Question

What is the optimal strategy for Urinary Tract Infections and asymptomatic bacteriuria in patients with Diabetes Mellitus?

Recommendation

It is not necessary to treat ASB in women with diabetes and, therefore, screening is not indicated.

 

A 7-day regimen of nitrofurantoin is recommended in diabetic women with cystitis.

 

For the treatment of diabetic men or diabetic women with a pyelonephritis or a UTI with systemic symptoms we refer to the sections “Men” and “Empirical treatment”.

Introduction

This guideline does not include individual introductions to each module. A general introduction can be found in the attachments under the heading 'related'.

Conclusions

Level 1

Patients with diabetes mellitus (DM) have a higher prevalence of ASB than patients without DM [(101) A1]. 

Level 2

Patients with DM have a higher incidence of UTIs than patients without DM [(102) B; (103) B], but this is less clear for patients with DM type 1 [(106) B] 

Level 2

Patients with DM develop more complications of their UTI [(102) B; (107) B; (108) B].

Level 2

Diabetic patients with ASB more often develop a UTI compared to diabetic patients without ASB [(111) B; (112) B].

Level 2

ASB (with and without antimicrobial treatment) in women with DM does not result in renal function decline [(109) A2; (110) B]

Level 2

The resistance percentages for E. coli and other uropathogens from the urine of patients with and without DM are comparable [(114) B; (115) B].

 

Level 2

It is not clear whether the chance of therapeutic failure is increased after treatment of UTI among women with DM compared to women without DM [(117) B; (104) B;  (105) B; (22) B; (116) B].

Literature summary

Epidemiology

In a systematic review and meta-analysis on asymptomatic bacteriuria (ASB) in diabetic patients, 22 studies were included. ASB was present in 439 of 3,579 (12.2%) patients with diabetes mellitus (DM) and in 121 of 2,702 (4.5%) healthy control subjects. ASB was more common both in patients with type 1 DM (OR 3.0 [95% CI 1.1-8.0]) and type 2 DM (3.2 [2.0-5.2]) than in control subjects. The point prevalence of ASB was higher in both women (14.2 vs. 5.1%; 2.6 [1.6-4.1]) and men (2.3 vs. 0.8%; 3.7 [1.3-10.2]) (101).

 

It has been shown that diabetic patients have an increased risk for UTI (102); (103). A recent study in primary care patients from the Netherlands demonstrated that relapses and reinfections were reported in 7.1% and 15.9% of women with DM, respectively, vs, 2.0% and 4.1% of women without DM, respectively. There was a higher risk of recurrent UTI in women with DM compared with women without DM (OR 2.0; 95% CI 1.4-2.9). Women who had had DM for at least 5 years (OR 2.9; 95% CI 1.9-4.4) or who had retinopathy (OR 4.1; 95% CI 1.9-9.1) were at risk of recurrent UTI (104). This increased recurrence rate was confirmed in one study (105), but not in another (22).In contrast, in an American study in women with DM type 1, sexual activity rather than measures of diabetes control and complications was the main risk factor for UTI. The prevalence of cystitis was similar to that in non-diabetic women participants in a national survey (106).

 

In addition, diabetic patients more often develop complications: bacteremia (107) and longer hospitalization (108), (102), due to their UTI. For this reason a cystitis in a patient with DM is considered a complicated UTI.

 

WHAT IS THE OPTIMAL TREATMENT OF ASB AND UTI IN PATIENTS WITH DIABETES MELLITUS?

It has been demonstrated that ASB in women with DM is benign and that 20% of diabetic subjects with ASB remained bacteriuric with the original infecting organism for a long period of observation. Women infected with gram-negative organisms were more likely to have persistent bacteriuria. Many women with resolution of initial bacteriuria, with or without antibiotics, became bacteriuric again during follow-up. Treatment may reduce the overall proportion of time infected in the long term and carriage of a unique strain, but most treatment regimens were followed by subsequent recolonization. Infecting strains did not have virulence factors characteristic of uropathogenic E. coli (109). Furthermore, ASB in women with DM does not result in renal function decline (110). However, more women with ASB will develop a symptomatic UTI compared to those without (111). Also, in another study with male and female patients with DM type 1 and 2, the presence of ASB was associated with an increased risk of hospitalization for urosepsis as principal diagnosis (hazard ratio [95% CI] 4.4 [1.2-16.5]; P=0.004) (112).

 

Because in the above-mentioned prospective study (110) no evidence was found that ASB in itself can lead toa decline in renal function (in women with type 1 or type 2 DM), it is unlikely that treatmentof ASB will lead to a decrease in the incidence of diabeticnephropathy. This is in accordance with a study ofwomen with DM and with ASB in which a comparison was made betweenwomen who received antibiotic therapy and women who receivedplacebo. In that study, no difference was seen in serum creatininelevels after a mean follow-up of 2 years (113).

