scholarly journals Impact of low-level fluoroquinolone resistance genes qnrA1, qnrB19 and qnrS1 on ciprofloxacin treatment of isogenic Escherichia coli strains in a murine urinary tract infection model

2012 ◽  
Vol 67 (10) ◽  
pp. 2438-2444 ◽  
Author(s):  
L. Jakobsen ◽  
V. Cattoir ◽  
K. S. Jensen ◽  
A. M. Hammerum ◽  
P. Nordmann ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Resistance Genes ◽  
Fluoroquinolone Resistance ◽  
Infection Model ◽  
Low Level

scholarly journals Ciprofloxacin Pharmacokinetics/Pharmacodynamics against Susceptible and Low-Level Resistant Escherichia coli Isolates in an Experimental Ascending Urinary Tract Infection Model in Mice

2020 ◽  
Vol 65 (1) ◽  
pp. e01804-20
Author(s):  
Lotte Jakobsen ◽  
Carina Vingsbro Lundberg ◽  
Niels Frimodt-Møller
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Infection Model ◽  
Bladder Tissue ◽  
Content Type ◽  
E Coli ◽  
Low Level ◽  
Level Resistance

ABSTRACTThe mouse ascending urinary tract infection model was used to study the pharmacokinetic/pharmacodynamic (PKPD) relationships of the effect of ciprofloxacin in subcutaneous treatment for 3 days with varying doses and dosing intervals against a susceptible Escherichia coli strain (MIC, 0.032 mg/liter). Further, a humanized dose of ciprofloxacin was administered for 3 days against three E. coli strains with low-level resistance, i.e., MICs of 0.06, 0.25, and 1 mg/liter, respectively. Against the susceptible isolate, ciprofloxacin was highly effective in clearing the urine with daily doses from 10 mg/kg, but the dosing regimen had to be divided into at least two doses for optimal effect. Ciprofloxacin could not clear the urine or kidneys for the low-level-resistant strains. PKPD correlations with all strains combined showed that for the AUC24/MIC there was a slightly higher correlation with effect in urine and kidneys (R2, 0.71 and 0.69, respectively) than the %T>MIC (R2, 0.41 and 0.61, respectively). Equal correlations for the two PKPD indices were found for reduction of colony counts (CFU) in the bladder tissue, but not even the highest dose of 28 mg/kg × 6 could clear the bladder tissue. In conclusion, ciprofloxacin is highly effective in clearing the urine and kidney tissue for fully susceptible E. coli, while even low-level resistance in E. coli obscures this effect. While the effect of ciprofloxacin is mostly AUC/MIC driven against E. coli infection in the urinary tract, the effect in urine depends on the presence of ciprofloxacin in the urine during most of a 24-h period.

scholarly journals Efficacy of mecillinam against clinical multidrug-resistant Escherichia coli in a murine urinary tract infection model

2020 ◽  
Vol 55 (2) ◽  
pp. 105851
Author(s):  
Ilya Nikolaevich Zykov ◽  
Niels Frimodt-Møller ◽  
Lars Småbrekke ◽  
Arnfinn Sundsfjord ◽  
Ørjan Samuelsen
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Multidrug Resistant ◽  
Infection Model

scholarly journals Antimicrobial Resistance in Urinary Isolates of Escherichia coli with Special Reference to Fluoroquinolone Resistance and Extended Spectrum Beta-Lactamase (ESBL) Production

2021 ◽  
Vol 10 (9) ◽  
pp. 583-588
Author(s):  
Jyoti Rajowar ◽  
Sangeeta Dey Akoijam ◽  
Aninda Sen ◽  
Kahkashan Akhter ◽  
Shreshy Singh
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Urine Samples ◽  
Fluoroquinolone Resistance ◽  
Beta Lactamase ◽  
Esbl Production ◽  
Extended Spectrum Beta Lactamase ◽  
Esbl Producers

