Effect of alkalinisation and increased fluid intake on bacterial phagocytosis and killing in urine

Gargan, R.A.; Hamilton‐Miller, J. M. T.; Brumfitt, W.

doi:10.1007/bf01970959

Cited by 9 publications

(2 citation statements)

References 25 publications

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“…It has been speculated that these infections are promoted, in part, by constituents of urine that impair phagocyte activity. One possible inhibitory factor is the hyperosmolality of urine, which may inhibit PMN phagocytosis [6] and oxidative metabolism [7] without affecting PMN viability. However, increased osmolality from inorganic salts may be only partially responsible for inhibition of PMN oxidative activity (particularly as measured by luminol-enhanced chemiluminescence).…”

Section: Introductionmentioning

confidence: 99%

Cyanate-mediated inhibition of neutrophil myeloperoxidase activity

Qian

Eaton

Wolff

1997

Biochemical Journal

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Cyanate (CNO-) forms spontaneously in solutions containing urea, and is present in urine and the body fluids of uraemic patients. We have explored the possibility that CNO- might be one of the unknown substances responsible for the reported impairment, by urine and uraemic plasma, of neutrophil oxidative metabolism (especially as measured by luminol-enhanced chemiluminescence). Luminol-enhanced chemiluminescence generated by human neutrophils derives predominantly from the activity of myeloperoxidase (MPO) which produces hypochlorous acid from H2O2 and Cl-. We hypothesized that CNO- (which resembles the 'pseudohalide' thiocyanate, an alternative substrate for MPO) might somehow interfere with the activity of MPO. In support of this, we find: (i) CNO- inhibits both peroxidative and halogenating activities of MPO and also inhibits the enzyme within intact human neutrophils; (ii) the inhibition is H2O2-dependent, irreversible, accompanied by covalent addition of [14C]CNO- (or a carbon-containing fragment thereof) to the enzyme; (iii) CNO- also inhibits Cl-/H2O2/MPO-mediated bacterial killing. Impairment of this arm of neutrophil bactericidal activity by CNO- formed from urea may be one factor in the risk of urinary-tract infection associated with urinary stasis and perhaps in the generalized increase in susceptibility to infection in uraemic patients.

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Section: Introductionmentioning

confidence: 99%

Cyanate-mediated inhibition of neutrophil myeloperoxidase activity

Qian

Eaton

Wolff

1997

Biochemical Journal

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“…and doxycycline for P. aeruginosa [121][122][123][124]. Furthermore, changes in urinary pH (acidic or alkaline) can alter antimicrobial activity [125][126][127][128][129][130].…”

Section: Antimicrobial Urinary Pharmacokineticsmentioning

confidence: 99%

Antimicrobial pharmacokinetics and preclinicalin vitromodels to support optimized treatment approaches for uncomplicated lower urinary tract infections

Abbott

Roberts

Meletiadis

et al. 2020

Expert Review of Anti-infective Therapy

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Introduction: Urinary tract infections (UTIs) are extremely common. Millions of people, particularly healthy women, are affected worldwide every year. One-in-two women will have a recurrence within 12-months of an initial UTI. Inadequate treatment risks worsening infection leading to acute pyelonephritis, bacteremia and sepsis. In an era of increasing antimicrobial resistance, it is critical to provide optimized antimicrobial treatment.Areas covered: Literature was searched using PubMed and Google Scholar (up to 06/2020), examining the etiology, diagnosis and oral antimicrobial therapy for uncomplicated UTIs, with emphasis on urinary antimicrobial pharmacokinetics (PK) and the application of dynamic in vitro models for the pharmacodynamic (PD) profiling of pathogen response.Expert opinion: The majority of antimicrobial agents included in international guidelines were developed decades ago without well-described dose-response relationships. Microbiology laboratories still apply standard diagnostic methodology that has essentially remained unchanged for decades. Furthermore, it is uncertain how relevant standard in vitro susceptibility is for predicting antimicrobial efficacy in urine. In order to optimize UTI treatments, clinicians must exploit the urine-specific PK of antimicrobial agents. Dynamic in vitro models are valuable tools to examine the PK/PD and urodynamic variables associated with UTIs, while informing uropathogen susceptibility reporting, optimized dosing schedules, clinical trials and treatment guidelines.

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Management of Urinary Tract Infections Caused by Multiresistant Organisms

Hamilton‐Miller¹

2004

Management of Multiple Drug-Resistant Infections

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Effect of alkalinisation and increased fluid intake on bacterial phagocytosis and killing in urine

Cited by 9 publications

References 25 publications

Cyanate-mediated inhibition of neutrophil myeloperoxidase activity

Cyanate-mediated inhibition of neutrophil myeloperoxidase activity

Antimicrobial pharmacokinetics and preclinicalin vitromodels to support optimized treatment approaches for uncomplicated lower urinary tract infections

Management of Urinary Tract Infections Caused by Multiresistant Organisms

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