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Update in Adult Urinary Tract Infection

Abstract

Urinary tract infection remains a common problem for many populations. Recent studies have expanded our understanding of the host innate immune response and its role in the familial association observed for recurrent uncomplicated urinary tract infection in healthy women. Therapeutic management for uncomplicated infection has been compromised by increasing antimicrobial resistance, particularly global dissemination of the CTXM-15 extended spectrum β-lactamase (ESBL) producing Escherichia coli ST-131 strain. Prevention strategies exploring non-antimicrobial approaches continue to show limited promise, and approaches to limit empiric antimicrobials are now being explored. For complicated urinary tract infection, increasing antimicrobial resistance limits therapeutic options for many patients. In addition to ESBL producing E. coli, NDM-1 E. coli and Klebsiella pneumoniae and other resistant Gram negatives, such as Acinetobacter species, are being isolated more frequently. There has been renewed interest in catheter-acquired urinary tract infection, the most common health–care associated infection, with several recent evidence-based guidelines for infection prevention available. However, technologic progress in development of adherence-resistant catheter materials remains disappointing.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Scholes D, Hawn TR, Roberts PL, et al.: Family history and risk of recurrent cystitis and pyelonephritis in women. J Urol. 2010;184:564–9. This large case control study confirms the previously described familial propensity of acute uncomplicated urinary infection in healthy women.

    PubMed  Article  Google Scholar 

  2. • Hawn TR, Scholes D, Wang H, et al.: Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women. PLoS One 2009;4(12):e8300. A comprehensive analysis identifying genetic polymorphisms of TLR’s potentially associated with asymptomatic bacteriuria.

    PubMed  Article  Google Scholar 

  3. • Nielubowicz GR, Mobley HLT: Host-pathogen interactions in urinary tract infection. Natur Rev/Urol. 2010;7:430–41. This review summarizes the current understanding of interactions of E. coli and Proteus mirabilis virulence and host response relevant to urinary infection.

    CAS  Google Scholar 

  4. Lundstedt AC, Leijonhufvud I, Ragnarsdothr B, et al. Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection. J Infect Dis. 2007;195:1227–34.

    PubMed  Article  Google Scholar 

  5. •• Hawn TR, Scholes D, Li SS, et al.: Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women. PLos One 2009;4(6):e5990. A comprehensive study of a large number of healthy young women which identifies TLR polymorphisms associated with recurrent cystitis or pyelonephritis. The genetic variation may explain some part of the familial propensity to infection.

    PubMed  Article  Google Scholar 

  6. • Ali ASM, Townes CL, Hall J, et al.: Maintaining a sterile urinary tract: the role of antimicrobial peptides. J Urol. 2009;182:21–8. A review of current information describing the occurrence and variation of antimicrobial peptides in the normal and infected urinary tract.

    PubMed  Article  CAS  Google Scholar 

  7. Nygaard I, Barber MD, Murgio KL, et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008;300:1311–6.

    PubMed  Article  CAS  Google Scholar 

  8. • Minardi D, D’Anzeo G, Parri G, et al.: The role of uroflowmetry biofeedback and biofeedback training of the pelvic floor muscles in the treatment of recurrent urinary tract infections in women with dysfunctional voiding: a randomized, controlled prospective study. Urology 2010;75:1299–304. Three interventions to manage dysfunctional voiding were equally effective to improve symptoms, urodynamic parameters, and decrease urinary tract infection. However, improvements were not sustained at 2 years.

    PubMed  Article  Google Scholar 

  9. • Croxen MA, Finlay BB: Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev /Microbiol. 2010;8:26–38. An extensive review of mechanisms of E. coli pathogenicity.

    CAS  Google Scholar 

  10. Mysorekar IU, Hultgren SJ. Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proc Natl Acad Sci USA. 2006;103:14170–5.

    PubMed  Article  CAS  Google Scholar 

  11. Rosen DA, Hooton TM, Stamm WE, et al. Detection of intracellular bacterial communities in human urinary tract infection. PLoS One. 2007;4(12):e329.

    Google Scholar 

  12. • Czaja CA, Stamm WE, Stapleton AE, et al.: Prospective cohort study of microbial and inflammatory events immediately preceeding Escherichia coli recurrent urinary tract infection in women. J Infect Dis. 2009;200:528–36. Daily monitoring of urine and periurethral cultures in women until a second episode of cystitis was diagnosed showed that the infecting E. coli isolate was present in periurethral cultures 24 hours or more prior to symptom onset, consistent with reinfection from an external gut or vaginal reservoir.

