Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection

Khawaldeh, Abdelkarim; Morales, Sandra; Dillon, Belinda; Alavidze, Zemphira; Ginn, Andrew N.; Thomas, L.; Chapman, Scott; Dublanchet, A.; Smithyman, Anthony M.; Iredell, Jonathan R.

doi:10.1099/jmm.0.029744-0

Cited by 159 publications

(93 citation statements)

References 12 publications

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“…240 They are often highly target specific and synergistic with antibiotics, 241 and they may be valuable in antibiotic resistant and biofilm-type infections, infecting target bacteria and disappearing as they are consumed. 242 Empiric treatment usually requires a phage "cocktail" to overcome resistance, but problems associated with resistance, targeting, immunogenicity, and diffusion must be resolved before they can be used routinely. 241 243 244 Intrinsic bacterial defense systems such as the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 attack complex, which ordinarily functions as an adaptive immune mechanism to combat bacteriophages and foreign DNA, can be re-engineered to specifically target resistance, virulence, or other autologous DNA sequences, including with phage delivery.…”

Section: Fosfomycinmentioning

confidence: 99%

Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications

Iredell

Brown

Tagg

2016

BMJ

252

177

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Resistance of the Enterobacteriaceae to antibiotics, especially of the β lactam type, is increasingly dominated by the mobilization of continuously expressed single genes that encode efficient drug modifying enzymes. Strong and ubiquitous selection pressure has seemingly been accompanied by a shift from "natural" resistance, such as inducible chromosomal enzymes, membrane impermeability, and drug efflux, to the modern paradigm of mobile gene pools that largely determine the epidemiology of modern antibiotic resistance. In this way, antibiotic resistance is more available than ever before to organisms such as Escherichia coli and Klebsiella pneumoniae that are important causes of major sepsis. Modulation of the phenotype by host bacteria makes gene transmission less obvious and may in part explain why tracking and control of carbapenem resistance has been particularly problematic in the Enterobacteriaceae. This review discusses the underlying principles and clinical implications of the mobility and fixation of resistance genes and the exploitable opportunities and potential threats arising from apparent limitations on diversity in these mobile gene pools. It also provides some illustrative paradoxes and clinical corollaries, as well as a summary of future options.

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Section: Fosfomycinmentioning

confidence: 99%

Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications

Iredell

Brown

Tagg

2016

BMJ

252

177

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“…However, animal and human trials in the west with the purpose of satisfying western regulatory agencies have only been undertaken recently. While efficacy has appeared in animal studies (Debarbieux et al 2010) and in human studies where phages are employed on a "compassionate use" basis (Khawaldeh et al 2011), large-scale human trials are still working through safety evaluation (see for review Harper and Enright 2011).…”

Section: Introductionmentioning

confidence: 99%

Characterization of lytic Pseudomonas aeruginosa bacteriophages via biological properties and genomic sequences

Karumidze

Thomas

Kvatadze

et al. 2012

Appl Microbiol Biotechnol

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Pseudomonas aeruginosa is an important cause of infections, especially in patients with immunodeficiency or diabetes. Antibiotics are effective in preventing morbidity and mortality from Pseudomonas infection, but because of spreading multidrug-resistant bacterial strains, bacteriophages are being explored as an alternative therapy. Two newly purified broad host range Pseudomonas phages, named vB_Pae-Kakheti25 and vB_Pae-TbilisiM32, were characterized as candidates for use in phage therapy. Morphology, host range, growth properties, thermal stability, serology, genomic sequence, and virion composition are reported. When phages are used as bactericides, they are used in mixtures to overcome the development of resistance in the targeted bacterial population. These two phages are representative of diverse siphoviral and podoviral phage families, respectively, and hence have unrelated mechanisms of infection and no cross-antigenicity. Composing bactericidal phage mixtures with members of different phage families may decrease the incidence of developing resistance through a common mechanism.

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“…In addition, resistance optimization by direct adaption of bacteriophages was possible,52 and phages can degrade even uropathogenic E. coli biofilms 53. Recently, initial case reports of phage use in humans for UTI treatment have been reported 54. Therefore, phages may be the most promising future option for treatment and prevention of UTI.…”

Section: Uti Preventionmentioning

confidence: 99%

Management of urinary tract infections in patients with neurogenic bladder: challenges and solutions

Pannek¹,

Wöllner²

2017

RRU

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IntroductionUrinary tract infections (UTIs) are one of the most common morbidities in persons with neurogenic lower urinary tract dysfunction (NLUTD). They are associated with a significant morbidity and mortality, and they affect the quality of life of the affected patients. Diagnosis and treatment of UTI in this group of patients are challenging. In this review, the current strategies regarding diagnosis, treatment, and prevention are summarized.Diagnosticsit is important to correctly diagnose a UTI, as treatment of bacteriuria should strictly be avoided. A UTI is defined as a combination of laboratory findings (leukocyturia and bacteriuria) and symptoms. Laboratory findings without symptoms are classified as asymptomatic bacteriuria. Routine urine screening is not advised.TreatmentOnly UTI should be treated; treatment of asymptomatic bacteriuria is not indicated. Prior to treatment, urine for a urine culture should be obtained. Antibiotic treatment for ~7 days is advised.PreventionIn recurrent UTI, bladder management should be optimized and morphologic causes for UTI should be excluded. If UTIs persist, medical prophylaxis should be considered. Currently, no prophylactic measure with evidence-based efficacy exists. Long-term antibiotic prophylaxis should be used merely as an ultimate measure. Among the various mentioned innovative approaches for UTI prevention, bacteriophages, intravesical instillations, complementary and alternative medicine techniques, and probiotics seem to be most promising.ConclusionRecently, several promising innovative options for UTI prophylaxis have been developed which may help overcome the current therapeutic dilemma. However, further well designed studies are necessary to evaluate the safety and efficacy of these approaches.

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Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection

Cited by 159 publications

References 12 publications

Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications

Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications

Characterization of lytic Pseudomonas aeruginosa bacteriophages via biological properties and genomic sequences

Management of urinary tract infections in patients with neurogenic bladder: challenges and solutions

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