 82.4% specificity with a total score of ≥ 6 points), the severity of the symptoms can be estimated, the patient’s progress can be followed, and the treatment effect is rendered measurable (evidence level IIb) (19, 20).

eFigure 5

Acute uncomplicated pyelonephritis (AUP)In addition to establishing the patient’s general medical history, physical examination and urinalysis including urine culture should be carried out (evidence level V-A). Moreover, further investigations (e.g., sonography) should be considered with the goal of excluding complicating factors (evidence level V-A) (e3).

Asymptomatic bacteriuria (ASB)It is strongly recommended that no screening for asymptomatic bacteriuria be performed in nonpregnant women with no relevant comorbidity (evidence level Ia-A) (e4e6).

Recurring urinary tract infection (rUTI)In patients with rUTI, urine ought to be cultured and sonography ought to be performed once only. No other invasive diagnostic tests ought to be carried out (evidence level Ib-B) (e7, e8). In patients with persisting hematuria or persisting presence of pathogens other than E. coli, urethrocystoscopy and further imaging are recommended (evidence level V-B) (e2, e9, e10).

Diagnosis in pregnant women without relevant comorbidity

Acute uncomplicated cystitis (AUC)The patient’s medical history ought to be taken just as in nonpregnant patients, but physical examination and urinalysis including urine culture are strongly recommended (evidence level V-A). Following the antibiotic treatment of AUC in pregnancy, eradication of the pathogen should be verified by urine culture (evidence level V-A).

Acute uncomplicated pyelonephritis (AUP)The diagnosis of AUP in pregnant women is analogous to that in nonpregnant patients (evidence level V). Physical examination and urinalysis including urine culture are mandatory (evidence level V-A). If pyelonephritis is suspected, sonography of the kidneys and urinary tract should be carried out (evidence level V-A) (e11, e12). Following the antibiotic treatment of pyelonephritis in pregnancy, eradication of the pathogen should be verified by urine culture (evidence level V-A).

Asymptomatic bacteriuria (ASB)Systematic screening for ASB ought not to be carried out in pregnant women (EG Ib-B) (21, e13e18). The strip tests generally used for this purpose have low sensitivity (14 to 50%) for ASB in pregnancy (2123).

Use of strip tests alone is inadequate for diagnosis of ASB in pregnancy (evidence level IV) (2123).

Recurring urinary tract infection (rUTI)—The diagnostic work-up in pregnant women without relevant comorbidity broadly corresponds to that in young women with no relevant comorbidity.

An overview of the reference values for the diagnosis of various UTIs and ASB can be found in eTable 2.

Treatment

The following criteria should be taken into account when deciding which antibiotic to use (evidence level Ia-A):

  • The patient’s individual risk
  • The spectrum of pathogens and antibiotic sensitivity
  • The efficacy of the antimicrobial substance
  • The adverse drug reactions
  • The effects on the resistance situation in the individual patient (collateral damage) and/or the general population (epidemiological effects)

Acute uncomplicated cystitis: standard group

The spontaneous recovery rate in AUC is high (at 1 week: clinically 28%, clinically and microbiologically 37%). The central goal of treatment is swift relief of the clinical symptoms, i.e., within a matter of days (24). The small number of placebo-controlled studies performed have shown that the symptoms resolve more rapidly with antibiotic treatment than with placebo (25). In a recent study, Gágyor et al. compared the effect of primarily symptomatic ibuprofen treatment with that of immediate administration of an antibiotic. Around two thirds of patients with purely symptomatic treatment needed no further antibiotic (26). In light of these findings, nonantibiotic, symptomatic treatment may be considered in cases of AUC with mild or moderate symptoms (evidence level IA-B). Due consideration should be paid to the patients’ preferences when deciding what course of treatment to follow. This is especially true for primarily nonantibiotic treatment, which may be associated with a greater burden of symptoms (freedom from symptoms after 7 days: ibuprofen 163/232 patients versus fosfomycin 186/227 patients, 95% confidence interval [−19.4; −4.0]) (26). The decision should be made together with the patient.

Asymptomatic bacteriuria

The presence of ASB increases the risk of infection for patients undergoing urinary tract interventions in which mucosal trauma can be anticipated. For this reason ASB should be actively sought in such cases, and if found it should be treated (evidence level IA-A) (27).

The evidence from randomized studies in this respect is primarily for transurethral resection of the prostate. There is no evidence regarding low-risk interventions, e.g., urethrocystocopy.

Kazemier et al. showed that in women with low risk pregnancy and ASB the risk of symptomatic cystitis increased from 7.9% to 20.2% if they were treated with placebo or not at all (for pyelonephritis from 0.6% to 2.4%) (28). However, ASB did not increase the risk of premature birth for nontreated patients in this low risk pregnancy population (28).

General comment on antibiotic treatment of acute uncomplicated cystitis

Among the group of antibiotics or classes of antibiotic drugs that are basically suitable for the treatment of AUC—aminopenicillins in combination with a betalactamase inhibitor, group 2 and 3 cephalosporins, fluoroquinolones, fosfomycin-trometamol, nitrofurantoin, nitroxolin, pivmecillinam, trimethoprim or cotrimoxazole—the fluoroquinolones and cephalosporins are associated with the greatest risk of microbiological collateral damage in the form of selection of multiresistant pathogens and development of Clostridium difficile-associated colitis (29).

Since fluoroquinolones and cephalosporins have an important role in complicated infections, the clinical consequences of increased resistance by using them in uncomplicated infections was rated as more severe than for other antibiotics recommended for the treatment of AUC. (evidence level V). It is thus strongly recommended that the fluoroquinolones and cephalosporins are not used in the treatment of AUC unless there is a contraindication for alternative substances (evidence level V-A) (Table 1). In addition, patient-relevant clinical endpoints (clinical improvement of symptoms, recurrences, ascending infections) and the individual risk (e.g., Achilles tendon rupture with the fluoroquinolones) should be taken into account.

Acute uncomplicated pyelonephritis: standard group

Patients with AUP should receive efficacious antibiotic treatment as soon as possible, because kidney damage (30), though not frequent, is more likely with increasing duration, severity, and frequency of such infections. In choosing the best antibiotic, the eradication rates, sensitivity, collateral damage, and special characteristics with regard to adverse drug reactions should be taken into account (evidence level V) (Table 2, eFigure 4). Because the prevalence is much lower than that of AUC (0.16%) (1), less heed has to be paid to collateral damage (1).

