Antimicrobial therapy of complicated urinary

Initiative: SWAB Number of modules: 14

Prevention in patients with recurrent UTI

Question

What are the possible prevention methods in patients with recurrent UTI?

Recommendation

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.

Considerations

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.

Evidence

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

Level 4

It is important to differentiate between persistence, relapse and reinfection, because this has treatment consequences.

 

Level 1 

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].

Level 3 

No significant difference in rates of UTIs were found between postcoital versus continuous daily ciprofloxacin [(156) A2].

Level 2 

Women can accurately self-diagnose and self-treat recurrent UTIs [(154) B; (158) B; (159) B].

Level 3

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].

Level 3

There is clinical benefit from the use of ascorbic acid (vitamin C) in the prevention of UTIs in pregnant women [(161) B].

 

Level 1 

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].

 

Level 3

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].

 

Level 3

Prophylaxis with Lactobacillus crispatus intravaginal suppository probiotic after treatment for cystitis is associated with a reduction in recurrent UTI in premenopausal women [(167) A2].

 

Level 3

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].

Level 1

Topical vaginal estrogen is a potential intervention to decrease the number of recurrent episodes for postmenopausal women [(163) A1].

Level 3

Use of an estriol-containing pessary is less effective than oral nitrofurantoin in the prevention of bacteriuria in postmenopausal women [(166) A2].

 

 

Level 1

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.

 

Antimicrobial prophylaxis

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).

 

Nonantimicrobial strategies

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.

 

Vitamin C

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.

 

Cranberries

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).

 

Estrogens

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).

 

Lactobacilli

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

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).

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.

 

