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1
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Stærk K, Andersen K, Hjelmager JS, Jensen LK, Jørgensen BM, Møller-Jensen J, Lund L, Andersen TE. Effect of Bladder Catheterization On Bacterial Interference With Asymptomatic Escherichia coli Strain 83972 in an Experimental Porcine Model of Urinary Tract Infection. J Infect Dis 2025; 231:e355-e363. [PMID: 39163139 PMCID: PMC12086672 DOI: 10.1093/infdis/jiae404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 08/09/2024] [Accepted: 08/14/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND Urinary tract infection (UTI) is a common disease with a significant risk of relapse. Deliberate bladder colonization with asymptomatic Escherichia coli is being explored as a potential strategy to fend off invading uropathogens, thereby mitigating the risk of symptomatic UTI. Currently, one major obstacle is the low success rates for achieving persistent bladder colonization with asymptomatic bacteria and experimental challenge studies are lacking. Here, we assessed the influence of an indwelling bladder catheter on the ability of asymptomatic E. coli to colonize the bladder and to assess the protective efficacy of such colonization against experimental UTI with uropathogenic E. coli. METHODS Pigs with or without indwelling bladder catheters were experimentally inoculated with the asymptomatic E. coli strain 83972 and subsequently challenged by inoculation with a uropathogenic E. coli isolate, UTI89. The animals were monitored with regular urine and blood samples and bladders and kidneys were harvested at termination. RESULTS All pigs with indwelling catheters were colonized by E. coli 83972 in response to inoculation, compared to pigs without catheters in which only 1 of 8 animals were colonized. When removing the catheter, E. coli 83972 were spontaneously cleared. Colonization with E. coli 83972 prevented experimental infection in 50% of animals, whereas all control animals became infected. CONCLUSIONS The presence of indwelling bladder catheters strongly facilitates the colonization of E. coli 83972, indicating that individuals with catheters may be particularly suited for receiving this treatment. The research supports prophylactic colonization with E. coli 83972 as a potential strategy to reduce the risk of UTIs.
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Affiliation(s)
- Kristian Stærk
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
| | - Karin Andersen
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Urology, Odense University Hospital, Odense, Denmark
| | | | - Louise Kruse Jensen
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Jakob Møller-Jensen
- Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
| | - Lars Lund
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Urology, Odense University Hospital, Odense, Denmark
| | - Thomas Emil Andersen
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark
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2
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Alyasi AS, Alsaad DB, Alshammary EM, Abdulrahman AA, Ghazwani MH, Almuayrifi MJ, Alharbi SS, Alali EMA, Daghestani MA, Alrefaei SM, Alolaywi HKH. Understanding and Managing Pediatric Urinary Tract Infections in Vesicoureteral Reflux: Insights Into Pathophysiology and Care. Cureus 2024; 16:e76144. [PMID: 39835023 PMCID: PMC11745421 DOI: 10.7759/cureus.76144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2024] [Indexed: 01/22/2025] Open
Abstract
Vesicoureteral reflux (VUR) is a pediatric condition identified by the backward flow of urine from the bladder to one or both ureters and kidneys, predisposing patients to recurrent urinary tract infections (UTIs) and kidney scarring. Continuous antibiotic prophylaxis has long been a mainstay of management aimed at preventing recurrent UTIs and resulting renal damage. This review critically discusses the evidence supporting the utilization of antibiotic prophylaxis in VUR, with a focus on its efficacy, safety, long-term outcomes, and future directions in management. The literature reveals that continuous antibiotic use as a prophylactic measure minimizes the possibility of having recurrent UTIs in VUR children, especially in high-grade reflux children. However, the overall benefit of continuous antibiotic prophylaxis in protecting against kidney scarring remains controversial. Furthermore, concerns about antibiotic resistance, adverse drug reactions, and the psychosocial burden on families have led to a reevaluation of this option's role in managing VUR. Emerging evidence supports the role of non-antibiotic interventions and the potential of surgical management in select cases. Future research should focus on identifying criteria of patients who would benefit most from continuous antibiotic prophylaxis and on developing novel therapeutic approaches to minimize the need for prolonged antibiotic use.
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Affiliation(s)
- Alaa S Alyasi
- Pediatrics and Neonatology, Maternal and Child Health Care Center, Tabuk, SAU
| | - Deema Badr Alsaad
- General Pediatrics, King Abdullah Bin Abdulaziz University Hospital, Riyadh, SAU
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3
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Ross SS, Forster CS, Borawski K. Urinary Tract Infection and Neuropathic Bladder. Urol Clin North Am 2024; 51:551-559. [PMID: 39349022 DOI: 10.1016/j.ucl.2024.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/02/2024]
Abstract
Urinary tract infections (UTIs) are the most common infection in patients with neurogenic bladder. Diagnosis is fraught with challenges since there is no globally accepted definition for UTI and symptoms can vary widely. Due to the increased risk of morbidity, it is important to have a thorough understanding of the risk of UTI, diagnostic criteria, and to treat aggressively when UTI is confirmed. Prevention of UTI is optimal but more studies are needed to identify the best methods to prevent UTIs in this population.
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Affiliation(s)
- Sherry S Ross
- Department of Urology, The University of North Carolina at Chapel Hill, Campus Box 7235, Chapel Hill, NC 27599, USA.
| | - Catherine S Forster
- Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224-1334, USA
| | - Kristy Borawski
- Department of Urology, The University of North Carolina at Chapel Hill, Campus Box 7235, Chapel Hill, NC 27599, USA
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4
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Grant A, Cohen Z, Cooper KL. Management of Asymptomatic Bacteriuria in Non-Catheterized Adults. Urol Clin North Am 2024; 51:561-570. [PMID: 39349023 DOI: 10.1016/j.ucl.2024.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/02/2024]
Abstract
Understanding the management of asymptomatic bacteriuria (ASB) is important given the prevalence of the condition, associated risks in certain patient populations, and the risks associated with inappropriate antibiotic administration. Generally, screening and treatment is only recommended in pregnant women and in those undergoing urologic procedures that will violate the urothelium. Knowing the appropriate time to screen and treat ASB is critical for managing high-risk patients and preventing the growth of antibiotic resistance. Recent research into the protective nature of avirulent strains of Escherichia coli might offer a new approach to management of ASB.
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Affiliation(s)
- Allison Grant
- Department of Urology, Columbia University Irving Medical Center, 161 Fort Washington Avenue, 11th Floor, New York, NY 10032, USA.
| | - Zoë Cohen
- Department of Urology, Columbia University Irving Medical Center, 161 Fort Washington Avenue, 11th Floor, New York, NY 10032, USA
| | - Kimberly L Cooper
- Department of Urology, Columbia University Irving Medical Center, 161 Fort Washington Avenue, 11th Floor, New York, NY 10032, USA
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5
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Segev G, Chen H, Dear JD, Martínez López B, Pires J, Klumpp DJ, Schaeffer AJ, Westropp JL. Evaluation of the efficacy of a live Escherichia coli biotherapeutic product (asymptomatic bacteriuria E. coli 212). J Vet Intern Med 2024; 38:2548-2555. [PMID: 39285460 PMCID: PMC11423479 DOI: 10.1111/jvim.17167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Accepted: 07/31/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND Recurrent bacterial cystitis, often referred to as recurrent urinary tract infection (UTI), can be difficult to manage and alternative treatments are needed. HYPOTHESIS/OBJECTIVE Intravesicular administration of asymptomatic bacteriuria (ASB) E. coli 212 will not be inferior to antimicrobial treatment for the management of recurrent UTI in dogs. ANIMALS Thirty-four dogs with >1 UTI in the 12 months before presentation. METHODS All dogs were deemed normal otherwise based on absence of abnormalities on physical examination, CBC, serum biochemical panel, and abdominal ultrasonography. Dogs were randomized to 1 of 2 treatment groups: Group 1 antimicrobials for 7 days or group 2 intravesicular administration of ASB E. coli 212. Owners were provided a voiding questionnaire regarding their dogs' clinical signs, which was completed daily for 14 days to assess clinical cure. Dogs were examined on days 7 and 14 to assess clinical cure, and urine specimens were submitted for urinalysis and bacterial culture. RESULTS Clinical cure rates for ASB E. coli 212-treated dogs were not inferior to 7 days of antimicrobial treatment with a 12% margin of difference to determine non-inferiority. No significant difference was found between the treatment groups on days 7 and 14 in the proportion of dogs achieving ≥50% or ≥75% reduction in their clinical score compared with baseline. CONCLUSIONS AND CLINICAL IMPORTANCE These data suggest that intravesicular administration of ASB E. coli 212 is not inferior to antimicrobials for the treatment of recurrent UTI in dogs. This biotherapeutic agent could help alleviate the need for antimicrobials for some dogs with recurrent UTI, improving antimicrobial stewardship.
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Affiliation(s)
- Gilad Segev
- Koret School of Veterinary MedicineThe Hebrew University of JerusalemJerusalemIsrael
| | - Hilla Chen
- Koret School of Veterinary MedicineThe Hebrew University of JerusalemJerusalemIsrael
| | - Jonathan D. Dear
- Department of Medicine and Epidemiology, School of Veterinary MedicineUniversity of California, DavisDavisCaliforniaUSA
| | - Beatriz Martínez López
- Department of Medicine and Epidemiology, School of Veterinary MedicineUniversity of California, DavisDavisCaliforniaUSA
| | - Jully Pires
- Veterinary Center for Clinical TrialsUniversity of California, DavisDavisCaliforniaUSA
| | - David J. Klumpp
- Department of Urology, Feinberg School of MedicineNorthwestern UniversityEvanstonIllinoisUSA
| | - Anthony J. Schaeffer
- Department of Urology, Feinberg School of MedicineNorthwestern UniversityEvanstonIllinoisUSA
| | - Jodi L. Westropp
- Department of Medicine and Epidemiology, School of Veterinary MedicineUniversity of California, DavisDavisCaliforniaUSA
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6
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George I, Kalairaj MS, Zimmern PE, Ware TH, Subashchandrabose S. Competitive fitness of asymptomatic bacteriuria E. coli strain 83972 against uropathogens in human urine. Infect Immun 2024; 92:e0017324. [PMID: 38780216 PMCID: PMC11237815 DOI: 10.1128/iai.00173-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 05/04/2024] [Indexed: 05/25/2024] Open
Abstract
Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. The main causative agent of UTI is uropathogenic Escherichia coli (UPEC). There is an immediate need for novel prophylactic and treatment strategies against UTI because of the increasing incidence of antimicrobial resistance among uropathogens. ABU 83972, an asymptomatic bacteriuria-causing E. coli strain, prevents UTI by suppressing the colonization of UPEC. However, the nature of competition and growth repression of UPEC by ABU 83972 is unclear and is the subject of our investigation. Here, we characterized the growth kinetics of ABU 83972 and uropathogens in human urine and laboratory media. Next, we performed a series of competitive co-culture experiments where ABU 83972 and uropathogens were inoculated at a 1:1 ratio in human urine and in various media, and their relative abundance was determined. In human urine, ABU 83972 outcompeted UPEC and additional uropathogens, reaching up to 90% of the total population after 24 hours of incubation. In contrast, UPEC outcompeted ABU 83972 in LB and M9 minimal media and exhibited superior colonization than ABU 83972 in the mouse urinary bladder. Since engineered living materials (ELMs) can be used to retain an organism of interest in a particular location, we developed ABU 83972-containing ELMs that effectively outcompeted UPEC in human urine. In summary, our work establishes that ABU 83972 outcompetes UPEC in a milieu- and cell-density-dependent manner, highlighting the importance of the metabolites and nutrients found in the human urine as determinants of the competitive fitness of ABU 83972.
