scholarly journals 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

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Hina Saini ◽  
Anitha Vadekeetil ◽  
Sanjay Chhibber ◽  
Kusum Harjai
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Murine Model ◽  
Biofilm Formation ◽  
Bacterial Colonization ◽  
Silicone Implants ◽  
Urinary Catheters ◽  
Content Type ◽  
Tract Infections

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.

scholarly journals Enterococcal Biofilm Formation and Virulence in an Optimized Murine Model of Foreign Body-Associated Urinary Tract Infections

2010 ◽  
Vol 78 (10) ◽  
pp. 4166-4175 ◽  
Author(s):  
Pascale S. Guiton ◽  
Chia S. Hung ◽  
Lynn E. Hancock ◽  
Michael G. Caparon ◽  
Scott J. Hultgren
Keyword(s):  
Urinary Tract ◽  
Foreign Body ◽  
Urinary Tract Infections ◽  
Murine Model ◽  
Biofilm Formation ◽  
Significant Advance ◽  
Virulence Determinants ◽  
Indwelling Catheters ◽  
Tract Infections

ABSTRACT Catheter-associated urinary tract infections (CAUTIs) constitute the majority of nosocomial UTIs and pose significant clinical challenges. Enterococcal species are among the predominant causative agents of CAUTIs. However, very little is known about the pathophysiology of Enterococcus-mediated UTIs. We optimized a murine model of foreign body-associated UTI in order to mimic conditions of indwelling catheters in patients. In this model, the presence of a foreign body elicits major histological changes and induces the expression of several proinflammatory cytokines in the bladder. In addition, in contrast to naïve mice, infection of catheter-implanted mice with Enterococcus faecalis induced the specific expression of interleukin 1β (IL-1β) and macrophage inflammatory protein 1α (MIP-1α) in the bladder. These responses resulted in a favorable niche for the development of persistent E. faecalis infections in the murine bladders and kidneys. Furthermore, biofilm formation on the catheter implant in vivo correlated with persistent infections. However, the enterococcal autolytic factors GelE and Atn (also known as AtlA), which are important in biofilm formation in vitro, are dispensable in vivo. In contrast, the housekeeping sortase A (SrtA) is critical for biofilm formation and virulence in CAUTIs. Overall, this murine model represents a significant advance in the understanding of CAUTIs and underscores the importance of urinary catheterization during E. faecalis uropathogenesis. This model is also a valuable tool for the identification of virulence determinants that can serve as potential antimicrobial targets for the treatment of enterococcal infections.

scholarly journals Dissemination and Systemic Colonization of Uropathogenic Escherichia coli in a Murine Model of Bacteremia

mBio ◽  
2010 ◽  
Vol 1 (5) ◽  
Author(s):  
Sara N. Smith ◽  
Erin C. Hagan ◽  
M. Chelsea Lane ◽  
Harry L. T. Mobley
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Murine Model ◽  
Systemic Disease ◽  
Content Type ◽  
E Coli ◽  
Bacterial Genes ◽  
Tract Infections ◽  
K 12