    PubMed  Article  CAS  Google Scholar 

  13. • Claessens YE, Schmidt J, Batard E, et al.: Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic peptide measurements guide choice of in-patient or out-patient care in acute pyelonephritis? Biomarkers in Sepsis multicenter study. Clin Microbiol Infect. 2010;16:753–60. These biomarkers for sepsis were not useful to discriminate between patients with acute pyelonephritis who required hospitalization and those who could be adequately managed with outpatient oral therapy.

    PubMed  Article  CAS  Google Scholar 

  14. Lemiale V, Renaud B, Moutereau S, et al. A single procalcitonin level does not predict adverse outcomes of women with pyelonephritis. Eur Urol. 2007;51:1394–401.

    PubMed  Article  CAS  Google Scholar 

  15. • Yang WJ, Cho IR, Seong DH, et al.: Clinical implication of serum C-reactive protein in patients with uncomplicated acute pyelonephritis as marker of prolonged hospitalization and recurrence. Urology 2009;73:19–22. The C-reactive protein level on admission did not predict outcome of infection. However, CRP level at discharge correlated with subsequent recurrence of acute pyelonephritis.

    PubMed  Article  Google Scholar 

  16. Cagnacci S, Gualco L, Debbia E, et al. European emergence of ciprofloxacin resistant Escherichia coli clonal groups 025:H4-ST131 and 015:K52:H1 causing community-acquired uncomplicated cystitis. J Clin Microbiol. 2008;46:2605–12.

    PubMed  Article  CAS  Google Scholar 

  17. • Johnson JR, Menard M, Johnston B, et al.: Epidemic clonal groups of Escherichia coli as a cause of antimicrobial-resistant urinary tract infections in Canada, 2002 to 2004. Antimicrob Agents Chemother. 2009;53:2733–9. From 2002–2004, three uropathogenic clones contributed 37.2% of 199 E. coli urinary strains from ambulatory patients. All isolates from these clones had TMP/SMX resistance, fluoroquinolone resistance, or both, and no isolates susceptible to both TMP/SMX and fluoroquinolone were from these three clonal groups.

    PubMed  Article  CAS  Google Scholar 

  18. Rodríguez-Baño J, Alcalá JC, Cisneros JM, et al. Multivariate analysis of risk factors for community-acquired infection due to ESBL-producing Escherichia coli. Arch Intern Med. 2008;168:1897–902.

    PubMed  Article  Google Scholar 

  19. Laupland KB, Church DL, Vidakovitch J, et al. Community-onset extended-spectrum β lactamase (ESBL) producing E. coli: importance of international travel. J Infect. 2008;57:441–8.

    PubMed  Article  Google Scholar 

  20. Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6(11):e280.

    PubMed  Article  Google Scholar 

  21. •• Gupta K, Hooton TM, Naber KG, 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 Clinical Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52:561–4. This international guideline provides recommendations for the empiric treatment of acute uncomplicated cystitis and pyelonephritis in the context of the increasing antimicrobial resistance observed in community acquired E. coli strains.

    Article  Google Scholar 

  22. • Schito GC, Naber KG, Botto H, et al.: The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections. Int J Antimicrob Agents 2009;34:407–13. In vitro susceptibility of urine bacterial isolates from acute uncomplicated urinary tract infection collected from 70 European and Brazilian centers over three years. The lowest rates of resistance were for fosfomycin, nitrofurantoin, and pivmecillinam.

    PubMed  Article  CAS  Google Scholar 

  23. •• Little P, Moore MV, Turner S, et al.: Effectiveness of five different approaches in management of urinary tract infection: randomized controlled trial. BMJ 2010;340:c199. Five strategies for management of women presenting with acute cystitis were equally effective for symptom resolution, but there were significant differences in laboratory testing and antimicrobial exposure with the different approaches.

    PubMed  Article  CAS  Google Scholar 

  24. Turner D, Little P, Raferty J, et al. Cost effectiveness of management strategies for urinary tract infections: results from randomized controlled trial. BMJ. 2010;340:c346.

    PubMed  Article  Google Scholar 

  25. Leydon GM, Turner S, Smith H, Little P. Women’s views about management and cause of urinary tract infection: qualitative interview study. BMJ. 2010;340:c279.