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Affiliation(s)
- Iris George
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
| | | | - Philippe E. Zimmern
- Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Taylor H. Ware
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA
- Department of Materials Science and Engineering, Texas A&M University, College Station, Texas, USA
| | - Sargurunathan Subashchandrabose
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA
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7
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Raatz M, de Azevedo-Lopes A, Drabik K, Traulsen A, Waclaw B. Pathogen non-planktonic phases within the urinary tract impact early infection and resistance evolution. THE ISME JOURNAL 2024; 18:wrae191. [PMID: 39325970 PMCID: PMC11499890 DOI: 10.1093/ismejo/wrae191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 04/12/2024] [Accepted: 09/25/2024] [Indexed: 09/28/2024]
Abstract
Treatment of urinary tract infections and the prevention of their recurrence is a pressing global health problem. In a urinary infection, pathogenic bacteria not only reside in the bladder lumen but also attach to and invade the bladder tissue. Planktonic, attached, and intracellular bacteria face different selection pressures from physiological processes such as micturition, immune response, and antibiotic treatment. Here, we use a mathematical model of the initial phase of infection to unravel the effects of these different selective pressures on the ecological and evolutionary dynamics of urinary infections. We explicitly model planktonic bacteria in the bladder lumen, bacteria attached to the bladder wall, and bacteria that have invaded the epithelial cells of the bladder. We find that the presence of non-planktonic bacteria substantially increases the risk of infection establishment and affects evolutionary trajectories leading to resistance during antibiotic treatment. We also show that competitive inoculation with a fast-growing non-pathogenic strain can reduce the pathogen load and increase the efficacy of an antibiotic, but only if the antibiotic is used in moderation. Our study shows that including different compartments is essential to create more realistic models of urinary infections, which may help guide new treatment strategies.
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Affiliation(s)
- Michael Raatz
- Department of Theoretical Biology, Max Planck Institute for Evolutionary Biology, 24306 Plön, Germany
| | - Amanda de Azevedo-Lopes
- Department of Theoretical Biology, Max Planck Institute for Evolutionary Biology, 24306 Plön, Germany
| | - Karolina Drabik
- Dioscuri Centre for Physics and Chemistry of Bacteria, Institute of Physical Chemistry (IChF), Polish Academy of Sciences, 01-224 Warsaw, Poland
| | - Arne Traulsen
- Department of Theoretical Biology, Max Planck Institute for Evolutionary Biology, 24306 Plön, Germany
| | - Bartlomiej Waclaw
- Dioscuri Centre for Physics and Chemistry of Bacteria, Institute of Physical Chemistry (IChF), Polish Academy of Sciences, 01-224 Warsaw, Poland
- School of Physics and Astronomy, University of Edinburgh, EH9 3FD Edinburgh, United Kingdom
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8
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Mak Q, Greig J, Ahmed K, Khan S, Dasgupta P, Malde S, Raison N. Competitive Inoculation as an Effective Prophylaxis Against Recurrent Urinary Tract Infections: A Systematic Review. Int Neurourol J 2023; 27:79-87. [PMID: 37401018 DOI: 10.5213/inj.2346052.026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 05/09/2023] [Indexed: 07/05/2023] Open
Abstract
Urinary tract infection (UTI) is a common condition defined as the presence of bacteria within the urine above a certain threshold (usually >100,000 m/L). The lifetime risk in women is estimated to be 50%, of whom 25% will develop recurrence within 6 months. Unfortunately, the use of antibiotics to treat and manage recurrent UTI (rUTI) is a growing problem, due to the burden of growing antibiotic resistance on public health. As such, new approaches to manage rUTI are being investigated and developed. Competitive inoculation via instillation of Escherichia coli 83972 or HU2117 in the bladder is a new prophylactic non-antimicrobial therapy for rUTIs. It utilizes the principle of the protective nature of asymptomatic bacteriuria to prevent recurrence of symptomatic UTIs. However, the effectiveness and safety of this technique remains unclear. This systematic review examined the current outcomes data on competitive inoculation as an effective and safe treatment for rUTI prophylaxis. Based on a limited number of studies, current evidence suggests that competitive inoculation is an effective and safe prophylactic measure against UTIs in a select group of patients with incomplete bladder emptying. However, administration of the technology is both resource and time intensive, and there is strong data demonstrating low successful colonisation rates. Competitive inoculation is an alternative to antibiotics only to rUTI patients with incomplete bladder emptying. There is no evidence to suggest that the technology would be suitable for other subsets of rUTI patients. Further randomized controlled trials should be conducted to improve the evidence base before drawing conclusions for clinical practice, and ideas to improve colonisation rates and simplify the administration process should be explored.
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Affiliation(s)
- Quentin Mak
- GKT School of Medical Education, King's College London, London, UK
| | - Julian Greig
- GKT School of Medical Education, King's College London, London, UK
| | - Kamran Ahmed
- MRC Centre for Transplantation, Guy's Hospital, King's College London, London, UK
- Khalifa University, Abu Dhabi, United Arab Emirates
| | - Shamim Khan
- Department of Urology, Guys and St Thomas' NHS Foundation Trust, London, UK
| | - Prokar Dasgupta
- MRC Centre for Transplantation, Guy's Hospital, King's College London, London, UK
- Department of Urology, Guys and St Thomas' NHS Foundation Trust, London, UK
| | - Sachin Malde
- Department of Urology, Guys and St Thomas' NHS Foundation Trust, London, UK
| | - Nicholas Raison
- MRC Centre for Transplantation, Guy's Hospital, King's College London, London, UK
- Department of Urology, Guys and St Thomas' NHS Foundation Trust, London, UK
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9
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Kuznetzova AB, Prazdnova EV, Chistyakov VA, Kutsevalova OY, Batiushin MM. Are Probiotics Needed in Nephrology? NEPHROLOGY (SAINT-PETERSBURG) 2022; 26:18-30. [DOI: 10.36485/1561-6274-2022-26-4-18-30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Affiliation(s)
- A. B. Kuznetzova
- Academy of Biology and Biotechnology named after D.I. Ivanovsky, Southern Federal University
| | - E. V. Prazdnova
- Academy of Biology and Biotechnology named after D.I. Ivanovsky, Southern Federal University
| | - V. A. Chistyakov
- Academy of Biology and Biotechnology named after D.I. Ivanovsky, Southern Federal University
| | - O. Yu. Kutsevalova
- Federal State Budgetary Institution "National Medical Research Center of Oncology"
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10
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Kenneally C, Murphy CP, Sleator RD, Culligan EP. The Urinary Microbiome and Biological Therapeutics: Novel Therapies For Urinary Tract Infections. Microbiol Res 2022; 259:127010. [DOI: 10.1016/j.micres.2022.127010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/15/2022] [Accepted: 03/16/2022] [Indexed: 12/12/2022]
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Biofilm Matrix Formation in Human: Clinical Significance, Diagnostic Techniques, and Therapeutic Drugs. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2021. [DOI: 10.5812/archcid.107919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Context: Some recent reports have indicated that almost 80% of clinical infections in humans have biofilm origin and impose additional healthcare costs. This study was an updated review of extracellular polymeric substance matrix (Biofilm) formation in humans and elaborated on its clinical significance, diagnosis, and therapeutic approaches. Evidence Acquisition: This narrative study reviewed the most recent information on the significance of microbial biofilm formation in clinical settings, common biofilm-producing bacterial species, its diagnosis, antibiotic drug resistance, and new approaches to the treatment of infections associated with biofilm formation. Results: Evidence indicated a permanent increase in the frequency of microbial biofilm in the central venous catheter, mechanical heart valve, and urinary catheter, as well as persistent infections. However, antimicrobial resistance induced by biofilms formation and the antimicrobial treatment of biofilms were problematic. Moreover, several assays and lab devices were described to evaluate biofilm formation. Furthermore, new attitudes towards anti-biofilm treatments were introduced in this paper. Conclusions: The number of different mechanisms were in accordance with the recent knowledge on how biofilms play a critical role in the disease pathogenesis. Biofilm strikes the treatment and surveillance of patients bearing infectious diseases under different conditions. The use of new methods in anti-biofilm treatments is effective for the recovery of infected patients.
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12
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Ambite I, Butler D, Wan MLY, Rosenblad T, Tran TH, Chao SM, Svanborg C. Molecular determinants of disease severity in urinary tract infection. Nat Rev Urol 2021; 18:468-486. [PMID: 34131331 PMCID: PMC8204302 DOI: 10.1038/s41585-021-00477-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/07/2021] [Indexed: 02/06/2023]
Abstract
The most common and lethal bacterial pathogens have co-evolved with the host. Pathogens are the aggressors, and the host immune system is responsible for the defence. However, immune responses can also become destructive, and excessive innate immune activation is a major cause of infection-associated morbidity, exemplified by symptomatic urinary tract infections (UTIs), which are caused, in part, by excessive innate immune activation. Severe kidney infections (acute pyelonephritis) are a major cause of morbidity and mortality, and painful infections of the urinary bladder (acute cystitis) can become debilitating in susceptible patients. Disease severity is controlled at specific innate immune checkpoints, and a detailed understanding of their functions is crucial for strategies to counter microbial aggression with novel treatment and prevention measures. One approach is the use of bacterial molecules that reprogramme the innate immune system, accelerating or inhibiting disease processes. A very different outcome is asymptomatic bacteriuria, defined by low host immune responsiveness to bacteria with attenuated virulence. This observation provides the rationale for immunomodulation as a new therapeutic tool to deliberately modify host susceptibility, control the host response and avoid severe disease. The power of innate immunity as an arbitrator of health and disease is also highly relevant for emerging pathogens, including the current COVID-19 pandemic.
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Affiliation(s)
- Ines Ambite
- grid.4514.40000 0001 0930 2361Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden
| | - Daniel Butler
- grid.4514.40000 0001 0930 2361Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden
| | - Murphy Lam Yim Wan
- grid.4514.40000 0001 0930 2361Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden
| | - Therese Rosenblad
- grid.4514.40000 0001 0930 2361Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden
| | - Thi Hien Tran
- grid.4514.40000 0001 0930 2361Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden
| | - Sing Ming Chao
- Nephrology Service, Department of Paediatrics, KK Hospital, Singapore, Singapore
| | - Catharina Svanborg
- grid.4514.40000 0001 0930 2361Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden
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13
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Abstract
The role of microbiome milieu in the urinary tract, their interplay in diverse urological conditions and their therapeutic implications are not completely understood. The microbiome has contributed towards urinary tract infections, urolithiasis and urological cancers. The possibility of manipulating microbiome for diagnosis and treatment is evolving. Probiotics might help in overcoming the problems of recurrent infection and antibiotic resistance. Novel applications like stents and catheters coated with non-pathogenic organisms are being developed. Research in the urinary microbiome has progressed from using mouse models to the presently available three- dimensional cultured organoids, thus making it more feasible. As our knowledge regarding the urinary microbiome increases, justice can be done to many patients in whom the advancements can be used for prophylaxis, diagnosis, treatment and even in improving their quality of life. The growing amount of antibiotic resistance is also a matter of concern and probiotics might be the answer to this upcoming calamity. In this review, we have discussed the role of the urinary microbiome in pathogenesis, diagnosis and treatment of urological conditions and pondered upon its future prospects.
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14
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Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, Eckert LO, Geerlings SE, Köves B, Hooton TM, Juthani-Mehta M, Knight SL, Saint S, Schaeffer AJ, Trautner B, Wullt B, Siemieniuk R. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis 2020; 68:e83-e110. [PMID: 30895288 DOI: 10.1093/cid/ciy1121] [Citation(s) in RCA: 153] [Impact Index Per Article: 30.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 12/27/2018] [Indexed: 12/22/2022] Open
Abstract
Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB.