ABSTRACTInfection with uropathogenicEscherichia coli(UPEC), the causative agent of most uncomplicated urinary tract infections, proceeds in an ascending manner and, if left untreated, may result in bacteremia and urosepsis. To examine the fate of UPEC after its entry into the bloodstream, we developed a murine model of sublethal bacteremia. CBA/J mice were inoculated intravenously with 1 × 106 CFU of pyelonephritis strainE. coliCFT073 carrying a bioluminescent reporter. Biophotonic imaging, used to monitor the infection over 48 h, demonstrated that the bacteria disseminated systemically and appeared to localize at discrete sites. UPEC was recovered from the spleen, liver, kidneys, lungs, heart, brain, and intestines as early as 20 min postinoculation, peaking at 24 h postinoculation. A nonpathogenicE. coliK-12 strain, however, disseminated at significantly lower levels (P< 0.01) and was cleared from the liver and cecum by 24 h postinoculation. Isogenic mutants lacking type 1 fimbriae, P fimbriae, capsule, TonB, the heme receptors Hma and ChuA, or particularly the sialic acid catabolism enzyme NanA were significantly outcompeted by wild-type CFT073 during bacteremia (P< 0.05), while flagellin and hemolysin mutants were not.IMPORTANCEE. coliis the primary cause of urinary tract infections. In severe cases of kidney infection, bacteria can enter the bloodstream and cause systemic disease. While the ability ofE. colito cause urinary tract infection has been extensively studied, the fate of these bacteria once they enter the bloodstream is largely unknown. Here we used an imaging technique to develop a mouse model ofE. colibloodstream infection and identify bacterial genes that are important for the bacteria to spread to and infect various organs. Understanding how urinary tract pathogens likeE. colicause disease after they enter the bloodstream may aid in the development of protective and therapeutic treatments.

scholarly journals Results of a Multicenter Population Pharmacokinetic Study of Ciprofloxacin in Children with Complicated Urinary Tract Infection

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Kevin Meesters ◽  
Robin Michelet ◽  
Reiner Mauel ◽  
Ann Raes ◽  
Jan Van Bocxlaer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Body Weight ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Complicated Urinary Tract Infection ◽  
Fat Free Mass ◽  
Population Pharmacokinetic ◽  
Content Type ◽  
Tract Infections ◽  
Significant Covariates

ABSTRACTResistance rates for ciprofloxacin, which is labeled for treating complicated urinary tract infections in children, are rapidly rising. As there is limited knowledge on developmental pharmacology of ciprofloxacin, the primary aim of this study was to develop a population pharmacokinetic model for ciprofloxacin in children treated for complicated urinary tract infections. Children to whom ciprofloxacin was prescribed, intravenous (10 to 15 mg/kg body weight every 12 h) orper os(15 to 20 mg/kg every 12 h), were enrolled. One hundred eight serum and 119 urine samples were obtained during 10 intravenous and 13 oral courses of ciprofloxacin in 22 patients (age range, 0.31 to 15.51 years). A one-compartment model best described our data. Fat-free mass and glomerular filtration rate (estimated by a formula using cystatin C and creatinine), standardized for body surface area, were significant covariates for ciprofloxacin clearance. In our population, ciprofloxacin clearance is 0.16 to 0.43 liter/h/kg of body weight, volume of distribution 0.06 to 2.88 liters/kg, and bioavailability 59.6%. All of our patients had a clinical cure of their infection. Based on target attainment simulations across doses, all children reached the pharmacodynamic target forEnterobacteriaceae, but on average only 53% did forPseudomonas aeruginosaand 3% forStaphylococcus aureus, at the 15-mg/kg oral dose. For treating urinary tract infections caused byPseudomonas aeruginosa, oral doses should be at least 20 mg/kg. Furthermore, in our population, fat-free mass and kidney function should be considered, as they prove to be significant covariates for ciprofloxacin clearance and, hence, exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT02598362.)

scholarly journals Presence of Putative Repeat-in-Toxin Gene tosA in Escherichia coli Predicts Successful Colonization of the Urinary Tract

mBio ◽  
2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Patrick D. Vigil ◽  
Ann E. Stapleton ◽  
James R. Johnson ◽  
Thomas M. Hooton ◽  
Andrew P. Hodges ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Virulence Factors ◽  
Urinary Tract Infections ◽  
Murine Model ◽  
Toxin Gene ◽  
Content Type ◽  
E Coli ◽  
Tract Infections ◽  
Successful Colonization

