scholarly journals The Amino Acid Changes T55A, A273P and R277C in the Beta-Lactamase CTX-M-14 Render E. coli Resistant to the Antibiotic Nitrofurantoin, a First-Line Treatment of Urinary Tract Infections

2020 ◽  
Vol 8 (12) ◽  
pp. 1983
Author(s):  
Yasir Edowik ◽  
Thomas Caspari ◽  
Hugh Merfyn Williams
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Adult Women ◽  
Line Treatment ◽  
First Line ◽  
Gram Negative ◽  
E Coli ◽  
Tract Infections ◽  
M 14 ◽  
First Line Treatment

The antibiotic nitrofurantoin is a furan flanked by a nitro group and a hydantoin ring. It is used to treat lower urinary tract infections (UTIs) that have a lifetime incidence of 50−60% in adult women. UTIs are typically caused by uropathogenic Escherichia coli (UPEC), which are increasingly expressing extended-spectrum beta-lactamases (ESBL), rendering them multi-drug resistant. Nitrofurantoin is a first-line treatment for gram-negative ESBL-positive UTI patients, given that resistance to it is still rare (0% to 4.4%). Multiplex PCR of β-lactamase genes of the blaCTX-M groups 1, 2, 9 and 8/25 from ESBL-positive UTI patients treated at three referral hospitals in North Wales (UK) revealed the presence of a novel CTX-M-14-like gene harbouring the missense mutations T55A, A273P and R277C. While R277 is close to the active site, T55 and A273 are both located in external loops. Recombinant expression of CTX-M-14 and the mutated CTX-M-14 in the periplasm of E. coli revealed a significant increase in the Minimum Inhibitory Concentration (MIC) for nitrofurantoin from ≥6 μg/mL (CTX-M-14) to ≥512 μg/mL (mutated CTX-M-14). Consistent with this finding, the mutated CTX-M protein hydrolysed nitrofurantoin in a cell-free assay. Detection of a novel nitrofurantoin resistance gene indicates an emerging clinical problem in the treatment of gram-negative ESBL-positive UTI patients.

scholarly journals Role of Urinary Cathelicidin LL-37 and Human β-Defensin 1 in Uncomplicated Escherichia coli Urinary Tract Infections

2014 ◽  
Vol 82 (4) ◽  
pp. 1572-1578 ◽  
Author(s):  
Karen L. Nielsen ◽  
Pia Dynesen ◽  
Preben Larsen ◽  
Lotte Jakobsen ◽  
Paal S. Andersen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Adult Women ◽  
Content Type ◽  
E Coli ◽  
Innate Defense ◽  
High Level ◽  
Tract Infections

ABSTRACTCathelicidin (LL-37) and human β-defensin 1 (hBD-1) are important components of the innate defense in the urinary tract. The aim of this study was to characterize whether these peptides are important for developing uncomplicatedEscherichia coliurinary tract infections (UTIs). This was investigated by comparing urinary peptide levels of UTI patients during and after infection to those of controls, as well as characterizing the fecal flora of participants with respect to susceptibility to LL-37 andin vivovirulence. Forty-seven UTI patients and 50 controls who had never had a UTI were included. Participants were otherwise healthy, premenopausal, adult women. LL-37 MIC levels were compared for fecalE. coliclones from patients and controls and were also compared based on phylotypes (A, B1, B2, and D).In vivovirulence was investigated in the murine UTI model by use of selected fecal isolates from patients and controls. On average, UTI patients had significantly more LL-37 in urine during infection than postinfection, and patient LL-37 levels postinfection were significantly lower than those of controls. hBD-1 showed similar urine levels for UTI patients and controls. FecalE. coliisolates from controls had higher LL-37 susceptibility than fecal and UTIE. coliisolates from UTI patients.In vivostudies showed a high level of virulence of fecalE. coliisolates from both patients and controls and showed no difference in virulence correlated with the LL-37 MIC level. The results indicate that the concentration of LL-37 in the urinary tract and low susceptibility to LL-37 may increase the likelihood of UTI in a complex interplay between host and pathogen attributes.

scholarly journals Moderate and Timely Water Intake Followed By Micturition Reduces Frequency of Recurrent Urinary Tract Infections and the Prevalence of Virulent Uropathogens in Adult Women

2020 ◽  
Vol 5 (08) ◽  
pp. 268-270
Author(s):  
Kamel El-Reshaid ◽  
Shaikha Al-Bader
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Water Intake ◽  
Married Women ◽  
High Rate ◽  
Plain Water ◽  
Adult Women ◽  
E Coli ◽  
Recurrent Urinary Tract Infections ◽  
Tract Infections