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Affiliation(s)
- Lindsay E Nicolle
- Department of Internal Medicine, School of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
| | - Kalpana Gupta
- Division of Infectious Diseases, Veterans Affairs Boston Healthcare System and Boston University School of Medicine, West Roxbury, Massachusetts
| | | | - Richard Colgan
- Department of Family and Community Medicine, University of Maryland, Baltimore
| | - Gregory P DeMuri
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison
| | - Dimitri Drekonja
- Division of Infectious Diseases, University of Minnesota, Minneapolis
| | - Linda O Eckert
- Department of Obstetrics and Gynecology and Department of Global Health, University of Washington, Seattle
| | - Suzanne E Geerlings
- Department of Internal Medicine, Amsterdam University Medical Center, The Netherlands
| | - Béla Köves
- Department of Urology, South Pest Teaching Hospital, Budapest, Hungary
| | - Thomas M Hooton
- Division of Infectious Diseases, University of Miami, Florida
| | | | - Shandra L Knight
- Library and Knowledge Services, National Jewish Health, Denver, Colorado
| | - Sanjay Saint
- Department of Internal Medicine, Veterans Affairs Ann Arbor and University of Michigan, Ann Arbor
| | | | - Barbara Trautner
- Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Bjorn Wullt
- Division of Microbiology, Immunology and Glycobiology, Lund, Sweden
| | - Reed Siemieniuk
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
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Loubet P, Ranfaing J, Dinh A, Dunyach-Remy C, Bernard L, Bruyère F, Lavigne JP, Sotto A. Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections. Front Microbiol 2020; 11:1509. [PMID: 32719668 PMCID: PMC7350282 DOI: 10.3389/fmicb.2020.01509] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 06/10/2020] [Indexed: 12/29/2022] Open
Abstract
Urinary tract infections (UTIs) mainly caused by Uropathogenic Escherichia coli (UPEC), are common bacterial infections. Many individuals suffer from chronically recurring UTIs, sometimes requiring long-term prophylactic antibiotic regimens. The global emergence of multi-drug resistant uropathogens in the last decade underlines the need for alternative non-antibiotic therapeutic and preventative strategies against UTIs. The research on non-antibiotic therapeutic options in UTIs has focused on the following phases of the pathogenesis: colonization, adherence of pathogens to uroepithelial cell receptors and invasion. In this review, we discuss vaccines, small compounds, nutraceuticals, immunomodulating agents, probiotics and bacteriophages, highlighting the challenges each of these approaches face. Most of these treatments show interesting but only preliminary results. Lactobacillus-containing products and cranberry products in conjunction with propolis have shown the most robust results to date and appear to be the most promising new alternative to currently used antibiotics. Larger efficacy clinical trials as well as studies on the interplay between non-antibiotic therapies, uropathogens and the host immune system are warranted.
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Affiliation(s)
- Paul Loubet
- VBMI, INSERM U1047, Université de Montpellier, Service des Maladies Infectieuses et Tropicales, CHU Nîmes, Nîmes, France
| | - Jérémy Ranfaing
- VBMI, INSERM U1047, Université de Montpellier, Service de Microbiologie et Hygiène Hospitalière, CHU Nîmes, Nîmes, France
| | - Aurélien Dinh
- Service des Maladies Infectieuses, AP-HP Raymond-Poincaré, Garches, France
| | - Catherine Dunyach-Remy
- VBMI, INSERM U1047, Université de Montpellier, Service de Microbiologie et Hygiène Hospitalière, CHU Nîmes, Nîmes, France
| | - Louis Bernard
- PRES Centre Val de Loire, Université François Rabelais de Tours, Tours, France.,Service des Maladies Infectieuses, CHU Tours, Tours, France
| | - Franck Bruyère
- PRES Centre Val de Loire, Université François Rabelais de Tours, Tours, France.,Service d'Urologie, CHU Tours, Tours, France
| | - Jean-Philippe Lavigne
- VBMI, INSERM U1047, Université de Montpellier, Service de Microbiologie et Hygiène Hospitalière, CHU Nîmes, Nîmes, France
| | - Albert Sotto
- VBMI, INSERM U1047, Université de Montpellier, Service des Maladies Infectieuses et Tropicales, CHU Nîmes, Nîmes, France
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Denzer L, Schroten H, Schwerk C. From Gene to Protein-How Bacterial Virulence Factors Manipulate Host Gene Expression During Infection. Int J Mol Sci 2020; 21:ijms21103730. [PMID: 32466312 PMCID: PMC7279228 DOI: 10.3390/ijms21103730] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 05/19/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023] Open
Abstract
Bacteria evolved many strategies to survive and persist within host cells. Secretion of bacterial effectors enables bacteria not only to enter the host cell but also to manipulate host gene expression to circumvent clearance by the host immune response. Some effectors were also shown to evade the nucleus to manipulate epigenetic processes as well as transcription and mRNA procession and are therefore classified as nucleomodulins. Others were shown to interfere downstream with gene expression at the level of mRNA stability, favoring either mRNA stabilization or mRNA degradation, translation or protein stability, including mechanisms of protein activation and degradation. Finally, manipulation of innate immune signaling and nutrient supply creates a replicative niche that enables bacterial intracellular persistence and survival. In this review, we want to highlight the divergent strategies applied by intracellular bacteria to evade host immune responses through subversion of host gene expression via bacterial effectors. Since these virulence proteins mimic host cell enzymes or own novel enzymatic functions, characterizing their properties could help to understand the complex interactions between host and pathogen during infections. Additionally, these insights could propose potential targets for medical therapy.
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Probiotic Lactobacillus and Bifidobacterium strains possess safety characteristics, antiviral activities and host adherence factors revealed by genome mining. EPMA J 2019; 10:337-350. [PMID: 31832110 DOI: 10.1007/s13167-019-00184-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 08/11/2019] [Indexed: 02/07/2023]
Abstract
Background Probiotics belonging to Lactobacillus and Bifidobacterium spp. have been exploited for their health benefits in treatment and prevention of many pathological conditions and promoting human health. Recent advances in understanding probiotics-human interaction through microbiome research in the context of various medical conditions suggest their provisional role in preventive, personalized, and predictive medicine. To streamline their application in disease prevention, development of personalized-based treatments, or their use as biomarkers for predictive diagnosis, in vitro screening for strains with potential probiotic properties should be performed. In this work, we aimed to emphasize the probiotic features of four Lactobacillus and two Bifidobacterium probiotic strains which showed antagonistic properties against microbial pathogens. Methods Firstly, cytotoxicity assessment of cell-free preparations from these strains was performed using a baby hamster kidney (BHK) cells and cell viability was measured by means of sulfo-rhodamine B stain. Secondly, Newcastle disease (ND) and infectious bursal disease (IBD) viruses which pose a great threat in infected poultry were used for assessing antiviral activity of probiotics. Thirdly, the genomes of six probiotic strains were used to identify genes encoding host adherence factors that mediate interaction with human tissues. Results Probiotic preparations exhibited insignificant toxicity as indicated by the high survival rate of BHK cells (surviving fraction varied from 0.82 to 0.99) as compared to the untreated control. Cell-free preparations of probiotics mixed with equal volume of ND and IBD viruses (106 and 104 Tissue Culture Infectious Dose 50, respectively) reduced the titer of ND and IBD viruses on chicken embryo fibroblast cells. Genome mining analysis revealed that the draft genomes of these strains were predicted to encode LPXTG-containing proteins, surface layer proteins, tight adherence pili, sortase-dependent pili, fibronectin, or collagen binding proteins and other factors that adhere to human tissues such as mucus. Such adherence factors enable probiotic bacteria to interact and colonize the host. Conclusion Taken together, safety privileges, antiviral activities, and genomically encoded host interaction factors confirmed probiotic features of the six probiotic strains and their potential in promoting human health.
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Symeonidis EN, Falagas ME, Dimitriadis F. Urinary tract infections in patients undergoing radical cystectomy and urinary diversion: challenges and considerations in antibiotic prophylaxis. Transl Androl Urol 2019; 8:286-289. [PMID: 31555550 PMCID: PMC6732096 DOI: 10.21037/tau.2019.07.12] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 07/21/2019] [Indexed: 11/06/2022] Open
Affiliation(s)
- Evangelos N. Symeonidis
- 1 Department of Urology, Aristotle University of Thessaloniki, “G. Gennimatas” General Hospital, Thessaloniki, Greece
| | - Matthew E. Falagas
- Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece
- Department of Medicine, Henry Dunant Hospital Center, Athens, Greece
- Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Fotios Dimitriadis
- 1 Department of Urology, Aristotle University of Thessaloniki, “G. Gennimatas” General Hospital, Thessaloniki, Greece
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19
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The impact of microbiome in urological diseases: a systematic review. Int Urol Nephrol 2019; 51:1677-1697. [PMID: 31301004 DOI: 10.1007/s11255-019-02225-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Accepted: 07/04/2019] [Indexed: 12/26/2022]
Abstract
OBJECTIVE The term microbiome is used to signify the ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space, in which there were increasing evidences to suggest that they might have potential roles in various medical conditions. While the study of microbiome in the urinary system is not as robust as the systems included in the Human Microbiome Project, there are still evidences in the literature showing that microbiome may have a role in urological diseases. Therefore, we would like to perform a systematic review on the topic and summarize the available evidence on the impact of microbiome on urological diseases. METHODOLOGY This review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. After screening 589 abstracts and including additional studies (such as references from review papers), 76 studies were included for review and discussion. RESULTS Studies had suggested that there were correlations of microbiome of different body cavities (e.g., fecal, urinary and seminal fluid) with urological diseases. Also, different diseases would have different microbiome profile in different body cavities. Unfortunately, the studies on the association of microbiome and urological diseases were still either weak or inconsistent. CONCLUSION Studies suggested that there might be some relationship between microbiome and various urological diseases. However, further large-scale studies with control of confounding factors should be performed under a standardized methodology in order to have better understanding of the relationship. Also, more standardized reporting protocol for microbiome studies should be considered for better communications in future studies.
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Ambite I, Butler DSC, Stork C, Grönberg-Hernández J, Köves B, Zdziarski J, Pinkner J, Hultgren SJ, Dobrindt U, Wullt B, Svanborg C. Fimbriae reprogram host gene expression - Divergent effects of P and type 1 fimbriae. PLoS Pathog 2019; 15:e1007671. [PMID: 31181116 PMCID: PMC6557620 DOI: 10.1371/journal.ppat.1007671] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 03/01/2019] [Indexed: 01/03/2023] Open
Abstract
Pathogens rely on a complex virulence gene repertoire to successfully attack their hosts. We were therefore surprised to find that a single fimbrial gene reconstitution can return the virulence-attenuated commensal strain Escherichia coli 83972 to virulence, defined by a disease phenotype in human hosts. E. coli 83972pap stably reprogrammed host gene expression, by activating an acute pyelonephritis-associated, IRF7-dependent gene network. The PapG protein was internalized by human kidney cells and served as a transcriptional agonist of IRF-7, IFN-β and MYC, suggesting direct involvement of the fimbrial adhesin in this process. IRF-7 was further identified as a potent upstream regulator (-log (p-value) = 61), consistent with the effects in inoculated patients. In contrast, E. coli 83972fim transiently attenuated overall gene expression in human hosts, enhancing the effects of E. coli 83972. The inhibition of RNA processing and ribosomal assembly indicated a homeostatic rather than a pathogenic end-point. In parallel, the expression of specific ion channels and neuropeptide gene networks was transiently enhanced, in a FimH-dependent manner. The studies were performed to establish protective asymptomatic bacteriuria in human hosts and the reconstituted E. coli 83972 variants were developed to improve bacterial fitness for the human urinary tract. Unexpectedly, P fimbriae were able to drive a disease response, suggesting that like oncogene addiction in cancer, pathogens may be addicted to single super-virulence factors. Urinary tract infections affect millions of individuals annually, and many patients suffer from recurring infections several times a year. Antibiotic resistance is increasing rapidly and new strategies are needed to treat even these common bacterial infections. One approach is to use the protective power of asymptomatic bacterial carriage, which has been shown to protect the host against symptomatic urinary tract infection. Instilling “nice” bacteria in the urinary bladder is therefore a promising alternative approach to antibiotic therapy. In an effort to increase the therapeutic use of asymptomatic bacteriuria, we reintroduced bacterial adhesion molecules into the therapeutic Escherichia coli strain 83972 and inoculated patients who are in need of alternative therapy. To our great surprise, the P fimbriated variant caused symptoms, despite lacking other virulence factors commonly thought to be necessary to cause disease. In contrast, type 1 fimbriae, did not provoke symptoms but enhanced the beneficial properties of the wild-type strain. This is explained by a divergent effect of these fimbrial types on host gene expression, where P fimbriae activate the IRF-7 transcription factor that regulates pathology in infected kidneys, suggesting that a single, potent virulence gene may be sufficient to create virulence in human hosts.