ABSTRACTUropathogenicEscherichia coli(UPEC) strains, which cause the majority of uncomplicated urinary tract infections (UTIs), carry a unique assortment of virulence or fitness genes. However, no single defining set of virulence or fitness genes has been found in all strains of UPEC, making the differentiation between UPEC and fecal commensal strains ofE. colidifficult without the use of animal models of infection or phylogenetic grouping. In the present study, we consider three broad categories of virulence factors simultaneously to better define a combination of virulence factors that predicts success in the urinary tract. A total of 314 strains ofE. coli, representing isolates from fecal samples, asymptomatic bacteriuria, complicated UTIs, and uncomplicated bladder and kidney infections, were assessed by multiplex PCR for the presence of 15 virulence or fitness genes encoding adhesins, toxins, and iron acquisition systems. The results confirm previous reports of gene prevalence among isolates from different clinical settings and identify several new patterns of gene associations. One gene,tosA, a putative repeat-in-toxin (RTX) homolog, is present in 11% of fecal strains but 25% of urinary isolates. WhereastosA-positive strains carry an unusually high number (11.2) of the 15 virulence or fitness genes,tosA-negative strains have an average of only 5.4 virulence or fitness genes. The presence oftosAwas predictive of successful colonization of a murine model of infection, even among fecal isolates, and can be used as a marker of pathogenic strains of UPEC within a distinct subset of the B2 lineage.IMPORTANCEEscherichia coliis the primary cause of urinary tract infections, the most common bacterial infection of humans. Virulence of a uropathogenic strain is typically defined by the clinical source of the isolate, the ability to colonize the bladder and kidneys in a murine model, the phylogenetic group of the bacterium, and virulence gene content. Here we describe a novel single gene, the repeat-in-toxin genetosA, the presence of which predicts virulence ofE. coliisolates regardless of source. Rapid identification of uropathogenic strains ofE. colimay aid in the development of therapeutic and preventive therapies.

scholarly journals Catheter-Associated Urinary Tract Infection by Pseudomonas aeruginosa Is Mediated by Exopolysaccharide-Independent Biofilms

2014 ◽  
Vol 82 (5) ◽  
pp. 2048-2058 ◽  
Author(s):  
Stephanie J. Cole ◽  
Angela R. Records ◽  
Mona W. Orr ◽  
Sara B. Linden ◽  
Vincent T. Lee
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Biofilm Formation ◽  
Extracellular Dna ◽  
Extracellular Polysaccharides ◽  
Indwelling Catheters ◽  
Content Type ◽  
Tract Infections

ABSTRACTPseudomonas aeruginosais an opportunistic human pathogen that is especially adept at forming surface-associated biofilms.P. aeruginosacauses catheter-associated urinary tract infections (CAUTIs) through biofilm formation on the surface of indwelling catheters.P. aeruginosaencodes three extracellular polysaccharides, PEL, PSL, and alginate, and utilizes the PEL and PSL polysaccharides to form biofilmsin vitro; however, the requirement of these polysaccharides duringin vivoinfections is not well understood. Here we show in a murine model of CAUTI that PAO1, a strain harboringpel,psl, andalggenes, and PA14, a strain harboringpelandalggenes, form biofilms on the implanted catheters. To determine the requirement of exopolysaccharide duringin vivobiofilm infections, we tested isogenic mutants lacking thepel,psl, andalgoperons and showed that PA14 mutants lacking these operons can successfully form biofilms on catheters in the CAUTI model. To determine the host factor(s) that induces the ΔpelDmutant to form biofilm, we tested mouse, human, and artificial urine and show that urine can induce biofilm formation by the PA14 ΔpelDmutant. By testing the major constituents of urine, we show that urea can induce apel-,psl-, andalg-independent biofilm. Thesepel-,psl-, andalg-independent biofilms are mediated by the release of extracellular DNA. Treatment of biofilms formed in urea with DNase I reduced the biofilm, indicating that extracellular DNA supports biofilm formation. Our results indicate that the opportunistic pathogenP. aeruginosautilizes a distinct program to form biofilms that are independent of exopolysaccharides during CAUTI.

