Multidrug-resistant Gram-negative pathogens are rapidly emerging and spreading globally
These multidrug-resistant pathogens are frequently associated with major pathologies, including urinary tract infections
Routine urological practices are affected by multidrug-resistant pathogens
Knowledge of the local epidemiology of multidrug-resistant Gram-negative bacteria is essential for determining empirical antimicrobial therapy
Antibiotic resistance in Gram-negative uropathogens is a major global concern. Worldwide, the prevalence of Enterobacteriaceae that produce extended-spectrum β-lactamase or carbapenemase enzymes continues to increase at alarming rates. Likewise, resistance to other antimicrobial agents including aminoglycosides, sulphonamides and fluoroquinolones is also escalating rapidly. Bacterial resistance has major implications for urological practice, particularly in relation to catheter-associated urinary tract infections (UTIs) and infectious complications following transrectal-ultrasonography-guided biopsy of the prostate or urological surgery. Although some new drugs with activity against Gram-negative bacteria with highly resistant phenotypes will become available in the near future, the existence of a single agent with activity against the great diversity of resistance is unlikely. Responding to the challenges of Gram-negative resistance will require a multifaceted approach including considered use of current antimicrobial agents, improved diagnostics (including the rapid detection of resistance) and surveillance, better adherence to basic measures of infection prevention, development of new antibiotics and research into non-antibiotic treatment and preventive strategies.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
The Use and Effectiveness of Ceftazidime–Avibactam in Real-World Clinical Practice: EZTEAM Study
Infectious Diseases and Therapy Open Access 10 February 2023
Bacterial infections epidemiology and factors associated with multidrug resistance in the northern region of Ghana
Scientific Reports Open Access 21 December 2022
UTI assessment tool for intermittent catheter users: a way to include user perspectives and enhance quality of UTI management
BMC Nursing Open Access 06 October 2022
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Lloyd, W. F. Two lectures on the checks to population (Oxford University Press, 1833).
Hardin, G. The tragedy of the commons. The population problem has no technical solution; it requires a fundamental extension in morality. Science 162, 1243–1248 (1968).
Bhullar, K. et al. Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS ONE 7, e34953 (2012).
Ronald, A. R. et al. Urinary tract infection in adults: research priorities and strategies. Int. J. Antimicrob. Agents 17, 343–348 (2001).
Totsika, M. et al. Uropathogenic Escherichia coli mediated urinary tract infection. Curr. Drug Targets 13, 1386–1399 (2012).
Stamm, W. E. & Norrby, S. R. Urinary tract infections: disease panorama and challenges. J. Infect. Dis. 183 (Suppl. 1), S1–S4 (2001).
Barber, A. E., Norton, J. P., Spivak, A. M. & Mulvey, M. A. Urinary tract infections: current and emerging management strategies. Clin. Infect. Dis. 57, 719–724 (2013).
Foxman, B. The epidemiology of urinary tract infection. Nat. Rev. Urol. 7, 653–660 (2010).
Flores-Mireles, A. L., Walker, J. N., Caparon, M. & Hultgren, S. J. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat. Rev. Microbiol. 13, 269–284 (2015).
Foxman, B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am. J. Med. 113 (Suppl. 1A), 5s–13s (2002).
Zalmanovici Trestioreanu, A., Green, H., Paul, M., Yaphe, J. & Leibovici, L. Antimicrobial agents for treating uncomplicated urinary tract infection in women. Cochrane Database of Systemetic Reviews, Issue 10. Art. No.: CD007182. http://dx.doi.org/10.1002/14651858.CD007182.pub2.
Costelloe, C., Metcalfe, C., Lovering, A., Mant, D. & Hay, A. D. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 340, c2096 (2010).
Paterson, D. L. & Bonomo, R. A. Extended-spectrum beta-lactamases: a clinical update. Clin. Microbiol. Rev. 18, 657–686 (2005).
Doi, Y. et al. Community-associated extended-spectrum beta-lactamase-producing Escherichia coli infection in the United States. Clin. Infect. Dis. 56, 641–648 (2013).
Van Boeckel, T. P. et al. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect. Dis. 14, 742–750 (2014).
World Health Organization. Antimicrobial resistance global report on surveillance 2014. World Health Organization [online], (2014).
Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention [online], (2013).
