What is the optimal empirical treatment strategy concerning the choice of drug, also for patients with an increased risk for Extended-Spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae?
In patients suspected of having a complicated UTI, a urine culture and susceptibility test should always be performed.
Amoxicillin, co-amoxiclav, TMP and TMP-SMX are not suitable for the empirical treatment of complicated UTI.
The combination of amoxicillin + an aminoglycoside, a 2nd generation cephalosporin + an aminoglycoside or a 3rd generation cephalosporin intravenously can be recommended as empirical treatment of complicated UTI.
Ciprofloxacin can only be recommended when the whole treatment is given orally, when patients do not require hospitalization or when the patient has an anaphylaxis for beta-lactam antibiotics, provided that the local resistance percentages are < 10%.
Ciprofloxacin and other fluoroquinolones are not suitable for the empirical treatment of complicated UTI in patients from the urology department or when patients have used fluoroquinolones in the last 6 months.
If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial 1-time intravenous dose of a long-acting antimicrobial, such as a 3rd generation cephalosporin or an aminoglycoside, is recommended while resistance data are pending.
If the prevalence of fluoroquinolone resistance is thought to be higher than 10% and the patient has contra indications for 3rd generation cephalosporins or an aminoglycoside, ciprofloxacin can be prescribed as an empirical treatment in women with an uncomplicated pyelonephritis.
In the event of hypersensitivity to penicillin, a 3rd generation cephalosporin can still be prescribed, with the exception of systemic anaphylaxis in the past.
In patients with a UTI with systemic symptoms empirical treatment should cover ESBL in the initial treatment only in patients who are colonised with ESBL-producing micro-organisms. The resistance pattern of the ESBL strain should guide empirical therapy.
When the results of the urine culture are known, therapy must be adjusted and if possible narrowed down. If the clinical condition of the patient allows it and if the patient does not vomit, oral therapy can be prescribed.
If the patient no longer has symptoms, there is no indication for follow-up cultures.
This guideline does not include individual introductions to each module. A general introduction can be found in the attachments under the heading 'related'.
Escherichia coli is the causative organism in most cases of complicated UTIs.
E. coli isolated from patients presenting to unselected outpatient hospital departments (not urology or intensive care units) have high resistance percentages to amoxicillin, co-amoxiclav, trimethoprim and trimethoprim-sulfamethoxazole (TMP-SMX).
E. coli isolated from patients presenting to unselected outpatient hospital departments (not urology or intensive care units) have to ciprofloxacin a resistance rate of 17%, but in isolates from patients from general practice offices this is 10% and in isolates from urology departments it is 25%. The resistance percentages of norfloxacin, levofloxacin and moxifloxacin are similar to those of ciprofloxacin.
E. coli isolated from patients presenting to unselected outpatient hospital departments show the following resistance percentages to intravenous antimicrobial agents: gentamicin 8%, second-generation cephalosporin 13%, all third-generation cephalosporins 5%, and “last line” antimicrobial agents: piperacilin-tazobactam 8%, imipenem and meronepenem 0.03%.
Evaluating the SWAB guideline from 2006, the combination of amoxicillin and gentamicin is the most adequate (inadequate treatment rate of 6%). Second-generation cephalosporins had the highest inadequate treatment rate, i.e. 24%; the inadequate treatment rate for third-generation cephalosporins was 18%, for co-amoxiclav 14% and for ciprofloxacin it was 23%. Leaving out enterococci decreased the inadequate treatment rate, third-generation cephalosporins were now adequate in 10% of cases [(Spoorenberg submitted) C].
CAUSATIVE MICRO-ORGANISMS AND RESISTANCE
Although there is a greater diversity of causative micro-organisms in complicated UTIs than in uncomplicated UTIs, Escherichia coli remains in most cases of complicated UTIs the causative organism. Using the Infectious Diseases Surveillance Information System on Antimicrobial Resistance (ISIS-AR) and data selected from patients in the urology and internal medicine departments of 19 Dutch hospitals (Spoorenberg et al. submitted), we found the following causative micro-organisms: E. coli (45-62%), Enterococcus spp. (7-15%), Proteus mirabilis (6-8%), and Klebsiella pneumoniae (7-9%).