  1. 1 - Rubenstein JN, Schaeffer AJ. Managing complicated urinary tract infections: the urologic view. Infect Dis Clin North Am 2003 Jun;17(2):333-51.
  2. 2 - Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin North Am 2003 Jun;17(2):303-32.
  3. 3 - Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011 Mar 1;52(5):e103-e120.
  4. 4 - 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.
  5. 5 - Vogel T, Verreault R, Gourdeau M, Morin M, Grenier-Gosselin L, Rochette L. Optimal duration of antibiotic therapy for uncomplicated urinary tract infection in older women: a double-blind randomized controlled trial. CMAJ 2004 Feb 17;170(4):469-73.
  6. 6 - Burgers JS, van Everdingen JJ. [Evidence-based guideline development in the Netherlands: the EBRO platform]. Ned Tijdschr Geneeskd 2004 Oct 16;148(42):2057-9.
  7. 7 - van der Starre WE, van NC, Paltansing S, van't Wout JW, Groeneveld GH, Becker MJ, et al. Risk factors for fluoroquinolone-resistant Escherichia coli in adults with community-onset febrile urinary tract infection. J Antimicrob Chemother 2011 Mar;66(3):650-6.
  8. 8 - Jeon JH, Kim K, Han WD, Song SH, Park KU, Rhee JE, et al. Empirical use of ciprofloxacin for acute uncomplicated pyelonephritis caused by Escherichia coli in communities where the prevalence of fluoroquinolone resistance is high. Antimicrob Agents Chemother 2012 Jun;56(6):3043-6.
  9. 9 - Gruchalla RS, Pirmohamed M. Clinical practice. Antibiotic allergy. N Engl J Med 2006 Feb 9;354(6):601-9.
  10. 10 - Mombelli G, Pezzoli R, Pinoja-Lutz G, Monotti R, Marone C, Franciolli M. Oral vs intravenous ciprofloxacin in the initial empirical management of severe pyelonephritis or complicated urinary tract infections: a prospective randomized clinical trial. Arch Intern Med 1999 Jan 11;159(1):53-8.
  11. 11 - Sanchez M, Collvinent B, Miro O, Horcajada JP, Moreno A, Marco F, et al. Short-term effectiveness of ceftriaxone single dose in the initial treatment of acute uncomplicated pyelonephritis in women. A randomised controlled trial. Emerg Med J 2002 Jan;19(1):19-22.
  12. 12 - Schwaber MJ, Carmeli Y. Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. J Antimicrob Chemother 2007 Nov;60(5):913-20.
  13. 13 - Pena C, Gudiol C, Calatayud L, Tubau F, Dominguez MA, Pujol M, et al. Infections due to Escherichia coli producing extended-spectrum beta-lactamase among hospitalised patients: factors influencing mortality. J Hosp Infect 2008 Feb;68(2):116-22.
  14. 14 - Kola A, Maciejewski O, Sohr D, Ziesing S, Gastmeier P. Clinical impact of infections caused by ESBL-producing E. coli and K. pneumoniae. Scand J Infect Dis 2007;39(11-12):975-82.
  15. 15 - Stamm WE, McKevitt M, Counts GW. Acute renal infection in women: treatment with trimethoprim-sulfamethoxazole or ampicillin for two or six weeks. A randomized trial. Ann Intern Med 1987 Mar;106(3):341-5.
  16. 16 - van der Starre WE, van Dissel JT, van Nieuwkoop C. Treatment duration of febrile urinary tract infections. Curr Infect Dis Rep 2011 Dec;13(6):571-8.
  17. 17 - Talan DA, Stamm WE, Hooton TM, Moran GJ, Burke T, Iravani A, et al. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial. JAMA 2000 Mar 22;283(12):1583-90.
  18. 18 - Sandberg T, Skoog G, Hermansson AB, Kahlmeter G, Kuylenstierna N, Lannergard A, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet 2012 Jun 20.
  19. 19 - Klausner HA, Brown P, Peterson J, Kaul S, Khashab M, Fisher AC, et al. A trial of levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400 mg and/or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis. Curr Med Res Opin 2007 Nov;23(11):2637-45.
  20. 20 - Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology 2008 Jan;71(1):17-22.
  21. 21 - Richard GA, Klimberg IN, Fowler CL, Callery-D'Amico S, Kim SS. Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis. Urology 1998 Jul;52(1):51-5.
  22. 22 - Carrie AG, Metge CJ, Collins DM, Harding GK, Zhanel GG. Use of administrative healthcare claims to examine the effectiveness of trimethoprim-sulfamethoxazole versus fluoroquinolones in the treatment of community-acquired acute pyelonephritis in women. J Antimicrob Chemother 2004 Mar;53(3):512-7.
  23. 23 - Ulleryd P, Sandberg T. Ciprofloxacin for 2 or 4 weeks in the treatment of febrile urinary tract infection in men: a randomized trial with a 1 year follow-up. Scand J Infect Dis 2003;35(1):34-9.
  24. 24 - Sandberg T, Englund G, Lincoln K, Nilsson LG. Randomised double-blind study of norfloxacin and cefadroxil in the treatment of acute pyelonephritis. Eur J Clin Microbiol Infect Dis 1990 May;9(5):317-23.
  25. 25 - Cronberg S, Banke S, Bergman B, Boman H, Eilard T, Elbel E, et al. Fewer bacterial relapses after oral treatment with norfloxacin than with ceftibuten in acute pyelonephritis initially treated with intravenous cefuroxime. Scand J Infect Dis 2001;33(5):339-43.