Rogers, B. A. et al. Community-onset Escherichia coli infection resistant to expanded-spectrum cephalosporins in low-prevalence countries. Antimicrob. Agents Chemother. 58, 2126–2134 (2014).
Munoz-Price, L. S. et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect. Dis. 13, 785–796 (2013).
Wailan, A. M. & Paterson, D. L. The spread and acquisition of NDM-1: a multifactorial problem. Expert Rev. Anti. Infect. Ther. 12, 91–115 (2014).
Poirel, L., Potron, A. & Nordmann, P. OXA-48-like carbapenemases: the phantom menace. J. Antimicrob. Chemother. 67, 1597–1606 (2012).
Peleg, A. Y. & Hooper, D. C. Hospital-acquired infections due to gram-negative bacteria. N. Engl. J. Med. 362, 1804–1813 (2010).
Blair, J. M., Webber, M. A., Baylay, A. J., Ogbolu, D. O. & Piddock, L. J. Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol. 13, 42–51 (2015).
Magiorakos, A. P. et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 18, 268–281 (2012).
Ramirez, M. S. & Tolmasky, M. E. Aminoglycoside modifying enzymes. Drug Resist. Updat. 13, 151–171 (2010).
Aldred, K. J., Kerns, R. J. & Osheroff, N. Mechanism of quinolone action and resistance. Biochemistry 53, 1565–1574 (2014).
Huovinen, P. Resistance to trimethoprim-sulfamethoxazole. Clin. Infect. Dis. 32, 1608–1614 (2001).
Li, X. Z., Plesiat, P. & Nikaido, H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin. Microbiol. Rev. 28, 337–418 (2015).
Fernandez, L. & Hancock, R. E. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin. Microbiol. Rev. 25, 661–681 (2012).
Hackel, M., Badal, R., Lob, D. & Hoban, D. J. Susceptibility and Multidrug Resistance among E. coli from Urinary Tract Infections in Asia/Pacific—SMART 2012–2013 Abstract from the 15th Asia-Pacific Congress for Clinical Microbiology and Infection (APCCMI), Kuala Lumpur, 28th November 2014.
Turnidge, J. D. et al. Community-onset Gram-negative Surveillance Program annual report, 2012. Commun. Dis. Intell. Q. Rep. 38, E54–E58 (2014).
European Centre for Disease Prevention and Control. Antimicrobial resistance interactive database (EARS-Net). European Centre for Disease Prevention and Control [online], (2013).
Hoban, D. J. et al. Antimicrobial susceptibility of Enterobacteriaceae, including molecular characterization of extended-spectrum beta-lactamase-producing species, in urinary tract isolates from hospitalized patients in North America and Europe: results from the SMART study 2009–2010. Diagn. Microbiol. Infect. Dis. 74, 62–67 (2012).
Petty, N. K. et al. Global dissemination of a multidrug resistant Escherichia coli clone. Proc. Natl Acad. Sci. USA 111, 5694–5699 (2014).
Nordmann, P., Naas, T. & Poirel, L. Global spread of Carbapenemase-producing Enterobacteriaceae. Emerg. Infect. Dis. 17, 1791–1798 (2011).
Tsutsui, A. et al. Genotypes and infection sites in an outbreak of multidrug-resistant Pseudomonas aeruginosa. J. Hosp. Infect. 78, 317–322 (2011).
Zowawi, H. M., Balkhy, H. H., Walsh, T. R. & Paterson, D. L. beta-Lactamase production in key gram-negative pathogen isolates from the Arabian Peninsula. Clin. Microbiol. Rev. 26, 361–380 (2013).
Dortet, L., Poirel, L. & Nordmann, P. Worldwide dissemination of the NDM-type carbapenemases in Gram-negative bacteria. Biomed. Res. Int. 2014, 249856 (2014).
Evans, B. A. & Amyes, S. G. OXA beta-lactamases. Clin. Microbiol. Rev. 27, 241–263 (2014).
Hannan, T. J. et al. Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection. FEMS Microbiol. Rev. 36, 616–648 (2012).
Nielubowicz, G. R. & Mobley, H. L. Host–pathogen interactions in urinary tract infection. Nat. Rev. Urol. 7, 430–441 (2010).
Waksman, G. & Hultgren, S. J. Structural biology of the chaperone-usher pathway of pilus biogenesis. Nat. Rev. Microbiol. 7, 765–774 (2009).