Urinary tract infection (UTI) is the most common type of infection in women. Preventive measures included local hygiene, clothing, diet, limiting activities, and prophylactic antibiotics. In this study; we evaluated the role of a simple technique of 5-timely oral water flushing of the urinary bladder in its prevention. The technique entailed an intake of 250 ml of plain water followed by micturition 15-30 minute later at; early morning, 30 minute after the 3 daily meals and 1 hour before night sleep. Moreover, married women had an additional similar bolus intake 30 minute before sexual intercourse and micturition immediately after coitus. This prophylactic regimen has been evaluated in 422 adult non-menopausal females with high-rate of recurrent UTI (>2 UTI/year) for a median duration of 33 months. Married women; had higher rate of UTI/patient year and incidence of non-E coli bacteriuria compared to non-married ones. Our prophylactic technique resulted in; (a) decrease in UTI rate/patient year on follow up from 2.3(0.8) to 0(0.3), (b) clearance of bacteriuria in 69% of women, and decrease of non-E coli pathogens from 31% to 2% (p< 0.001). The latter was due to limiting the use of antibiotics. Married women had similar encouraging results. In conclusion; moderate and timely water intake followed by micturition reduces frequency of recurrent urinary tract infections and the prevalence of virulent uropathogens in adult women.

scholarly journals OXA-48 Carbapenemase-Encoding Transferable Plasmids of Klebsiella pneumoniae Recovered from Egyptian Patients Suffering from Complicated Urinary Tract Infections

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 889
Author(s):  
Ann A. Elshamy ◽  
Sarra E. Saleh ◽  
Mohammad Y. Alshahrani ◽  
Khaled M. Aboshanab ◽  
Mohammad M. Aboulwafa ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Tertiary Care ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
Gram Negative ◽  
E Coli ◽  
Tract Infections

Gram-negative bacteria are common causes of urinary tract infections (UTIs). Such pathogens can acquire genes encoding multiple mechanisms of antimicrobial resistance, including carbapenem resistance. The aim of this study was to detect the carbapenemase-producing ability of some Gram-negative bacterial isolates from urine specimens of patients suffering from complicated UTIs at two vital tertiary care hospitals in Cairo, Egypt; to determine the prevalence of carbapenemase genes among plasmid-bearing isolates; and explore the possibility of horizontal gene transfer to other bacterial species. The collected isolates were subjected to antimicrobial susceptibility testing, phenotypic analysis of carbapenemase production, and molecular detection of plasmid-borne carbapenemase genes, then the extracted plasmids were transformed into competent E. coli DH5α. A total of 256 Gram-negative bacterial clinical isolates were collected, 65 (25.4%) isolates showed carbapenem resistance of which 36 (55.4%) were carbapenemase-producers, and of these 31 (47.7%) harbored plasmids. The extracted plasmids were used as templates for PCR amplification of blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP carbapenemase genes. The blaOXA-48 gene was detected in 24 (77.4%) of the tested isolates while blaVIM gene was detected in 8 (25.8%), both blaKPC and blaNDM genes were co-present in 1 (3.2%) isolate. Plasmids carrying the blaOXA-48 gene from 4 K. pneumoniae clinical isolates were successfully transformed into competent E. coli DH5α. The transformants were carbapenemase-producers and acquired resistance to some of the tested antimicrobial agents as compared to untransformed E. coli DH5α. The study concluded that the rate of carbapenem resistance among Gram-negative bacterial uropathogens in Cairo, Egypt is relatively high and can be transferred horizontally to other bacterial host(s).

scholarly journals Community-Acquired Antibiotic Resistance in Urinary Isolates from Adult Women in Canada

2006 ◽  
Vol 17 (6) ◽  
pp. 337-340 ◽  
Author(s):  
Warren J McIsaac ◽  
Tony Mazzulli ◽  
Joanne Permaul ◽  
Rahim Moineddin ◽  
Donald E Low
Keyword(s):  
British Columbia ◽  
Urinary Tract ◽  
Urine Culture ◽  
Multidrug Resistant ◽  
Adult Women ◽  
Limited Data ◽  
First Line ◽  
Acute Cystitis ◽  
E Coli ◽  
Tract Infections