Prevention of recurring urinary tract infection: standard group

Before initiation of long-term prophylactic drug treatment, a woman with rUTI should be counseled in detail on avoidance of risks (e.g., not drinking enough, overcooling, excessive intimate hygiene) (evidence level Ib-A) (e19, e20). If appropriate preventive measures have been taken but rUTI persists, long-term antibiotic prophylaxis ought to be preceded by oral administration of an E. coli lysate (OM-89) for 3 months (evidence level Ia-B) (e21). Immunoprophylaxis by means of three parenteral injections of inactivated specified enterobacteria at 1-week intervals may be considered (evidence level Ib-C) (28). Moreover, mannose may be considered (e22); alternatively, various phytotherapeutic agents may be considered (evidence level Ib-C) (e23, e24). If the patient’s level of suffering is high, failure of behavioral modification and nonantibiotic prophylaxis ough to be followed by continual long-term antibiotic prophylaxis for 3 to 6 months (evidence level IV-B) (31) (Table 3). In the presence of an association with sexual intercourse, postcoital prophylaxis with a single dose ought to be used instead of long-term administration of antibiotics (evidence level Ib-B) (31, e25, e26).

Conclusion

The high frequency of uncomplicated bacterial community-acquired urinary tract infections in adults and their treatment with antibiotics exerts massive antibiotic selection pressure on the bacteria involved and also on the collateral flora, resulting in significant influence on the selection of antibiotic-resistant bacteria in the population. Careful use of antibiotics for this indication is therefore extremely important in safeguarding the efficacy of antibiotic treatment. The treatment recommendations were thus crucially influenced by considerations of antibiotic stewardship. The evidence- and consensus-based recommendations of the updated S3 guideline therefore need to be widely implemented by all categories of medical professionals entrusted with the treatment of urinary tract infections in order to improve the standards of care and ensure a forward-looking policy on the use of antibiotics.

Acknowledgments
International reviewer: Gernot Bonkat (Switzerland)

Coordination and external moderation: Ina Kopp, AWMF Institute for Medical Knowledge Management, University of Marburg

We are especially grateful to Alexandra Pulst, scientific assistant at the Department of Care Research, Institute for Public Health and Nursing Care Research, University of Bremen for her support in compiling the guideline synopsis and evidence assessment.

Conflict of interest statement

Prof. Wagenlehner has received consultancy fees from Achaogen, Astra Zeneca, Bionorica, MSD, Pfizer, Rosen Pharma, Vifor Pharma, and Leo Pharma. Furthermore, he has received funds to conduct clinical studies from MSD, Pfizer, Vifor Pharma, Rosen Pharma, and Leo Pharma.

Dr. Kranz has received funds to carry out a systematic review from Leo Pharma.

Dr. Schmidt has received funds to carry out a systematic review from Leo Pharma.

The remaining authors declare that no conflict of interest exists.

Manuscript submitted on 30 August 2017, revised version accepted on
25 October 2017

Translated from the original German by David Roseveare

Corresponding author
Dr. med. Jennifer Kranz, FEBU
Klinik für Urologie und Kinderurologie, St. Antonius-Hospital
Akademisches Lehrkrankenhaus der RWTH Aachen
Dechant-Deckers-Str. 8
52249 Eschweiler, Germany
jennifer.kranz@sah-eschweiler.de

Supplementary material
For eReferences please refer to:
www.aerzteblatt-international.de/ref5017