The most useful resistance data on the above-mentioned micro-organisms were provided by the report “Nethmap” (www.swab.nl) and ISIS-AR.
In Nethmap, information has been collected on the prevalence of resistance against antibiotics in the Netherlands in the period up to 2010. The interpretation of susceptibility test follows the guidelines of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). For treatment of a UTI with systemic symptoms the antimicrobial drug must achieve high concentrations in urine, kidney tissue and prostate. Therefore, nitrofurantoin and fosfomycin are not registered for the treatment of a UTI with systemic symptoms.
On the basis of resistance data from 2009/2010 (Nethmap 2011), E. coli isolated from patients presenting to unselected outpatient hospital departments have high resistance percentages for amoxicillin, co-amoxiclav, trimethoprim (TMP) and of trimethoprim-sulfamethoxazole (TMP-SMX) (Table 1). For ciprofloxacin the resistance percentage was 17% for E. coli isolated from patients presenting to unselected outpatient hospital departments (not urology or intensive care units), but in isolates from patients from urology departments it was 25%. The most important risk factor for ciprofloxacin resistance was the use of this agent in the last 6 months (7) (odds ratio (OR) 17.5, 95% confidence interval (CI) 6.0-50.7). The resistance percentages of norfloxacin, levofloxacin and moxifloxacin are similar to those of ciprofloxacin.
For intravenous antibiotics the resistance percentages of E.coli isolated from patients presenting to unselected outpatient hospital departments (not urology or intensive care units) are shown in Table 1.
Table 1 Data from Nethmap (SWAB) and *the Infectious Diseases Surveillance Information System on Antimicrobial Resistance (ISIS-AR) of 32,785 (first urine) isolates from 26,711 patients (complicated UTI was defined as a urine-isolate from a hospitalised patient).
Resistance percentages 2009/2010
ciprofloxacin (unselected departments)
cefuroxime (2nd generation cephalosporin)
3rd generation cephalosporins (cefotaxime)
imipenem and meronepenem
amoxicillin + third-generation cephalosporins
co-amoxiclav + gentamicin
GP = general practitioner
Other uropathogens (K. pneumoniae, P. mirabilis) showed (besides their intrinsic resistance) comparable resistant patterns, with the exception of co-amoxiclav for which the resistance percentages were 11-12%.
To evaluate the adequacy of the SWAB guideline for antimicrobial treatment of complicated UTI from 2006, a study was performed in the urology and internal medicine departments of 19 Dutch hospitals. Patients from these hospitals were representative for the patient population in Dutch hospitals since university, teaching and non-teaching hospitals located throughout the Netherlands participated. We considered a guideline-recommended or prescribed empirical therapy to be adequate if the cultured uropathogen was reported to be susceptible to the recommended or prescribed antibiotic. A guideline-recommended or prescribed empirical therapy was considered to be inadequate in case of resistance or inadequate coverage of the cultured uropathogen.
We evaluated all patients with a complicated UTI without other conditions (n=810). The combination of amoxicillin and gentamicin was the most adequate (inadequate treatment rate of 6%) Second-generation cephalosporins had the highest inadequate treatment rate, i.e. 24% (inadequate coverage 16%, resistance 8%), the inadequate treatment rate for third-generation cephalosporins was 18% (inadequate coverage 16%, resistance 2%), for co-amoxiclav 14% (inadequate coverage 7%, resistance 7%) and for ciprofloxacin it was 23% (inadequate coverage 9%, resistance 14%). Enterococcus species usually have low virulence, and it is debatable whether they should be covered in empirical therapy. Leaving out enterococci (7% of all uropathogens) decreased the inadequate treatment rate for some regimens: third-generation cephalosporins were now adequate in 10% of cases. All other regimens remained inadequate in > 10% of patients (Spoorenberg et al., submitted).