Wright, K. J. & Hultgren, S. J. Sticky fibers and uropathogenesis: bacterial adhesins in the urinary tract. Future Microbiol. 1, 75–87 (2006).
Wurpel, D. J., Beatson, S. A., Totsika, M., Petty, N. K. & Schembri, M. A. Chaperone-usher fimbriae of Escherichia coli. PLoS ONE 8, e52835 (2013).
Connell, I. et al. Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract. Proc. Natl Acad. Sci. USA 93, 9827–9832 (1996).
Mulvey, M. A. et al. Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282, 1494–1497 (1998).
Armbruster, C. E. & Mobley, H. L. Merging mythology and morphology: the multifaceted lifestyle of Proteus mirabilis. Nat. Rev. Microbiol. 10, 743–754 (2012).
Anderson, G. G. et al. Intracellular bacterial biofilm-like pods in urinary tract infections. Science 301, 105–107 (2003).
World Health Organization. Prevention of hospital-acquired infections: a practical guide. 2nd edition. World Health Organization [online], (2002).
Klevens, R. M. et al. Estimating health care-associated infections and deaths in U. S. hospitals, 2002. Public Health Rep. 122, 160–166 (2007).
Smith, P. W. et al. SHEA/APIC guideline: infection prevention and control in the long-term care facility, July 2008. Infect. Control Hosp. Epidemiol. 29, 785–814 (2008).
Tambyah, P. A., Knasinski, V. & Maki, D. G. The direct costs of nosocomial catheter-associated urinary tract infection in the era of managed care. Infect. Control Hosp. Epidemiol. 23, 27–31 (2002).
Kunin, C. M., Chin, Q. F. & Chambers, S. Morbidity and mortality associated with indwelling urinary catheters in elderly patients in a nursing home—confounding due to the presence of associated diseases. J. Am. Geriatr. Soc. 35, 1001–1006 (1987).
Rodriguez-Bano, J. et al. Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Arch. Intern. Med. 168, 1897–1902 (2008).
Ho, P. L., Chan, W. M., Tsang, K. W., Wong, S. S. & Young, K. Bacteremia caused by Escherichia coli producing extended-spectrum beta-lactamase: a case-control study of risk factors and outcomes. Scand. J. Infect. Dis. 34, 567–573 (2002).
Shilo, S. et al. Risk factors for bacteriuria with carbapenem-resistant Klebsiella pneumoniae and its impact on mortality: a case-control study. Infection 41, 503–509 (2013).
Wagenlehner, F. M., Niemetz, A., Dalhoff, A. & Naber, K. G. Spectrum and antibiotic resistance of uropathogens from hospitalized patients with urinary tract infections: 1994–2000. Int. J. Antimicrob. Agents 19, 557–564 (2002).
Maki, D. G. & Tambyah, P. A. Engineering out the risk for infection with urinary catheters. Emerg. Infect. Dis. 7, 342–347 (2001).
Kass, E. H. & Schneiderman, L. J. Entry of bacteria into the urinary tracts of patients with inlying catheters. N. Engl. J. Med. 256, 556–557 (1957).
Platt, R., Polk, B. F., Murdock, B. & Rosner, B. Reduction of mortality associated with nosocomial urinary tract infection. Lancet 1, 893–897 (1983).
Tambyah, P. A., Halvorson, K. T. & Maki, D. G. A prospective study of pathogenesis of catheter-associated urinary tract infections. Mayo Clin. Proc. 74, 131–136 (1999).
Djeribi, R., Bouchloukh, W., Jouenne, T. & Menaa, B. Characterization of bacterial biofilms formed on urinary catheters. Am. J. Infect. Control 40, 854–859 (2012).
Chartier-Kastler, E. & Denys, P. Intermittent catheterization with hydrophilic catheters as a treatment of chronic neurogenic urinary retention. Neurourol. Urodyn. 30, 21–31 (2011).
Beattie, M. & Taylor, J. Silver alloy vs. uncoated urinary catheters: a systematic review of the literature. J. Clin. Nurs. 20, 2098–2108 (2011).
Desai, D. G., Liao, K. S., Cevallos, M. E. & Trautner, B. W. Silver or nitrofurazone impregnation of urinary catheters has a minimal effect on uropathogen adherence. J. Urol. 184, 2565–2571 (2010).
Pickard, R. et al. Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial. Lancet 380, 1927–1935 (2012).