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Affiliation(s)
- Ines Ambite
- Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Klinikgatan, Lund, Sweden
| | - Daniel S. C. Butler
- Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Klinikgatan, Lund, Sweden
| | - Christoph Stork
- Institute of Hygiene, University of Münster, Mendelstr, Münster, Germany
| | - Jenny Grönberg-Hernández
- Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Klinikgatan, Lund, Sweden
| | - Bela Köves
- Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Klinikgatan, Lund, Sweden
| | - Jaroslaw Zdziarski
- Institute for Molecular Biology of Infectious Diseases, University of Würzburg, Würzburg, Germany
| | - Jerome Pinkner
- Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri, United States of America
- Center for Women's Infectious Disease Research (CWIDR), Washington University School of Medicine, St Louis, Missouri, United States of America
| | - Scott J. Hultgren
- Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri, United States of America
- Center for Women's Infectious Disease Research (CWIDR), Washington University School of Medicine, St Louis, Missouri, United States of America
| | - Ulrich Dobrindt
- Institute of Hygiene, University of Münster, Mendelstr, Münster, Germany
- Institute for Molecular Biology of Infectious Diseases, University of Würzburg, Würzburg, Germany
| | - Björn Wullt
- Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Klinikgatan, Lund, Sweden
| | - Catharina Svanborg
- Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Klinikgatan, Lund, Sweden
- * E-mail:
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21
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Hsu PC, Lo YC, Wu PY, Chiu JW, Jeng MJ. The relationship of seasonality and the increase in urinary tract infections among hospitalized patients with spinal cord injury. J Chin Med Assoc 2019; 82:401-406. [PMID: 31058713 DOI: 10.1097/jcma.0000000000000040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Urinary tract infection (UTI) is the most frequent complication in patients who have spinal cord injury (SCI). The occurrence rate of UTI in this type of hospitalized patients was correlated to seasonality, age, and gender. METHODS Patients hospitalized during the 4-year study period with underlying SCI were identified from Taiwan's National Health Insurance Research Database. Patients with a discharge diagnosis of UTI were identified as those with SCI and UTI; they were divided into the following four age groups: <18 years, 18 to 44 years, 45 to 64 years, and ≥65 years. The gender, monthly number of cases, major complication rate, seasonal differences, and odds ratios (ORs) of associated factors were analyzed. RESULTS Data of 30 149 hospitalized patients diagnosed with SCI were retrieved. SCI and UTI were diagnosed in 3405 (11.3%) patients, of them 2296 were males (67.4%) and 1109 were females (32.6%). The UTI occurrence rate in hospitalized SCI patients was higher in males (11.8%) than in females (10.4%) (OR: 1.24; 95% CI: 1.15-1.34); it was highest in the ≥65-year-old age group (12.8%) and lowest in the <18-year-old age group (5.8%) (OR: 2.51; 95% CI: 1.83-3.44). The UTI occurrence rate varied from 7% to 18%, and it was highest in the summer (13.0% ± 2.6%) and lowest in the winter (10.2% ± 1.9%) (OR: 1.27; 95% CI: 1.15-1.40). Acute pyelonephritis was the most common complication in SCI and UTI cases. CONCLUSION The mean occurrence rate of UTI in hospitalized SCI patients was 11.3%; it was higher in males, in patients aged ≥65 years, and in the summer. Therefore, physicians should pay attention to the occurrence of UTI in aged male patients with SCI, especially in the summer.
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Affiliation(s)
- Po-Cheng Hsu
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yu-Cheng Lo
- Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Pediatrics, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Pin-Yi Wu
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Jan-Wei Chiu
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Mei-Jy Jeng
- Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Pediatrics, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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Laan BJ, Geerlings SE. Non-antibiotic prevention strategies against catheter-associated urinary tract infections. THE LANCET. INFECTIOUS DISEASES 2019; 19:562-564. [PMID: 30987815 DOI: 10.1016/s1473-3099(18)30758-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 12/04/2018] [Indexed: 12/18/2022]
Affiliation(s)
- Bart J Laan
- Internal Medicine, Infectious Diseases, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
| | - Suzanne E Geerlings
- Internal Medicine, Infectious Diseases, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
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International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Vet J 2019; 247:8-25. [PMID: 30971357 DOI: 10.1016/j.tvjl.2019.02.008] [Citation(s) in RCA: 225] [Impact Index Per Article: 37.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 02/19/2019] [Accepted: 02/21/2019] [Indexed: 02/08/2023]
Abstract
Urinary tract disease is a common clinical presentation in dogs and cats, and a common reason for antimicrobial prescription. This document is a revision and expansion on the 2011 Antimicrobial Use Guidelines for Treatment of Urinary Tract Disease in Dogs and Cats, providing recommendations for diagnosis and management of sporadic bacterial cystitis, recurrent bacterial cystitis, pyelonephritis, bacterial prostatitis, and subclinical bacteriuria. Issues pertaining to urinary catheters, medical dissolution of uroliths and prophylaxis for urological procedures are also addressed.
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Storm DW, Braga LH, Cooper CS. Continuous Antibiotic Prophylaxis in Pediatric Urology. Urol Clin North Am 2018; 45:525-538. [PMID: 30316308 DOI: 10.1016/j.ucl.2018.06.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Continuous antibiotic prophylaxis (CAP) for urinary tract infection prevention in children with vesicoureteral reflux, hydronephrosis, and hydroureteronephrosis is reviewed. A more selective use of CAP is advocated based on a review of known individual risk factors in each of these conditions that subsequently helps identify the children most likely to benefit from CAP. Both short-term and potential long-term side effects of CAP are reviewed, including the impact of prophylactic antibiotics on bacterial resistance and the microbiome. Alternatives to continuous antibiotic prophylaxis including Vaccinium macrocarpon (Cranberry), probiotics, and vaccines are reviewed.
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Affiliation(s)
- Douglas W Storm
- Department of Urology, University of Iowa, Carver College of Medicine, 200 Hawkins Drive, 3RCP, Iowa City, IA 5224, USA
| | - Luis H Braga
- Department of Surgery, Division of Urology, Mcmaster University, McMaster Children's Hospital, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada
| | - Christopher S Cooper
- Department of Urology, University of Iowa, Carver College of Medicine, 200 Hawkins Drive, 3RCP, Iowa City, IA 5224, USA.
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Gupta V, Nag D, Garg P. Recurrent urinary tract infections in women: How promising is the use of probiotics? Indian J Med Microbiol 2018; 35:347-354. [PMID: 29063878 DOI: 10.4103/ijmm.ijmm_16_292] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Urinary tract infections (UTIs) currently rank amongst the most prevalent bacterial infections, representing a major health hazard. UTIs in females usually start as vaginal infections and ascend to the urethra and bladder. Recurrent UTIs (rUTIs) can be defined as at least three episodes of UTI in 1 year or two episodes in 6 months. Various antibiotics have been the mainstay of therapy in ameliorating the incidence of UTIs, but recurrent infections continue to afflict many women. It necessitates the exploitation of alternative antimicrobial therapy. Probiotics have been shown to be effective in varied clinical trials for long-term preventions of rUTI. Because Escherichia coli is the primary pathogen involved in UTIs which spreads from the rectum to vagina and then ascends up the sterile urinary tract, improving the gut or vaginal flora will thus impact the urinary tract. Since a healthy vaginal microbiota is mainly dominated by Lactobacillus species, in this context, exogenously administered probiotics containing Lactobacilli play a pivotal role in reducing the risk of rUTI. The concept of artificially boosting the Lactobacilli numbers through probiotic administration has long been conceived but has been recently shown to be possible. Lactobacilli may especially be useful for women with a history of recurrent, complicated UTIs or on prolonged antibiotic use. Probiotics do not cause antibiotic resistance and may offer other health benefits due to vaginal re-colonisation with Lactobacilli. However, more comprehensive research is still needed, to recommend for probiotics as an alternative to antibiotics.
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Affiliation(s)
- Varsha Gupta
- Department of Microbiology, Government Medical College Hospital, Chandigarh, India
| | - Deepika Nag
- Department of Microbiology, Government Medical College Hospital, Chandigarh, India
| | - Pratibha Garg
- Department of Microbiology, Government Medical College Hospital, Chandigarh, India
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Tradewell M, Pariser JJ, Nimeh T, Elliott SP. Systematic review and practice policy statements on urinary tract infection prevention in adults with spina bifida. Transl Androl Urol 2018; 7:S205-S219. [PMID: 29928619 PMCID: PMC5989108 DOI: 10.21037/tau.2018.04.21] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 12/03/2022] Open
Abstract
Urinary tract infection (UTI) is a source of morbidity and healthcare costs in adults with spina bifida (ASB). UTI prevention strategies are often recommended, but the evidence of various approaches remains unclear. We performed a systematic review to inform a best practice policy statement for UTI prevention in ASB. On behalf of the Neurogenic Bladder Research Group (NBRG.org), we developed an a priori protocol and searched the published English literature for 30 outcomes questions addressing UTI prevention in ASB. The questions spanned the categories of antibiotics, oral supplements, bladder management factors and social support. Where there was little literature in ASB, we included literature from similar populations with neurogenic bladder (NB). Data was abstracted and then reviewed with recommendations made by consensus of all authors. Level of Evidence (LoE) and Grade of Recommendation (GoR) were according to the Oxford grading system. Of 6,433 articles identified by our search, we included 99 publications. There was sufficient evidence to support use of the following: saline bladder irrigation (LoE 1, GoR B), gentamicin bladder instillation (LoE 3, GoR C), single-use intermittent catheterization (IC) (LoE 2, GoR B), hydrophilic catheters for IC (LoE 2, GoR C), intradetrusor onabotulinumtoxinA injection (LoE 3, GoR C), hyaluronic acid (HA) instillation (LoE 1, GoR B), and care coordination (LoE 3, GoR C). There was sufficient evidence to recommend against use of the following: sterile IC (LoE 1, GoR B), oral antibiotic prophylaxis (LoE 2, GoR B), treatment of asymptomatic bacteriuria (LoE 2, GoR B), cranberry (LoE 2, GoR B), methenamine salts (LoE 1, GoR B), and ascorbic acid (LoE1, GoR B). There was insufficient evidence to make a recommendation for other outcomes. Overall, there are few studies in UTI prevention in the specific population of ASB. Research in populations similar to ASB helps to guide recommendations for UTI prevention in the challenging patient group of ASB. Future studies in UTI prevention specific to ASB are needed and should focus on areas shown to be of benefit in similar populations.
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Affiliation(s)
- Michael Tradewell
- Department of Urology, University of Minnesota, Minneapolis, MN, USA
| | - Joseph J Pariser
- Department of Urology, University of Minnesota, Minneapolis, MN, USA
| | - Tony Nimeh
- Department of Urology, University of Minnesota, Minneapolis, MN, USA
| | - Sean P Elliott
- Department of Urology, University of Minnesota, Minneapolis, MN, USA
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Falcou L, Davido B, Even A, Bouchand F, Salomon J, Sotto A, Denys P, Dinh A. [Original strategy for prevention of recurrent symptomatic urinary tract infections in patients with neurogenic bladder: Bacterial interference, state of the art]. Prog Urol 2018; 28:307-314. [PMID: 29699855 DOI: 10.1016/j.purol.2018.03.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 01/08/2018] [Accepted: 03/14/2018] [Indexed: 12/01/2022]
Abstract
PURPOSE Urinary tract infection (UTI) is the most common complication in patients with neurogenic bladder. The long-term use of antibiotic drugs induces an increase in antimicrobial resistance and adverse drug reactions. Bacterial interference is a new concept to prevent recurrent UTI which consists in a bladder colonization with low virulence bacteria. We performed a literature review on this emerging therapy. MATERIALS AND METHODS Literature review of bacterial interference to prevent symptomatic urinary tract infection in neurological population. RESULTS Seven prospectives study including 3 randomized, double-blind and placebo controlled trial were analyzed. The neurological population was spinal cord injured in most cases. The bladder colonization was performed with 2 non-pathogen strains of Escherichia coli: HU 2117 and 83972. At 1 month, 38 to 83% of patients were colonized. Mean duration of colonization was 48.5 days to 12.3 months. All studies showed that colonization might reduce the number of urinary tract infections and is safe with absence of serious side effects. CONCLUSION Bacterial interference is a promising alternative therapy for the prevention of recurrent symptomatic urinary tract infections in neurogenic patients. This therapy should have developments for a daily use practice and for a long-term efficacy.