  26. 26 - van Nieuwkoop C, van't Wout JW, Spelt IC, Becker M, Kuijper EJ, Blom JW, et al. Prospective cohort study of acute pyelonephritis in adults: safety of triage towards home based oral antimicrobial treatment. J Infect 2010 Feb;60(2):114-21.
  27. 27 - van Nieuwkoop C, van't Wout JW, Assendelft WJ, Elzevier HW, Leyten EM, Koster T, et al. Treatment duration of febrile urinary tract infection (FUTIRST trial): a randomized placebo-controlled multicenter trial comparing short (7 days) antibiotic treatment with conventional treatment (14 days). BMC Infect Dis 2009;9:131.
  28. 28 - Naber KG, Bergman B, Bishop MC, Bjerklund-Johansen TE, Botto H, Lobel B, et al. EAU guidelines for the management of urinary and male genital tract infections. Urinary Tract Infection (UTI) Working Group of the Health Care Office (HCO) of the European Association of Urology (EAU). Eur Urol 2001 Nov;40(5):576-88.
  29. 29 - Corrado ML, Grad C, Sabbaj J. Norfloxacin in the treatment of urinary tract infections in men with and without identifiable urologic complications. Am J Med 1987 Jun 26;82(6B):70-4.
  30. 30 - Smith JW, Segal M. Urinary tract infection in men--an internist's viewpoint. Infection 1994;22 Suppl 1:S31-S34.
  31. 31 - Ulleryd P, Zackrisson B, Aus G, Bergdahl S, Hugosson J, Sandberg T. Selective urological evaluation in men with febrile urinary tract infection. BJU Int 2001 Jul;88(1):15-20.
  32. 32 - Collins MM, Stafford RS, O'Leary MP, Barry MJ. How common is prostatitis? A national survey of physician visits. J Urol 1998 Apr;159(4):1224-8.
  33. 33 - Krieger JN, McGonagle LA. Diagnostic considerations and interpretation of microbiological findings for evaluation of chronic prostatitis. J Clin Microbiol 1989 Oct;27(10):2240-4.
  34. 34 - Brunner H, Weidner W, Schiefer HG. Studies on the role of Ureaplasma urealyticum and Mycoplasma hominis in prostatitis. J Infect Dis 1983 May;147(5):807-13.
  35. 35 - de la Rosette JJ, Hubregtse MR, Meuleman EJ, Stolk-Engelaar MV, Debruyne FM. Diagnosis and treatment of 409 patients with prostatitis syndromes. Urology 1993 Apr;41(4):301-7.
  36. 36 - Krieger JN, Nyberg L, Jr., Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999 Jul 21;282(3):236-7.
  37. 37 - Lipsky BA. Prostatitis and urinary tract infection in men: what's new; what's true? Am J Med 1999 Mar;106(3):327-34.
  38. 38 - Lipsky BA, Byren I, Hoey CT. Treatment of bacterial prostatitis. Clin Infect Dis 2010 Jun 15;50(12):1641-52.
  39. 39 - Charalabopoulos K, Karachalios G, Baltogiannis D, Charalabopoulos A, Giannakopoulos X, Sofikitis N. Penetration of antimicrobial agents into the prostate. Chemotherapy 2003 Dec;49(6):269-79.
  40. 40 - Dunn BL, Stamey TA. Antibacterial concentrations in prostatic fluid. 1. Nitrofurantoin. J Urol 1967 Mar;97(3):505-7.
  41. 41 - Ulleryd P, Zackrisson B, Aus G, Bergdahl S, Hugosson J, Sandberg T. Prostatic involvement in men with febrile urinary tract infection as measured by serum prostate-specific antigen and transrectal ultrasonography. BJU Int 1999 Sep;84(4):470-4.
  42. 42 - Smith JW, Jones SR, Reed WP, Tice AD, Deupree RH, Kaijser B. Recurrent urinary tract infections in men. Characteristics and response to therapy. Ann Intern Med 1979 Oct;91(4):544-8.
  43. 43 - Sabbaj J, Hoagland VL, Cook T. Norfloxacin versus co-trimoxazole in the treatment of recurring urinary tract infections in men. Scand J Infect Dis Suppl 1986;48:48-53.
  44. 44 - Bundrick W, Heron SP, Ray P, Schiff WM, Tennenberg AM, Wiesinger BA, et al. Levofloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis: a randomized double-blind multicenter study. Urology 2003 Sep;62(3):537-41.
  45. 45 - Giannarini G, Mogorovich A, Valent F, Morelli G, De MM, Manassero F, et al. Prulifloxacin versus levofloxacin in the treatment of chronic bacterial prostatitis: a prospective, randomized, double-blind trial. J Chemother 2007 Jun;19(3):304-8.
  46. 46 - Naber KG. Lomefloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis. Int J Antimicrob Agents 2002 Jul;20(1):18-27.
  47. 47 - Paulson DF, White RD. Trimethoprium-sulfamethoxazole and minocycline- hydrochloride in the treatment of culture-proved bacterial prostatitis. J Urol 1978 Aug;120(2):184-5.
  48. 48 - Gleckman R, Crowley M, Natsios GA. Therapy of recurrent invasive urinary-tract infections of men. N Engl J Med 1979 Oct 18;301(16):878-80.
  49. 49 - Naber KG. Antimicrobial Treatment of Bacterial Prostatitis. Eur Urol Suppl 2003;2(2):23-6.
  50. 50 - Peppas T, Petrikkos G, Deliganni V, Zoumboulis P, Koulentianos E, Giamarellou H. Efficacy of long-term therapy with norfloxacin in chronic bacterial prostatitis. J Chemother 1989 Jul;1(4 Suppl):867-8.
  51. 51 - Schaeffer AJ, Darras FS. The efficacy of norfloxacin in the treatment of chronic bacterial prostatitis refractory to trimethoprim-sulfamethoxazole and/or carbenicillin. J Urol 1990 Sep;144(3):690-3.