Lo, E. et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals: 2014 update. Infect. Control Hosp. Epidemiol. 35, 464–479 (2014).
Tenke, P. et al. European and Asian guidelines on management and prevention of catheter-associated urinary tract infections. Int. J. Antimicrob. Agents 31 (Suppl. 1), S68–S78 (2008).
Gould, C. V., Umscheid, C. A., Agarwal, R. K., Kuntz, G. & Pegues, D. A. Guideline for prevention of catheter-associated urinary tract infections 2009. Infect. Control Hosp. Epidemiol. 31, 319–326 (2010).
Morton, S. C. et al. Antimicrobial prophylaxis for urinary tract infection in persons with spinal cord dysfunction. Arch. Phys. Med. Rehabil. 83, 129–138 (2002).
Apisarnthanarak, A. et al. Effectiveness of multifaceted hospitalwide quality improvement programs featuring an intervention to remove unnecessary urinary catheters at a tertiary care center in Thailand. Infect. Control Hosp. Epidemiol. 28, 791–798 (2007).
Fakih, M. G. et al. Effect of nurse-led multidisciplinary rounds on reducing the unnecessary use of urinary catheterization in hospitalized patients. Infect. Control Hosp. Epidemiol. 29, 815–819 (2008).
Williamson, D. A. et al. Infectious complications following transrectal ultrasound-guided prostate biopsy: new challenges in the era of multidrug-resistant Escherichia coli. Clin. Infect. Dis. 57, 267–274 (2013).
Loeb, S. et al. Systematic review of complications of prostate biopsy. Eur. Urol. 64, 876–892 (2013).
Grabe, M. et al. Guidelines on urological infections. European Association of Urology [online], (2015).
Roberts, M. J. et al. Multifocal abscesses due to multiresistant Escherichia coli after transrectal ultrasound-guided prostate biopsy. Med. J. Aust. 198, 282–284 (2013).
Wagenlehner, F. M., Pilatz, A., Waliszewski, P., Weidner, W. & Johansen, T. E. Reducing infection rates after prostate biopsy. Nat. Rev. Urol. 11, 80–86 (2014).
Williamson, D. A. et al. Clinical and molecular correlates of virulence in Escherichia coli causing bloodstream infection following transrectal ultrasound-guided (TRUS) prostate biopsy. J. Antimicrob. Chemother. 68, 2898–2906 (2013).
Carignan, A. et al. Increasing risk of infectious complications after transrectal ultrasound-guided prostate biopsies: time to reassess antimicrobial prophylaxis? Eur. Urol. 62, 453–459 (2012).
Lundstrom, K. J. et al. Nationwide population based study of infections after transrectal ultrasound guided prostate biopsy. J. Urol. 192, 1116–1122 (2014).
Wagenlehner, F. M. E. et al. Infective complications after prostate biopsy: outcome of the global prevalence study of infections in urology (GPIU) 2010 and 2011, a prospective multinational multicentre prostate biopsy study. Eur. Urol. 63, 521–527 (2013).
Womble, P. R. et al. Infection related hospitalizations after prostate biopsy in a statewide quality improvement collaborative. J. Urol. 191, 1787–1792 (2014).
Williamson, D. A., Masters, J., Freeman, J. & Roberts, S. Travel-associated extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection following transrectal ultrasound-guided prostate biopsy. BJU Int. 109, E21–E22 (2012).
Williamson, D. A. et al. Escherichia coli bloodstream infection after transrectal ultrasound-guided prostate biopsy: implications of fluoroquinolone-resistant sequence type 131 as a major causative pathogen. Clin. Infect. Dis. 54, 1406–1412 (2012).
Roberts, M. J. et al. Baseline prevalence of antimicrobial resistance and subsequent infection following prostate biopsy using empirical or altered prophylaxis: a bias-adjusted meta-analysis. Int. J. Antimicrob. Agents 43, 301–309 (2014).
Djavan, B., Remzi, M., Schulman, C. C., Marberger, M. & Zlotta, A. R. Repeat prostate biopsy: who, how and when?: a review. Eur. Urol. 42, 93–103 (2002).
Klotz, L. et al. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J. Clin. Oncol. 28, 126–131 (2010).
Bangma, C. H., Bul, M. & Roobol, M. The Prostate cancer Research International: Active Surveillance study. Curr. Opin. Urol. 22, 216–221 (2012).