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Affiliation(s)
- L Falcou
- Unité d'urodynamique, hôpital universitaire R.-Poincaré, UVSQ, AP-HP, 92380 Garches, France
| | - B Davido
- Unité de maladies infectieuses, hôpital universitaire R.-Poincaré, UVSQ, AP-HP, 104, boulevard R.-Poincaré, 92380 Garches, France
| | - A Even
- Unité d'urodynamique, hôpital universitaire R.-Poincaré, UVSQ, AP-HP, 92380 Garches, France
| | - F Bouchand
- Pharmacie, hôpital universitaire R.-Poincaré, UVSQ, AP-HP, 92380 Garches, France
| | - J Salomon
- Unité de maladies infectieuses, hôpital universitaire R.-Poincaré, UVSQ, AP-HP, 104, boulevard R.-Poincaré, 92380 Garches, France
| | - A Sotto
- Service de maladies infectieuses, CHU de Nîmes, 30189 Nîmes, France
| | - P Denys
- Unité d'urodynamique, hôpital universitaire R.-Poincaré, UVSQ, AP-HP, 92380 Garches, France
| | - A Dinh
- Unité d'urodynamique, hôpital universitaire R.-Poincaré, UVSQ, AP-HP, 92380 Garches, France; Unité de maladies infectieuses, hôpital universitaire R.-Poincaré, UVSQ, AP-HP, 104, boulevard R.-Poincaré, 92380 Garches, France.
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28
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Gerber D, Forster CS, Hsieh M. The Role of the Genitourinary Microbiome in Pediatric Urology: a Review. Curr Urol Rep 2018; 19:13. [PMID: 29468401 DOI: 10.1007/s11934-018-0763-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW In this review, we highlight the effects of the microbiome on urologic diseases that affect the pediatric patient. RECENT FINDINGS Perturbations in the urinary microbiome have been shown to be associated with a number of urologic diseases affecting children, namely urinary tract infection, overactive bladder/urge urinary incontinence, and urolithiasis. Recently, improved cultivation and sequencing technologies have allowed for the discovery of a significant and diverse microbiome in the bladder, previously assumed to be sterile. Early studies aimed to identify the resident bacterial species and demonstrate the efficacy of sequencing and enhanced quantitative urine culture. More recently, research has sought to elucidate the association between the microbiome and urologic disease, as well as to demonstrate effects of manipulation of the microbiome on various urologic pathologies. With an improved appreciation for the impact of the urinary microbiome on urologic disease, researchers have begun to explore the impact of these resident bacteria in pediatric urology.
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Affiliation(s)
- Daniel Gerber
- Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC, 20007, USA
| | - Catherine S Forster
- Children's National Health System, 111 Michigan Avenue NW Suite M4800, Washington, DC, 20010, USA.,Biomedical Research Institute, 9410 Key West Avenue, Rockville, MD, 20850, USA
| | - Michael Hsieh
- Children's National Health System, 111 Michigan Avenue NW Suite M4800, Washington, DC, 20010, USA. .,Biomedical Research Institute, 9410 Key West Avenue, Rockville, MD, 20850, USA.
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29
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Segev G, Sykes JE, Klumpp DJ, Schaeffer AJ, Antaki EM, Byrne BA, Yaggie RE, Westropp JL. Evaluation of the Live Biotherapeutic Product, Asymptomatic Bacteriuria Escherichia coli 2-12, in Healthy Dogs and Dogs with Clinical Recurrent UTI. J Vet Intern Med 2017; 32:267-273. [PMID: 29243301 PMCID: PMC5787194 DOI: 10.1111/jvim.14851] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Revised: 07/21/2017] [Accepted: 08/30/2017] [Indexed: 12/03/2022] Open
Abstract
Background Antimicrobial resistance is an emerging problem. Hypothesis/Objective To investigate the safety and efficacy of a live biotherapeutic product, ASB E. coli 2‐12 for UTI treatment. Animals Six healthy research dogs; nine client‐owned dogs with recurrent UTI. Methods Prospective noncontrolled clinical trial. For safety data, research dogs were sedated, a urinary catheter was inserted into the bladder; 1010CFU/mL of ASB E. coli 2‐12 was instilled. Urine was cultured on days 1, 3, and 8 post‐instillation and dogs were observed for lower urinary tract signs (LUTS). For client‐owned dogs, ASB E. coli 2‐12 was instilled similarly and urine cultures analyzed on days 1, 7, and 14 days postinstillation. Results No LUTS were noted in any of the 6 research dogs after ASB E. coli 2‐12 infusion. Pulse field gel electrophoresis (PFGE) studies confirmed the bacterial strains isolated matched that ASB E. coli 2‐12 strain. Four of the nine client‐owned dogs had complete or nearly complete clinical cures by day 14. Of these four dogs, 3 also had microbiologic cures at day 14; one of these dogs had subclinical bacteriuria (in addition to ASB E. coli 2‐12). Three of these four dogs had ASB E. coli 2‐12 isolated from their urine at day 14. With the exception of mild, temporary, self‐limiting, hyporexia in two dogs on the day of biotherapeutic administration, there were no major adverse effects. Conclusions and Clinical Importance These results suggest ASB E. coli 2‐12 is safe and should be investigated in a larger controlled study evaluating clinical UTI in dogs.
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Affiliation(s)
- G Segev
- Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot, Israel
| | - J E Sykes
- Departments of Veterinary Medicine and Epidemiology, University of California Davis, Davis, CA
| | - D J Klumpp
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - A J Schaeffer
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - E M Antaki
- Western Center for Food Safety, University of California Davis, Davis, CA
| | - B A Byrne
- Department of Pathology, Microbiology and Immunology, University of California Davis, Davis, CA
| | - R E Yaggie
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - J L Westropp
- Departments of Veterinary Medicine and Epidemiology, University of California Davis, Davis, CA
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30
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Ohlemacher SI, Giblin DE, d'Avignon DA, Stapleton AE, Trautner BW, Henderson JP. Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria. J Clin Invest 2017; 127:4018-4030. [PMID: 28945201 DOI: 10.1172/jci92464] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 08/02/2017] [Indexed: 11/17/2022] Open
Abstract
Escherichia coli and other Enterobacteriaceae are among the most common pathogens of the human urinary tract. Among the genetic gains of function associated with urinary E. coli isolates is the Yersinia high pathogenicity island (HPI), which directs the biosynthesis of yersiniabactin (Ybt), a virulence-associated metallophore. Using a metabolomics approach, we found that E. coli and other Enterobacteriaceae expressing the Yersinia HPI also secrete escherichelin, a second metallophore whose chemical structure matches a known synthetic inhibitor of the virulence-associated pyochelin siderophore system in Pseudomonas aeruginosa. We detected escherichelin during clinical E. coli urinary tract infection (UTI) and experimental human colonization with a commensal, potentially probiotic E. coli bacteriuria strain. Escherichelin production by colonizing enterobacteria may help human hosts resist opportunistic infections by Pseudomonas and other pyochelin-expressing bacteria. This siderophore-based mechanism of microbial antagonism may be one of many elements contributing to the protective effects of the human microbiome. Future UTI-preventive probiotic strains may benefit by retaining the escherichelin biosynthetic capacity of the Yersinia HPI while eliminating the Ybt biosynthetic capacity.
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Affiliation(s)
- Shannon I Ohlemacher
- Center for Women's Infectious Diseases Research.,Division of Infectious Diseases.,Department of Internal Medicine, and
| | - Daryl E Giblin
- Department of Chemistry, Washington University, St. Louis, Missouri, USA
| | - D André d'Avignon
- Department of Chemistry, Washington University, St. Louis, Missouri, USA
| | - Ann E Stapleton
- Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
| | - Barbara W Trautner
- The Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.,Section of Infectious Diseases, Departments of Medicine and Surgery, Baylor College of Medicine, Houston, Texas, USA
| | - Jeffrey P Henderson
- Center for Women's Infectious Diseases Research.,Division of Infectious Diseases.,Department of Internal Medicine, and
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31
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Toh S, Boswell‐Ruys CL, Lee BSB, Simpson JM, Clezy KR, Cochrane Kidney and Transplant Group. Probiotics for preventing urinary tract infection in people with neuropathic bladder. Cochrane Database Syst Rev 2017; 9:CD010723. [PMID: 28884476 PMCID: PMC6483743 DOI: 10.1002/14651858.cd010723.pub2] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Neuropathic or neurogenic bladder describes a process of dysfunctional voiding as the result of injury in the brain, spinal cord or nerves innervating the bladder. People with neuropathic bladder, such as from spinal cord injury (SCI), are at significant risk of morbidity from urinary tract infections (UTI). Effective methods to prevent UTI in people with SCI have been sought for many years. Probiotics (micro-organisms that exert beneficial health effects in the host) have been recommended for bacterial interference of the urological tract to reduce colonisation by uropathogen and to manage the dual problems of infection and antibiotic resistance. OBJECTIVES This review looked at the benefits and harms of probiotics in preventing symptomatic UTI in people with neuropathic bladder compared with placebo, no therapy, or non-antibiotic prophylaxis (cranberry juice, methenamine hippurate, topical oestrogen). SEARCH METHODS We searched the Cochrane Kidney and Transplant Specialised Register up to 10 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA All randomised controlled trials (RCTs), quasi-RCTs and cross-over RCTs looking at the use of probiotics for the prophylaxis of UTI in people with neuropathic bladders was considered for inclusion. Men, women and children of all ages with neuropathic bladders from neurological injury such as suprapontine, supra sacral and sacral aetiologies was included. All bladder management types, including reflex voiding, time voiding, indwelling and intermittent catheterization were eligible for this review.Studies comparing probiotics to placebo, no treatment or other non-antibiotic prophylaxis was included. Studies comparing probiotics with antibiotics or in combination with antibiotics were excluded. DATA COLLECTION AND ANALYSIS Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI were planned for continuous outcomes. MAIN RESULTS This review includes a total of three studies (one cross-over and two parallel RCTs) which involved 110 participants. All three studies looked at intravesical instillation of a low virulent Escherichia coli (E. coli) strain in reducing the risk of symptomatic UTI in participants with neuropathic bladder, predominantly from SCI. Two studies used the E. coli 83972 strain and one study used the E. coli HU2117 strain.We did not find any RCTs involving other probiotics or other routes of administration for preventing UTI in people with neuropathic bladder.There was consistency in definition of symptomatic UTI in all three studies. Symptoms that all studies considered were relevant to diagnose UTI were adequately defined. All three studies defined microbiological diagnosis of symptomatic UTI.Asymptomatic bacteriuria was not considered an outcome measure in any of the included studies; however it was defined in two studies to establish successful inoculation.It is uncertain if the risk of symptomatic UTI is reduced with bladder inoculation using E. coli because the certainty of the evidence is very low (3 studies, 110 participants: RR 0.32, 95% CI 0.08 to 1.19; I2 = 82%).Two studies reported adverse events. One study reported one episode of autonomic dysreflexia. One study reported three symptomatic UTI occurring in two patients, and two studies mentioned the absence of septicaemia and pyelonephritis. Intravesical instillation was reported as "generally safe". One study reported high attrition rates in participants due to the need to adhere to strict instillation protocols.The overall quality of the studies was poor. All three studies had high risk of attrition bias due to failure of an intention-to-treat analysis which undermines the randomisation process and weakened the results of the studies. All three studies also had high risk of reporting bias. AUTHORS' CONCLUSIONS In this review, there were no studies identified addressing oral probiotics in preventing UTI in people with neuropathic bladder. It is uncertain if the risk of symptomatic UTI is reduced in people with neuropathic bladders via intravesical instillation of non-pathogenic E. coli as data were derived from small studies with high risk of bias.Although very minimal levels of harm was reported with this procedure, due to variable success rates, the need for strict adherence to instillation protocols together with high attrition rates in these studies, it is doubtful bladder instillation will be a widely accepted intervention in its current form.It is recommended that further appropriately powered RCTs with more robust methodological reporting be carried out.