  52. 52 - Weidner W, Schiefer HG, Brahler E. Refractory chronic bacterial prostatitis: a re-evaluation of ciprofloxacin treatment after a median followup of 30 months. J Urol 1991 Aug;146(2):350-2.
  53. 53 - Naber KG, Busch W, Focht J. Ciprofloxacin in the treatment of chronic bacterial prostatitis: a prospective, non-comparative multicentre clinical trial with long-term follow-up. The German Prostatitis Study Group. Int J Antimicrob Agents 2000 Mar;14(2):143-9.
  54. 54 - Meares EM, Stamey TA. Bacteriologic localization patterns in bacterial prostatitis and urethritis. Invest Urol 1968 Mar;5(5):492-518.
  55. 55 - Schaeffer AJ, Knauss JS, Landis JR, Propert KJ, Alexander RB, Litwin MS, et al. Leukocyte and bacterial counts do not correlate with severity of symptoms in men with chronic prostatitis: the National Institutes of Health Chronic Prostatitis Cohort Study. J Urol 2002 Sep;168(3):1048-53.
  56. 56 - Nickel JC, Alexander RB, Schaeffer AJ, Landis JR, Knauss JS, Propert KJ. Leukocytes and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome compared to asymptomatic controls. J Urol 2003 Sep;170(3):818-22.
  57. 57 - Muller CH, Berger RE, Mohr LE, Krieger JN. Comparison of microscopic methods for detecting inflammation in expressed prostatic secretions. J Urol 2001 Dec;166(6):2518-24.
  58. 58 - McNaughton-Collins M, Fowler FJ, Jr., Elliott DB, Albertsen PC, Barry MJ. Diagnosing and treating chronic prostatitis: do urologists use the four-glass test? Urology 2000 Mar;55(3):403-7.
  59. 59 - Litwin MS, McNaughton-Collins M, Fowler FJ, Jr., Nickel JC, Calhoun EA, Pontari MA, et al. The National Institutes of Health chronic prostatitis symptom index: development and validation of a new outcome measure. Chronic Prostatitis Collaborative Research Network. J Urol 1999 Aug;162(2):369-75.
  60. 60 - Patterson TF, Andriole VT. Detection, significance, and therapy of bacteriuria in pregnancy. Update in the managed health care era. Infect Dis Clin North Am 1997 Sep;11(3):593-608.
  61. 61 - Macejko AM, Schaeffer AJ. Asymptomatic bacteriuria and symptomatic urinary tract infections during pregnancy. Urol Clin North Am 2007 Feb;34(1):35-42.
  62. 62 - Millar LK, Cox SM. Urinary tract infections complicating pregnancy. Infect Dis Clin North Am 1997 Mar;11(1):13-26.
  63. 63 - Kass EH. Bacteriuria and pyelonephritis of pregnancy. Arch Intern Med 1960 Feb;105:194-8.
  64. 64 - Hill JB, Sheffield JS, McIntire DD, Wendel GD, Jr. Acute pyelonephritis in pregnancy. Obstet Gynecol 2005 Jan;105(1):18-23.
  65. 65 - Smaill F. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2001;(2):CD000490.
  66. 66 - Vazquez JC, Abalos E. Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev 2011;(1):CD002256.
  67. 67 - Vazquez JC, Villar J. Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev 2000;(3):CD002256.
  68. 68 - Ben DS, Einarson T, Ben DY, Nulman I, Pastuszak A, Koren G. The safety of nitrofurantoin during the first trimester of pregnancy: meta-analysis. Fundam Clin Pharmacol 1995;9(5):503-7.
  69. 69 - Usta TA, Dogan O, Ates U, Yucel B, Onar Z, Kaya E. Comparison of single-dose and multiple-dose antibiotics for lower urinary tract infection in pregnancy. Int J Gynaecol Obstet 2011 Sep;114(3):229-33.
  70. 70 - Wing DA, Hendershott CM, Debuque L, Millar LK. Outpatient treatment of acute pyelonephritis in pregnancy after 24 weeks. Obstet Gynecol 1999 Nov;94(5 Pt 1):683-8.
  71. 71 - Wing DA. Pyelonephritis in pregnancy: treatment options for optimal outcomes. Drugs 2001;61(14):2087-96.
  72. 72 - Berkovitch M, Diav-Citrin O, Greenberg R, Cohen M, Bulkowstein M, Shechtman S, et al. First-trimester exposure to amoxycillin/clavulanic acid: a prospective, controlled study. Br J Clin Pharmacol 2004 Sep;58(3):298-302.
  73. 73 - 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 Mar 1;40(5):643-54.
  74. 74 - Katchman EA, Milo G, Paul M, Christiaens T, Baerheim A, Leibovici L. Three-day vs longer duration of antibiotic treatment for cystitis in women: systematic review and meta-analysis. Am J Med 2005 Nov;118(11):1196-207.
  75. 75 - Jolley JA, Wing DA. Pyelonephritis in pregnancy: an update on treatment options for optimal outcomes. Drugs 2010 Sep 10;70(13):1643-55.
  76. 76 - Allen VM, Yudin MH, Bouchard C, Boucher M, Caddy S, Castillo E, et al. Management of group B streptococcal bacteriuria in pregnancy. J Obstet Gynaecol Can 2012 May;34(5):482-6.
  77. 77 - Nordeng H, Lupattelli A, Romoren M, Koren G. Neonatal outcomes after gestational exposure to nitrofurantoin. Obstet Gynecol 2013 Feb;121(2 Pt 1):306-13.
  78. 78 - Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE, Craig AS, et al. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med 2002 Jul 25;347(4):233-9.