Ehdaie, B. et al. The impact of repeat biopsies on infectious complications in men with prostate cancer on active surveillance. J. Urol. 191, 660–664 (2014).
Adibi, M., Pearle, M. S. & Lotan, Y. Cost-effectiveness of standard vs intensive antibiotic regimens for transrectal ultrasonography (TRUS)-guided prostate biopsy prophylaxis. BJU Int. 110, E86–E91 (2012).
Batura, D. & Gopal Rao, G. The national burden of infections after prostate biopsy in England and Wales: a wake-up call for better prevention. J. Antimicrob. Chemother. 68, 247–249 (2013).
Nam, R. K. et al. Increasing hospital admission rates for urological complications after transrectal ultrasound guided prostate biopsy. J. Urol. 183, 963–968 (2010).
Gopal Rao, G. & Batura, D. Emergency hospital admissions attributable to infective complications of prostate biopsy despite appropriate prophylaxis: need for additional infection prevention strategies? Int. Urol. Nephrol. 46, 309–315 (2014).
Zani, E. L., Clark, O. A. & Rodrigues Netto, N. Jr. Antibiotic prophylaxis for transrectal prostate biopsy. Cochrane Database of Systematic Reviews, Issue 5. Art. No.: CD006576. http://dx.doi.org/10.1002/14651858.CD006576.pub2.
El-Hakim, A. & Moussa, S. CUA guidelines on prostate biopsy methodology. Can. Urol. Assoc. J. 4, 89–94 (2010).
Davis, M., Sofer, M., Kim, S. S. & Soloway, M. S. The procedure of transrectal ultrasound guided biopsy of the prostate: a survey of patient preparation and biopsy technique. J. Urol. 167, 566–570 (2002).
Vance-Bryan, K., Guay, D. R. & Rotschafer, J. C. Clinical pharmacokinetics of ciprofloxacin. Clin. Pharmacokinet. 19, 434–461 (1990).
Goto, T. et al. Diffusion of piperacillin, cefotiam, minocycline, amikacin and ofloxacin into the prostate. Int. J. Urol. 5, 243–246 (1998).
Gonzalez, C. et al. AUA/SUNA White Paper on the Incidence, Prevention and Treatment of Complications Related to Prostate Needle Biopsy. American Urological Association [online], (2012).
Kehinde, E. O., Al-Maghrebi, M., Sheikh, M. & Anim, J. T. Combined ciprofloxacin and amikacin prophylaxis in the prevention of septicemia after transrectal ultrasound guided biopsy of the prostate. J. Urol. 189, 911–915 (2013).
Batura, D., Rao, G. G., Bo Nielsen, P. & Charlett, A. Adding amikacin to fluoroquinolone-based antimicrobial prophylaxis reduces prostate biopsy infection rates. BJU Int. 107, 760–764 (2011).
Rhodes, N. J. et al. Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis. J. Antimicrob. Chemother. 70, 2068–2073 (2015).
Gardiner, B. J. et al. Is fosfomycin a potential treatment alternative for multidrug-resistant gram-negative prostatitis? Clin. Infect. Dis. 58, e101–e105 (2014).
Yang, J. C., Tang, J., Li, Y., Fei, X. & Shi, H. Contrast-enhanced transrectal ultrasound for assessing vascularization of hypoechoic BPH nodules in the transition and peripheral zones: comparison with pathological examination. Ultrasound Med. Biol. 34, 1758–1764 (2008).
Ongun, S., Aslan, G. & Avkan-Oguz, V. The effectiveness of single-dose fosfomycin as antimicrobial prophylaxis for patients undergoing transrectal ultrasound-guided biopsy of the prostate. Urol. Int. 89, 439–444 (2012).
Lista, F. et al. Efficacy and safety of fosfomycin-trometamol in the prophylaxis for transrectal prostate biopsy. Prospective randomized comparison with ciprofloxacin. Actas Urol. Esp. 38, 391–316 (2014).
Dewar, S., Reed, L. C. & Koerner, R. J. Emerging clinical role of pivmecillinam in the treatment of urinary tract infection in the context of multidrug-resistant bacteria. J. Antimicrob. Chemother. 69, 303–308 (2014).
Losco, G., Studd, R. & Blackmore, T. Ertapenem prophylaxis reduces sepsis after transrectal biopsy of the prostate. BJU Int. 113 (Suppl. 2), 69–72 (2014).