scholarly journals Antimicrobial Activities of Ceftazidime-Avibactam and Comparator Agents against Gram-Negative Organisms Isolated from Patients with Urinary Tract Infections in U.S. Medical Centers, 2012 to 2014

2016 ◽  
Vol 60 (7) ◽  
pp. 4355-4360 ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Antimicrobial Activities ◽  
Broth Microdilution ◽  
Gram Negative ◽  
Content Type ◽  
Medical Centers ◽  
Gram Negative Organisms ◽  
Tract Infections

ABSTRACTA total of 7,272 unique patient clinical isolates were collected from 71 U.S. medical centers from patients with urinary tract infections in 2012 to 2014 and tested for susceptibility to ceftazidime-avibactam and comparators by broth microdilution methods. Ceftazidime-avibactam inhibited >99.9% of allEnterobacteriaceaeat the susceptible breakpoint of ≤8 μg/ml (there were only three nonsusceptible strains). Ceftazidime-avibactam was also active againstPseudomonas aeruginosaisolates (MIC50, 2 μg/ml; MIC90, 4 μg/ml; 97.7% susceptible), including many isolates not susceptible to meropenem, ceftazidime, and/or piperacillin-tazobactam.

Detection of tox A gene in Pseudomonas aeruginosa that isolates from different clinical cases by using PCR.

2018 ◽  
pp. 26
Author(s):  
Rana M. Abdullah Al-Shwaikh ◽  
Abbas Falih Alornaaouti
Keyword(s):  
Molecular Weight ◽  
Pseudomonas Aeruginosa ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Otitis Media ◽  
Urinary Tract Infections ◽  
Gel Electrophoresis ◽  
Wound Infections ◽  
Tract Infections

       Current study obtained (75) isolate of Pseudomonas aeruginosa collected from different cases included : 28 isolates from otitis media, 23 isolates from burn infections, 10 isolates from wound infections, 8 isolates from urinary tract infections and 6 isolates from blood, during the period between 1/9/2014 to 1/11/2014        The result revealed that the tox A gene was present in 54 isolates (72%) of Pseudomonas aeruginosa. The gel electrophoresis showed that the molecular weight of tox A gene was 352 bp. The result shows 17 isolates (60.71%) from otitis media has tox A gene, 18 isolates (78.26%) from burn followed by 8 isolate (80%) from wound infection and 5 isolates (62.5%) from urinary tract infection , finally 6 isolates (100%) from blood have this gene.

scholarly journals Implementation of a Female External Urinary Catheter Reduces Indwelling Urinary Catheter Use and Catheter-Associated Urinary Tract Infections

2020 ◽  
Vol 41 (S1) ◽  
pp. s482-s483
Author(s):  
Paul Gentile ◽  
Jesse Jacob ◽  
Shanza Ashraf
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Urinary Catheter ◽  
Improve Patient Safety ◽  
Academic Medical Center ◽  
Secondary Outcome ◽  
Successful Implementation ◽  
Urinary Catheters ◽  
Tract Infections ◽  
The Impact