  79. 79 - Smaill F. Asymptomatic bacteriuria in pregnancy. Best Pract Res Clin Obstet Gynaecol 2007 Jun;21(3):439-50.
  80. 80 - Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010 Mar 1;50(5):625-63.
  81. 81 - Niel-Weise BS, van den Broek PJ. Antibiotic policies for short-term catheter bladder drainage in adults. Cochrane Database Syst Rev 2005;(3):CD005428.
  82. 82 - Niel-Weise BS, van den Broek PJ. Urinary catheter policies for long-term bladder drainage. Cochrane Database Syst Rev 2005;(1):CD004201.
  83. 83 - Rutschmann OT, Zwahlen A. Use of norfloxacin for prevention of symptomatic urinary tract infection in chronically catheterized patients. Eur J Clin Microbiol Infect Dis 1995 May;14(5):441-4.
  84. 84 - Beerepoot MA, ter RG, Nys S, van der Wal WM, de Borgie CA, de Reijke TM, et al. Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women. Arch Intern Med 2011 Jul 25;171(14):1270-8.
  85. 85 - Warren JW, Damron D, Tenney JH, Hoopes JM, Deforge B, Muncie HL, Jr. Fever, bacteremia, and death as complications of bacteriuria in women with long-term urethral catheters. J Infect Dis 1987 Jun;155(6):1151-8.
  86. 86 - Jewes LA, Gillespie WA, Leadbetter A, Myers B, Simpson RA, Stower MJ, et al. Bacteriuria and bacteraemia in patients with long-term indwelling catheters--a domiciliary study. J Med Microbiol 1988 May;26(1):61-5.
  87. 87 - Polastri F, Auckenthaler R, Loew F, Michel JP, Lew DP. Absence of significant bacteremia during urinary catheter manipulation in patients with chronic indwelling catheters. J Am Geriatr Soc 1990 Nov;38(11):1203-8.
  88. 88 - Bregenzer T, Frei R, Widmer AF, Seiler W, Probst W, Mattarelli G, et al. Low risk of bacteremia during catheter replacement in patients with long-term urinary catheters. Arch Intern Med 1997 Mar 10;157(5):521-5.
  89. 89 - Romanelli G, Giustina A, Cravarezza P, Bossoni S, Bodini C, Girelli A, et al. A single dose of aztreonam in the prevention of urinary tract infections in elderly catheterized patients. J Chemother 1990 Jun;2(3):178-81.
  90. 90 - Wazait HD, Patel HR, van der Meulen JH, Ghei M, Al-Buheissi S, Kelsey M, et al. A pilot randomized double-blind placebo-controlled trial on the use of antibiotics on urinary catheter removal to reduce the rate of urinary tract infection: the pitfalls of ciprofloxacin. BJU Int 2004 Nov;94(7):1048-50.
  91. 91 - Hustinx WN, Mintjes-de Groot AJ, Verkooyen RP, Verbrugh HA. Impact of concurrent antimicrobial therapy on catheter-associated urinary tract infection. J Hosp Infect 1991 May;18(1):45-56.
  92. 92 - Pfefferkorn U, Lea S, Moldenhauer J, Peterli R, von FM, Ackermann C. Antibiotic prophylaxis at urinary catheter removal prevents urinary tract infections: a prospective randomized trial. Ann Surg 2009 Apr;249(4):573-5.
  93. 93 - van Hees BC, Vijverberg PL, Hoorntje LE, Wiltink EH, Go PM, Tersmette M. Single-dose antibiotic prophylaxis for urinary catheter removal does not reduce the risk of urinary tract infection in surgical patients: a randomized double-blind placebo-controlled trial. Clin Microbiol Infect 2011 Jul;17(7):1091-4.
  94. 94 - Barents JW, Dankert J, Ilic P, Laanbroek HJ, de VH. [The indwelling catheter in gynecology and the development of bacteriuria; a comparative study of patients with the transurethral and the suprapubic catheter]. Ned Tijdschr Geneeskd 1978 Sep 9;122(36):1321-7.
  95. 95 - Garcia Leoni ME, Esclarin De RA. Management of urinary tract infection in patients with spinal cord injuries. Clin Microbiol Infect 2003 Aug;9(8):780-5.
  96. 96 - Raz R, Schiller D, Nicolle LE. Chronic indwelling catheter replacement before antimicrobial therapy for symptomatic urinary tract infection. J Urol 2000 Oct;164(4):1254-8.
  97. 97 - Joshi A, Darouiche RO. Regression of pyuria during the treatment of symptomatic urinary tract infection in patients with spinal cord injury. Spinal Cord 1996 Dec;34(12):742-4.
  98. 98 - Harding GK, Nicolle LE, Ronald AR, Preiksaitis JK, Forward KR, Low DE, et al. How long should catheter-acquired urinary tract infection in women be treated? A randomized controlled study. Ann Intern Med 1991 May 1;114(9):713-9.
  99. 99 - Mohler JL, Cowen DL, Flanigan RC. Suppression and treatment of urinary tract infection in patients with an intermittently catheterized neurogenic bladder. J Urol 1987 Aug;138(2):336-40.
  100. 100 - Dow G, Rao P, Harding G, Brunka J, Kennedy J, Alfa M, et al. A prospective, randomized trial of 3 or 14 days of ciprofloxacin treatment for acute urinary tract infection in patients with spinal cord injury. Clin Infect Dis 2004 Sep 1;39(5):658-64.
  101. 101 - Renko M, Tapanainen P, Tossavainen P, Pokka T, Uhari M. Meta-analysis of the significance of asymptomatic bacteriuria in diabetes. Diabetes Care 2011 Jan;34(1):230-5.
  102. 102 - Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003 Feb;26(2):510-3.