Shakil, J. et al. Use of outpatient parenteral antimicrobial therapy for transrectal ultrasound-guided prostate biopsy prophylaxis in the setting of community-associated multidrug-resistant Escherichia coli rectal colonization. Urology 83, 710–713 (2014).
Armand-Lefevre, L. et al. Emergence of imipenem-resistant gram-negative bacilli in intestinal flora of intensive care patients. Antimicrob. Agents Chemother. 57, 1488–1495 (2013).
Liss, M. A. et al. Fluoroquinolone resistant rectal colonization predicts risk of infectious complications after transrectal prostate biopsy. J. Urol. 192, 1673–1678 (2014).
Liss, M., Nakamura, K. & Peterson, E. Targeted prophylaxis prior to transrectal prostate biopsy: a comparison of broth enrichment to direct plating for the evaluation of rectal cultures. J. Urol. 187, e439 (2012).
Taylor, A. K. et al. Targeted antimicrobial prophylaxis using rectal swab cultures in men undergoing transrectal ultrasound guided prostate biopsy is associated with reduced incidence of postoperative infectious complications and cost of care. J. Urol. 187, 1275–1279 (2012).
Duplessis, C. A. et al. Rectal cultures before transrectal ultrasound-guided prostate biopsy reduce post-prostatic biopsy infection rates. Urology 79, 556–561 (2012).
Suwantarat, N. et al. Modification of antimicrobial prophylaxis based on rectal culture results to prevent fluoroquinolone-resistant Escherichia coli infections after prostate biopsy. Infect. Control Hosp. Epidemiol. 34, 973–976 (2013).
Pu, C. et al. Reducing the risk of infection for transrectal prostate biopsy with povidone-iodine: a systematic review and meta-analysis. Int. Urol. Nephrol. 46, 1691–1698 (2014).
Issa, M. M. et al. Formalin disinfection of biopsy needle minimizes the risk of sepsis following prostate biopsy. J. Urol. 190, 1769–1775 (2013).
Shen, P. F. et al. The results of transperineal versus transrectal prostate biopsy: a systematic review and meta-analysis. Asian J. Androl. 14, 310–315 (2012).
Grummet, J. P. et al. Sepsis and 'superbugs': should we favour the transperineal over the transrectal approach for prostate biopsy? BJU Int. 114, 384–388 (2014).
Overduin, C. G., Futterer, J. J. & Barentsz, J. O. MRI-guided biopsy for prostate cancer detection: a systematic review of current clinical results. Curr. Urol. Rep. 14, 209–213 (2013).
Steensels, D. et al. Fluoroquinolone-resistant E. coli in intestinal flora of patients undergoing transrectal ultrasound-guided prostate biopsy—should we reassess our practices for antibiotic prophylaxis? Clin. Microbiol. Infect. 18, 575–581 (2012).
Patel, U. et al. Infection after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use. BJU Int. 109, 1781–1785 (2012).
Loeb, S., Carter, H. B., Berndt, S. I., Ricker, W. & Schaeffer, E. M. Complications after prostate biopsy: data from SEER-Medicare. J. Urol. 186, 1830–1834 (2011).
Bruyere, F. et al. Prosbiotate: a multicenter, prospective analysis of infectious complications after prostate biopsy. J. Urol. 193, 145–150 (2015).
Gupta, K. 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. 52, e103–e120 (2011).
Grigoryan, L., Trautner, B. W. & Gupta, K. Diagnosis and management of urinary tract infections in the outpatient setting: a review. JAMA 312, 1677–1684 (2014).
Lipsky, B. A. Prostatitis and urinary tract infection in men: what's new; what's true? Am. J. Med. 106, 327–334 (1999).
Dow, G. 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. 39, 658–664 (2004).
Drekonja, D. M., Rector, T. S., Cutting, A. & Johnson, J. R. Urinary tract infection in male veterans: treatment patterns and outcomes. JAMA Intern. Med. 173, 62–68 (2013).
Sandberg, T. 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 380, 484–490 (2012).
Eliakim-Raz, N., Yahav, D., Paul, M. & Leibovici, L. Duration of antibiotic treatment for acute pyelonephritis and septic urinary tract infection—7 days or less versus longer treatment: systematic review and meta-analysis of randomized controlled trials. J. Antimicrob. Chemother. 68, 2183–2191 (2013).