BACKGROUND:There are currently limited data regarding the prevalence of antimicrobial-resistant organisms causing community-acquired urinary tract infections among adult women in Canada. Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line empirical antibiotic treatment, unless resistance ofEscherichia colito TMP-SMX exceeds 20%.OBJECTIVE:To assess current levels of TMP-SMX-resistantE coliin community-acquired cases of urinary tract infection in adult women.METHOD:Assessment of urine culture reports obtained from 21 laboratories across Canada, submitted by family physicians for women aged 16 years and older.RESULTS:In 2199 adult women with a positive urine culture, 1079 (49.1%) of pathogens isolated were resistant to at least one antibiotic and 660 (30.0%) were multidrug-resistant (resistant to two or more antibiotics). TMP-SMX resistance was seen in 245 of 1613 (15.2%)E coliisolates (95% CI 13.5 to 17.0). This proportion was higher in women 50 years of age and older (155 of 863 isolates [18.0%]; P=0.001), in British Columbia (70 of 342 isolates [20.5%]) and in Ontario (62 of 370 isolates [16.8%]) when compared with eastern provinces (65 of 572 isolates [11.4%]; P=0.001). Fluoroquinolone-resistantE colioccurred in 107 of 1557 (6.9%) isolates (95% CI 5.7 to 8.2), with the highest level found in British Columbia (54 of 341 isolates [15.8%]; P=0.001).CONCLUSION:TMP-SMX continues to be appropriate as first-line empirical treatment of acute cystitis in adult women in Canada, as resistance remains below 20%. However, TMP-SMX resistance is higher in older women and in some provinces. The level of fluoroquinolone-resistantE coliis highest in British Columbia.

scholarly journals Pharmacodynamic Evaluation of Fosfomycin against Escherichia coli and Klebsiella spp. from Urinary Tract Infections and the Influence of pH on Fosfomycin Activities

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Nayara Helisandra Fedrigo ◽  
Josmar Mazucheli ◽  
James Albiero ◽  
Danielle Rosani Shinohara ◽  
Fernanda Gomes Lodi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Urinary Tract Infections ◽  
Bacterial Isolates ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Tract Infections

ABSTRACT Fosfomycin is widely used for the treatment of uncomplicated urinary tract infection (UTI), and it has recently been recommended that fosfomycin be used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacilli. Whether urine acidification can improve bacterial susceptibility to fosfomycin oral dosing regimens has not been analyzed. The MIC of fosfomycin for 245 Gram-negative bacterial isolates, consisting of 158 Escherichia coli isolates and 87 Klebsiella isolates which were collected from patients with urinary tract infections, were determined at pH 6.0 and 7.0 using the agar dilution method. Monte Carlo simulation of the urinary fosfomycin area under the concentration-time curve (AUC) after a single oral dose of 3,000 mg fosfomycin and the MIC distribution were used to determine the probability of target attainment (PTA). Fosfomycin was effective against E. coli (MIC90 ≤ 16 μg/ml) but not against Klebsiella spp. (MIC90 > 512 μg/ml). Acidification of the environment increased the susceptibility of 71% of the bacterial isolates and resulted in a statistically significant decrease in bacterial survival. The use of a regimen consisting of a single oral dose of fosfomycin against an E. coli isolate with an MIC of ≤64 mg/liter was able to achieve a PTA of ≥90% for a target pharmacodynamic index (AUC/MIC) of 23 in urine; PTA was not achieved when the MIC was higher than 64 mg/liter. The cumulative fractions of the bacterial responses (CFR) were 99% and 55% against E. coli and Klebsiella spp., respectively, based on simulated drug exposure in urine with an acidic pH of 6.0. A decrease of the pH from 7.0 to 6.0 improved the PTA and CFR of the target pharmacodynamic index in both E. coli and Klebsiella isolates.

scholarly journals Promising Roles of Alternative Medicine and Plant-Based Nanotechnology as Remedies for Urinary Tract Infections

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5593
Author(s):  
Harish Chandra ◽  
Chanchal Singh ◽  
Pragati Kumari ◽  
Saurabh Yadav ◽  
Abhay P. Mishra ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
The Body ◽  
Adult Women ◽  
Functional Abnormality ◽  
E Coli ◽  
Time Usage ◽  
Long Time ◽  
Active Research ◽  
Tract Infections