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Affiliation(s)
- Swee‐Ling Toh
- Prince of Wales HospitalSpinal Medicine DepartmentLevel 2, High Street EntranceRandwickNSWAustralia2031
| | | | - Bon San B Lee
- Prince of Wales HospitalSpinal Medicine DepartmentLevel 2, High Street EntranceRandwickNSWAustralia2031
| | - Judy M Simpson
- The University of SydneySydney School of Public HealthEdward Ford Building, A27SydneyNSWAustralia2006
| | - Kate R Clezy
- Prince of Wales HospitalInfectious DiseasesBarker StreetRandwickNSWAustralia2031
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Bossa L, Kline K, McDougald D, Lee BB, Rice SA. Urinary catheter-associated microbiota change in accordance with treatment and infection status. PLoS One 2017; 12:e0177633. [PMID: 28628622 PMCID: PMC5476236 DOI: 10.1371/journal.pone.0177633] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Accepted: 05/01/2017] [Indexed: 12/25/2022] Open
Abstract
The use of long-term catheterisation to manage insensate bladders, often associated with spinal cord injury (SCI), increases the risk of microbial colonisation and infection of the urinary tract. Urinary tract infection (UTI) is typically diagnosed and treated based on the culturing of organisms from the urine, although this approach overlooks low titer, slow growing and non-traditional pathogens. Here, we present an investigation of the urinary tract microbiome in catheterised SCI individuals, using T-RFLP and metagenomic sequencing of the microbial community. We monitored three neurogenic patients over a period of 12 months, who were part of a larger study investigating the efficacy of probiotics in controlling UTIs, to determine how their urinary tract microbial community composition changed over time and in relation to probiotic treatment regimens. Bacterial biofilms adherent to urinary catheters were examined as a proxy for bladder microbes. The microbial community composition of the urinary tract differed significantly between individuals. Probiotic therapy resulted in a significant change in the microbial community associated with the catheters. The community also changed as a consequence of UTI and this shift in community composition preceded the clinical diagnosis of infection. Changes in the microbiota due to probiotic treatment or infection were transient, resolving to microbial communities similar to their pre-treatment communities, suggesting that the native community was highly resilient. Based on these results, we propose that monitoring a patient's microbial community can be used to track the health of chronically catheterized patients and thus, can be used as part of a health-status monitoring program.
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Affiliation(s)
- Laetitia Bossa
- Neuroscience Research Australia (NEURA), Sydney, New South Wales, Australia
| | - Kimberly Kline
- The Singapore Centre for Environmental Life Sciences Engineering, The School of Biological Sciences, Nanyang Technological University, Singapore
| | - Diane McDougald
- The Singapore Centre for Environmental Life Sciences Engineering, The School of Biological Sciences, Nanyang Technological University, Singapore
- The ithree Institute, The University of Technology Sydney, Sydney NSW Australia
| | - Bonsan Bonne Lee
- Neuroscience Research Australia (NEURA), Sydney, New South Wales, Australia
- Prince of Wales Hospital, Spinal Medicine Department, Randwick, NSW, Australia
| | - Scott A. Rice
- The Singapore Centre for Environmental Life Sciences Engineering, The School of Biological Sciences, Nanyang Technological University, Singapore
- The ithree Institute, The University of Technology Sydney, Sydney NSW Australia
- The Centre for Marine Bio-Innovation, The School of Biological, Earth and Environmental Sciences, The University of New South Wales, Sydney, NSW Australia
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33
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Azithromycin-Ciprofloxacin-Impregnated Urinary Catheters Avert Bacterial Colonization, Biofilm Formation, and Inflammation in a Murine Model of Foreign-Body-Associated Urinary Tract Infections Caused by Pseudomonas aeruginosa. Antimicrob Agents Chemother 2017; 61:AAC.01906-16. [PMID: 28031194 DOI: 10.1128/aac.01906-16] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 12/12/2016] [Indexed: 11/20/2022] Open
Abstract
Pseudomonas aeruginosa is a multifaceted pathogen causing a variety of biofilm-mediated infections, including catheter-associated urinary tract infections (CAUTIs). The high prevalence of CAUTIs in hospitals, their clinical manifestations, such as urethritis, cystitis, pyelonephritis, meningitis, urosepsis, and death, and the associated economic challenges underscore the need for management of these infections. Biomaterial modification of urinary catheters with two drugs seems an interesting approach to combat CAUTIs by inhibiting biofilm. Previously, we demonstrated the in vitro efficacy of urinary catheters impregnated with azithromycin (AZM) and ciprofloxacin (CIP) against P. aeruginosa Here, we report how these coated catheters impact the course of CAUTI induced by P. aeruginosa in a murine model. CAUTI was established in female LACA mice with uncoated or AZM-CIP-coated silicone implants in the bladder, followed by transurethral inoculation of 108 CFU/ml of biofilm cells of P. aeruginosa PAO1. AZM-CIP-coated implants (i) prevented biofilm formation on the implant's surface (P ≤ 0.01), (ii) restricted bacterial colonization in the bladder and kidney (P < 0.0001), (iii) averted bacteriuria (P < 0.0001), and (iv) exhibited no major histopathological changes for 28 days in comparison to uncoated implants, which showed persistent CAUTI. Antibiotic implants also overcame implant-mediated inflammation, as characterized by trivial levels of inflammatory markers such as malondialdehyde (P < 0.001), myeloperoxidase (P < 0.05), reactive oxygen species (P ≤ 0.001), and reactive nitrogen intermediates (P < 0.01) in comparison to those in uncoated implants. Further, AZM-CIP-coated implants showed immunomodulation by manipulating the release of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-10 to the benefit of the host. Overall, the study demonstrates long-term in vivo effectiveness of AZM-CIP-impregnated catheters, which may possibly be a key to success in preventing CAUTIs.
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34
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Abstract
Urinary tract infections (UTI) are among the most common bacterial infections in humans, affecting millions of people every year. UTI cause significant morbidity in women throughout their lifespan, in infant boys, in older men, in individuals with underlying urinary tract abnormalities, and in those that require long-term urethral catheterization, such as patients with spinal cord injuries or incapacitated individuals living in nursing homes. Serious sequelae include frequent recurrences, pyelonephritis with sepsis, renal damage in young children, pre-term birth, and complications of frequent antimicrobial use including high-level antibiotic resistance and Clostridium difficile colitis. Uropathogenic E. coli (UPEC) cause the vast majority of UTI, but less common pathogens such as Enterococcus faecalis and other enterococci frequently take advantage of an abnormal or catheterized urinary tract to cause opportunistic infections. While antibiotic therapy has historically been very successful in controlling UTI, the high rate of recurrence remains a major problem, and many individuals suffer from chronically recurring UTI, requiring long-term prophylactic antibiotic regimens to prevent recurrent UTI. Furthermore, the global emergence of multi-drug resistant UPEC in the past ten years spotlights the need for alternative therapeutic and preventative strategies to combat UTI, including anti-infective drug therapies and vaccines. In this chapter, we review recent advances in the field of UTI pathogenesis, with an emphasis on the identification of promising drug and vaccine targets. We then discuss the development of new UTI drugs and vaccines, highlighting the challenges these approaches face and the need for a greater understanding of urinary tract mucosal immunity.
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35
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Garcia-Arguello LY, O'Horo JC, Farrell A, Blakney R, Sohail MR, Evans CT, Safdar N. Infections in the spinal cord-injured population: a systematic review. Spinal Cord 2016; 55:526-534. [PMID: 27922625 DOI: 10.1038/sc.2016.173] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 10/27/2016] [Accepted: 10/30/2016] [Indexed: 11/09/2022]
Abstract
STUDY DESIGN Spinal cord injury (SCI) patients are an increasing population due to recent military conflicts. SCI patients are at an increased risk of infection, but the epidemiology management and prevention strategies for these infections are unclear. OBJECTIVE To review the incidence, microbiology and management of pneumonia, skin and soft tissue infections (SSTI), urinary tract infections (UTI) and bloodstream infections in the SCI population via literature review. METHODS With the assistance of an experienced medical librarian, we developed a search strategy for the Ovid MEDLINE database and then adapted it for the Ovid Embase, Scopus and Web of Science databases. The databases were searched from their inception to April 2014 with no restrictions on language or time period. Data were extracted using a standardized form. All studies were reviewed by two independent investigators. RESULTS Forty-one studies reporting on the described infections were identified. UTIs were the most commonly identified infections, but studies failed to identify consistently effective preventive strategies. SSTIs were also common, and the best preventive strategies focused on decubitus ulcer prevention and skin decolonization protocols. Pneumonia management and course were not significantly different from the general population. Bloodstream infections were associated with delays in recognition, and were most often secondary to UTI, pneumonia or SSTI. CONCLUSION There is a paucity of literature on consistently effective infection prevention strategies in SCI patients. Identification and implementation of evidence-based interventions that optimize prevention and management of infections in this patient population are needed.
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Affiliation(s)
- L Y Garcia-Arguello
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.,Multidisciplinary Epidemiology and Translational Research in Critical Care (METRIC) Group, Mayo Clinic, Rochester, MN, USA
| | - J C O'Horo
- Multidisciplinary Epidemiology and Translational Research in Critical Care (METRIC) Group, Mayo Clinic, Rochester, MN, USA.,Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN, USA
| | - A Farrell
- Department of Library Services, Mayo Clinic, Rochester, MN, USA
| | - R Blakney
- Center of Innovation for Complex Chronic Healthcare and Spinal Cord Injury Quality Enhancement Research Initiative, Edward Hines Jr. VA Hospital, Hines, IL, USA.,Department of Preventive Medicine and Center for Healthcare Studies, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - M R Sohail
- Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN, USA
| | - C T Evans
- Center of Innovation for Complex Chronic Healthcare and Spinal Cord Injury Quality Enhancement Research Initiative, Edward Hines Jr. VA Hospital, Hines, IL, USA.,Department of Preventive Medicine and Center for Healthcare Studies, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - N Safdar
- Department of Medicine, Section of Infectious Diseases, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.,William S. Middleton Veterans Affairs Hospital, Madison, WI, USA
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36
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Xu B, Du Y, Lin J, Qi M, Shu B, Wen X, Liang G, Chen B, Liu D. Simultaneous Identification and Antimicrobial Susceptibility Testing of Multiple Uropathogens on a Microfluidic Chip with Paper-Supported Cell Culture Arrays. Anal Chem 2016; 88:11593-11600. [PMID: 27934103 DOI: 10.1021/acs.analchem.6b03052] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Affiliation(s)
- Banglao Xu
- Department
of Laboratory Medicine, Guangzhou First People’s Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
- Clinical Molecular Medicine and Molecular Diagnosis Key Laboratory of Guangdong Province, Guangzhou 510180, China
| | - Yan Du
- Department
of Laboratory Medicine, Guangzhou First People’s Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
| | - Jinqiong Lin
- Department
of Laboratory Medicine, Guangzhou First People’s Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
| | - Mingyue Qi
- Department
of Laboratory Medicine, Guangzhou First People’s Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
| | - Bowen Shu
- Department
of Laboratory Medicine, Guangzhou First People’s Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
- Clinical Molecular Medicine and Molecular Diagnosis Key Laboratory of Guangdong Province, Guangzhou 510180, China
| | - Xiaoxia Wen
- Department
of Laboratory Medicine, Guangzhou First People’s Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
| | - Guangtie Liang
- Department
of Laboratory Medicine, Guangzhou First People’s Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
- Clinical Molecular Medicine and Molecular Diagnosis Key Laboratory of Guangdong Province, Guangzhou 510180, China
| | - Bin Chen
- Department
of Laboratory Medicine, Guangzhou First People’s Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
- Clinical Molecular Medicine and Molecular Diagnosis Key Laboratory of Guangdong Province, Guangzhou 510180, China
| | - Dayu Liu
- Department
of Laboratory Medicine, Guangzhou First People’s Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
- Clinical Molecular Medicine and Molecular Diagnosis Key Laboratory of Guangdong Province, Guangzhou 510180, China
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Abstract
Asymptomatic bacteriuria is very common. In healthy women, asymptomatic bacteriuria increases with age, from <1% in newborns to 10% to 20% of women age 80 years, but is uncommon in men until after age 50 years. Individuals with underlying genitourinary abnormalities, including indwelling devices, may also have a high frequency of asymptomatic bacteriuria, irrespective of age or gender. The prevalence is very high in residents of long-term-care facilities, from 25% to 50% of women and 15% to 40% of men. Escherichia coli is the most frequent organism isolated, but a wide variety of other organisms may occur. Bacteriuria may be transient or persist for a prolonged period. Pregnant women with asymptomatic bacteriuria identified in early pregnancy and who are untreated have a risk of pyelonephritis later in pregnancy of 20% to 30%. Bacteremia is frequent in bacteriuric subjects following mucosal trauma with bleeding, with 5% to 10% of patients developing severe sepsis or septic shock. These two groups with clear evidence of negative outcomes should be screened for bacteriuria and appropriately treated. Asymptomatic bacteriuria in other populations is benign and screening and treatment are not indicated. Antimicrobial treatment has no benefits but is associated with negative outcomes including reinfection with antimicrobial resistant organisms and a short-term increased frequency of symptomatic infection post-treatment. The observation of increased symptomatic infection post-treatment, however, has led to active investigation of bacterial interference as a strategy to prevent symptomatic episodes in selected high risk patients.