    PubMed  Article  CAS  Google Scholar 

  26. •• Bleidorn J, Gagyor I, Kochen MM, et al.: Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection? Results of a randomized controlled pilot trial. BMC Med. 2010;8:30 http://www.biomedcentral.com/1741-7015/8/30. This pilot study reported that treatment with an anti-inflammatory alone (ibuprofen) for acute cystitis was equivalent for symptom resolution to treatment with empiric ciprofloxacin for three days. This strategy could potentially limit empiric antimicrobial use for cystitis.

    PubMed  Article  Google Scholar 

  27. • Barbosa-Cesnik C, Brown MB, Buxton M, et al.: Cranberry juice fails to prevent recurrent urinary tract infection: Results from a randomized placebo-controlled trial. Clin Infect Dis. 2011;52:23–30. There were no benefits with daily cranberry juice compared to placebo juice for prevention of recurrent cystitis in young women.

    PubMed  Article  Google Scholar 

  28. • Sivick KE, Mobley HLT: Waging war against uropathogenic Escherichia coli: winning back the urinary tract. Infect Immun. 2010;78:568–85. This review considers uropathogenic E. coli and host response in urinary tract infection from the perspective of vaccine development.

    PubMed  Article  CAS  Google Scholar 

  29. • Naber KG, Cho Y-H, Matsumoto T, Schaeffer AJ: Immunoactive prophylaxis of recurrent urinary tract infections: a meta-analysis. Int J Antimicrob Agents 2009;33:111–9. A review of the use of bacterial lysates as immune stimulants for the prevention of recurrent urinary tract infection. Two of the products described had modest efficacy for infection prevention in the short term when given as a prime plus booster regimen.

    PubMed  Article  CAS  Google Scholar 

  30. • van Nieuwkoop C, van’t Wout JW, Spelt IC, et al.: Prospective cohort study of acute pyelonephritis in adults: safety of triage towards home based oral antimicrobial treatment. J Infect. 2010;6(2):114–21. This large prospective cohort of adults with febrile pyelonephritis presenting to primary care practices or emergency rooms in the Netherlands assessed the validity of Netherlands guidelines for treatment of patients with oral therapy or hospital referral. Outpatient oral antimicrobial therapy used as recommended was safe and effective for management.

    Article  Google Scholar 

  31. van Nieuwkoop C, Hoppe BP, Bonten TN, et al. Predicting the need for radiologic imaging in adults with febrile urinary tract infection. Clin Infect Dis. 2010;51(11):1266–72.

    PubMed  Article  Google Scholar 

  32. van Nieuwkoop C, Bonten TN, Van’t Wout JW, et al. Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observation study. Crit Care. 2010;14(6):R206.

    PubMed  Article  Google Scholar 

  33. van Nieuwkoop C, Bonten TN, Wout JW, et al. Risk factors for bacteremia with uropathogen not cultured from urine in adults with febrile urinary tract infection. Clin Infect Dis. 2010;50(11):e69–72.

    PubMed  Article  Google Scholar 

  34. van der Starre WE, van Nieuwkoop C, Paltansing S, et al.: Risk factors for fluoroquinolone-resistant Escherichia coli in adults with community-onset febrile urinary tract infection. J Antimicrob Chemother. 2010 Dec 1.

  35. van Nieuwkoop C, der Zalm PJ Voorham-van, van Laar AM, et al. Pelvic floor dysfunction is not a risk factor for febrile urinary tract infection in adults. BJU Int. 2010;105(12):1689–95.

    PubMed  Article  Google Scholar 

  36. • Popovic M, Steinort D, Pillai S, Joukhadar C: Fosfomycin: an old, new friend? Eur J Clin Microbiol Infect Dis. 2010;29:127–42. A review of development, history, mechanisms of action, characteristics, in vitro susceptibility, pharmacokinetics and clinical uses of fosfomycin.

    PubMed  Article  CAS  Google Scholar 

  37. • Auer S, Wojna A, Hell M: Oral treatment options for ambulatory patients with urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli. Antimicrob Agents Chemother. 2010;54:4006–8. For 100 ESBL producing E. coli isolates from ambulatory patients, the in vitro susceptibility was greatest for fosfomycin, nitrofurantoin and pivmecillinam.

    PubMed  Article  CAS  Google Scholar 

  38. •• Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE: Fosfomycin for the treatment of multi-drug resistant, including extended-spectrum β-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect. 2010;10:43–50. A systematic review of the in vitro susceptibility and clinical use of fosfomycin trometomol for treatment of resistant organisms isolated from complicated and uncomplicated urinary infection.