eFigures, eBox, eTables:
www.aerzteblatt-international.de/17m0866

1.
Dicheva S: Harnwegsinfekte bei Frauen. In: Glaeske G, Schicktanz C: Barmer GEK Arzneimittelreport 2015; 107–37.
2.
Johnson CC: Definitions, classification, and clinical presentation of urinary tract infections. Med Clin North Am 1991; 75: 241–52 CrossRef
3.
Cai T, Verze P, Brugnolli A, et al.: Adherence to European Association of urology guidelines on prophylactic antibiotics: an important step in antimicrobial stewardship. Eur Urol 2016; 69: 276–83 CrossRef MEDLINE
4.
Zhou Y, Ma LY, Zhao X, Tian SH, Sun LY, Cui YM: Impact of pharmacist intervention on antibiotic use and prophylactic use in urology clean operations. J Clin Pharm Ther 2015; 40: 404–8 CrossRef MEDLINE
5.
Wagenlehner FME, Bartoletti R, Cek M, et al.: Antibiotic stewardship: a call for action by the urologic community. Eur Urol 2013; 64: 358–60 CrossRef MEDLINE
6.
Niersächisches Gesundheitsamt: ARMIN. www.nlga.niedersachsen.de/infektionsschutz/armin_resistenzentwicklung/armin_interaktiv/ (last accessed on 7 October 2017).
7.
Naber KG, Schito GC, Botto H, Palou J, Mazzei T: Surveillance study in Europe and Brazil on clinical aspects and antimicrobial resistance epidemiology in females with cystitis (ARESC): Implications for empiric therapy. European Urology 2008; 54: 164–78 CrossRef MEDLINE
8.
Zwirner M, Bialek R, Roth T, et al.: Local resistance profile of bacterial isolates in uncomplicated urinary tract infections (LORE study). Kongressabstract DGHM 2016.
9.
German Association of the Scientific Medical Societies (AWMF) Standing Guidelines Commission. AWMF Guidance Manual and Rules for Guideline Development, 1st edition 2012. English version. Available at: http://www.awmf.org/leitlinien/awmf-regelwerk.html (last accessed on July 30, 2017)
10.
Leitlinienprogramm DGU: Interdisziplinäre S3 Leitlinie: Epidemiologie, Diagnostik, Therapie, Prävention und Management unkomplizierter, bakterieller, ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten. Langversion 1.1–2, 2017 AWMF Registernummer: 043/044. www.awmf.org/leitlinien/detail/ll/043–044.html (last accessed on 12 November 2017).
11.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA): www.prisma-statement.org (last accessed on 7 October 2017).
12.
Scottish Intercollegiate Guidelines Network, Healthcare Improvement Scotland: www.sign.ac.uk/checklists-and-notes.html (last accessed on 7 October 2017).
13.
International Cochrane Collaboration: www.handbook.cochrane.org/chapter_8/table_8_5_d_criteria_for_judging_risk_of_ bias_in_the_risk_of.htm (last accessed on 7 October 2017).
14.
Centre for evidence based Medicine (CEBM): www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ (last accessed on 7 October 2017).
15.
Appraisal of Guidelines for Research and Evaluation (AGREE): www.agreetrust.org/ (last accessed on 7 October 2017).
16.
Knottnerus BJ, Geerlings SE, Moll van Charante EP, ter Riet G, Toward A: Simple diagnostic index for acute uncomplicated urinary tract infections. Ann Fam Med 2013: 442–51 CrossRef MEDLINE PubMed Central
17.
Little P, Turner S, Rumsby K, et al.: Developing clinical rules to predict urinary tract infection in primary care settings: sensitivity and specificity of near patient tests (dipsticks) and clinical scores. Br J Gen Pract 2006; 56: 606–12 MEDLINE PubMed Central
18.
Rothberg MB, Wong JB: All dysuria is local. A cost-effectiveness model for designing sitespecific management algorithms. J Gen Intern Med 2004; 19: 433–43 CrossRef MEDLINE PubMed Central
19.
Alidjanov JF, Pilatz A, Abdufattaev UA, et al.: [German validation of the acute cystitis symptom score]. Urologe A 2015; 54: 1269–76 CrossRef MEDLINE
20.
Alidjanov JF, Lima HA, Pilatz A, et al.: Preliminary Clinical Validation of the English Language Version of the Acute Cystitis Symptom Score. JOJ uro & nephron. 2017; 1: 555561
21.
Bachman JW, Heise RH, Naessens JM, Timmerman MG: A study of various tests to detect asymptomatic urinary tract infections in an obstetric population. JAMA 1993; 270: 1971–4 CrossRef CrossRef
22.
Lumbiganon P, Chongsomchai C, Chumworathayee B, Thinkhamrop J: Reagent strip testing is not sensitive for the screening of asymptomatic bacteriuria in pregnant women. J Med Assoc Thai 2002; 85: 922–7 MEDLINE
23.
Tincello DG, Richmond DH: Evaluation of reagent strips in detecting asymptomatic bacteriuria in early pregnancy: prospective case series. BMJ 1998; 316: 435–7 CrossRef
24.
Ferry SA, Holm SE, Stenlund H, Monson TJ: The natural course of uncomplicated lower urinary tract infection in women illustrated by a randomized placebo controlled study. Scand J Infect Dis 2004; 36: 296–301 CrossRef
25.
Christiaens TC, de Meyere M, Verschraegen G, Peersman W, Heytens S, de Maeseneer JM: Randomised controlled trial of nitrofurantoin versus placebo in the treatment of uncomplicated urinary tract infection in adult women. Br J Gen Pract 2002; 52: 729–34 MEDLINE PubMed Central
26.
Gágyor I, Bleidorn J, Kochen MM, Schmiemann G, Wegscheider K, Hummers-Pradier E: Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial. BMJ 2015; 351: h 6544.
27.
Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM: Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005; 40: 643–54 CrossRef MEDLINE
28.
Kazemier BM, Koningstein FN, Schneeberger C, et al.: Maternal and neonatal consequences of treated and untreated asymptomatic bacteriuria in pregnancy: a prospective cohort study with an embedded randomised controlled trial. Lancet Infect Dis 2015; 15: 1324–33 CrossRef
29.
S3-Leitlinie Strategien zur Sicherung rationale Antibiotika-Anwendung im Krankenhaus AWMF-Registernummer 092/001. www.awmf.org/leitlinien/detail/ll/092–001.html (last accessed on 7 October 2017).
30.
Frei U, Schober-Halstenberg HJ: Nierenersatztherapie in Deutschland. Bericht über Dialysebehandlung und Nierentransplantation in Deutschland 2006/2007. www.bundesverband-niere.de/fileadmin/user_upload/QuaSi-Niere-Bericht_2006–2007.pdf (last accessed on 7 October 2017).
31.
