What are the possible prevention methods in patients with recurrent UTI?
For recurrent UTI in men or in patients with a catheter we refer to the section on UTI in men or in patients with a catheter.
A differentiation must be made between persistence, relapse and reinfection of the UTI.
In a persistent UTI the cause must be evaluated. In a relapse of the UTI the treatment can given for a longer period.
All women can usually self-diagnose and self-treat a recurrent UTI.
The use of ascorbic acid (vitamin C) is not recommended in the prevention of UTIs.
In premenopausal women with recurrent UTI the following prophylaxis can be recommended to decrease the number of recurrent episodes:
- Daily or postcoital low dose antimicrobial therapy
- Cranberry products
- Lactobacillus crispatus intravaginal suppository
In postmenopausal women with recurrent UTI the following prophylaxis can be recommended to decrease the number of recurrent episodes:
- Daily or postcoital low-dose antimicrobial therapy
- Estrogens locally
- Oral capsules with L rhamnosus GR-1 and L. reuteri RC-14
Methenamine hippurate can be used for a maximum of 1 week to prevent UTI in patients without renal tract abnormalities.
When the patient has a persistent UTI, the cause of this persistence must be evaluated (renal abcess, etc.). Experts are of the opinion that when the patient has a relapse of a UTI, the UTI has to be treated again, but with a longer treatment duration (for example 4 instead of 2 weeks). All recommendations in this Guideline concern patients with reinfections.
The results of the above-mentioned studies show that low-dose antimicrobial prophylaxis is the most effective in the prevention of rUTIs. However, this results in increasing resistance of the commensal flora. The recently updated IDSA guideline on the treatment of uncomplicated UTI recommends to take into account this “collateral damage” (3). Furthermore, it has been shown that different antimicrobial agents have different effects. In one study the gram-negative aerobic flora was strongly affected during the administration of norfloxacin and TMP/SMX, but not during nitrofurantoin (170). These findings help in the selection of the most appropriate antimicrobial agent for prophylaxis in recurrent UTIs.
Furthermore, prophylaxis with non-antimicrobial agents might not result in an increase of antimicrobial resistance of the commensal flora (84), (168). Therefore, the use of cranberry prophylaxis oral or Lactobacillus crispatus intravaginal in premenopausal women and oral capsules with L rhamnosus GR-1 and L. reuteri RC-14 or topical vaginal estrogen in post-menopausal women can still be recommended.
Concerning the recommendation about the use of vitamin C, it is difficult to understand the positive effect of the prevention trial in pregnant women, because the daily vitamin C dose was much lower (1 x 100 mg instead of 4 x 500 mg) than in the trial with the negative results. Moreover, the trial was not blinded and the endpoint was highly subjective (161).Therefore, the Guideline committee is of the opinion that prophylaxis with vitamin C cannot be recommended.
This guideline does not include individual introductions to each module. A general introduction can be found in the attachments under the heading 'related'.
It is important to differentiate between persistence, relapse and reinfection, because this has treatment consequences.
Continuous antibiotic prophylaxis (with different agents) for 6-12 months reduced the rate of UTI during prophylaxis compared to placebo in women with recurrent, acute uncomplicated urinary tract infection [(153) A1; (157) A2].
No significant difference in rates of UTIs were found between postcoital versus continuous daily ciprofloxacin [(156) A2].
Women can accurately self-diagnose and self-treat recurrent UTIs [(154) B; (158) B; (159) B].
There is no clinical benefit from the use of ascorbic acid (vitamin C) in the prevention of UTIs in spinal cord injury patients [(160) B].
There is clinical benefit from the use of ascorbic acid (vitamin C) in the prevention of UTIs in pregnant women [(161) B].
The effect of daily cranberry products (juice or tablets) decreases the frequency of recurrent infection in women with rUTIs by about 30-40%. It is not clear what the optimum dosage or method of administration is [(162) A1].