Zoeken en selecteren
Resistance data were obtained from the report Nethmap 2011 (www.swab.nl) and from the Infectious Diseases Surveillance Information System on Antimicrobial Resistance (ISIS-AR).
For other articles the databases of Pubmed and the Cochrane Library were searched.
Keywords: urinary tract infection AND treatment
Limits: Last 2 years for Pubmed (IDSA guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women were published in 2011) (3)), English, adults, humans, clinical trials, guideline, meta-analysis, RCT
Pubmed: 101 results, all titles screened, 1 abstract screened, 1 additional article included.
Cochrane Library: 35 results, all titles screened, 0 abstracts screened, 0 reviews included.
Articles on antimicrobial agents which are not available in the Netherlands, or on the treatment of uncomplicated UTIs, were excluded.
- 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 - Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin North Am 2003 Jun;17(2):303-32.
- 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 - 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 - 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 - 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 - 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 - 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 - Gruchalla RS, Pirmohamed M. Clinical practice. Antibiotic allergy. N Engl J Med 2006 Feb 9;354(6):601-9.
- 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Smith JW, Segal M. Urinary tract infection in men--an internist's viewpoint. Infection 1994;22 Suppl 1:S31-S34.
- 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 - 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 - 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 - 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 - 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 - Krieger JN, Nyberg L, Jr., Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999 Jul 21;282(3):236-7.
- 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 - Lipsky BA, Byren I, Hoey CT. Treatment of bacterial prostatitis. Clin Infect Dis 2010 Jun 15;50(12):1641-52.
- 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 - Dunn BL, Stamey TA. Antibacterial concentrations in prostatic fluid. 1. Nitrofurantoin. J Urol 1967 Mar;97(3):505-7.
- 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 - 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 - 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 - 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 - 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 - Naber KG. Lomefloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis. Int J Antimicrob Agents 2002 Jul;20(1):18-27.
- 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 - 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 - Naber KG. Antimicrobial Treatment of Bacterial Prostatitis. Eur Urol Suppl 2003;2(2):23-6.
- 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 - 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 - 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 - 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 - Meares EM, Stamey TA. Bacteriologic localization patterns in bacterial prostatitis and urethritis. Invest Urol 1968 Mar;5(5):492-518.
- 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 - 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 - 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 - 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 - 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 - 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 - Macejko AM, Schaeffer AJ. Asymptomatic bacteriuria and symptomatic urinary tract infections during pregnancy. Urol Clin North Am 2007 Feb;34(1):35-42.
- 62 - Millar LK, Cox SM. Urinary tract infections complicating pregnancy. Infect Dis Clin North Am 1997 Mar;11(1):13-26.
- 63 - Kass EH. Bacteriuria and pyelonephritis of pregnancy. Arch Intern Med 1960 Feb;105:194-8.
- 64 - Hill JB, Sheffield JS, McIntire DD, Wendel GD, Jr. Acute pyelonephritis in pregnancy. Obstet Gynecol 2005 Jan;105(1):18-23.
- 65 - Smaill F. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev 2001;(2):CD000490.
- 66 - Vazquez JC, Abalos E. Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev 2011;(1):CD002256.
- 67 - Vazquez JC, Villar J. Treatments for symptomatic urinary tract infections during pregnancy. Cochrane Database Syst Rev 2000;(3):CD002256.
- 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 - 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 - 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 - Wing DA. Pyelonephritis in pregnancy: treatment options for optimal outcomes. Drugs 2001;61(14):2087-96.
- 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 - 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 - 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 - Jolley JA, Wing DA. Pyelonephritis in pregnancy: an update on treatment options for optimal outcomes. Drugs 2010 Sep 10;70(13):1643-55.
- 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 - 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 - 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 - Smaill F. Asymptomatic bacteriuria in pregnancy. Best Pract Res Clin Obstet Gynaecol 2007 Jun;21(3):439-50.