Grabe M, Bartoletti R, Bjerklund Johansen TE, et al.: Guidelines on urological infections. EAU Guidelines 2015. www.uroweb.org/wp-content/uploads/19-Urological-infections_LR2.pdf (last accessed on 7 October 2017).
e1.
Christiaens T, Callewaert L, de Sutter A, van Royen P: Aanbeveling voor goede medische praktijkvoering: cystitis bij de vrouw. Huisarts nu: maandblad van de Wetenschappelijke Vereniging van Vlaamse Huisartsen 2000; 29: 282–8.
e2.
Epp A, Larochelle A: SOGC clinical practice guideline: recurrent urinary tract infection. J Obstet Gynaecol Can 2010; 1082–90 MEDLINE
e3.
van Nieuwkoop C, Hoppe BP, Bonten TN, et al.: Predicting the need for radiologic imaging in adults with febrile urinary tract infection. Clin Infect Dis 2010; 51: 1266–72 CrossRef MEDLINE
e4.
Nicolle LE: Asymptomatic bacteriuria: review and discussion of the IDSA guidelines. Int J Antimicrob Agents 2006; 28(Suppl): 42–8 CrossRef
e5.
Nicolle LE: Asymptomatic bacteriuria: when to screen and when to treat. Infect Dis Clin North Am 2003; 17: 367–94 MEDLINE
e6.
Scottish Intercollegiate Guidelines Network. SIGN 88 management of suspected bacterial urinary tract infection in adults. 2012. www.sign.ac.uk/sign-88-management-of-suspected-bacterial-urinary-tract-infection-in-adults.html (last accessed on 12 November 2017).
e7.
Parsons SR, Cornish NC, Martin B, Evans SD: Investigation of uncomplicated recurrent urinary tract infections in women. J Clin Urol 2016; 4: 234–8.
e8.
Wagenlehner FME, Wagenlehner C, Savov O, Gulaco L, Schito G, Naber KG: Klinik und Epidemiologie der unkomplizierten Zystitis bei Frauen. Urologe 2010; 49: 253–61 CrossRef
e9.
van Pinxteren B, Knottnerus BJ, Geerlings SE, et al.: De standaard en wetenschappelijke verantwoording zijn geactualiseerd ten opzichte van de vorigeversie. Huisarts Wet 2005; 8: 341–52.
e10.
American Urological Association: Diagnoses, evaluation and follow up of asymptomatic microhematuria (AMH) in adults. www.auanet.org/education/guidelines/asymptomatic-microhematuria.cfm (last accessed on 7 October 2017).
e11.
McDermott S, Callaghan W, Szwejbka L, Mann H, Daguise V: Urinary tract infections during pregnancy and mental retardation and developmental delay. Obstet Gynecol 2000; 96: 113–9 CrossRef CrossRef
e12.
McDermott S, Daguise V, Mann H, Szwejbka L, Callaghan W: Perinatal risk for mortality and mental retardation associated with maternal urinary-tract infections. J Fam Pract 2001; 50: 433–7 MEDLINE
e13.
Delzell JE, Lefevre ML: Urinary tract infections during pregnancy. Am Fam Physician 2000; 61: 713–21 MEDLINE
e14.
Force U: Guide to clinical preventive services: report of the U.S. Preventive Service Task Force. Baltimore: Williams & Wilkins 1996.
e15.
McNair RD, MacDonald SR, Dooley SL, Peterson LR: Evaluation of the centrifuged and gram-stained smear, urinalysis, and reagent strip testing to detect asymptomatic bacteriuria in obstetric patients. Am J Obstet Gynecol 2000; 182: 1076–9 CrossRef
e16.
Millar L, DeBuque L, Leialoha C, Grandinetti A, Killeen J: Rapid enzymatic urine screening test to detect bacteriuria in pregnancy. Obstet Gynecol 2000; 95: 601–4 CrossRef CrossRef
e17.
Ovalle A, Levancini M: Urinary tract infections in pregnancy. Curr Opin Urol 2001; 11: 55–9 CrossRef
e18.
Santos JF, Ribeiro RM, Rossi P, et al.: Urinary tract infections in pregnant women. Int Urogynecol J Pelvic Floor Dysfunct 2002; 13: 204–9 CrossRef MEDLINE
e19.
Lumsden L, Hyner GC: Effects of an educational intervention on the rate of recurrent urinary tract infection. Women & Health 1985; 10/1: 79–86 CrossRef MEDLINE
e20.
Su SB, Wang JN, Lu CW, Guo HR: Reducing urinary tract infections among female clean room workers. J Womens Health 2006; 15 /7: 870–6 CrossRef MEDLINE
e21.
Beerepoot MA, Geerlings SE, van Haarst EP, van Charante NM, ter Riet G: Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials. J Urol 2013; 190: 1981–9 CrossRef MEDLINE
e22.
Albrecht U, Goos KH, Schneider B: A randomised, double-blind, placebo-controlled trial of a herbal medicinal product containing tropaeoli majoris herba (nasturtium) and armoraciae rusticanae radix (horseradish) for the prophylactic treatment of patients with chronically recurrent lower urinary tract infections. Curr Med Res Opin 2007; 23/10: 2415–22 CrossRef MEDLINE
e23.
Kranjcec B, Papes D, Altarac S: D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol 2014; 32: 79–84 CrossRef MEDLINE
e24.
Larsson B, Jonasson A, Fianu S: Prophylactic effect of UVA-E in women with recurrent cystitis: a preliminary report. Curr Ther Res 1993; 53/4: 441–3 CrossRef
e25.
Melekos MD, Asbach H, Gerharz E, Zarakovitis I, Weingärtner K, Naber K: Postintercourse versus daily ciprofloxacin prophylaxis for recurrent urinary tract infections in premenopausal women. J Urol 1997; 101: 935–9.
e26.
Pfau A, Sacks TG: Effective postcoital prophylaxis of recurrent urinary tract infections in premenopausal women: a review. Int Urogynecol J 1991; 2: 156–60 CrossRef
e27.
Rubin RH, Shapiro ED, Andriole VT, Davis RJ, Stamm WE: Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Infectious Diseases Society of America and the Food and Drug Administration. Clin Infect Dis 1992; 15(Suppl 1): 216–27.
e28.
Bleidorn J, Gágyor I, Kochen MM, Wegscheider K, Hummers-Pradier E: Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection?—results of a randomized controlled pilot trial. BMC Med 2010; 8: 30 CrossRef MEDLINE PubMed Central
e29.
Ceran N, Mert D, Kocdogan FY, et al.: A randomized comparative study of single-dose fosfomycin and 5-day ciprofloxacin in female patients with uncomplicated lower urinary tract infections. J Infect Chemother 2010; 16: 42430 CrossRef MEDLINE
e30.
Hooton TM, Roberts PL, Stapleton AE: Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial. JAMA 2012; 307: 583–9 MEDLINE PubMed Central
e31.
Palou J, Angula JC, Ramón de Fata F, et al.: [Randomized comparative study for the assessment of a new therapeutic sched-ule of fosfomycin trometamol in postmenopausal women with uncomplicated lower urinary tract infection]. Actas Urol Esp 2013; 37: 147–55 CrossRef CrossRef MEDLINE