Choice of drug

Because the resistance percentages for E. coli and other uropathogens from the urine of patients with and without DM are comparable (114), (115), the choice of antibiotic treatment is not different for diabetic patients.

 

Duration of therapy 

No prospective trials are available in which the optimal treatment (agent choice and duration) in these patients has been investigated. Some studies show that patients with diabetes have more complications (107), (108) related to their UTI compared to non-diabetic patients. Concerning the recurrence rate of UTI in diabetic compared to non-diabetic women, two studies using Dutch registration database containing pharmacy dispensing data from 2 different time periods show contradictory results (116), (117). In the largest study (117), the prescriptions of 10,366 women with diabetes and 200,258 women without diabetes were compared. Women with diabetes more often received a long treatment, but still had a higher recurrence rate of UTIs compared with those without diabetes.

Search and select

For all articles databases were Pubmed and the Cochrane Library.

Keywords first search: diabetes mellitus AND urinary tract infection AND treatment;

Limits: Last 7 years for Pubmed (SWAB guideline for the treatment of complicated UTI was published in 2005), English, adults, humans

Pubmed: 142 results, all titles screened, 10 abstracts screened, 6 additional articles included.

Cochrane Library, keywords urinary tract infection and diabetes mellitus: 3 results, no abstracts screened, no additional articles included.

Keywords second search: diabetes mellitus AND asymptomatic bacteriuria

Limits: Last 10 years for Pubmed (IDSA guideline for screening and treatment of ASB was published in 2005), English, adults, humans

Pubmed: 36 results, all titles screened, 4 abstracts screened, 4 additional articles included.

Cochrane Library: 5 results, 3 abstracts screened, 1 additional article included.

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Evidence tables

This guideline does not include evidence tables.

Considerations

ASB in women with DM does not result in renal function decline and the majority of women does not develop a symptomatic UTI. In addition, because women with symptomatic UTI will present with symptoms and because of the collateral damage of treatment (resistance, side-effects), the Guideline committee recommends not to treat ASB in women with DM. Therefore, screening for ASB is not indicated in these patients. This is in accordance with the IDSA guideline for the diagnosis and treatment of asymptomatic bacteriuria in adults (73).

 

Considering the resistance percentages of the causative micro-organisms, patients with UTI and DM can be treated with the same agents as those without DM; therefore, nitrofurantoin for women with DM and only cystitis seems to be a good choice. In the largest study from the Netherlands, more recurrent UTIs were demonstrated even with a treatment duration of longer than 5 days [(117). However, we do not know whether a longer treatment duration will result in a lower recurrence rate.

 

The Guideline committee decided to recommend (in accordance with the NHG standard) a longer duration of therapy, namely 7 days, for the treatment of a lower UTI in a woman with DM. For the treatment of a pyelonephritis in a woman with DM, we refer to the General section above.

Authorization date and validity

Last review : 01-03-2013

Last authorization : 01-03-2013

This guideline was developed and approved by representatives of the professional medical societies, mentioned in the introduction and methods sections and therefore represents the current professional standard in 2013. The guideline contains general recommendations. It is possible that, in individual cases, these recommendations do not apply. Applicability of the guideline in clinical practice resorts to the responsibility of every individual practitioner. Facts or circumstances may occur, in which deviation of the guideline is justified, in order to provide optimal quality of care for the patient.

Initiative and authorization

Initiative : Stichting Werkgroep Antibioticabeleid

Authorized by:
  • Nederlandse Huisartsen Genootschap
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging voor Medische microbiologie
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
  • Nederlandse Vereniging voor Urologie

General details

Development of this guideline was supported and financed by the SKMS (Kwaliteitsgelden Medisch Specialisten).

Scope and target group

The objective of these guidelines is to update clinicians with regard to important advances and controversies in the antibiotic treatment of patients with complicated urinary tract infections (UTIs).

 

The guidelines described here cover the empirical antimicrobial therapy of adult patients (for this guideline 12 years or older) with a complicated UTI admitted to a hospital (emergency room or ward) in the Netherlands. Uncomplicated UTIs are treated predominantly by the general practitioner. For the relevant guidelines, see the recently updated Standard for Urinary Tract Infections of the Dutch Society of General Practitioners (NHG). We have tried to adhere to this standard insofar as possible. Urethritis and epididymitis are not included in this guideline.