- 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 - 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 - Niel-Weise BS, van den Broek PJ. Urinary catheter policies for long-term bladder drainage. Cochrane Database Syst Rev 2005;(1):CD004201.
- 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003 Feb;26(2):510-3.
- 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011 Dec;13(6):579-87.
- 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - de Souza RM, Olsburgh J. Urinary tract infection in the renal transplant patient. Nat Clin Pract Nephrol 2008 May;4(5):252-64.
- 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 - 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 - 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 - 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 - Saemann M, Horl WH. Urinary tract infection in renal transplant recipients. Eur J Clin Invest 2008 Oct;38 Suppl 2:58-65.
- 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 - 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 - 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 - KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009 Nov;9 Suppl 3:S1-155.
- 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 - 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 - 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 - 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 - 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 - 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 - Nicolle LE. Asymptomatic bacteriuria: when to screen and when to treat. Infect Dis Clin North Am 2003 Jun;17(2):367-94.
- 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 - Gibson P, Watson ML. Cyst infection in polycystic kidney disease: a clinical challenge. Nephrol Dial Transplant 1998 Oct;13(10):2455-7.
- 146 - McNamara JJ. Pyelonefritis in polycystic disease of the kidney. Am J Surg 1965 Feb;109:178-81.
- 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 - 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 - 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 - 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 - Rossleigh MA. Scintigraphic imaging in renal infections. Q J Nucl Med Mol Imaging 2009 Feb;53(1):72-7.
- 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2008;(1):CD001321.
- 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 - 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 - 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 - 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 - 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 - 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 - Lee BB, Simpson JM, Craig JC, Bhuta T. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev 2007;(4):CD003265.
- 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 - 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 - 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.
Optimal therapy for UTI with systemic symptoms depends on the severity of illness at presentation, as well as local resistance patterns and specific host factors (such as allergies). In addition, urine culture and susceptibility testing should be performed, and initial empirical therapy should be tailored and followed by (oral) administration of an appropriate antibiotic agent on the basis of the isolated uropathogen.
Collateral damage, a term describing ecological adverse effects of antimicrobial therapy, such as the selection of drug-resistant organisms and colonization or infection with multidrug-resistant organisms, has been associated with the use of broad-spectrum antimicrobial agents (3). Therefore, last line antimicrobial agents like piperacilin-tazobactam, imipenem and meropenem are not recommended as first choice empirical therapy.
EMPIRICAL TREATMENT: DRUG OF CHOICE
In the recent updated IDSA guidelines for the treatment of uncomplicated UTI, it is recommended that the resistance percentages of causative micro-organisms must be below 20% to consider an agent suitable for empirical treatment of a lower UTI and must be below 10% for treatment of an upper UTI. Considering the resistance percentages of amoxicillin, co-amoxiclav, TMP and TMP-SMX, we can conclude that these agents are not suitable for the empirical treatment of pyelonephritis in a normal host and, therefore, also not for treatment of all other complicated UTIs. The same applies to ciprofloxacin and other fluoroquinolones in patients from the urology departments.
Therefore, patients with a UTI with systemic symptoms requiring hospitalization should be initially treated with an intravenous antimicrobial regimen, such as an aminoglycoside, with or without amoxicillin or a second generation cephalosporin; or a third generation cephalosporin or extended-spectrum penicillin, with or without an aminoglycoside. The choice between these agents should be based on local resistance data, and the regimen should be tailored on the basis of susceptibility results (3). These recommendations are not only suitable for pyelonephritis but for all complicated UTIs.
In view of the high degree of resistance, in particular among patients admitted to the department of urology, fluoroquinolones are not automatically suitable as empirical antimicrobial therapy, especially when the patient has used ciprofloxacin in the last 6 months (7). Therefore, this agent can only be recommended as empirical treatment when the patient is not seriously ill and it is considered safe to start initial oral treatment or if the patient has had an anaphylactic reaction to β-lactam antibiotics.