Bursle, E. C. et al. Risk factors for urinary catheter associated bloodstream infection. J. Infect. 70, 585–591 (2015).
Leis, J. A. et al. Reducing antimicrobial therapy for asymptomatic bacteriuria among noncatheterized inpatients: a proof-of-concept study. Clin. Infect. Dis. 58, 980–983 (2014).
Lee, C. S. & Doi, Y. Therapy of infections due to carbapenem-resistant Gram-negative pathogens. Infect. Chemother. 46, 149–164 (2014).
Prasad, P., Sun, J., Danner, R. L. & Natanson, C. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin. Infect. Dis. 54, 1699–1709 (2012).
Zhanel, G. G. et al. Ceftazidime-avibactam: a novel cephalosporin/beta-lactamase inhibitor combination. Drugs 73, 159–177 (2013).
Drawz, S. M., Papp-Wallace, K. M. & Bonomo, R. A. New beta-lactamase inhibitors: a therapeutic renaissance in an MDR world. Antimicrob. Agents Chemother. 58, 1835–1846 (2014).
Vazquez, J. A. et al. Efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study. Curr. Med. Res. Opin. 28, 1921–1931 (2012).
Sader, H. S., Farrell, D. J., Flamm, R. K. & Jones, R. N. Ceftolozane/tazobactam activity tested against aerobic Gram-negative organisms isolated from intra-abdominal and urinary tract infections in European and United States hospitals (2012). J. Infect. 69, 266–277 (2014).
Poulikakos, P. & Falagas, M. E. Aminoglycoside therapy in infectious diseases. Expert Opin. Pharmacother. 14, 1585–1597 (2013).
US National Library of Medicine. ClinicalTrials.gov [online], (2015).
US National Library of Medicine. ClinicalTrials.gov [online], (2014).
Papp-Wallace, K. M., Endimiani, A., Taracila, M. A. & Bonomo, R. A. Carbapenems: past, present, and future. Antimicrob. Agents Chemother. 55, 4943–4960 (2011).
Wang, X. et al. Biapenem versus meropenem in the treatment of bacterial infections: a multicenter, randomized, controlled clinical trial. Indian J. Med. Res. 138, 995–1002 (2013).
Livermore, D. M. & Tulkens, P. M. Temocillin revived. J. Antimicrob. Chemother. 63, 243–245 (2009).
Balakrishnan, I. et al. Temocillin use in England: clinical and microbiological efficacies in infections caused by extended-spectrum and/or derepressed AmpC beta-lactamase-producing Enterobacteriaceae. J. Antimicrob. Chemother. 66, 2628–2631 (2011).
Naber, K. G., Niggemann, H., Stein, G. & Stein, G. Review of the literature and individual patients' data meta-analysis on efficacy and tolerance of nitroxoline in the treatment of uncomplicated urinary tract infections. BMC Infect. Dis. 14, 628 (2014).
Fishman, N. et al. Policy Statement on Antimicrobial Stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infect. Control Hosp. Epidemiol. 33, 322–327 (2012).
Darouiche, R. O. & Hull, R. A. Bacterial interference for prevention of urinary tract infection. Clin. Infect. Dis. 55, 1400–1407 (2012).
Andersson, P. et al. Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence. Infect. Immun. 59, 2915–2921 (1991).
Roos, V., Ulett, G. C., Schembri, M. A. & Klemm, P. The asymptomatic bacteriuria Escherichia coli strain 83972 outcompetes uropathogenic E. coli strains in human urine. Infect. Immun. 74, 615–624 (2006).
Darouiche, R. O. et al. Multicenter randomized controlled trial of bacterial interference for prevention of urinary tract infection in patients with neurogenic bladder. Urology 78, 341–346 (2011).
Klemm, P., Hancock, V. & Schembri, M. A. Mellowing out: adaptation to commensalism by Escherichia coli asymptomatic bacteriuria strain 83972. Infect. Immun. 75, 3688–3695 (2007).
Sunden, F., Hakansson, L., Ljunggren, E. & Wullt, B. Bacterial interference—is deliberate colonization with Escherichia coli 83972 an alternative treatment for patients with recurrent urinary tract infection? Int. J. Antimicrob. Agents 28 (Suppl. 1), S26–S29 (2006).