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Wullt B, Svanborg C. Deliberate Establishment of Asymptomatic Bacteriuria-A Novel Strategy to Prevent Recurrent UTI. Pathogens 2016; 5:E52. [PMID: 27483325 PMCID: PMC5039432 DOI: 10.3390/pathogens5030052] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 07/19/2016] [Accepted: 07/21/2016] [Indexed: 01/06/2023] Open
Abstract
We have established a novel strategy to reduce the risk for recurrent urinary tract infection (UTI), where rapidly increasing antibiotic resistance poses a major threat. Epidemiologic studies have demonstrated that asymptomatic bacteriuria (ABU) protects the host against symptomatic infections with more virulent strains. To mimic this protective effect, we deliberately establish ABU in UTI-prone patients, who are refractory to conventional therapy. The patients are inoculated with Escherichia coli (E. coli) 83972, now widely used as a prototype ABU strain. Therapeutic efficacy has been demonstrated in a placebo-controlled trial, supporting the feasibility of using E. coli 83972 as a tool to prevent recurrent UTI and, potentially, to outcompete antibiotic-resistant strains from the human urinary tract. In addition, the human inoculation protocol offers unique opportunities to study host-parasite interaction in vivo in the human urinary tract. Here, we review the clinical evidence for protection using this approach as well as some molecular insights into the pathogenesis of UTI that have been gained during these studies.
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Affiliation(s)
- Björn Wullt
- Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, 221 00 Lund, Sweden.
| | - Catharina Svanborg
- Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, 221 00 Lund, Sweden.
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39
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Cooper FPM, Alexander CE, Sinha S, Omar MI, Cochrane Incontinence Group. Policies for replacing long-term indwelling urinary catheters in adults. Cochrane Database Syst Rev 2016; 7:CD011115. [PMID: 27457774 PMCID: PMC6457973 DOI: 10.1002/14651858.cd011115.pub2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Long-term indwelling catheters are used commonly in people with lower urinary tract problems in home, hospital and specialised health-care settings. There are many potential complications and adverse effects associated with long-term catheter use. The effect of health-care policies related to the replacement of long-term urinary catheters on patient outcomes is unclear. OBJECTIVES To determine the effectiveness of different policies for replacing long-term indwelling urinary catheters in adults. SEARCH METHODS We searched the Cochrane Incontinence Specialised Trials Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 19 May 2016), and the reference lists of relevant articles. SELECTION CRITERIA All randomised controlled trials investigating policies for replacing long-term indwelling urinary catheters in adults were included. DATA COLLECTION AND ANALYSIS At least two review authors independently performed data extraction and assessed risk of bias of all the included trials. Quality of evidence was assessed by adopting the GRADE approach. Any discrepancies were resolved by discussion between the review authors or an independent arbitrator. We contacted the authors of included trials to seek clarification where required. MAIN RESULTS Three trials met the inclusion criteria, with a total of 107 participants in three different health-care settings: A USA veterans administration nursing home; a geriatric centre in Israel; and a community nursing service in Hong Kong. Data were available for three of the pre-stated comparisons. Priefer and colleagues evaluated different time intervals between catheter replacement (n = 17); Firestein and colleagues evaluated the use of antibiotic prophylaxis at the time of replacement (n = 70); and Cheung and colleagues compared two different types of cleaning solutions (n = 20).All the included trials were small and under-powered. The reporting of the trials was inadequate and as a result, risk of bias assessment was judged to be unclear for the majority of the domains in two out of the three trials. There was insufficient evidence to indicate that (i) there was a lower incidence of symptomatic UTI in people whose catheter was changed both monthly and when clinically indicated (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.13 to 0.95; very low quality evidence) compared to only when clinically indicated, (ii) there was not enough evidence to assess the effect of antibiotic prophylaxis on reducing: positive urine cultures at 7 days (RR 0.91, 95% CI 0.79 to 1.04); infection (RR 1.41, 95% CI 0.55 to 3.65); or death (RR 2.12, 95% CI 0.20 to 22.30; very low quality evidence), (iii) there was no statistically significant difference in the incidence of asymptomatic bacteruria at 7 days (RR 0.80, 95% CI 0.42 to 1.52) between people receiving water or chlorhexidine solution for periurethral cleansing at the time of catheter replacement. However, none of the 16 participants developed a symptomatic catheter-associated urinary tract infection (CAUTI) at day 14.The following outcomes were considered critical for decision-making and were also selected for the 'Summary of findings' table: (i) participant satisfaction, (ii) condition-specific quality of life, (iii) urinary tract trauma, and (iv) formal economic analysis. However, none of the trials reported these outcomes.None of the trials compared the following comparisons: (i) replacing catheter versus other policy e.g. washouts, (ii) replacing in the home environment versus clinical environment, (iii) clean versus aseptic technique for replacing catheter, (iv) lubricant A versus lubricant B or no lubricant, and (v) catheter user versus carer versus health professional performing the catheter replacement procedure. AUTHORS' CONCLUSIONS There is currently insufficient evidence to assess the value of different policies for replacing long-term urinary catheters on patient outcomes. In particular, there are a number of policies for which there are currently no trial data; and a number of important outcomes which have not been assessed, including patient satisfaction, quality of life, urinary tract trauma, and economic outcomes. There is an immediate need for rigorous, adequately powered randomised controlled trials which assess important clinical outcomes and abide by the principles and recommendations of the CONSORT statement.
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Affiliation(s)
- Fergus PM Cooper
- University of AberdeenAcademic Urology UnitHealth Sciences BuildingForesterhillAberdeenUKAB25 2ZD
| | - Cameron Edwin Alexander
- University of AberdeenAcademic Urology UnitHealth Sciences BuildingForesterhillAberdeenUKAB25 2ZD
| | | | - Muhammad Imran Omar
- University of AberdeenAcademic Urology UnitHealth Sciences BuildingForesterhillAberdeenUKAB25 2ZD
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Lee BB, Toh SL, Ryan S, Simpson JM, Clezy K, Bossa L, Rice SA, Marial O, Weber G, Kaur J, Boswell-Ruys C, Goodall S, Middleton J, Tudehope M, Kotsiou G. Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial. BMC Urol 2016; 16:18. [PMID: 27084704 PMCID: PMC4833921 DOI: 10.1186/s12894-016-0136-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 03/28/2016] [Indexed: 01/20/2023] Open
Abstract
Background Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. Method This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons with SCI. The primary outcome will be analysed using survival analysis of factorial groups, with Cox regression modelling to test the effect of each treatment while allowing for the other, assuming no interaction effect. Hazard ratios and Kaplan-Meier survival curves will be used to summarise results. Discussion If these probiotics are shown to be effective in preventing UTI and MRO colonisation, they would be a very attractive alternative for UTI prophylaxis and for combating the increasing rate of antibiotic resistance after SCI. Trial registration Australian New Zealand Clinical Trials Registry [ACTRN 12610000512022]. Date of registration: 21 June 2010. Electronic supplementary material The online version of this article (doi:10.1186/s12894-016-0136-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Bonsan Bonne Lee
- Neuroscience Research Australia [NeuRA] and the University of New South Wales, Sydney, Australia.,Department of Spinal and Rehabilitation Medicine, Prince of Wales Hospital, Sydney, Australia
| | - Swee-Ling Toh
- Department of Spinal and Rehabilitation Medicine, Prince of Wales Hospital, Sydney, Australia. .,School of Public Health, University of Sydney, Sydney, Australia.
| | - Suzanne Ryan
- Neuroscience Research Australia [NeuRA] and the University of New South Wales, Sydney, Australia
| | - Judy M Simpson
- School of Public Health, University of Sydney, Sydney, Australia
| | - Kate Clezy
- Department of Infectious Diseases, Prince of Wales Hospital, Sydney, Australia
| | - Laetitia Bossa
- Neuroscience Research Australia [NeuRA] and the University of New South Wales, Sydney, Australia.,Centre for Marine Bio-Innovation, University of New South Wales, Sydney, Australia
| | - Scott A Rice
- Centre for Marine Bio-Innovation, University of New South Wales, Sydney, Australia.,The Singapore Centre for Life Sciences Engineering and the School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
| | - Obaydullah Marial
- Department of Spinal and Rehabilitation Medicine, Prince of Wales Hospital, Sydney, Australia.,Royal Rehabilitation Centre Sydney, Sydney, Australia.,Royal North Shore Hospital, Sydney, Australia
| | - Gerard Weber
- Royal Rehabilitation Centre Sydney, Sydney, Australia
| | | | - Claire Boswell-Ruys
- Neuroscience Research Australia [NeuRA] and the University of New South Wales, Sydney, Australia
| | - Stephen Goodall
- Centre for Health Economics Research and Evaluation [CHERE], University of Technology Sydney, Sydney, Australia
| | - James Middleton
- John Walsh Centre for Rehabilitation Research, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, 2065, Australia.,Sydney Medical School Northern, University of Sydney, Sydney, Australia
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Michau A, Dinh A, Denys P, Levy J, Chartier-Kastler E, Bernard L, Dommergues M, Nizard J. Control Cross-sectional Study Evaluating an Antibiotic Prevention Strategy in 30 Pregnancies Under Clean Intermittent Self-catheterization and Review of Literature. Urology 2016; 91:58-63. [PMID: 26905030 DOI: 10.1016/j.urology.2016.02.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 01/22/2016] [Accepted: 02/03/2016] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To assess the efficacy and safety of a weekly oral cycling antibiotic (WOCA) strategy to prevent UTI in women. MATERIALS AND METHODS We performed a monocentric, comparative, retrospective, cross-sectional study on pregnant women under clean intermittent self catheterization between January 2008 and December 2014. WOCA consisted the administration of a single-dose antibiotic, alternating antibiotic A and B once every 2 weeks, according to previous urine cultures. RESULTS Twenty-five women carried out 30 pregnancies. Thirteen pregnancies (43.3%) were in the WOCA group (WCG) strategy and 17 were in the non-WOCA group (NWCG) (56.7%). In the 19 (63.3%) pregnancies with urinary tract infection (UTI), 5 (38.4%) were in WCG, 14 (82.3%) were not (P = .023). There were more cystitis in NWCG (76.5% vs 23.1% P = .009) but more colonization in WCG (46.2% vs 5.8% P = .025). UTIs were due to Escherichia coli, Enterobacter cloacae, and Klebsiella pneumoniae. There was a nonsignificant increase in preterm birth in NWCG (35.3% vs 7.7% P = .10), no small for gestational age neonates, and no significant difference for the mode of delivery, birthweight, and neonatal outcome. CONCLUSION According to our result, WOCA seems safe and effective on symptomatic UTI frequency and could be promoted to help physicians to manage specific risks in pregnancy.