The Guidelines give a general therapy advice for all UTI with systemic symptoms because, at first presentation of a patient, it is not always possible to differentiate between an acute prostatitis, pyelonephritis or urosepsis. In addition, this differentiation has no consequences for the choice of empirical antimicrobial therapy. Apart from these general guidelines, we give specific advice for certain groups of patients separately.

Member of workgroup

Preparation of the guideline text was carried out by a multidisciplinary committee consisting of experts, delegated from the professional societies for infectious diseases (VIZ), medical microbiology (NVMM), hospital pharmacists (NVZA), urology (NVU), gynaecology (NVO), nephrology (NFN) and general practice (NHG). After consultation with the members of these professional societies, the definitive guideline was drawn up by the delegates and approved by the board of SWAB.

 

  • Dr. S.E. Geerlings (coordinator, SWAB), Internal Medicine/Infectious Diseases specialist, Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam
  • Dr. C. van Nieuwkoop (VIZ, NIV), Internal Medicine, Emergency Medicine and Infectious Diseases specialist, Department of Internal Medicine, Hagaziekenhuis, the Hague
  • E. van Haarst (NVU), Urologist, Department of Urology, St. Lucas Andreas Hospital, Amsterdam
  • Dr. M. van Buren (NFN), Internal Medicine and Nephrology specialist, Department of Internal Medicine, Hagaziekenhuis, the Hague
  • Dr. B.J. Knottnerus (NHG), General Practitioner, Department General Practice, Academic Medical Center, Amsterdam
  • Dr. E. E. Stobberingh (NVMM), Medical microbiologist, Lab Medical Microbiology, Maastricht Univerisity Medical Center, Maastricht
  • Prof. dr. C.J. de Groot (NVOG), Gynaecologist, Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Center, Amsterdam
  • Prof. dr. J.M. Prins (SWAB), Internal Medicine/Infectious Diseases specialist, Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam

 

The Guideline committee would also like to thank Frederique Bemelman (nephrologist) for her comments on the chapter about renal transplantation and Albert Vollaard (infectious disease specialist) for his comments on the subchapter about methenamine.

Declaration of interest

The SWAB employs strict guidelines with regard to potential conflicts of interests as described in the SWAB Format for Guideline Development (www.swab.nl). Members of the preparatory committee reported the following potential conflicts of interest:

 

SE Geerlings: for the RCTs mentioned in the reference numbers 84 en 168 (Beerepoot et al.): Ref 84: Cranberry capsules and placebo capsules for this trial were delivered by Springfield Nutraceuticals, Oud Beijerland, The Netherlands. Ref 168: Chr Hansen A/S, Denmark has the patents for Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 and donated the placebo capsules for this trial.

E v Haarst: has received speaker fees on a national urological symposium from GlaxoSmithKline, the manufacturer of amoxicillin-clavulanic acid.

Other authors: no potential conflicts of interest declared.

Patient involvement

This guideline does not include patient involvement.

Method of development

Evidence based

Implementation

This guideline does not include an implementation strategy.

Methods and proces

This guideline was drawn up according to the recommendations for evidence-based development of guidelines (6), (Evidence-Based Richtlijn-Ontwikkeling (EBRO) and Appraisal of Guidelines Research and Evaluation (AGREE), www.agreecollaboration.org). The guidelines are derived from a review of literature based on the 9 key questions concerning the treatment of UTI. Studies were assigned a degree of evidential value according to the handbook of the Dutch Institute for Healthcare Improvement (Centraal Begeleidingsorgaan/Kwaliteitsinstituut voor de gezondheidszorg, CBO) (CBO. Evidence-based Richtlijnontwikkeling, handleiding voor werkgroepleden. Utrecht: CBO; 2007). Conclusions were drawn, completed with the specific level of evidence, according to the grading system adopted by SWAB (Table 1 and 2). The only exception concerns Nethmap, an annual report from which the resistance surveillance data were used. The Guideline committee cannot give Nethmap a level of evidence and decided to use an asterix (*), but is of the opinion that the results can be given substantial weight, since the surveillance data described in Nethmap cover 30% of the Dutch population. Subsequently, specific recommendations were formulated.

In order to develop recommendations for the optimal treatment of UTI, the literature was searched for the key questions. For each question a literature search was performed in the PubMed database (January 1966 to January 2012) as well as in the Cochrane Register of Controlled Trials (CENTRAL). For resistance surveillance data NethMap 2011 was used, and for the interpretation of susceptibility test results, in addition, reports of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were used. When scientific verification could not be found, the guideline text was formulated on the basis of the opinions and experiences of the members of the Guideline committee.

Search strategy

Searches are available upon request. Please contact the Richtlijnendatabase.