Koves, B. et al. Rare emergence of symptoms during long-term asymptomatic Escherichia coli 83972 carriage without an altered virulence factor repertoire. J. Urol. 191, 519–528 (2014).
Darouiche, R. O., Thornby, J. I., Cerra-Stewart, C., Donovan, W. H. & Hull, R. A. Bacterial interference for prevention of urinary tract infection: a prospective, randomized, placebo-controlled, double-blind pilot trial. Clin. Infect. Dis. 41, 1531–1534 (2005).
Silverman, J. A., Schreiber, H. L., Hooton, T. M. & Hultgren, S. J. From physiology to pharmacy: developments in the pathogenesis and treatment of recurrent urinary tract infections. Curr. Urol. Rep. 14, 448–456 (2013).
Cusumano, C. K. & Hultgren, S. J. Bacterial adhesion—a source of alternate antibiotic targets. IDrugs 12, 699–705 (2009).
Cegelski, L., Marshall, G. R., Eldridge, G. R. & Hultgren, S. J. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 6, 17–27 (2008).
Cusumano, C. K. et al. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Sci. Transl. Med. 3, 109ra115 (2011).
Pinkner, J. S. et al. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria. Proc. Natl Acad. Sci. USA 103, 17897–17902 (2006).
Cegelski, L. et al. Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation. Nat. Chem. Biol. 5, 913–919 (2009).
Totsika, M. et al. A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug-resistant uropathogenic Escherichia coli ST131. J. Infect. Dis. 208, 921–928 (2013).
Langermann, S. et al. Vaccination with FimH adhesin protects cynomolgus monkeys from colonization and infection by uropathogenic Escherichia coli. J. Infect. Dis. 181, 774–778 (2000).
Roberts, J. A. et al. Antibody responses and protection from pyelonephritis following vaccination with purified Escherichia coli PapDG protein. J. Urol. 171, 1682–1685 (2004).
Brumbaugh, A. R. & Mobley, H. L. Preventing urinary tract infection: progress toward an effective Escherichia coli vaccine. Expert Rev. Vaccines 11, 663–676 (2012).
Alteri, C. J., Hagan, E. C., Sivick, K. E., Smith, S. N. & Mobley, H. L. Mucosal immunization with iron receptor antigens protects against urinary tract infection. PLoS Pathog. 5, e1000586 (2009).
H.M.Z. acknowledges an academic scholarship from the government of Saudi Arabia to pursue postgraduate studies in the field of clinical microbiology and infectious diseases, and research support from the Ministry of National Guard, Health Affairs, King Abdullah International Medical Research Centre, Saudi Arabia (project no. IRBC/193/12). P.N.A.H. is supported by an Australian Postgraduate Award from the University of Queensland, Australia. M.J.R. is supported by a Doctor in Training Research Scholarship from Avant Mutual Group Ltd., a Cancer Council Queensland PhD Scholarship and Professor William Burnett Research Fellowship from the Discipline of Surgery, School of Medicine, The University of Queensland, Australia.
P.A.T. has received research support from ADAMAS, Baxter, Fabentech, Inviragen, Merlion Pharmaceuticals and Sanofi Pasteur, and has received honoraria from AstraZeneca and Novartis. D.L.P. has participated in advisory boards and received honoraria from AstraZeneca, Bayer, Cubist, Leo Pharmaceuticals, Merck and Pfizer. The other authors declare no competing interests.
Supplementary Table 1
Studies reporting resistance in Gram-negative uropathogens published 2009–2014 (DOC 127 kb)
Rights and permissions
About this article
Cite this article
Zowawi, H., Harris, P., Roberts, M. et al. The emerging threat of multidrug-resistant Gram-negative bacteria in urology. Nat Rev Urol 12, 570–584 (2015). https://doi.org/10.1038/nrurol.2015.199
This article is cited by
The Use and Effectiveness of Ceftazidime–Avibactam in Real-World Clinical Practice: EZTEAM Study
Infectious Diseases and Therapy (2023)
UTI assessment tool for intermittent catheter users: a way to include user perspectives and enhance quality of UTI management
BMC Nursing (2022)
Natural selenium stress influences the changes of antibiotic resistome in seleniferous forest soils
Environmental Microbiome (2022)
Gut–bladder axis in recurrent UTI
Nature Microbiology (2022)
Bacterial infections epidemiology and factors associated with multidrug resistance in the northern region of Ghana
Scientific Reports (2022)