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Affiliation(s)
- Adélie Michau
- Department of Obstetrics and Gynaecology, APHP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Aurélien Dinh
- Infectious Disease Department, APHP, Hôpitaux Universitaires Paris Ile de France Ouest, Garches, France
| | - Pierre Denys
- Neuro Urology Unit, APHP, Hôpitaux Universitaires Paris Ile de France Ouest, Garches, France
| | - Jonathan Levy
- Physical Medicine and Rehabiltation, APHP, Hôpitaux Universitaires Paris Ile de France Ouest, Garches, France
| | | | - Louis Bernard
- Infectious Disease Department, Hôpital Universitaire Bretonneau, Tours, France
| | - Marc Dommergues
- Department of Obstetrics and Gynaecology, APHP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Jacky Nizard
- Department of Obstetrics and Gynaecology, APHP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Sorbonne Université, CNRS UMR 7222, INSERM U1150, UPMC Univ Paris 06, Paris, France.
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Saini H, Chhibber S, Harjai K. Antimicrobial and antifouling efficacy of urinary catheters impregnated with a combination of macrolide and fluoroquinolone antibiotics against Pseudomonas aeruginosa. BIOFOULING 2016; 32:511-522. [PMID: 26982572 DOI: 10.1080/08927014.2016.1155564] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
The incidence of catheter associated urinary tract infections (CAUTIs) is increasing worldwide. This study was designed to modify a biomaterial by impregnating a silicone urinary catheter with combination of a macrolide, azithromycin (AZM) and a fluoroquinolone, ciprofloxacin (CIP). Drug release profiles showed slow yet continuous release of antibiotics from catheters for one month. In vitro efficacy testing showed that group B catheters [3% (w v(-1)) CIP + 6% (w v(-1)) AZM] outperformed group A catheters [2% (w v(-1)) CIP + 5% (w v(-1)) AZM] by (1) showing larger zones of inhibition (>31 mm) compared to group A (<28 mm) for up to 30 days against Pseudomonas aeruginosa PAO1; (2) killing adhered bacteria in 24 h compared to 24-48 h in group A; (3) showing longer antimicrobial durability for four weeks; and (4) exhibiting a stable real-time shelf life of one year, suggesting that these catheters can be explored in clinical settings, especially in long-term CAUTI.
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Affiliation(s)
- Hina Saini
- a Department of Microbiology, Basic Medical Sciences Block I , Panjab University , Chandigarh , India
| | - Sanjay Chhibber
- a Department of Microbiology, Basic Medical Sciences Block I , Panjab University , Chandigarh , India
| | - Kusum Harjai
- a Department of Microbiology, Basic Medical Sciences Block I , Panjab University , Chandigarh , India
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Zowawi HM, Harris PNA, Roberts MJ, Tambyah PA, Schembri MA, Pezzani MD, Williamson DA, Paterson DL. The emerging threat of multidrug-resistant Gram-negative bacteria in urology. Nat Rev Urol 2015; 12:570-84. [PMID: 26334085 DOI: 10.1038/nrurol.2015.199] [Citation(s) in RCA: 250] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
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.
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Affiliation(s)
- Hosam M Zowawi
- The University of Queensland, UQ Centre for Clinical Research, Building 71/918 Royal Brisbane Hospital, Herston, QLD 4006, Australia
| | - Patrick N A Harris
- The University of Queensland, UQ Centre for Clinical Research, Building 71/918 Royal Brisbane Hospital, Herston, QLD 4006, Australia
| | - Matthew J Roberts
- The University of Queensland, UQ Centre for Clinical Research, Building 71/918 Royal Brisbane Hospital, Herston, QLD 4006, Australia
| | - Paul A Tambyah
- Division of Infectious Diseases, National University Health System, 1E Kent Ridge Road, 119228, Singapore
| | - Mark A Schembri
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
| | - M Diletta Pezzani
- Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, G. B. Grassi 74, 20157 Milan, Italy
| | - Deborah A Williamson
- Department of Pathology, University of Otago, 23A Mein Street, Newtown, Wellington 6242, New Zealand
| | - David L Paterson
- The University of Queensland, UQ Centre for Clinical Research, Building 71/918 Royal Brisbane Hospital, Herston, QLD 4006, Australia
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Tewary K, Narchi H. Recurrent urinary tract infections in children: Preventive interventions other than prophylactic antibiotics. World J Methodol 2015; 5:13-19. [PMID: 26140267 PMCID: PMC4482817 DOI: 10.5662/wjm.v5.i2.13] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Revised: 03/03/2015] [Accepted: 04/16/2015] [Indexed: 02/06/2023] Open
Abstract
Urinary tract infection (UTI) is one of the most common childhood infections. Permanent renal cortical scarring may occur in affected children, especially with recurrent UTIs, leading to long-term complications such as hypertension and chronic renal failure. To prevent such damage, several interventions to prevent UTI recurrences have been tried. The most established and accepted prevention at present is low dose long-term antibiotic prophylaxis. However it has a risk of break through infections, adverse drug reactions and also the risk of developing antibiotic resistance. The search is therefore on-going to find a safer, effective and acceptable alternative. A recent meta-analysis did not support routine circumcision for normal boys with no risk factors. Vaccinium Macrocarpon (cranberry), commonly used against UTI in adult women, is also effective in reducing the number of recurrences and related antimicrobial use in children. Sodium pentosanpolysulfate, which prevents bacterial adherence to the uroepithelial cells in animal models, has shown conflicting results in human trials. When combined with antibiotic, Lactobacillus acidophilus (LA-5) and Bifidobacterium, by blocking the in vitro attachment of uropathogenic bacteria to uroepithelial cells, significantly reduce in the incidence of febrile UTIs. Deliberate colonization of the human urinary tract of patients with recurrent UTI with Escherichia-coli (E. coli) 83972 has resulted in subjective benefit and less UTI requiring treatment. The non-pathogenic E. coli isolate NU14 DeltawaaL is a candidate to develop live-attenuated vaccine for the treatment and prevention of acute and recurrent UTI. Diagnosing and treating dysfunctional elimination syndromes decrease the incidence of recurrent UTI. A meta-analysis found the lack of robust prospective randomized controlled trials limited the strength of the established guidelines for surgical management of vesicoureteral reflux. In conclusion, several interventions, other than antibiotic prophylaxis, for the prevention of recurrent UTI have been tried and, although showing some promise, they do not provide so far a definitive effective answer. Finding suitable alternatives still requires further high quality research of those seemingly promising interventions.
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Salameh A, Mohajer MA, Daroucihe RO. Prevention of urinary tract infections in patients with spinal cord injury. CMAJ 2015; 187:807-811. [PMID: 26078464 DOI: 10.1503/cmaj.141044] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Affiliation(s)
- Ahmad Salameh
- Department of Medicine (Salameh, Al Mohajer), University of Arizona, Tucson, Ariz.; Spinal Cord Injury and Medical Care Lines, Infectious Disease Section, Michael E. DeBakey Veterans Affairs Medical Center, and Baylor College of Medicine (Daroucihe), Houston, Tex
| | - Mayar Al Mohajer
- Department of Medicine (Salameh, Al Mohajer), University of Arizona, Tucson, Ariz.; Spinal Cord Injury and Medical Care Lines, Infectious Disease Section, Michael E. DeBakey Veterans Affairs Medical Center, and Baylor College of Medicine (Daroucihe), Houston, Tex.
| | - Rabih O Daroucihe
- Department of Medicine (Salameh, Al Mohajer), University of Arizona, Tucson, Ariz.; Spinal Cord Injury and Medical Care Lines, Infectious Disease Section, Michael E. DeBakey Veterans Affairs Medical Center, and Baylor College of Medicine (Daroucihe), Houston, Tex
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Darouiche RO, Riosa S, Hull RA. Comparison ofEscherichia coliStrains as Agents for Bacterial Interference. Infect Control Hosp Epidemiol 2015; 31:659-61. [DOI: 10.1086/653070] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Bacteriophage-mediated control of a two-species biofilm formed by microorganisms causing catheter-associated urinary tract infections in an in vitro urinary catheter model. Antimicrob Agents Chemother 2014; 59:1127-37. [PMID: 25487795 DOI: 10.1128/aac.03786-14] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Microorganisms from a patient or their environment may colonize indwelling urinary catheters, forming biofilm communities on catheter surfaces and increasing patient morbidity and mortality. This study investigated the effect of pretreating hydrogel-coated silicone catheters with mixtures of Pseudomonas aeruginosa and Proteus mirabilis bacteriophages on the development of single- and two-species biofilms in a multiday continuous-flow in vitro model using artificial urine. Novel phages were purified from sewage, characterized, and screened for their abilities to reduce biofilm development by clinical isolates of their respective hosts. Our screening data showed that artificial urine medium (AUM) is a valid substitute for human urine for the purpose of evaluating uropathogen biofilm control by these bacteriophages. Defined phage cocktails targeting P. aeruginosa and P. mirabilis were designed based on the biofilm inhibition screens. Hydrogel-coated catheters were pretreated with one or both cocktails and challenged with approximately 1×10(3) CFU/ml of the corresponding pathogen(s). The biofilm growth on the catheter surfaces in AUM was monitored over 72 to 96 h. Phage pretreatment reduced P. aeruginosa biofilm counts by 4 log10 CFU/cm2 (P≤0.01) and P. mirabilis biofilm counts by >2 log10 CFU/cm2 (P≤0.01) over 48 h. The presence of P. mirabilis was always associated with an increase in lumen pH from 7.5 to 9.5 and with eventual blockage of the reactor lines. The results of this study suggest that pretreatment of a hydrogel urinary catheter with a phage cocktail can significantly reduce mixed-species biofilm formation by clinically relevant bacteria.
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Antibiotic stewardship challenges in the management of community-acquired infections for prevention of escalating antibiotic resistance. J Glob Antimicrob Resist 2014; 2:245-253. [DOI: 10.1016/j.jgar.2014.08.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2013] [Revised: 07/28/2014] [Accepted: 08/05/2014] [Indexed: 11/20/2022] Open
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Asymptomatic bacteriuria Escherichia coli are live biotherapeutics for UTI. PLoS One 2014; 9:e109321. [PMID: 25405579 PMCID: PMC4236008 DOI: 10.1371/journal.pone.0109321] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 08/29/2014] [Indexed: 12/30/2022] Open
Abstract
Urinary tract infections (UTI) account for approximately 8 million clinic visits annually with symptoms that include acute pelvic pain, dysuria, and irritative voiding. Empiric UTI management with antimicrobials is complicated by increasing antimicrobial resistance among uropathogens, but live biotherapeutics products (LBPs), such as asymptomatic bacteriuria (ASB) strains of E. coli, offer the potential to circumvent antimicrobial resistance. Here we evaluated ASB E. coli as LBPs, relative to ciprofloxacin, for efficacy against infection and visceral pain in a murine UTI model. Visceral pain was quantified as tactile allodynia of the pelvic region in response to mechanical stimulation with von Frey filaments. Whereas ciprofloxacin promoted clearance of uropathogenic E. coli (UPEC), it did not reduce pelvic tactile allodynia, a measure of visceral pain. In contrast, ASB E. coli administered intravesically or intravaginally provided comparable reduction of allodynia similar to intravesical lidocaine. Moreover, ASB E. coli were similarly effective against UTI allodynia induced by Proteus mirabilis, Enterococccus faecalis and Klebsiella pneumoniae. Therefore, ASB E. coli have anti-infective activity comparable to the current standard of care yet also provide superior analgesia. These studies suggest that ASB E. coli represent novel LBPs for UTI symptoms.
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Strategies for Prevention of Urinary Tract Infections in Neurogenic Bladder Dysfunction. Phys Med Rehabil Clin N Am 2014; 25:605-18, viii. [DOI: 10.1016/j.pmr.2014.04.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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