scholarly journals Serum Immunoglobulin Response and Protection from Homologous Challenge by Proteus mirabilis in a Mouse Model of Ascending Urinary Tract Infection

1999 ◽  
Vol 67 (12) ◽  
pp. 6683-6687 ◽  
Author(s):  
David E. Johnson ◽  
Farah K. Bahrani ◽  
C. Virginia Lockatell ◽  
Cinthia B. Drachenberg ◽  
J. Richard Hebel ◽  
...  

ABSTRACT We tested the hypothesis that experimental Proteus mirabilis urinary tract infection in mice would protect against homologous bladder rechallenge. Despite production of serum immunoglobulin G (IgG) and IgM (median titers of 1:320 and 1:80, respectively), vaccinated (infected and antibiotic-cured) mice did not show a decrease in mortality upon rechallenge; the survivors experienced only modest protection from infection (mean log10 number of CFU of P. mirabilisNalr HI4320 per milliliter or gram in vaccinated mice versus sham-vaccinated mice: urine, 100-fold less [3.5 versus 5.5;P = 0.13]; bladder, 100-fold less [3.1 versus 5.1;P = 0.066]; kidneys, 40-fold less [2.7 versus 4.3;P = 0.016]). Western blots using protein from the wild-type strain and isogenic mutants demonstrated antibody responses to MR/P and PMF fimbriae and flagella. There was no correlation between serum IgG or IgM levels and protection from mortality or infection. There was a trend toward elevated serum IgA titers and protection from subsequent challenge (P ≥ 0.09), although only a few mice developed significant serum IgA levels. We conclude that prior infection with P. mirabilis does not protect significantly against homologous challenge.

2008 ◽  
Vol 2 (1) ◽  
pp. 19-32
Author(s):  
Ghydaa H. A al-jeboury ◽  
Abdul Wahed Baker

The aim of the study was to use lactic acid bacteria (LAB), as probiotic, to treat growth and adhesion property of Proteus mirabilis isolated from patients suffering from urinary tract infection (UTI). For this purpose, one P. mirabilis isolate (P.M.9) was selected out of 9 isolates obtained from 150 urine specimens. Due to its resistance to 11 antibiotics tested, this isolate was treated with three-fold concentrated filtrates of two lactobacillus isolates (as probiotic). Results after treatment, showed that the filtrates exhibited significant inhibitory effect against the pathogenic P.M.9 and its adhesion property especially when only an average of 3-10 bacteria /cell were adhered to each epithelial cell compared to 44-55 bacteria/cell.


2016 ◽  
Vol 85 (2) ◽  
Author(s):  
Chelsie E. Armbruster ◽  
Sara N. Smith ◽  
Alexandra O. Johnson ◽  
Valerie DeOrnellas ◽  
Kathryn A. Eaton ◽  
...  

ABSTRACT Urinary catheter use is prevalent in health care settings, and polymicrobial colonization by urease-positive organisms, such as Proteus mirabilis and Providencia stuartii, commonly occurs with long-term catheterization. We previously demonstrated that coinfection with P. mirabilis and P. stuartii increased overall urease activity in vitro and disease severity in a model of urinary tract infection (UTI). In this study, we expanded these findings to a murine model of catheter-associated UTI (CAUTI), delineated the contribution of enhanced urease activity to coinfection pathogenesis, and screened for enhanced urease activity with other common CAUTI pathogens. In the UTI model, mice coinfected with the two species exhibited higher urine pH values, urolithiasis, bacteremia, and more pronounced tissue damage and inflammation compared to the findings for mice infected with a single species, despite having a similar bacterial burden within the urinary tract. The presence of P. stuartii, regardless of urease production by this organism, was sufficient to enhance P. mirabilis urease activity and increase disease severity, and enhanced urease activity was the predominant factor driving tissue damage and the dissemination of both organisms to the bloodstream during coinfection. These findings were largely recapitulated in the CAUTI model. Other uropathogens also enhanced P. mirabilis urease activity in vitro, including recent clinical isolates of Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. We therefore conclude that the underlying mechanism of enhanced urease activity may represent a widespread target for limiting the detrimental consequences of polymicrobial catheter colonization, particularly by P. mirabilis and other urease-positive bacteria.


2019 ◽  
Vol 69 (12) ◽  
pp. 2045-2056 ◽  
Author(s):  
Keith S Kaye ◽  
Louis B Rice ◽  
Aaron L Dane ◽  
Viktor Stus ◽  
Olexiy Sagan ◽  
...  

Abstract Background ZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gram-negative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States. Methods Hospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.5 g intravenous (IV) piperacillin-tazobactam (PIP-TAZ) q8h for a fixed 7-day course (no oral switch); patients with concomitant bacteremia could receive up to 14 days. Results Of 465 randomized patients, 233 and 231 were treated with ZTI-01 and PIP-TAZ, respectively. In the microbiologic modified intent-to-treat (m-MITT) population, ZTI-01 met the primary objective of noninferiority compared with PIP-TAZ with overall success rates of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% confidence interval [CI]: −0.4, 20.8). Clinical cure rates at test of cure (TOC, day 19–21) were high and similar between treatments (90.8% [167/184] vs 91.6% [163/178], respectively). In post hoc analysis using unique pathogens typed by pulsed-field gel electrophoresis, overall success rates at TOC in m-MITT were 69.0% (127/184) for ZTI-01 versus 57.3% (102/178) for PIP-TAZ (difference 11.7% 95% CI: 1.3, 22.1). ZTI-01 was well tolerated. Most treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mild and transient. Conclusions ZTI-01 was effective for treatment of cUTI including AP and offers a new IV therapeutic option with a differentiated MOA for patients with serious Gram-negative infections. Clinical Trial Registration NCT02753946


2009 ◽  
Vol 20 ◽  
pp. S248
Author(s):  
Maria Fraga ◽  
Maria João Nunes Da Silva ◽  
Álvaro Almeida ◽  
Margarida Lucas ◽  
Rui Vitorino

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