Impact of Allergy and Resistance on Antibiotic Selection for Recurrent Urinary Tract Infections in Older Women

Malik, Rena D.; Wu, Yuefeng; Christie, Alana; Alhalabi, Feras

doi:10.1016/j.urology.2017.08.070

Cited by 42 publications

(46 citation statements)

References 23 publications

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“…The use of clinical antibiotics to treat bacterial infections becomes more and more difficult because bacteria have developed resistance to antibiotics at an alarming speed. Urinary tract infections (UTIs) are very common infectious diseases in clinical, especially among women, elderly, and children [1][2][3] . With respect to the worldwide dissemination of drug-resistant bacterial strains, clinical treatment of UTI becomes a serious challenge 4 .…”

Section: Introductionmentioning

confidence: 99%

Discovery and antibacterial study of potential PPK1 inhibitors against uropathogenic E. coli

Peng

Zeng

Jin

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Novel antibacterial agents are urgently needed to address the infections caused by multi-drug resistant bacteria. Urinary tract infections are common infectious diseases in clinical. Most of these infections are caused by drug-resistant uropathogenic Escherichia coli. PPK1 is an essential kinase for bacterial motility, biofilm formation, quorum sensing, and virulence factors in the expression of uropathogenic E. coli. In the present study, two small molecules potentially targeting PPK1 were discovered through virtual screening and biological assays. The in vitro and in vivo results suggested that the interaction of these compounds with PPK1 can disrupt biofilm formation of uropathogenic E. coli and reduce invasive ability and resistance to oxidative stress of this strain. Moreover, the compounds exhibit good antibacterial bacterial activity in the mice with urinary tract infection. Taken together, our findings could provide a new chemotype for the development of antibacterials targeting PPK1.

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Section: Introductionmentioning

confidence: 99%

Discovery and antibacterial study of potential PPK1 inhibitors against uropathogenic E. coli

Peng

Zeng

Jin

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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show abstract

“…The mainstay of RUTI treatment has been dominated by antibiotics, but the persistence mechanism just described attenuates their effectiveness. Furthermore, antibiotic effectiveness is decreasing because of widespread allergy and resistance issues, which are particularly relevant to the older population of postmenopausal women who are often affected by RUTIs; new therapies to treat RUTIs are urgently needed (3). Not surprisingly, nonantibiotic therapies have received recent attention (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Rapid Growth and Metabolism of Uropathogenic Escherichia coli in Relation to Urine Composition

Reitzer

2019

Clin Microbiol Rev

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SUMMARYUropathogenicEscherichia coli(UPEC) strains cause a majority of urinary tract infections (UTIs). Since UPEC strains can become antibiotic resistant, adjunct or alternate therapies are urgently needed. UPEC strains grow extremely rapidly in patients with UTIs. Thus, this review focuses on the relation between urine composition and UPEC growth and metabolism. Compilation of urinary components from two major data sources suggests the presence of sufficient amino acids and carbohydrates as energy sources and abundant phosphorus, sulfur, and nitrogen sources. In a mouse UTI model, mutants lacking enzymes of the tricarboxylic acid cycle, gluconeogenesis, and the nonoxidative branch of the pentose cycle are less competitive than the corresponding parental strains, which is consistent with amino acids as major energy sources. Other evidence suggests that carbohydrates are required energy sources. UPEC strains in urineex vivoandin vivoexpress transporters for peptides, amino acids, carbohydrates, and iron and genes associated with nitrogen limitation, amino acid synthesis, nucleotide synthesis, and nucleotide salvage. Mouse models confirm the requirement for many, but not all, of these genes. Laboratory evolution studies suggest that rapid nutrient uptake without metabolic rewiring is sufficient to account for rapid growth. Proteins and pathways required for rapid growth should be considered potential targets for alternate or adjunct therapies.

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“…International guideline management recommendations include options such as prolonged low‐dose daily antibiotic suppression, post‐coital and self‐initiated therapy, and local and systemic hormonal therapy, among others . Furthermore, the development of antibiotic resistance and allergies in women with RUTIs can significantly constrain treatment options …”

Section: Introductionmentioning

confidence: 99%

“…4,6 Furthermore, the development of antibiotic resistance and allergies in women with RUTIs can significantly constrain treatment options. 7 While bacterial ascent into the bladder from extraurinary sources, such as the vagina or rectum, is believed to cause UTIs, studies in murine models have suggested that uropathogenic Escherichia coli invade urothelial cells to form IBC and subsequently QIR. Through the biofilm-like qualities of these bacterial populations, it is thought that organisms are able to persist and evade the immune response and antibiotic treatments.…”

Section: Introductionmentioning

confidence: 99%

Electrofulguration in the advanced management of antibiotic‐refractory recurrent urinary tract infections in women

Crivelli

Alhalabi

2019

Int J of Urology

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Objective To evaluate the long‐term efficacy of electrofulguration in women with recurrent urinary tract infections. Methods After institutional review board approval, a retrospective study of women who underwent electrofulguration alone was carried out. All patients had recurrent urinary tract infections defined as three or more urinary tract infections/year, and a preoperative office cystoscopy showing inflammatory lesions, categorized by location: urethra, bladder neck, trigone and beyond the trigone. All lesions were cauterized during outpatient electrofulguration under anesthesia. On 6‐month postoperative office cystoscopy, endoscopic success was defined as resolution of all lesions previously seen and no new lesions. The primary outcome was urinary tract infections/year, with urinary tract infection defined as antibiotic treatment for urinary tract infection‐like symptoms and/or for positive urine culture. Clinical cure was defined as no further urinary tract infections, clinical improvement as less than three urinary tract infections/year, and clinical failure as three or more urinary tract infections/year. Results Of 95 women who met the study criteria between 2004 and 2016, 62 (65%) were endoscopically successful, and 33 (35%) were endoscopic failures based on postoperative cystoscopy. Among all patients, over a median follow‐up period of 4.9 years, the median number of urinary tract infections/year was 0.8. Endoscopically successful patients had fewer urinary tract infections/year compared with endoscopic failures (0.6 vs 0.9, P = 0.03). Clinically, 14 (15%) patients were cured, 69 (73%) were improved and 12 (13%) failed. Compared with clinically improved patients, clinical failures were more likely to have infections with multiple organisms (92% vs 35%, P < 0.001) and highly resistant organisms (92% vs 23%, P < 0.001). Conclusions In our experience, nearly two‐thirds of women with recurrent urinary tract infection can be successfully treated with electrofulguration, and >80% experience long‐term clinical cure or improvement in urinary tract infections.

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Impact of Allergy and Resistance on Antibiotic Selection for Recurrent Urinary Tract Infections in Older Women

Cited by 42 publications

References 23 publications

Discovery and antibacterial study of potential PPK1 inhibitors against uropathogenic E. coli

Discovery and antibacterial study of potential PPK1 inhibitors against uropathogenic E. coli

Rapid Growth and Metabolism of Uropathogenic Escherichia coli in Relation to Urine Composition

Electrofulguration in the advanced management of antibiotic‐refractory recurrent urinary tract infections in women

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