BACKGROUND The commonest bacterial agent involved in causation of urinary tract infection (UTI) is Escherichia coli, both in the community as well as in the hospital. In this study Escherichia coli strains isolated from patients with UTI were studied especially for extended spectrum beta-lactamase (ESBL) production and determination of fluoroquinolone resistance. METHODS This descriptive study was conducted in the Department of Microbiology, Katihar Medical College and Hospital from December 2018 to May 2020. Urine samples from suspected UTI cases were processed and bacterial isolates were identified as per standard protocol. Antimicrobial susceptibility testing was done by Kirby-Bauer discdiffusion method on Mueller-Hinton agar. ESBL detection was done as per Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS Out of 3938 urine samples received in the microbiology laboratory, 708 samples showed significant growth of various bacteria and candida species, out of these only 105 patients had urinary tract infection caused by Escherichia coli. The male to female ratio was 0.25:1. Isolates were highly sensitive to nitrofurantoin (80.9 %) followed by amikacin (72.4 %) and imipenem (71.5 %). Maximum resistance was seen with amoxicillin (98.1 %), cefuroxime (96.2 %), cefpodoxime and cefotaxime (90.5 %), ceftriaxone (85.7 %), nalidixic acid (91.4 %) and ciprofloxacin (70.5 %). 70.5 % were found to be ESBL producers and 29.5 % were non-ESBL producers. The double disc synergy test (DDST) could detect only 42.8 % of ESBL producers whereas phenotypic confirmatory disc diffusion (PCDDT) detected 70.5 % of ESBL producers. CONCLUSIONS It was seen in the present study that a high proportion of community acquired strains of Escherichia coli were ESBL producers. In this study, 70.5 % of Escherichia coli strains were ESBL positive. It can therefore be recommended that all gram-negative isolates be tested for ESBL production preferably by the PCDDT test as this test was found to be most sensitive for detection of ESBL production. The PCDDT test requires minimum laboratory infrastructure, is cheap and easy as compared to molecular methods. KEY WORDS Escherichia coli, UTI, ESBL, PCDDT, DDST

scholarly journals Impact of Low-Level Resistance to Fluoroquinolones Due to qnrA1 and qnrS1 Genes or a gyrA Mutation on Ciprofloxacin Bactericidal Activity in a Murine Model of Escherichia coli Urinary Tract Infection

2009 ◽  
Vol 53 (10) ◽  
pp. 4292-4297 ◽  
Author(s):  
Nicolas Allou ◽  
Emmanuelle Cambau ◽  
Laurent Massias ◽  
Françoise Chau ◽  
Bruno Fantin
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Bactericidal Activity ◽  
Murine Model ◽  
Bacterial Counts ◽  
Low Level ◽  
The Impact ◽  
Level Resistance

ABSTRACT We investigated the impact of low-level resistance to fluoroquinolones on the bactericidal activity of ciprofloxacin in a murine model of urinary tract infection. The susceptible Escherichia coli strain CFT073 (ciprofloxacin MIC [CIP MIC] of 0.008 μg/ml) was compared to its transconjugants harboring qnrA1 or qnrS1 and to an S83L gyrA mutant. The three derivatives showed similar low-level resistance to fluoroquinolones (CIP MICs, 0.25 to 0.5 μg/ml). Bactericidal activity measured in vitro after 1, 3, and 6 h of exposure to 0.5 μg/ml of ciprofloxacin was significantly lower for the derivative strains (P < 0.01). In the murine model of urinary tract infection (at least 45 mice inoculated per strain), mice were treated with a ciprofloxacin regimen of 2.5 mg/kg, given subcutaneously twice daily for 2 days. In mice infected with the susceptible strain, ciprofloxacin significantly decreased viable bacterial counts (log10 CFU/g of tissue) in the bladder (4.2 ± 0.5 versus 5.5 ± 1.3; P = 0.001) and in the kidney (3.6 ± 0.8 versus 5.0 ± 1.1; P = 0.003) compared with those of untreated mice. In contrast, no significant decrease in viable bacterial counts was observed with any of the three derivative strains. The area under the concentration-time curve from 0 to 24 h/MIC and the maximum concentration of drug in serum/MIC ratios measured in plasma were indeed equal to 827 and 147, respectively, for the parental strain, and only 12.4 to 24.8 and 2.2 to 4.4, respectively, for the derivative strains. In conclusion, low-level resistance to fluoroquinolones conferred by a qnr gene is associated with decreased bactericidal activity of ciprofloxacin, similar to that obtained with a gyrA mutation.

scholarly journals DamX Controls Reversible Cell Morphology Switching in UropathogenicEscherichia coli

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Surabhi Khandige ◽  
Cecilie Antoinette Asferg ◽  
Karina Juhl Rasmussen ◽  
Martin Jakob Larsen ◽  
Martin Overgaard ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Cell Division ◽  
Urinary Tract ◽  
Tract Infection ◽  
Cell Morphology ◽  
Pathogenic Bacteria ◽  
Infection Model ◽  
Tract Infections