Cranberry capsules are less effective than low-dose TMP/SMX in the prevention of rUTIs in premenopausal women. However, in contrast to low-dose TMP/SMX, cranberries do not result in an increase in resistant micro-organisms in the commensal flora [(84) A2].
Prophylaxis with Lactobacillus crispatus intravaginal suppository probiotic after treatment for cystitis is associated with a reduction in recurrent UTI in premenopausal women [(167) A2].
In postmenopausal women with recurrent UTIs, oral capsules with L rhamnosus GR-1 and L. reuteri RC-14 marginally did not meet the non-inferiority criteria in the prevention of UTIs when compared with TMP-SMX. However, unlike TMP-SMX lactobacilli did not increase antibiotic resistance of the commensal flora [(168) A2].
Topical vaginal estrogen is a potential intervention to decrease the number of recurrent episodes for postmenopausal women [(163) A1].
Use of an estriol-containing pessary is less effective than oral nitrofurantoin in the prevention of bacteriuria in postmenopausal women [(166) A2].
Methenamine hippurate may be effective for preventing UTI in patients without renal tract abnormalities, particularly when used for short-term prophylaxis [(169) A1], but no evidence exists about long-term use or use in patients with urinary catheters and a potential health risk of prolonged exposure to formaldehyde may preclude long term administration.
Recurrent urinary tract infections (rUTIs) is a common health care problem and is defined in the literature by three episodes of UTI in the last 12 months, or two episodes in the last 6 months. Approximately 50-70% of women will have a UTI sometime during their lifetime and 20-30% of women who have a UTI will have a rUTI (153) (154). In general, in men and post-menopausal women it is recommended to exclude anatomical or functional abnormalities of the urogenital tract as a cause of rUTI. In pre-menopausal women the yield of most diagnostic procedures is low (155).
There are four patterns of response of bacteriuria to therapy: cure, bacteriologic persistence, bacteriologic relapse, or reinfection. Bacteriologic persistence is persistence of bacteriuria with the same microorganism after 48 hours of treatment. Relapse is an infection with the same micro-organism that caused initial infection and usually occurs within 1-2 weeks after the cessation of treatment. A relapse indicates that the infecting organism has persisted in the urinary tract. Reinfection is an infection after sterilization of the urine. Most of the time there is a change in bacterial species. Reinfection can be defined as a 'true' recurrence. Both persistence and relapse may be related to inadequate treatment. It is very important to determine whether rUTIs are relapses or reinfections and to make a differentiation between these patterns, since this has treatment consequences. Experts are of the opinion that in a persistent UTI the cause must be evaluated. In a relapse of the UTI the treatment can be given for a longer period. All recommendations in this guideline concern patients with reinfections.
The first consideration in prevention is to address modifiable behavioral practices. Other effective strategies can be divided into antimicrobial or nonantimicrobial.
Low-dose antimicrobial therapy remains an effective intervention to manage frequent, recurrent, acute uncomplicated UTI. The antimicrobial may be given as continuous daily or every-other-day therapy, usually at bedtime, or as postcoital prophylaxis. Experts suggest an initial duration of prophylaxis is 6 months; however, 50% of women will experience recurrence by 3 months after discontinuation of the prophylactic antimicrobial. When this occurs, prophylaxis may be reinstituted for as long as 1 or 2 years and remains effective.
Nineteen studies involving 1120 women were included in a Cochrane review (153). During active prophylaxis the rate range of microbiological recurrence per patient-year was 0-0.9 person-year in the antibiotic group vs. 0.8-3.6 with placebo. The RR of having one microbiological recurrence was 0.21 (95% CI 0.13-0.34) favoring antibiotic, and the number-needed-to-treat (NNT) was 1.85. For clinical recurrences the RR was 0.15 (95% CI 0.08-0.28) and the NNT was 1.85. The RR of having one microbiological recurrence after prophylaxis was 0.82 (95% CI 0.44-1.53). The RR for severe side-effects was 1.58 (95% CI 0.47-5.28) and for other side-effects the RR was 1.78 (CI 1.06-3.00) favoring placebo. Side-effects included vaginal and oral candidiasis and gastrointestinal symptoms (153). One RCT compared postcoital versus continuous daily ciprofloxacin and found no significant difference in rates of UTIs, suggesting that postcoital treatment could be offered to women who have UTI associated with sexual intercourse (156).