e32.
Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB: A double-blind, randomized comparison of levofloxacin 750mg once-daily for five days with ciprofloxacin 400/500mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology 2008; 71: 17–22 CrossRef MEDLINE
e33.
Estebanez A, Pascual R, Gil V, Ortiz F, Santibáñez M, Pérez Barba C: Fosfomycin in a single dose versus a 7-day course of amoxicillin-clavulanate for the treatment of asymptomatic bacteriuria during pregnancy. Eur J Clin Microbiol Infect Dis 2009; 28: 1457–64 CrossRef MEDLINE
e34.
Monsen TJ, Holm SE, Ferry BM, Ferry SA: Mecillinam resistance and outcome of pivmecillinam treatment in uncomplicated lower urinary tract infection in women. APMIS 2014; 122: 317–23 CrossRef MEDLINE
e35.
Bjerrum L, Gahrn-Hansen B, Grinsted P: Pivmecillinam versus sulfamethizole for shortterm treatment of uncomplicated acute cystitis in general practice: a randomized controlled trial. Scand J Prim Health Care 2009; 27: 6–11 CrossRef MEDLINE PubMed Central
e36.
Lumbiganon P, Villar J, Laopaiboon M, et al.: Oneday compared with 7-day nitrofurantoin for asymptomatic bacteriuria in pregnancy: a randomized controlled trial. Obstet Gynecol 2009; 113: 339–45 CrossRef MEDLINE
e37.
Little P, Moore MV, Turner S, et al.: Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial. BMJ 2010; 340: c199.
e38.
Monmaturapoj T, Montakantikul P, Mootsikapun P, Tragulpiankit P: A prospective, randomized, double dummy, placebo-controlled trial of oral cefditoren pivoxil 400mg once daily as switch therapy after intravenous ceftriaxone in the treatment of acute pyelonephritis. Int J Infect Dis 2012; 16: e843–9 CrossRef MEDLINE
e39.
Shaheen G, Usmanghani K, Nazar H, Akhtar N: Clinical evaluation of herbal coded formulation gran-off to urixin in the treatment of urinary tract infection. Pak J Pharm Sci 2015: 557–9 MEDLINE
e40.
Stein JC, Navab B, Frazee B, et al.: A randomized trial of computer kiosk-expedited management of cystitis in the emergency department. Acad Emerg Med 2011; 18: 1053–9 CrossRef MEDLINE
e41.
Turner D, Little P, Raftery J, et al.: Cost effectiveness of management strategies for urinary tract infections: results from randomised controlled trial. BMJ 2010; 340: c346.
e42.
Drozdov D, Schwarz S, Kutz A, et al.: Procalcitonin and pyuria-based algorithm reduces antibiotic use in urinary tract infections: a randomized controlled trial. BMC Med 2015; 13: 104 CrossRef MEDLINE PubMed Central
e43.
Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO: Ceftolozanetazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECTcUTI). Lancet 2015; 385: 1949–56 CrossRef
e44.
Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD: Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 2010; 18, 340: c2096.
e45.
Eliakim-Raz N, Yahav D, Paul M, Leibovici L: Duration of antibiotic treatment for acute pyelonephritis and septic urinary tract infection—7 days or less versus longer treatment: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 2013; 68: 2183–91 CrossRef MEDLINE
e46.
Falagas ME, Kotsantis IK, Vouloumanou EK, Rafailidis PI: Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a meta-analysis of randomized controlled trials. J Infect 2009; 58: 91–102 CrossRef MEDLINE
e47.
Falagas ME, Vouloumanou EK, Togias AG, et al.: Fosfomycin versus other antibiotics for the treatment of cystitis: a metaanalysis of randomized controlled trials. J Antimicrob Chemother 2010; 65: 1862–77 CrossRef MEDLINE
e48.
Flower A, Wang LQ, Lewith G, Liu JP, Li Q: Chinese herbal medicine for treating recurrent urinary tract infections in women. Cochrane Database Syst Rev 2015; 6: CD010446.
e49.
Guinto VT, de Guia B, Festin MR, Dowswell T: Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2010; 9: CD007855.
e50.
Gutiérrez-Castrellón P, Díaz-García L, de Colsa-Ranero A, Cuevas-Alpuche J, JiménezEscobar I: [Efficacy and safety of ciprofloxacin treatment in urinary tract infections (UTIs) in adults: a systematic review with meta-analysis]. Gac Med Mex 2015; 151: 225–44.1a.
e51.
Jepson RG, Mihaljevic L, Craig J: Cranberries for treating urinary tract infections. Cochrane Database Syst Rev 2014; 2: CD001322.
e52.
Knottnerus BJ, Grigoryan L, Geerlings SE, et al.: Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: network meta-analysis of randomized trials. Fam Pract 2012; 29: 659–70 CrossRef MEDLINE
e53.
Kyriakidou KG, Rafailidis P, Matthaiou DK, Athanasiou S, Falagas ME: Short-versus longcourse antibiotic therapy for acute pyelonephritis in adolescents and adults: a metaanalysis of randomized controlled trials. Clin Ther 2008; 30: 1859–68 CrossRef MEDLINE
e54.
Lutters M, Vogt-Ferrier NB: Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women. Cochrane Database Syst Rev 2008; 3: CD001535.
e55.
Naber KG, Niggemann H, Stein G, Stein G: Review of the literature and individual patients’ data meta-analysis on efficacy and tolerance of nitroxoline in the treatment of uncomplicated urinary tract infections. BMC Infect Dis 2014; 14: 628–43 CrossRef MEDLINE PubMed Central
e56.
Smaill FM, Vazquez JC: Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2015; 8: CD000490.
e57.
Widmer M, Lopez I, Gülmezoglu AM, Mignini L, Roganti A: Duration of treatment for asymptomatic bacteriuria during pregnancy. Cochrane Database Syst Rev 2015; 11: CD000491.
e58.
Vazquez JC, Abalos E: Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev 2011; 1: CD002256.
e59.
Zalmanovici Trestioreanu A, Green H, Paul M, Yaphe J, Leibovici L: Antimicrobial agents for treating uncomplicated urinary tract infection in women. Cochrane Database Syst Rev 2010; 10: CD007182.
*Joint first authors
Department of Urology and Pediatric Urology, St. Antonius Hospital Eschweiler, Academic Teaching Hospital of RWTH Aachen, Eschweiler: Dr. Kranz
UroEvidence@Deutsche Gesellschaft für Urologie, Berlin: Dr. Kranz, Dr. Schmidt, Dr. Schneidewind
Pharmacy, Nuremberg Hospitals: Dr. Lebert