    Article  CAS  Google Scholar 

  39. • Oteo J, Orden B, Bautista V, et al.: CTX-M-15 producing urinary Escherichia coli 025b-ST131-phylogroup B2 has acquired resistance to fosfomycin. J Antimicrob Chemother. 2009;64:712–7. In a Madrid outbreak of ESBL E. coli infections, resistance to fosfomycin emerged in the outbreak clone and correlated with the extent of fosfomycin use.

    PubMed  Article  CAS  Google Scholar 

  40. • Naber KG, Llorens L, Kaniga K, et al.: Intravenous doripenem at 500 milligrams versus levofloxacin at 250 mg with an option to switch to oral therapy for treatment of complicated lower urinary tract infection and pyelonephritis. Antimicrob Agents Chemother. 2009;53:3782–92. Doripenem is as effective as low dose levofloxacin for the treatment of complicated urinary tract infection and pyelonephritis.

    PubMed  Article  CAS  Google Scholar 

  41. • Kaniga K, Flamm R, Tong SY, et al.: Worldwide experience with the use of doripenem against extended-spectrum-beta-lactamase-producing and ciprofloxacin-resistant Enterobacteriacea: analysis of six phase 3 clinical studies. Antimicrob Agents Chemother. 2010;54:2119–24. Doripenem cured only 60% of a small number of patients with complicated urinary tract infection from which ESBL or fluoroquine resistant organisms were isolated.

    PubMed  Article  CAS  Google Scholar 

  42. • Geerlings SE, van Donselaar-vander Pant KA, Keur I: Successful treatment with tigecycline of two patients with complicated urinary tract infections caused by extended spectrum beta-lactamase producing Escherichia coli. J Antimicrob Chemother. 2010;65:2048–9. Case reports of two patients with ESBL producing E. coli in an infected renal cyst and prostatitis successfully treated with tigecycline.

    PubMed  Article  CAS  Google Scholar 

  43. • Pappas PG, Kauffman CA, Andes D, et al.: Clinical Practice Guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:503–35. These updated guidelines recommend fluconazole as first line treatment for candida urinary tract infection.

    PubMed  Article  CAS  Google Scholar 

  44. Lo E, Nicolle LE, Classen D, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29:S41–50.

    PubMed  Article  Google Scholar 

  45. •• Hooton TM, Bradley SE, Cardenas DD, et al.: Diagnosis, prevention and treatment of catheter-associated urinary tract infection in adults: 2009. International practice guidelines form the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:625–63. A comprehensive review of management of catheter associated urinary tract infection in adults, with evidence based recommendations for prevention and therapy.

    PubMed  Article  Google Scholar 

  46. •• Gould CV, Umscheid CA, Agarwal RK, et al.: Guideline for prevention of catheter-associated urinary tract infections 2009. Available at http://www.cdc.gov/hicpac/. CDC guidelines for the prevention of catheter associated urinary tract infections, including the revised National Healthcare Safety Network definitions.

  47. • Meddings J, Rogers MAM, Macy M, Saint S: Systematic review and meta-analysis: Reminder systems to reduce catheter-associated urinary tract infections and urinary catheter use in hospitalized patients. Clin Infect Dis. 2010;51:550–60. Use of reminder systems in hospitalized patients decreased catheter use and catheter-acquired bacteriuria.

    PubMed  Article  Google Scholar 

  48. • Johnson JR, Johnston BD, Kuskowski MA, et al.: In vitro activity of available antimicrobial coated Foley catheters against Escherichia coli including strains resistant to extended spectrum cephalosporins. J Urol. 2010;184:2572–7. In an in vitro study, silver alloy antimicrobial coated foley catheters were no more effective in preventing adherence of resistant or susceptible E. coli than non-coated catheters. Nitrofurazone coated catheters impaired adherence of E. coli for only 5 days.

    PubMed  Article  CAS  Google Scholar 

  49. • Desai GD, Liao KS, Cervallos ME, et al.: Silver or nitrofurantoin impregnation of urinary catheters has a minimal effect on uropathogen adherence. J Urol. 2010;184:2565–71. In an in vitro study, silver impregnation had little effect on bacterial adherence to catheters, and nitrofurazone inhibited adherence of E. coli for only five days.

    PubMed  Article  CAS  Google Scholar 

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Nicolle, L.E. Update in Adult Urinary Tract Infection. Curr Infect Dis Rep 13, 552 (2011). https://doi.org/10.1007/s11908-011-0212-x

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Keywords

  • Urinary tract infection
  • Uncomplicated
  • Complicated
  • Antimicrobial resistance
  • Antimicrobial therapy
  • Pyelonephritis
  • Catheter-acquired