Background: Using alternatives to indwelling urinary catheters plays a vital role in reducing catheter-associated urinary tract infections (CAUTIs). We assessed the impact of introducing female external catheters on urinary catheter utilization and CAUTIs. Methods: In a 500-bed academic medical center, female external catheters were implemented on October 1, 2017, with use encouraged for eligible females with urinary incontinence but not meeting other standard indications for urinary catheters. Nurses were educated and trained on female external catheter application and maintenance, and infection prevention staff performed surveillance case reviews with nursing and medical staff. We determined the number of catheter days for both devices based on nursing documentation of device insertion or application, maintenance, and removal. We used the CAUTI and DUR (device utilization ratio) definitions from the CDC NHSN. Our primary outcomes were changes in DUR for both devices 21 months before and 24 months after the intervention in both intensive care units (ICUs) and non-ICU wards. We used a generalized least-squares model to account for temporal autocorrelation and compare the trends before and after the intervention. Our secondary outcome was a reduction in CAUTIs, comparing females to males. Results: In total, there were 346,213 patient days in 35 months. The mean rate of patient days per month increased from 7,436.4 to 7,601.9 after the implementation of female external catheters, with higher catheter days for both urinary catheters (18,040 vs 19,625) and female external catheters (22 vs 12,675). After the intervention, the DUR for female external catheters increased (0 vs 0.07; P < .001) and for urinary catheters the DUR decreased (0.12 vs 0.10; P < .001) (Fig. 1). A reduction in urinary catheter DUR was observed in ICUs (0.29 vs 0.27; P < .001) but not wards (0.08 vs 0.08; P = NS) (Fig. 2). Of the 39 CAUTIs, there was no significant overall change in the rate per 1,000 catheter days (1.22 vs 0.87; P = .27). In females (n = 20 CAUTI), there was a 61% reduction in the CAUTI rate per 1,000 catheter days (0.78 vs 0.31; P = .02), but no significant change in the rate in males (0.44 vs 0.56; P = .64). The CAUTI rate per 1,000 catheter days among females decreased in the ICUs (1.14 vs 0.31; P = .04) but not in wards (0.6 vs 0.33; P = .96). Conclusions: In a setting with a baseline low UC DUR, successful implementation of female external catheters further modestly reduced UC DUR and was associated with a 61% decrease in CAUTI among females in the ICU but not in wards. Further interventions to better identify appropriate patients for female external catheters may improve patient safety and prevent patient harm.Funding: NoneDisclosures: None

592 Prevention of CAUTIs in a Burn ICU

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S138-S138
Author(s):  
Vina Vargas ◽  
Emiko Rivera ◽  
Teresa Sidhu ◽  
Lea Lyn Zaballero ◽  
Yvonne L Karanas
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Infection Prevention ◽  
Urinary Catheter ◽  
Antimicrobial Use ◽  
Research To Practice ◽  
Urinary Catheters ◽  
Open Forum ◽  
Excellent Care ◽  
Tract Infections

Abstract Introduction Catheter-associated urinary tract infections (CAUTIs) are the most common hospital-associated infection (HAI). Urinary catheter use is associated with urinary tract infections (UTIs) that can lead to complications such as cystitis, pyelonephritis, bacteremia, septic shock, and death. CAUTIs are associated with an excess length of stay of 2–4 days, increase costs of $0.4–0.5 billion per year nationally, and lead to unnecessary antimicrobial use. Through numerous implementations, a Burn ICU was able to drastically decrease their incidence of CAUTIs. Methods A Burn ICU implemented several interventions to reduce CAUTI rates. These interventions included: Results When this project was initiated in September of 2017, there were 9 CAUTIs identified in a Burn ICU, per the hospital’s Infection Prevention Department. By the end of 2017, there were 11, which equated to a rate of 14.67 per 1000 urinary catheter days. In 2018, the Burn ICU had 1 CAUTI, with a rate of 1.92 per 1000 urinary catheter days. In 2019 (through quarter 2), the Burn ICU has not had a CAUTI per the Infection Prevention Department. We believe the interventions made have drastically decreased the incidence of CAUTIs. Conclusions A Burn ICU implemented many new practices in 2017 when the CAUTI rate and SIR were above the hospital’s overall SIR. The Burn ICU staff now practice proper care and maintenance of urinary catheters and continue to provide excellent care. Although we have decreased our incidence of CAUTIs for 2018 and 2019, it is equally important we sustain this improvement. Therefore, we will continue to provide an open forum for discussion with staff so we can all do our part in keeping patients safe. Applicability of Research to Practice A Burn ICU decreased the incidence of CAUTIs by educating staff on proper care and maintenance of urinary catheters, removing catheters as soon as possible, and testing for UTIs upon admission to determine the patient’s baseline. By doing so, CAUTI rates went from 14.67 to 0 per 1000 urinary catheter days.

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