After the publication of the Cochrane review, in a new study 317 women with rUTI were randomized to receive one sachet containing fosfomycin trometamol equivalent 3 g or placebo every 10 days during 6 months. All endpoints concerning the incidence of UTIs were in favor of the fosfomycin (157).
Self-diagnosis and self treatment with antimicrobials
Studies of the natural history of rUTI demonstrate substantial variability in the number of recurrences, which often cluster in time. Thus, continuous prophylaxis may result in unnecessary antimicrobial use in women who have infrequent recurrences or clustered recurrences. An alternative strategy, namely patient self-diagnosis and self-treatment (in other words women start with antimicrobial treatment, which they already have at home, when they think that they have a UTI) of recurrent UTIs, may decrease antimicrobial use and improve patient convenience. In a prospective study the accuracy of self-diagnosis and the cure rates seen with self-treatment of UTIs in 172 women (mean age 23 years) who had a history of rUTIs was determined. A total number of 88 of 172 women self-diagnosed a total of 172 UTIs. Laboratory evaluation showed a uropathogen in 144 cases (84%), sterile pyuria in 19 cases (11%), and no pyuria or bacteriuria in 9 cases (5%). Clinical and microbiological cures occurred in 92% and 96%, respectively, of culture-confirmed episodes. No serious adverse events occurred (154).
In a smaller study 34 women (mean age 36 years) were enrolled. A total of 28 women followed for 355 months had 84 symptomatic episodes and 25 had 67 UTIs. Of the 84 symptomatic episodes 78 (92%) responded clinically. Of 78 cultured episodes 11 (14%) were negative. The remaining 67 cultured documented infections were cured microbiologically 5-7 days after therapy. No adverse effects occurred (158).
In another study, 68 postmenopausal women were randomized to take a low-dose antibiotic each night (continuous group, n=37) or a single-dose antibiotic each time they experienced conditions predisposing to UTI (intermittent group, n=31). During the 12-month study, 1.4 and 1.9 UTIs/patient developed in the continuous and the intermittent groups, respectively, which was significantly lower than the incidence of UTIs in the previous 12 months in these patients (4.7 and 5.1 UTIs/patient, respectively). The incidence of gastrointestinal adverse events was significantly lower in the intermittent group compared with the continuous group (9.1% versus 30.0%) (159).
Several nonantimicrobial strategies to prevent recurrent UTI have been developed and evaluated. In this guideline we describe the studies concerning vitamin C, cranberries, estrogens, lactobacilli and methenamine.
Many women use vitamin C as a prevention method against UTI, but only two trials (one in non-pregnant and one in pregnant women) have been performed, with contradictory results.
In the first study the effect of ascorbic acid on urine pH was studied in spinal cord injury patients. The study was designed to compare the baseline urine pH value and the urine pH value after the administration of placebo or ascorbic acid 4 x 500 mg per day. Thirty-eight patients began the study, but only 13 patients completed the study. A significant decrease in urine pH value was not obtained. There was no clinical benefit from the use of ascorbic acid, 2 patients in the vitamin C and 1 patient in the placebo group developed a UTI during the 6th and 8th day after start (160).
In the other non-randomized trial in pregnant women, it was shown that daily intake of 100 mg ascorbic acid reduced the incidence of UTIs by 30% (161). However, it is very difficult to understand the results of this trial, because the daily vitamin C dose was very low and the endpoint very subjective.