  103. 103 - Boyko EJ, Fihn SD, Scholes D, Chen CL, Normand EH, Yarbro P. Diabetes and the risk of acute urinary tract infection among postmenopausal women. Diabetes Care 2002 Oct;25(10):1778-83.
  104. 104 - Gorter KJ, Hak E, Zuithoff NP, Hoepelman AI, Rutten GE. Risk of recurrent acute lower urinary tract infections and prescription pattern of antibiotics in women with and without diabetes in primary care. Fam Pract 2010 Aug;27(4):379-85.
  105. 105 - Lawrenson RA, Logie JW. Antibiotic failure in the treatment of urinary tract infections in young women. J Antimicrob Chemother 2001 Dec;48(6):895-901.
  106. 106 - Czaja CA, Rutledge BN, Cleary PA, Chan K, Stapleton AE, Stamm WE. Urinary tract infections in women with type 1 diabetes mellitus: survey of female participants in the epidemiology of diabetes interventions and complications study cohort. J Urol 2009 Mar;181(3):1129-34.
  107. 107 - Carton JA, Maradona JA, Nuno FJ, Fernandez-Alvarez R, Perez-Gonzalez F, Asensi V. Diabetes mellitus and bacteraemia: a comparative study between diabetic and non-diabetic patients. Eur J Med 1992 Sep;1(5):281-7.
  108. 108 - Horcajada JP, Moreno I, Velasco M, Martinez JA, Moreno-Martinez A, Barranco M, et al. Community-acquired febrile urinary tract infection in diabetics could deserve a different management: a case-control study. J Intern Med 2003 Sep;254(3):280-6.
  109. 109 - Nicolle LE, Zhanel GG, Harding GK. Microbiological outcomes in women with diabetes and untreated asymptomatic bacteriuria. World J Urol 2006 Feb;24(1):61-5.
  110. 110 - Meiland R, Geerlings SE, Stolk RP, Netten PM, Schneeberger PM, Hoepelman AI. Asymptomatic bacteriuria in women with diabetes mellitus: effect on renal function after 6 years of follow-up. Arch Intern Med 2006 Nov 13;166(20):2222-7.
  111. 111 - Geerlings SE, Stolk RP, Camps MJ, Netten PM, Collet JT, Schneeberger PM, et al. Consequences of asymptomatic bacteriuria in women with diabetes mellitus. Arch Intern Med 2001 Jun 11;161(11):1421-7.
  112. 112 - Karunajeewa H, McGechie D, Stuccio G, Stingemore N, Davis WA, Davis TM. Asymptomatic bacteriuria as a predictor of subsequent hospitalisation with urinary tract infection in diabetic adults: The Fremantle Diabetes Study. Diabetologia 2005 Jul;48(7):1288-91.
  113. 113 - Harding GK, Zhanel GG, Nicolle LE, Cheang M. Antimicrobial treatment in diabetic women with asymptomatic bacteriuria. N Engl J Med 2002 Nov 14;347(20):1576-83.
  114. 114 - Meiland R, Geerlings SE, De Neeling AJ, Hoepelman AI. Diabetes mellitus in itself is not a risk factor for antibiotic resistance in Escherichia coli isolated from patients with bacteriuria. Diabet Med 2004 Sep;21(9):1032-4.
  115. 115 - Bonadio M, Costarelli S, Morelli G, Tartaglia T. The influence of diabetes mellitus on the spectrum of uropathogens and the antimicrobial resistance in elderly adult patients with urinary tract infection. BMC Infect Dis 2006;6:54.
  116. 116 - Goettsch WG, Janknegt R, Herings RM. Increased treatment failure after 3-days' courses of nitrofurantoin and trimethoprim for urinary tract infections in women: a population-based retrospective cohort study using the PHARMO database. Br J Clin Pharmacol 2004 Aug;58(2):184-9.
  117. 117 - Schneeberger C, Stolk RP, Devries JH, Schneeberger PM, Herings RM, Geerlings SE. Differences in the pattern of antibiotic prescription profile and recurrence rate for possible urinary tract infections in women with and without diabetes. Diabetes Care 2008 Jul;31(7):1380-5.
  118. 118 - Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011 Dec;13(6):579-87.
  119. 119 - Wilson CH, Bhatti AA, Rix DA, Manas DM. Routine intraoperative ureteric stenting for kidney transplant recipients. Cochrane Database Syst Rev 2005;(4):CD004925.
  120. 120 - Golebiewska J, Debska-Slizien A, Komarnicka J, Samet A, Rutkowski B. Urinary tract infections in renal transplant recipients. Transplant Proc 2011 Oct;43(8):2985-90.
  121. 121 - Giral M, Pascuariello G, Karam G, Hourmant M, Cantarovich D, Dantal J, et al. Acute graft pyelonephritis and long-term kidney allograft outcome. Kidney Int 2002 May;61(5):1880-6.
  122. 122 - Sadeghi M, Daniel V, Naujokat C, Wiesel M, Hergesell O, Opelz G. Strong inflammatory cytokine response in male and strong anti-inflammatory response in female kidney transplant recipients with urinary tract infection. Transpl Int 2005 Feb;18(2):177-85.
  123. 123 - Kamath NS, John GT, Neelakantan N, Kirubakaran MG, Jacob CK. Acute graft pyelonephritis following renal transplantation. Transpl Infect Dis 2006 Sep;8(3):140-7.
  124. 124 - Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers. Clin Transplant 2005 Apr;19(2):230-5.
  125. 125 - Brennan DC, Daller JA, Lake KD, Cibrik D, Del CD. Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med 2006 Nov 9;355(19):1967-77.