Hematology/Oncology, Department of Internal Medicine C, Faculty of Medicine, University of Greifswald: Dr. Schneidewind
Department of Care Research, Institute for Public Health and Nursing Care Research, University of Bremen: PD Dr. Schmiemann
Department of Urology, Pediatric Urology and Andrology, University Hospital of Gießen and Marburg Ltd., Justus-Liebig University Gießen: Prof. Wagenlehner
1.Dicheva S: Harnwegsinfekte bei Frauen. In: Glaeske G, Schicktanz C: Barmer GEK Arzneimittelreport 2015; 107–37.
2. Johnson CC: Definitions, classification, and clinical presentation of urinary tract infections. Med Clin North Am 1991; 75: 241–52 CrossRef
3.Cai T, Verze P, Brugnolli A, et al.: Adherence to European Association of urology guidelines on prophylactic antibiotics: an important step in antimicrobial stewardship. Eur Urol 2016; 69: 276–83 CrossRef MEDLINE
4.Zhou Y, Ma LY, Zhao X, Tian SH, Sun LY, Cui YM: Impact of pharmacist intervention on antibiotic use and prophylactic use in urology clean operations. J Clin Pharm Ther 2015; 40: 404–8 CrossRef MEDLINE
5.Wagenlehner FME, Bartoletti R, Cek M, et al.: Antibiotic stewardship: a call for action by the urologic community. Eur Urol 2013; 64: 358–60 CrossRef MEDLINE
6.Niersächisches Gesundheitsamt: ARMIN. www.nlga.niedersachsen.de/infektionsschutz/armin_resistenzentwicklung/armin_interaktiv/ (last accessed on 7 October 2017).
7.Naber KG, Schito GC, Botto H, Palou J, Mazzei T: Surveillance study in Europe and Brazil on clinical aspects and antimicrobial resistance epidemiology in females with cystitis (ARESC): Implications for empiric therapy. European Urology 2008; 54: 164–78 CrossRef MEDLINE
8.Zwirner M, Bialek R, Roth T, et al.: Local resistance profile of bacterial isolates in uncomplicated urinary tract infections (LORE study). Kongressabstract DGHM 2016.
9.German Association of the Scientific Medical Societies (AWMF) Standing Guidelines Commission. AWMF Guidance Manual and Rules for Guideline Development, 1st edition 2012. English version. Available at: http://www.awmf.org/leitlinien/awmf-regelwerk.html (last accessed on July 30, 2017)
10.Leitlinienprogramm DGU: Interdisziplinäre S3 Leitlinie: Epidemiologie, Diagnostik, Therapie, Prävention und Management unkomplizierter, bakterieller, ambulant erworbener Harnwegsinfektionen bei erwachsenen Patienten. Langversion 1.1–2, 2017 AWMF Registernummer: 043/044. www.awmf.org/leitlinien/detail/ll/043–044.html (last accessed on 12 November 2017).
11.Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA): www.prisma-statement.org (last accessed on 7 October 2017).
12.Scottish Intercollegiate Guidelines Network, Healthcare Improvement Scotland: www.sign.ac.uk/checklists-and-notes.html (last accessed on 7 October 2017).
13. International Cochrane Collaboration: www.handbook.cochrane.org/chapter_8/table_8_5_d_criteria_for_judging_risk_of_ bias_in_the_risk_of.htm (last accessed on 7 October 2017).
14.Centre for evidence based Medicine (CEBM): www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ (last accessed on 7 October 2017).
15. Appraisal of Guidelines for Research and Evaluation (AGREE): www.agreetrust.org/ (last accessed on 7 October 2017).
16.Knottnerus BJ, Geerlings SE, Moll van Charante EP, ter Riet G, Toward A: Simple diagnostic index for acute uncomplicated urinary tract infections. Ann Fam Med 2013: 442–51 CrossRef MEDLINE PubMed Central
17. Little P, Turner S, Rumsby K, et al.: Developing clinical rules to predict urinary tract infection in primary care settings: sensitivity and specificity of near patient tests (dipsticks) and clinical scores. Br J Gen Pract 2006; 56: 606–12 MEDLINE PubMed Central
18.Rothberg MB, Wong JB: All dysuria is local. A cost-effectiveness model for designing sitespecific management algorithms. J Gen Intern Med 2004; 19: 433–43 CrossRef MEDLINE PubMed Central
19.Alidjanov JF, Pilatz A, Abdufattaev UA, et al.: [German validation of the acute cystitis symptom score]. Urologe A 2015; 54: 1269–76 CrossRef MEDLINE
20.Alidjanov JF, Lima HA, Pilatz A, et al.: Preliminary Clinical Validation of the English Language Version of the Acute Cystitis Symptom Score. JOJ uro & nephron. 2017; 1: 555561
21.Bachman JW, Heise RH, Naessens JM, Timmerman MG: A study of various tests to detect asymptomatic urinary tract infections in an obstetric population. JAMA 1993; 270: 1971–4 CrossRef CrossRef
22.Lumbiganon P, Chongsomchai C, Chumworathayee B, Thinkhamrop J: Reagent strip testing is not sensitive for the screening of asymptomatic bacteriuria in pregnant women. J Med Assoc Thai 2002; 85: 922–7 MEDLINE
23. Tincello DG, Richmond DH: Evaluation of reagent strips in detecting asymptomatic bacteriuria in early pregnancy: prospective case series. BMJ 1998; 316: 435–7 CrossRef
24. Ferry SA, Holm SE, Stenlund H, Monson TJ: The natural course of uncomplicated lower urinary tract infection in women illustrated by a randomized placebo controlled study. Scand J Infect Dis 2004; 36: 296–301 CrossRef
25. Christiaens TC, de Meyere M, Verschraegen G, Peersman W, Heytens S, de Maeseneer JM: Randomised controlled trial of nitrofurantoin versus placebo in the treatment of uncomplicated urinary tract infection in adult women. Br J Gen Pract 2002; 52: 729–34 MEDLINE PubMed Central
26.Gágyor I, Bleidorn J, Kochen MM, Schmiemann G, Wegscheider K, Hummers-Pradier E: Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial. BMJ 2015; 351: h 6544.
27.Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM: Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005; 40: 643–54 CrossRef MEDLINE
28.Kazemier BM, Koningstein FN, Schneeberger C, et al.: Maternal and neonatal consequences of treated and untreated asymptomatic bacteriuria in pregnancy: a prospective cohort study with an embedded randomised controlled trial. Lancet Infect Dis 2015; 15: 1324–33 CrossRef
29.S3-Leitlinie Strategien zur Sicherung rationale Antibiotika-Anwendung im Krankenhaus AWMF-Registernummer 092/001. www.awmf.org/leitlinien/detail/ll/092–001.html (last accessed on 7 October 2017).
