An update on emerging therapies for urinary tract infections

Majeed, Aneela; Alarfaj, Sumaiah J.; Darouiche, Rabih O.; Mohajer, Mayar Al

doi:10.1080/14728214.2017.1293650

Cited by 13 publications

(14 citation statements)

References 48 publications

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“…Uncomplicated UTIs typically affect otherwise healthy individuals, who do not have structural or neurological urinary tract abnormalities. Complicated UTIs are defined as infections, which develop in patients with structurally or functionally abnormal urinary tract system (Hooton, 2012;Chen et al, 2013;Levison and Kaye, 2013;Flores-Mireles et al, 2015;Majeed et al, 2017). UTIs are caused by Gram-positive and Gram-negative bacteria and fungi.…”

Section: Introductionmentioning

confidence: 99%

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Amniotic Membrane Preparation Crucially Affects Its Broad-Spectrum Activity Against Uropathogenic Bacteria

2020

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Urinary tract infections are among the most common bacterial infections in humans. Moreover, they are highly recurrent and increasingly often resistant to antibiotics. The antimicrobial properties of the amniotic membrane (AM), the innermost layer of fetal membranes, have been briefly reported in the literature, however, the results of published studies are often inconsistent and unclear; moreover, its effect on uropathogenic bacteria has not yet been investigated. Further, there is no data in the literature about the effect of AM preparation and storage on its antimicrobial properties. To examine the impact of several preparation procedures on the antimicrobial properties of AM, we prepared patches and homogenates of fresh (fAM) and cryopreserved (cAM) human AM and tested them on 14 selected Gram-positive and Gram-negative uropathogenic bacteria. By employing novel antimicrobial efficiency assays we showed that fAM and cAM homogenates have broad-spectrum antimicrobial activity against all here tested uropathogenic bacteria, except for Serratia marcescens. Moreover, they had a potent effect also on the multiple-resistant clinical strains of uropathogenic Escherichia coli. Interestingly, the patches of fAM and cAM had no antimicrobial effect on any of the tested strains. We therefore prepared and stored AM patches according to the standard procedure for clinical use in ophthalmology, which includes the cryopreservation of antibiotic-treated AM, and performed antimicrobial efficiency assays. Our findings suggest that the ultrastructure of AM patches could enable the retention of added antibiotics. In addition, we also prepared gentamicin-resistant uropathogenic E. coli strains, which confirmed that the antimicrobial effect of antibiotic-treated AM patches can be attributed to the antibiotic alone. To summarize, here we describe novel protocols for preparation and storage of AM to ensure the preservation of its antimicrobial factors. Moreover, we describe the mechanism of AM retention of antibiotics, based on which the AM could potentially be used as a drug delivery vehicle in future clinically applicable approaches.

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Section: Introductionmentioning

confidence: 99%

“…(Nielubowicz and Mobley, 2010;Levison and Kaye, 2013;Foxman, 2014;Flores-Mireles et al, 2015). Some of UTI-causing agents are becoming progressively more problematic due to an increase of antibiotic resistance and therefore there is an urgent need for the development of new antimicrobial agents (Majeed et al, 2017;Zaman et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Amniotic Membrane Preparation Crucially Affects Its Broad-Spectrum Activity Against Uropathogenic Bacteria

2020

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“…Point mutations on β-lactamase genes are responsible for emergence of ESBLs. These new genes could be transmitted through small mobile genetic element DNA (plasmid, transposons) to other bacteria from same or other species [5,8].…”

Section: Mechanism Of Resistancementioning

confidence: 99%

“…This resulted in prolonged hospital stay, marked increases in the cost as well as increase in morbidity and mortality [3][4][5][6]. Furthermore, bloodstream infections associated with severe complicated urinary tract infections (CUTIs) are associated with high mortality rates of 20-50% among critically ill patients.…”

Section: Introductionmentioning

confidence: 99%

Resistant Gram-Negative Urinary Tract Bacterial Infections

Hamza¹,

Khalil²

2018

Urinary Tract Infection - The Result of the Strength of the Pathogen, or the Weakness of the Host

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Urinary tract infection (UTI) is one of the most common infections in both the community as well in hospital settings. It is mostly caused by Gram-negative bacteria (GNBs). Over the past two decades, GNBs have developed complex mechanisms of resistance against most of the potent antibiotics. This has been a global challenge which has been identified by the World Health Organization as "one of the greatest threats to human health." This crisis is mostly attributed to the overuse and misuse of these medications, as well as lack of new drug antimicrobials by the pharmaceutical industry. This resulted in prolonged hospital stay, marked increase in the cost as well as increase in morbidity and mortality. Furthermore, it increases the risks and complications of urological procedures. In this chapter, we review the management of the most common and challenging group of resistant Gram-negative organisms, the extended-spectrum β-lactamases producing organisms (ESBL) and the carbapenem-resistant organisms (CRE/CRP). The latter group includes carbapenem-resistant Enterobacteriaceae (CRE), as well as Pseudomonas aeruginosa carbapenemases (CRP). When treating these infections, clinicians have few effective antimicrobials options. A critical step in managing these organisms is the early recognition and appropriate empiric therapy. Both showed morbidity and mortality benefits.

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“…2,3 Indeed, half of all women will develop a UTI in their lifetime, and more than 40% of these individuals will experience a recurrent infection. 4,5 The incidence and recurrent nature of infection take on more urgency given that 10-25% of uncomplicated UTI patient isolates are resistant to trimethoprim/sulfamethoxazole 6,7 (TMP/SMX), a common antibiotic treatment regimen for UTI. When antibiotic treatment fails, bacteria persist in the bladder, increasing the cost of care and morbidity for the patient.…”

Section: Introductionmentioning

confidence: 99%

Metal-Organic Framework Encapsulated Whole-Cell Vaccines Enhance Humoral Immunity against Bacterial Infection

Luzuriaga¹,

Herbert²,

Brohlin³

et al. 2020

Preprint

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Urinary tract infection, most often caused by uropathogenic Escherichia coli (UPEC), is the second most common bacterial infection. Rates of antibiotic resistance among UPEC strains is high and front-line antibiotic therapies are losing efficacy. Untreated, UPEC can ascend to the kidneys and into the bloodstream to cause potentially fatal pyelonephritis and bacteremia, respectively. Vaccine development is hampered by the genetic diversity of UPEC strains making selection of antigens capable of inducing broad protection difficult. Whole cell UPEC vaccines offer a solution to the antigen selection problem, however, current inactivation methods are harsh and degrade surface antigens resulting in a weak immune response. Here, we demonstrate a method to gently inactivate whole cell UPEC by encasing them in a crystalline metalcoordination polymeric matrix called a Metal-Organic Framework. This process encapsulates read-to-use composites within 30 minutes in water and at ambient temperatures. We show this new formulation greatly improves survivability in a murine model of UPEC bacteremia compared to standard inactivated formulations. The simplicity of the preparation and use suggests this method could be applied as a point-of-care measure to create therapeutic and prophylactic vaccines against patient derived samples.

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An update on emerging therapies for urinary tract infections

Cited by 13 publications

References 48 publications

Amniotic Membrane Preparation Crucially Affects Its Broad-Spectrum Activity Against Uropathogenic Bacteria

Amniotic Membrane Preparation Crucially Affects Its Broad-Spectrum Activity Against Uropathogenic Bacteria

Resistant Gram-Negative Urinary Tract Bacterial Infections

Metal-Organic Framework Encapsulated Whole-Cell Vaccines Enhance Humoral Immunity against Bacterial Infection

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