  126. 126 - Alangaden GJ, Thyagarajan R, Gruber SA, Morawski K, Garnick J, El-Amm JM, et al. Infectious complications after kidney transplantation: current epidemiology and associated risk factors. Clin Transplant 2006 Jul;20(4):401-9.
  127. 127 - de Souza RM, Olsburgh J. Urinary tract infection in the renal transplant patient. Nat Clin Pract Nephrol 2008 May;4(5):252-64.
  128. 128 - Green H, Rahamimov R, Gafter U, Leibovitci L, Paul M. Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis 2011 Oct;13(5):441-7.
  129. 129 - Al-Hasan MN, Razonable RR, Kremers WK, Baddour LM. Impact of Gram-negative bloodstream infection on long-term allograft survival after kidney transplantation. Transplantation 2011 Jun 15;91(11):1206-10.
  130. 130 - Pelle G, Vimont S, Levy PP, Hertig A, Ouali N, Chassin C, et al. Acute pyelonephritis represents a risk factor impairing long-term kidney graft function. Am J Transplant 2007 Apr;7(4):899-907.
  131. 131 - Abbott KC, Swanson SJ, Richter ER, Bohen EM, Agodoa LY, Peters TG, et al. Late urinary tract infection after renal transplantation in the United States. Am J Kidney Dis 2004 Aug;44(2):353-62.
  132. 132 - Saemann M, Horl WH. Urinary tract infection in renal transplant recipients. Eur J Clin Invest 2008 Oct;38 Suppl 2:58-65.
  133. 133 - Pinheiro HS, Mituiassu AM, Carminatti M, Braga AM, Bastos MG. Urinary tract infection caused by extended-spectrum beta-lactamase-producing bacteria in kidney transplant patients. Transplant Proc 2010 Mar;42(2):486-7.
  134. 134 - Fiorante S, Lopez-Medrano F, Lizasoain M, Lalueza A, Juan RS, Andres A, et al. Systematic screening and treatment of asymptomatic bacteriuria in renal transplant recipients. Kidney Int 2010 Oct;78(8):774-81.
  135. 135 - Green H, Rahamimov R, Goldberg E, Leibovici L, Gafter U, Bishara J, et al. Consequences of treated versus untreated asymptomatic bacteriuria in the first year following kidney transplantation: retrospective observational study. Eur J Clin Microbiol Infect Dis 2012 Aug 25.
  136. 136 - KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009 Nov;9 Suppl 3:S1-155.
  137. 137 - Munoz P. Management of urinary tract infections and lymphocele in renal transplant recipients. Clin Infect Dis 2001 Jul 1;33 Suppl 1:S53-S57.
  138. 138 - Khosroshahi HT, Mogaddam AN, Shoja MM. Efficacy of high-dose trimethoprim-sulfamethoxazol prophylaxis on early urinary tract infection after renal transplantation. Transplant Proc 2006 Sep;38(7):2062-4.
  139. 139 - Rafat C, Vimont S, Ancel PY, Xu-Dubois YC, Mesnard L, Ouali N, et al. Ofloxacin: new applications for the prevention of urinary tract infections in renal graft recipients. Transpl Infect Dis 2011 Aug;13(4):344-52.
  140. 140 - Rabkin DG, Stifelman MD, Birkhoff J, Richardson KA, Cohen D, Nowygrod R, et al. Early catheter removal decreases incidence of urinary tract infections in renal transplant recipients. Transplant Proc 1998 Dec;30(8):4314-6.
  141. 141 - Renoult E, Aouragh F, Mayeux D, Hestin D, Lataste A, Hubert J, et al. Factors influencing early urinary tract infections in kidney transplant recipients. Transplant Proc 1994 Aug;26(4):2056-8.
  142. 142 - Grenier J, Fradette C, Morelli G, Merritt GJ, Vranderick M, Ducharme MP. Pomelo juice, but not cranberry juice, affects the pharmacokinetics of cyclosporine in humans. Clin Pharmacol Ther 2006 Mar;79(3):255-62.
  143. 143 - Nicolle LE. Asymptomatic bacteriuria: when to screen and when to treat. Infect Dis Clin North Am 2003 Jun;17(2):367-94.
  144. 144 - Sallee M, Rafat C, Zahar JR, Paulmier B, Grunfeld JP, Knebelmann B, et al. Cyst infections in patients with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 2009 Jul;4(7):1183-9.
  145. 145 - Gibson P, Watson ML. Cyst infection in polycystic kidney disease: a clinical challenge. Nephrol Dial Transplant 1998 Oct;13(10):2455-7.
  146. 146 - McNamara JJ. Pyelonefritis in polycystic disease of the kidney. Am J Surg 1965 Feb;109:178-81.
  147. 147 - Schwab SJ, Bander SJ, Klahr S. Renal infection in autosomal dominant polycystic kidney disease. Am J Med 1987 Apr;82(4):714-8.
  148. 148 - Migali G, Annet L, Lonneux M, Devuyst O. Renal cyst infection in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 2008 Jan;23(1):404-5.
  149. 149 - Idrizi A, Barbullushi M, Petrela E, Kodra S, Koroshi A, Thereska N. The influence of renal manifestations to the progression of autosomal dominant polycystic kidney disease. Hippokratia 2009 Jul;13(3):161-4.
  150. 150 - Idrizi A, Barbullushi M, Koroshi A, Dibra M, Bolleku E, Bajrami V, et al. Urinary tract infections in polycystic kidney disease. Med Arh 2011;65(4):213-5.
  151. 151 - Rossleigh MA. Scintigraphic imaging in renal infections. Q J Nucl Med Mol Imaging 2009 Feb;53(1):72-7.