30.Frei U, Schober-Halstenberg HJ: Nierenersatztherapie in Deutschland. Bericht über Dialysebehandlung und Nierentransplantation in Deutschland 2006/2007. www.bundesverband-niere.de/fileadmin/user_upload/QuaSi-Niere-Bericht_2006–2007.pdf (last accessed on 7 October 2017).
31.Grabe M, Bartoletti R, Bjerklund Johansen TE, et al.: Guidelines on urological infections. EAU Guidelines 2015. www.uroweb.org/wp-content/uploads/19-Urological-infections_LR2.pdf (last accessed on 7 October 2017).
e1. Christiaens T, Callewaert L, de Sutter A, van Royen P: Aanbeveling voor goede medische praktijkvoering: cystitis bij de vrouw. Huisarts nu: maandblad van de Wetenschappelijke Vereniging van Vlaamse Huisartsen 2000; 29: 282–8.
e2. Epp A, Larochelle A: SOGC clinical practice guideline: recurrent urinary tract infection. J Obstet Gynaecol Can 2010; 1082–90 MEDLINE
e3.van Nieuwkoop C, Hoppe BP, Bonten TN, et al.: Predicting the need for radiologic imaging in adults with febrile urinary tract infection. Clin Infect Dis 2010; 51: 1266–72 CrossRef MEDLINE
e4.Nicolle LE: Asymptomatic bacteriuria: review and discussion of the IDSA guidelines. Int J Antimicrob Agents 2006; 28(Suppl): 42–8 CrossRef
e5.Nicolle LE: Asymptomatic bacteriuria: when to screen and when to treat. Infect Dis Clin North Am 2003; 17: 367–94 MEDLINE
e6.Scottish Intercollegiate Guidelines Network. SIGN 88 management of suspected bacterial urinary tract infection in adults. 2012. www.sign.ac.uk/sign-88-management-of-suspected-bacterial-urinary-tract-infection-in-adults.html (last accessed on 12 November 2017).
e7.Parsons SR, Cornish NC, Martin B, Evans SD: Investigation of uncomplicated recurrent urinary tract infections in women. J Clin Urol 2016; 4: 234–8.
e8.Wagenlehner FME, Wagenlehner C, Savov O, Gulaco L, Schito G, Naber KG: Klinik und Epidemiologie der unkomplizierten Zystitis bei Frauen. Urologe 2010; 49: 253–61 CrossRef
e9.van Pinxteren B, Knottnerus BJ, Geerlings SE, et al.: De standaard en wetenschappelijke verantwoording zijn geactualiseerd ten opzichte van de vorigeversie. Huisarts Wet 2005; 8: 341–52.
e10.American Urological Association: Diagnoses, evaluation and follow up of asymptomatic microhematuria (AMH) in adults. www.auanet.org/education/guidelines/asymptomatic-microhematuria.cfm (last accessed on 7 October 2017).
e11.McDermott S, Callaghan W, Szwejbka L, Mann H, Daguise V: Urinary tract infections during pregnancy and mental retardation and developmental delay. Obstet Gynecol 2000; 96: 113–9 CrossRef CrossRef
e12.McDermott S, Daguise V, Mann H, Szwejbka L, Callaghan W: Perinatal risk for mortality and mental retardation associated with maternal urinary-tract infections. J Fam Pract 2001; 50: 433–7 MEDLINE
e13.Delzell JE, Lefevre ML: Urinary tract infections during pregnancy. Am Fam Physician 2000; 61: 713–21 MEDLINE
e14.Force U: Guide to clinical preventive services: report of the U.S. Preventive Service Task Force. Baltimore: Williams & Wilkins 1996.
e15.McNair RD, MacDonald SR, Dooley SL, Peterson LR: Evaluation of the centrifuged and gram-stained smear, urinalysis, and reagent strip testing to detect asymptomatic bacteriuria in obstetric patients. Am J Obstet Gynecol 2000; 182: 1076–9 CrossRef
e16.Millar L, DeBuque L, Leialoha C, Grandinetti A, Killeen J: Rapid enzymatic urine screening test to detect bacteriuria in pregnancy. Obstet Gynecol 2000; 95: 601–4 CrossRef CrossRef
e17.Ovalle A, Levancini M: Urinary tract infections in pregnancy. Curr Opin Urol 2001; 11: 55–9 CrossRef
e18.Santos JF, Ribeiro RM, Rossi P, et al.: Urinary tract infections in pregnant women. Int Urogynecol J Pelvic Floor Dysfunct 2002; 13: 204–9 CrossRef MEDLINE
e19.Lumsden L, Hyner GC: Effects of an educational intervention on the rate of recurrent urinary tract infection. Women & Health 1985; 10/1: 79–86 CrossRef MEDLINE
e20.Su SB, Wang JN, Lu CW, Guo HR: Reducing urinary tract infections among female clean room workers. J Womens Health 2006; 15 /7: 870–6 CrossRef MEDLINE
e21.Beerepoot MA, Geerlings SE, van Haarst EP, van Charante NM, ter Riet G: Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials. J Urol 2013; 190: 1981–9 CrossRef MEDLINE
e22.Albrecht U, Goos KH, Schneider B: A randomised, double-blind, placebo-controlled trial of a herbal medicinal product containing tropaeoli majoris herba (nasturtium) and armoraciae rusticanae radix (horseradish) for the prophylactic treatment of patients with chronically recurrent lower urinary tract infections. Curr Med Res Opin 2007; 23/10: 2415–22 CrossRef MEDLINE
e23. Kranjcec B, Papes D, Altarac S: D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol 2014; 32: 79–84 CrossRef MEDLINE
e24. Larsson B, Jonasson A, Fianu S: Prophylactic effect of UVA-E in women with recurrent cystitis: a preliminary report. Curr Ther Res 1993; 53/4: 441–3 CrossRef
e25. Melekos MD, Asbach H, Gerharz E, Zarakovitis I, Weingärtner K, Naber K: Postintercourse versus daily ciprofloxacin prophylaxis for recurrent urinary tract infections in premenopausal women. J Urol 1997; 101: 935–9.
e26.Pfau A, Sacks TG: Effective postcoital prophylaxis of recurrent urinary tract infections in premenopausal women: a review. Int Urogynecol J 1991; 2: 156–60 CrossRef
e27.Rubin RH, Shapiro ED, Andriole VT, Davis RJ, Stamm WE: Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Infectious Diseases Society of America and the Food and Drug Administration. Clin Infect Dis 1992; 15(Suppl 1): 216–27.
e28.Bleidorn J, Gágyor I, Kochen MM, Wegscheider K, Hummers-Pradier E: Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection?—results of a randomized controlled pilot trial. BMC Med 2010; 8: 30 CrossRef MEDLINE PubMed Central
e29.Ceran N, Mert D, Kocdogan FY, et al.: A randomized comparative study of single-dose fosfomycin and 5-day ciprofloxacin in female patients with uncomplicated lower urinary tract infections. J Infect Chemother 2010; 16: 42430 CrossRef MEDLINE
e30. Hooton TM, Roberts PL, Stapleton AE: Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial. JAMA 2012; 307: 583–9 MEDLINE PubMed Central