In a Cochrane review 10 studies (n=1049, 5 cross-over, 5 parallel group) were included. Cranberry/cranberry-lingonberry juice versus placebo, juice or water was evaluated in 7 studies, and cranberry tablets versus placebo in 4 studies (one study evaluated both juice and tablets). Cranberry products significantly reduced the incidence of UTIs at 12 months (RR 0.65, 95% CI 0.46-0.90) compared with placebo/control. Cranberry products were more effective in reducing the incidence of UTIs in women with recurrent UTIs, than in elderly men and women or people requiring catheterization. The authors concluded that there is some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12-month period, particularly for women with recurrent UTIs. Its effectiveness for other groups is less certain. The large number of dropouts/withdrawals indicates that cranberry juice may not be acceptable over long periods of time. It is not clear what is the optimum dosage or method of administration (e.g. juice, tablets or capsules). Daily cranberry products (juice or tablets) decrease the frequency of recurrent infection by about 30-40%, compared with 90-95% effectiveness of antimicrobial use (162).
In a recent study it was shown that cranberry capsules are less effective than low-dose TMP/SMX in the prevention of rUTIs in premenopausal women. However, in contrast to low-dose TMP/SMX, cranberries did not result into in an increase in resistant micro-organisms in the commensal flora [(84).
Estrogen replacement restores atrophic mucosa, lowers vaginal pH, and may prevent urinary tract infections. Therefore, topical vaginal estrogen is a potential intervention to decrease recurrent episodes for postmenopausal women, but its use also remains controversial.
Nine studies (3345 women) were included in a Cochrane review (163). Oral estrogens did not reduce UTI compared to placebo (4 studies, 2798 women: RR 1.08, 95% CI 0.88 to 1.33). Vaginal estrogens versus placebo reduced the number of women with UTIs in two small studies using different application methods. The RRs were 0.25 (95% CI 0.13-0.50) (164) in the first study and 0.64 (95% CI 0.47-0.86) in the second study (165). Adverse events for vaginal estrogens were breast tenderness, vaginal bleeding or spotting, nonphysiologic discharge, vaginal irritation, burning and itching.
In another study the efficacy and safety of estriol-containing vaginal pessary was compared with the use of oral nitrofurantoin macrocrystal therapy for preventing UTI in postmenopausal women with rUTI. Over a period of 9 months, 86 women received an estriol-containing vaginal pessary (0.5 mg estriol) twice weekly, and 85 women received nitrofurantoin (100 mg) once daily. A total number of 124 episodes of UTI in women who received estriol-releasing pessaries and 48 episodes of UTI in women treated with nitrofurantoin were recorded (P=0.0003). Twenty-eight women (32.6%) who received estriol had no episodes of UTI versus 41 women (48.2%) in the nitrofurantoin group. There was a significant increase in the number of superficial cells in women who received estriol, whereas in the NM group, no such changes occurred (166).
Probiotics to re-establish vaginal colonization with H2O2-producing lactobacilli, have also being investigated. A recent double-blind placebo-controlled trial studied a Lactobacillus crispatus intravaginal suppository probiotic (Lactin-V; Osel) (daily for 5 days, then once weekly for 10 weeks) for the prevention of recurrent UTI. A total of 100 premenopausal women with at least one prior UTI in the last 12 months (median number lifetime UTIs was 4.5) were randomized to receive either Lactin-V or placebo after treatment with antimicrobials for acute UTI. Recurrent UTI occurred in 7/48 (15%) of women receiving Lactin-V compared with 13/48 (27%) of women receiving placebo (RR 0.5; 95% CI 0.2-1.2). High-level vaginal colonization with L. crispatus (≥10e6 throughout follow-up) was associated with a significant reduction in recurrent UTI only for Lactin-V (RR for Lactin-V 0.07; RR for placebo 1.1; P < 0.01) (167).