  152. 152 - Bleeker-Rovers CP, de Sevaux RG, van Hamersvelt HW, Corstens FH, Oyen WJ. Diagnosis of renal and hepatic cyst infections by 18-F-fluorodeoxyglucose positron emission tomography in autosomal dominant polycystic kidney disease. Am J Kidney Dis 2003 Jun;41(6):E18-E21.
  153. 153 - Albert X, Huertas I, Pereiro II, Sanfelix J, Gosalbes V, Perrota C. Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Cochrane Database Syst Rev 2004;(3):CD001209.
  154. 154 - Gupta K, Hooton TM, Roberts PL, Stamm WE. Patient-initiated treatment of uncomplicated recurrent urinary tract infections in young women. Ann Intern Med 2001 Jul 3;135(1):9-16.
  155. 155 - van Haarst EP, van AG, Heldeweg EA, Schlatmann TJ, van der Horst HJ. Evaluation of the diagnostic workup in young women referred for recurrent lower urinary tract infections. Urology 2001 Jun;57(6):1068-72.
  156. 156 - Melekos MD, Asbach HW, Gerharz E, Zarakovitis IE, Weingaertner K, Naber KG. Post-intercourse versus daily ciprofloxacin prophylaxis for recurrent urinary tract infections in premenopausal women. J Urol 1997 Mar;157(3):935-9.
  157. 157 - Rudenko N, Dorofeyev A. Prevention of recurrent lower urinary tract infections by long-term administration of fosfomycin trometamol. Double blind, randomized, parallel group, placebo controlled study. Arzneimittelforschung 2005;55(7):420-7.
  158. 158 - Schaeffer AJ, Stuppy BA. Efficacy and safety of self-start therapy in women with recurrent urinary tract infections. J Urol 1999 Jan;161(1):207-11.
  159. 159 - Zhong YH, Fang Y, Zhou JZ, Tang Y, Gong SM, Ding XQ. Effectiveness and Safety of Patientinitiated Single-dose versus Continuous Low-dose Antibiotic Prophylaxis for Recurrent Urinary Tract Infections in Postmenopausal Women: a Randomized Controlled Study. J Int Med Res 2011;39(6):2335-43.
  160. 160 - Castello T, Girona L, Gomez MR, Mena MA, Garcia L. The possible value of ascorbic acid as a prophylactic agent for urinary tract infection. Spinal Cord 1996 Oct;34(10):592-3.
  161. 161 - Ochoa-Brust GJ, Fernandez AR, Villanueva-Ruiz GJ, Velasco R, Trujillo-Hernandez B, Vasquez C. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand 2007;86(7):783-7.
  162. 162 - Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2008;(1):CD001321.
  163. 163 - Perrotta C, Aznar M, Mejia R, Albert X, Ng CW. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev 2008;(2):CD005131.
  164. 164 - Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med 1993 Sep 9;329(11):753-6.
  165. 165 - Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol 1999 May;180(5):1072-9.
  166. 166 - Raz R, Colodner R, Rohana Y, Battino S, Rottensterich E, Wasser I, et al. Effectiveness of estriol-containing vaginal pessaries and nitrofurantoin macrocrystal therapy in the prevention of recurrent urinary tract infection in postmenopausal women. Clin Infect Dis 2003 Jun 1;36(11):1362-8.
  167. 167 - Stapleton AE, Au-Yeung M, Hooton TM, Fredricks DN, Roberts PL, Czaja CA, et al. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis 2011 May;52(10):1212-7.
  168. 168 - Beerepoot MA, ter RG, Nys S, van der Wal WM, de Borgie CA, de Reijke TM, et al. Lactobacilli vs Antibiotics to Prevent Urinary Tract Infections: A Randomized, Double-blind, Noninferiority Trial in Postmenopausal Women. Arch Intern Med 2012 May 14;172(9):704-12.
  169. 169 - Lee BB, Simpson JM, Craig JC, Bhuta T. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev 2007;(4):CD003265.
  170. 170 - Mavromanolakis E, Maraki S, Samonis G, Tselentis Y, Cranidis A. Effect of norfloxacin, trimethoprim-sulfamethoxazole and nitrofurantoin on fecal flora of women with recurrent urinary tract infections. J Chemother 1997 Jun;9(3):203-7.
  171. 171 - Wollersheim H, Hermens R, Hulscher M, Braspenning J, Ouwens M, Schouten J, et al. Clinical indicators: development and applications. Neth J Med 2007 Jan;65(1):15-22.
  172. 172 - Hermanides HS, Hulscher ME, Schouten JA, Prins JM, Geerlings SE. Development of quality indicators for the antibiotic treatment of complicated urinary tract infections: a first step to measure and improve care. Clin Infect Dis 2008 Mar 1;46(5):703-11.

This guideline does not include evidence tables.

Authorization date and validity

Last review  : 01-03-2013

Last authorization  : 01-03-2013

Planned reassessment  :

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:
  • Nederlands Huisartsen Genootschap
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging voor Medische Microbiologie
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
  • Nederlandse Vereniging voor Urologie
  • Stichting Werkgroep Antibioticabeleid

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.

Samenstelling werkgroep

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.

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Indicators for antibiotic theraphy for UTI