e31.Palou J, Angula JC, Ramón de Fata F, et al.: [Randomized comparative study for the assessment of a new therapeutic sched-ule of fosfomycin trometamol in postmenopausal women with uncomplicated lower urinary tract infection]. Actas Urol Esp 2013; 37: 147–55 CrossRef CrossRef MEDLINE
e32.Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB: A double-blind, randomized comparison of levofloxacin 750mg once-daily for five days with ciprofloxacin 400/500mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology 2008; 71: 17–22 CrossRef MEDLINE
e33. Estebanez A, Pascual R, Gil V, Ortiz F, Santibáñez M, Pérez Barba C: Fosfomycin in a single dose versus a 7-day course of amoxicillin-clavulanate for the treatment of asymptomatic bacteriuria during pregnancy. Eur J Clin Microbiol Infect Dis 2009; 28: 1457–64 CrossRef MEDLINE
e34.Monsen TJ, Holm SE, Ferry BM, Ferry SA: Mecillinam resistance and outcome of pivmecillinam treatment in uncomplicated lower urinary tract infection in women. APMIS 2014; 122: 317–23 CrossRef MEDLINE
e35. Bjerrum L, Gahrn-Hansen B, Grinsted P: Pivmecillinam versus sulfamethizole for shortterm treatment of uncomplicated acute cystitis in general practice: a randomized controlled trial. Scand J Prim Health Care 2009; 27: 6–11 CrossRef MEDLINE PubMed Central
e36. Lumbiganon P, Villar J, Laopaiboon M, et al.: Oneday compared with 7-day nitrofurantoin for asymptomatic bacteriuria in pregnancy: a randomized controlled trial. Obstet Gynecol 2009; 113: 339–45 CrossRef MEDLINE
e37.Little P, Moore MV, Turner S, et al.: Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial. BMJ 2010; 340: c199.
e38.Monmaturapoj T, Montakantikul P, Mootsikapun P, Tragulpiankit P: A prospective, randomized, double dummy, placebo-controlled trial of oral cefditoren pivoxil 400mg once daily as switch therapy after intravenous ceftriaxone in the treatment of acute pyelonephritis. Int J Infect Dis 2012; 16: e843–9 CrossRef MEDLINE
e39. Shaheen G, Usmanghani K, Nazar H, Akhtar N: Clinical evaluation of herbal coded formulation gran-off to urixin in the treatment of urinary tract infection. Pak J Pharm Sci 2015: 557–9 MEDLINE
e40.Stein JC, Navab B, Frazee B, et al.: A randomized trial of computer kiosk-expedited management of cystitis in the emergency department. Acad Emerg Med 2011; 18: 1053–9 CrossRef MEDLINE
e41. Turner D, Little P, Raftery J, et al.: Cost effectiveness of management strategies for urinary tract infections: results from randomised controlled trial. BMJ 2010; 340: c346.
e42. Drozdov D, Schwarz S, Kutz A, et al.: Procalcitonin and pyuria-based algorithm reduces antibiotic use in urinary tract infections: a randomized controlled trial. BMC Med 2015; 13: 104 CrossRef MEDLINE PubMed Central
e43. Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO: Ceftolozanetazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECTcUTI). Lancet 2015; 385: 1949–56 CrossRef
e44. Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD: Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 2010; 18, 340: c2096.
e45.Eliakim-Raz N, Yahav D, Paul M, Leibovici L: Duration of antibiotic treatment for acute pyelonephritis and septic urinary tract infection—7 days or less versus longer treatment: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 2013; 68: 2183–91 CrossRef MEDLINE
e46. Falagas ME, Kotsantis IK, Vouloumanou EK, Rafailidis PI: Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a meta-analysis of randomized controlled trials. J Infect 2009; 58: 91–102 CrossRef MEDLINE
e47.Falagas ME, Vouloumanou EK, Togias AG, et al.: Fosfomycin versus other antibiotics for the treatment of cystitis: a metaanalysis of randomized controlled trials. J Antimicrob Chemother 2010; 65: 1862–77 CrossRef MEDLINE
e48. Flower A, Wang LQ, Lewith G, Liu JP, Li Q: Chinese herbal medicine for treating recurrent urinary tract infections in women. Cochrane Database Syst Rev 2015; 6: CD010446.
e49.Guinto VT, de Guia B, Festin MR, Dowswell T: Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2010; 9: CD007855.
e50. Gutiérrez-Castrellón P, Díaz-García L, de Colsa-Ranero A, Cuevas-Alpuche J, JiménezEscobar I: [Efficacy and safety of ciprofloxacin treatment in urinary tract infections (UTIs) in adults: a systematic review with meta-analysis]. Gac Med Mex 2015; 151: 225–44.1a.
e51.Jepson RG, Mihaljevic L, Craig J: Cranberries for treating urinary tract infections. Cochrane Database Syst Rev 2014; 2: CD001322.
e52.Knottnerus BJ, Grigoryan L, Geerlings SE, et al.: Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: network meta-analysis of randomized trials. Fam Pract 2012; 29: 659–70 CrossRef MEDLINE
e53. Kyriakidou KG, Rafailidis P, Matthaiou DK, Athanasiou S, Falagas ME: Short-versus longcourse antibiotic therapy for acute pyelonephritis in adolescents and adults: a metaanalysis of randomized controlled trials. Clin Ther 2008; 30: 1859–68 CrossRef MEDLINE
e54.Lutters M, Vogt-Ferrier NB: Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women. Cochrane Database Syst Rev 2008; 3: CD001535.
e55.Naber KG, Niggemann H, Stein G, Stein G: Review of the literature and individual patients’ data meta-analysis on efficacy and tolerance of nitroxoline in the treatment of uncomplicated urinary tract infections. BMC Infect Dis 2014; 14: 628–43 CrossRef MEDLINE PubMed Central
e56. Smaill FM, Vazquez JC: Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2015; 8: CD000490.
e57.Widmer M, Lopez I, Gülmezoglu AM, Mignini L, Roganti A: Duration of treatment for asymptomatic bacteriuria during pregnancy. Cochrane Database Syst Rev 2015; 11: CD000491.
e58.Vazquez JC, Abalos E: Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev 2011; 1: CD002256.
e59.Zalmanovici Trestioreanu A, Green H, Paul M, Yaphe J, Leibovici L: Antimicrobial agents for treating uncomplicated urinary tract infection in women. Cochrane Database Syst Rev 2010; 10: CD007182.

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