ABSTRACTThe ability to change cell morphology is an advantageous characteristic adopted by multiple pathogenic bacteria in order to evade host immune detection and assault during infection. UropathogenicEscherichia coli(UPEC) exhibits such cellular dynamics and has been shown to transition through a series of distinct morphological phenotypes during a urinary tract infection. Here, we report the first systematic spatio-temporal gene expression analysis of the UPEC transition through these phenotypes by using a flow chamber-basedin vitroinfection model that simulates conditions in the bladder. This analysis revealed a novel association between the cell division genedamXand reversible UPEC filamentation. We demonstrate a lack of reversible bacterial filamentation in adamXdeletion mutantin vitroand absence of a filamentous response by this mutant in a murine model of cystitis. While deletion ofdamXabrogated UPEC filamentation and secondary surface colonization in tissue culture and in mouse infections, transient overexpression ofdamXresulted in reversible UPEC filamentation. In this study, we identify a hitherto-unknowndamX-mediated mechanism underlying UPEC morphotypical switching. Murine infection studies showed that DamX is essential for establishment of a robust urinary tract infection, thus emphasizing its role as a mediator of virulence. Our study demonstrates the value of anin vitromethodology, in which uroepithelium infection is closely simulated, when undertaking targeted investigations that are challenging to perform in animal infection models.IMPORTANCEUrinary tract infections (UTIs) are most often caused by uropathogenicEscherichia coli(UPEC) and account for a considerable health care burden. UPEC exhibits a dynamic lifestyle in the course of infection, in which the bacterium transiently adopts alternative morphologies ranging from rod shaped to coccoid and filamentous, rendering it better at immune evasion and host epithelium adhesion. This penchant for morphotype switching might in large measure account for UPEC’s success as a pathogen. In aiming to uncover genes underlying the phenomenon of UPEC morphotype switching, this study identifiesdamX, a cell division gene, as a mediator of reversible filamentation during UTI. DamX-mediated filamentation represents an additional pathway for bacterial cell shape control, an alternative to SulA-mediated FtsZ sequestration duringE. coliuropathogenesis, and hence represents a potential target for combating UTI.

scholarly journals Comparison of virulence factors and expression of specific genes between uropathogenic Escherichia coli and avian pathogenic E. coli in a murine urinary tract infection model and a chicken challenge model

Microbiology ◽  
2009 ◽  
Vol 155 (5) ◽  
pp. 1634-1644 ◽  
Author(s):  
Lixiang Zhao ◽  
Song Gao ◽  
Haixia Huan ◽  
Xiaojing Xu ◽  
Xiaoping Zhu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Virulence Genes ◽  
Iron Acquisition ◽  
Infection Model ◽  
Phylogenetic Groups ◽  
E Coli

Avian pathogenic Escherichia coli (APEC) and uropathogenic E. coli (UPEC) establish infections in extraintestinal habitats of different hosts. As the diversity, epidemiological sources and evolutionary origins of extraintestinal pathogenic E. coli (ExPEC) are so far only partially defined, in the present study,100 APEC isolates and 202 UPEC isolates were compared by their content of virulence genes and phylogenetic groups. The two groups showed substantial overlap in terms of their serogroups, phylogenetic groups and virulence genotypes, including their possession of certain genes associated with large transmissible plasmids of APEC. In a chicken challenge model, both UPEC U17 and APEC E058 had similar LD50, demonstrating that UPEC U17 had the potential to cause significant disease in poultry. To gain further information about the similarities between UPEC and APEC, the in vivo expression of 152 specific genes of UPEC U17 and APEC E058 in both a murine urinary tract infection (UTI) model and a chicken challenge model was compared with that of these strains grown statically to exponential phase in rich medium. It was found that in the same model (murine UTI or chicken challenge), various genes of UPEC U17 and APEC E058 showed a similar tendency of expression. Several iron-related genes were upregulated in the UTI model and/or chicken challenge model, indicating that iron acquisition is important for E. coli to survive in blood or the urinary tract. Based on these results, the potential for APEC to act as human UPEC or as a reservoir of virulence genes for UPEC should be considered. Further, this study compared the transcriptional profile of virulence genes among APEC and UPEC in vivo.

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