Urinary tract infections (UTIs) are considered to be the most common infections worldwide, having an incidence rate of 40−60% in women. Moreover, the prevalence of this disorder in adult women is 30 times more than in men. UTIs are usually found in many hospitals and clinical practice; as disorders, they are complicated and uncomplicated; in uncomplicated cases, there is no structural or functional abnormality in the urogenital tract. However, obstruction, retention of urine flow and use of catheters increase the complexity. There are several bacteria (e.g., E. coli, Klebsiella pneumoniae, Proteus vulgaris, etc.) successfully residing in the tract. The diagnosis must not only be accurate but rapid, so early detection is an important step in the control of UTIs caused by uropathogens. The treatment of UTIs includes appropriate antimicrobial therapy to control the infection and kill the causal microbes inside the body. A long-time usage of antibiotics has resulted in multidrug resistance causing an impediment in treatment. Thus, alternative, combinatorial medication approaches have given some hope. Available treatments considered Homeopathic, Ayurvedic, Unani, and other herbal-based drugs. There are new upcoming roles of nanoparticles in combating UTIs which needs further validation. The role of medicinal plant-based nanotechnology approaches has shown promising results. Therefore, there must be active research in phyto-based therapies of UTIs, such as Ayurvedic Biology.

scholarly journals URINARY TRACT INFECTIONS

2016 ◽  
Vol 23 (01) ◽  
pp. 010-014
Author(s):  
Muhammad Usman Anjum ◽  
Muhammad Safdar Khan ◽  
Abdul Razzaq Shahid ◽  
Syed Humayun Shah
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Antimicrobial Susceptibility ◽  
Geographical Area ◽  
Gram Negative ◽  
E Coli ◽  
Amoxicillin Clavulanic Acid ◽  
Gram Negative Organisms ◽  
Tract Infections ◽  
Micro Organisms

Background: Urinary tract infections (UTIs) constitute important bacterialdisease which contributes to significant morbidity world-wide. Empirical treatment in patientssuffering from UTI depends upon the local knowledge of common microorganisms responsiblefor UTI in that geographical area as well as their antimicrobial susceptibility patterns.Objectives: To determine the frequency and antimicrobial susceptibility of uropathogenswhich are responsible for urinary tract infections. Study Design: Experimental study. Setting:Department of Pathology, Frontier Medical & Dental College and Mohi Ud Din Islamic MedicalCollege. Period: January 2015 to June 2015. Material & methods: Total of 113 patients wereincluded in the study. Urine samples were cultured on MacConkey’s agar and Cysteine LactoseElectrolyte Deficient (CLED) agar. Micro-organisms were identified using standard tests andantimicrobial susceptibility was checked using modified Kirby Bauer method following Clinicaland Laboratory Standards Institute (CLSI) guidelines. Results: The average age of patientswas 32.19±16.47 years. Gram negative organisms accounted for majority of cases, about 89(78.76%) cases. Escherichia coli was the most common micro-organism which was found in50 (44.24%) cases followed by Staphylococcus aureus in 24 (21.24%), Enterobacter spp. in19 (16.81%), Klebsiella spp. in 11 (9.73%) and Proteus spp. in 9 (7.96%) cases. E. coli wassensitive to imipenem and ciprofloxacin and was resistant to amoxicillin/clavulanic acid andgentamicin. Conclusion: Gram negative organisms are largely responsible for UTIs and E. colibeing the most common etiological agent. E. coli is sensitive to commonly prescribed drugs forUTI like ciprofloxacin.

scholarly journals Ciprofloxacin Resistance in Hospital and Community-acquired Urinary Tract Infections by Escherichia coli: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Guanyu Zhou ◽  
Xiaoju Lv
Keyword(s):  
Systematic Review ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Main Concern ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Ciprofloxacin Resistance ◽  
Tract Infections ◽  
Hospital Acquired

AbstractIn recent years, antimicrobial resistance has been increasingly reported. One main concern is the resistance of gram-negative bacteria like E. coli to ciprofloxacin (fluoroquinolones). Gram-negative bacteria are the main cause of community and hospital-acquired urinary tract infections (UTI). We aimed to review and analyze the data on ciprofloxacin resistance in hospital and community-acquired UTI. A literature search of three electronic databases (PubMed, Medline, and Cochrane) was performed. We considered the papers that were published from January 2004 to May 2019. The search yielded a total of 16097 studies besides 31 studies from a manual search. Filtering yielded 1297 relevant full-text papers. Eighty-three papers, equivalent of 99 cohorts, were finally included in this systematic review and in the analysis. The analysis results suggest that pooled ciprofloxacin resistance for community and hospital-acquired E. coli UTI is 0.27 (95% CI 0.246–0.303) and 0.30 (95% CI 0.22–0.38), respectively. Pooled resistance rates according to regions are 0.43 (95% CI 0.31–0.54) for Asia ensued by Africa 0.31 (95% CI 0.22–0.35), the Middle East 0.21(95% CI 0.13-0.30), Europe 0.18 (95% CI 0.13-0.22), and Australia 0.06 (95% CI 0.04-0.08). The pooled estimates revealed that ciprofloxacin resistance was higher in developing countries compared to that in developed countries, 0.35 (95% CI 0.30-0.40) and 0.13 (95% CI 0.10-0.16), respectively. Finally, plotting resistance over time deemed statistically significant (n= 79, r= 0.29, p= 0.038). Our findings suggest that ciprofloxacin resistance among UTI patients is a highly prevalent and serious issue. The suggested risks are low-income, acquiring hospital infection, and falling in highly-vulnerable regions like Asia and Africa. We also shed light on some approaches to correct the perception of patients and general practitioners (GPs) for antibiotic usage. We also suggest ideas to impede the progress of the post-antibiotic era in countries known for high antibiotic resistance.