Oral ciprofloxacin (500 mg twice daily, with or without an initial 400-mg dose of intravenous ciprofloxacin) is an appropriate choice for therapy in patients not requiring hospitalization when the prevalence of resistance of community uropathogens to fluoroquinolones is not known to exceed 10%. If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial 1-time intravenous dose of a long-acting antimicrobial, such as 1 g of ceftriaxone or an aminoglycoside, is recommended (3) while resistance data are pending. However, a study in women with uncomplicated pyelonephritis showed there were no differences in the clinical success rates of women with a ciprofloxacin susceptible E. coli compared to those with a ciprofloxacin resistant E. coli (8). After a follow-up of 4-7 days, and 14-21 days after completion of therapy, the clinical success rates were 87.0% vs. 76.9% (P=0.14) and 98.6% vs. 94.9% (P=0.18) for the ciprofloxacin susceptible and ciprofloxacin resistant groups, respectively. Therefore, it seems that in women with uncomplicated pyelonephritis, even in higher percentages of ciprofloxacin resistance, ciprofloxacin can be prescribed as an empirical treatment (8).
Because there is only a small chance that cross-hypersensitivity exists between penicillin derivatives and cephalosporins (9), the Guideline committee is of the opinion that in the event of hypersensitivity for penicillin derivatives (a rash but not a systemic anaphylactic reaction), a 3rd generation cephalosporin can still be prescribed. If -lactam antibiotics have caused anaphylaxis in the past, a fluoroquinolone is recommended.
If the clinical condition of the patient allows it and if the patient does not vomit, then oral therapy can be prescribed (10), (11). If the patient no longer has symptoms, there is no indication for follow-up cultures.
When to cover ESBL in the empiric regimen?
In the SWAB guidelines for antibacterial therapy of adult patients with sepsis (SWAB 2010) the following recommendations are made:
- In (departments of) hospitals with a high prevalence of Extended-Spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae, a carbapenem with anti-pseudomonal activity (imipenem/meropenem) should be chosen as empirical antibacterial therapy if an infection caused by ESBL-producing bacteria is suspected. As no critical prevalence level has been identified, risk factors of ESBL infection should be used to target empirical therapy on an individual patient basis.
- In patients with community-acquired and nosocomial sepsis and prior use of cephalosporins or quinolones within 30 days before presentation and/or colonized with ESBL-producing micro-organisms, the antibacterial regimen should also be active against ESBL-producing micro-organisms. This can be achieved by the addition of an aminoglycoside to the regimen or by the use of a carbapenem.
The background of these recommendations is the assumption that inadequate empirical coverage will result in a delay of start of effective therapy, and a resulting excess mortality. For patients with bacteremia caused by ESBL-producing Enterobacteriaceae this assumption proved to be correct (12). However, in this meta-analysis the increased relative risk for mortality was not corrected for confounding. In general, mortality is low in patients with UTI, and for UTI patients no excess mortality could be demonstrated for ESBL compared to non-ESBL producing strains (13), (14). In a Dutch study on antibiotic treatment and outcome in patients with ESBL-producing Enterobacteriaceae bacteremia, urosepsis and intra-abdominal infections were major sources of bacteremia. After correcting for confounding, adequacy of antibiotic treatment within 24 hours was not associated with increased 30-day mortality (WC Rottier et al.. Submitted).
For these reasons, the Guideline committee recommends to cover ESBL in the initial treatment only in patients who are colonized with ESBL-producing micro-organisms. In that case, the resistance pattern of the ESBL strain should guide empirical therapy.
Autorisatiedatum en geldigheid
Laatst beoordeeld : 01-03-2013
Laatst geautoriseerd : 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.
Initiatief en autorisatie
Development of this guideline was supported and financed by the SKMS (Kwaliteitsgelden Medisch Specialisten).
Doel en doelgroep
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.
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.
This guideline does not include an implementation strategy.
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.
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