In another RCT 252 postmenopausal women with rUTIs were randomized to receive 12 months of prophylaxis with TMP-SMX 480 mg, once daily or oral capsules containing 10e9 colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 twice daily. The mean number of symptomatic UTIs in the year preceding randomization was 7.0 in the TMP-SMX group and 6.8 in the lactobacilli group. In the intention-to-treat analysis, after 12 months of prophylaxis, these numbers were 2.9 and 3.3, respectively. The between-treatment difference of 0.4 UTIs per year (95% CI, -0.4 to 1.5) was outside the non-inferiority margin. At least 1 symptomatic UTI occurred in 69.3% and 79.1% of the TMP-SMX and lactobacilli participants, respectively; median times to the first UTI were 6 and 3 months, respectively (log rank p=0.02). However, after 1 month of TMP-SMX prophylaxis, resistance to TMP-SMX, trimethoprim, and amoxicillin had increased from approximately 20-40% to approximately 80-95% in E. coli from the feces and urine of asymptomatic women and among E. coli causing a UTI. During the 3 months after TMP-SMX discontinuation, resistance levels gradually decreased. Resistance did not increase during lactobacilli prophylaxis (168).
Methenamine salts act via the production of formaldehyde from hexamine, which acts as a bacteriostatic agent without being affected by bacterial resistance mechanisms. They are well tolerated. In vitro and in vivo studies suggest that a urinary pH below 5.5 is needed for bacteriostatic concentrations of free formaldehyde to be generated from methenamine hippurate. Therefore, urinary tract infections with urease producing Proteus (and possibly Pseudomonas), that increase urine pH through hydrolyzation of urea to ammonia, will not be affected by methenamine due to insufficient generation of formaldehyde. Acidification of urine may be achieved with additional high dose vitamin C (1-4 gram) Thirteen studies (2032 participants) were included in a Cochrane review of methenamine hippurate (169). Subgroup analyses suggested that methenamine hippurate may have some benefit in patients without renal tract abnormalities or urinary catheters (symptomatic UTI: RR 0.24, 95% CI 0.07-0.89; bacteriuria: RR 0.56, 95% CI 0.37-0.83), but not in patients with known renal tract abnormalities (symptomatic UTI: RR 1.54, 95% CI 0.38- 6.20; bacteriuria: RR 1.29, 95% CI 0.54-3.07). For short-term treatment duration (1 week or less) there was a significant reduction in symptomatic UTI in those without renal tract abnormalities (RR 0.14, 95% CI 0.05-0.38). The rate of adverse events was low.
However, in 2011 formaldehyde was officially declared carcinogenic by the National Toxicology Program (NTP). The exposure in the bladder to formaldehyde can be high if it is used at high doses for a prolonged time, but the risk of bladder cancer from use of methenamine is a theoretical risk which has not been confirmed (National Toxicology Program, Department of Health and Human Services Report on Carcinogens, Twelfth Edition (2011) Formaldehyde).
Search and select
Databases were Pubmed and the Cochrane Library.
Keywords: urinary tract infection AND prevention or urinary tract infection AND prophylaxis or urinary tract infection AND self treatment.
Limits: From 1990 until now, English, adults, humans, clinical trials, guideline, meta-analysis, RCT.
Pubmed: 426 results, all titles screened, 40 abstracts screened, 12 articles included.
Cochrane Library: 22 results, all titles screened, 4 abstracts screened, 3 reviews included.
Patient groups were patients with recurrent UTI (rUTIs), not patients with an increased chance for a UTI as, for example, spinal cord injury patients or pregnant women. For these patients we refer to the guideline of the Werkgroep Infectie Preventie (WIP) Preventie van infecties als gevolg blaaskatherisatie. Also articles concerning non-antibiotic agents/prophylaxis were included, but only of available agents (e.g. not bacterial interference). Articles about behavioral strategies to prevent rUTI were excluded. Prevention/prophylaxis by using certain regimens during certain procedures (e.g. after operations/interventions) in patients without rUTIs or for the prevention of bacteriuria were excluded.
Prophylaxis with antimicrobial agents during catheter use, placement or removal is described in the module on Catheter-associated UTI, and after renal transplantation is described in the module on Renal Transplantation. For rUTI in men or in patients with a catheter we refer to the section on UTI in men or in patients with a catheter.
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This guideline does not include evidence tables.
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
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.
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.
This guideline does not include patient involvement.
Method of development
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.
Searches are available upon request. Please contact the Richtlijnendatabase.