Cinoxacin (Cinobac, Eli Lilly & Co.)

1982 ◽  
Vol 16 (12) ◽  
pp. 916-921 ◽  
Author(s):  
David R.P. Guay
Keyword(s):  
Urinary Tract ◽  
Organic Acid ◽  
Nalidixic Acid ◽  
Urinary Tract Infections ◽  
Antibacterial Agent ◽  
First Line ◽  
Gram Negative ◽  
Routine Treatment ◽  
Tract Infections

Cinoxacin, a synthetic organic acid antibacterial agent, related structurally to nalidixic and oxolinic acid, has been approved for the treatment of initial and recurrent urinary tract infections (UTIs) caused by susceptible gram-negative microorganisms. The role of cinoxacin in the treatment of UTIs, compared with the usual first-line agents, is uncertain at this time. The efficacy of cinoxacin in the treatment of pyelonephritis, compared with these proven agents, has been examined in only small numbers of patients, and cinoxacin is more expensive than these agents. Cinoxacin may prove valuable in the treatment of prostatitis and in the prophylaxis of recurrent UTIs; further study in these areas is warranted. In the routine treatment of acute UTIs, cinoxacin perhaps should be reserved only for those patients with organisms resistant to usual first-line agents or those who fail to respond to therapy with these agents. In this respect, cinoxacin may, in the future, replace nalidixic acid.

scholarly journals Gram-negative Organisms from Patients with Community-Acquired Urinary Tract Infections and Associated Risk Factors for Antimicrobial Resistance: A Single-Center Retrospective Observational Study in Japan

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 438 ◽  
Author(s):  
Naoki Kanda ◽  
Hideki Hashimoto ◽  
Tomohiro Sonoo ◽  
Hiromu Naraba ◽  
Yuji Takahashi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Nursing Home ◽  
Urinary Tract ◽  
Antimicrobial Resistance ◽  
Urinary Tract Infections ◽  
Strong Impact ◽  
Care Hospital ◽  
Gram Negative ◽  
E Coli ◽  
Tract Infections

A specific antibiogram is necessary for the empiric antibiotic treatment of community-acquired urinary tract infections (UTI) because of the global spread of antimicrobial resistance. This study aimed to develop an antibiogram specific for community-acquired UTI and assess the risk factors associated with community-acquired UTI caused by antimicrobial-resistant organisms. This cross-sectional observational retrospective study included patients with community-acquired UTI caused by Gram-negative rods (GNR) who were admitted to the emergency department at a tertiary care hospital in Ibaraki, Japan, in 2017–2018. A total of 172 patients were enrolled (including 38 nursing home residents). Of the 181 GNR strains considered as causative agents, 135 (75%) were Escherichia coli, and 40 (22%) exhibited third-generation cephalosporin resistance. Extended-spectrum β-lactamase (ESBL)-producing E. coli accounted for 25/40 (63%) of resistant GNR. Overall susceptibility rate of Enterobacterales was 92%, 81%, 100%, 75%, and 89% for cefmetazole, ceftriaxone, meropenem, levofloxacin, and trimethoprim–sulfamethoxazole, respectively. Residence in a nursing home (odds ratio (OR), 2.83; 95% confidence interval (CI), 1.18–6.79) and recent antibiotic use (OR, 4.52; 95% CI, 1.02–19.97) were independent risk factors for UTI with resistant GNR. ESBL-producing E. coli was revealed to have a strong impact on antimicrobial resistance pattern. Therefore, an antibiotic strategy based on a disease-specific antibiogram is required.

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