Treatment of chronic relapsing urinary tract infection with antibiotics selected by AtbFinder

Tetz, George; Kardava, K; Vecherkovskaya, Maria; Tsifansky, Michael D.; Tetz, Victor

doi:10.1016/j.eucr.2022.102312

Cited by 6 publications

(3 citation statements)

References 5 publications

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“…the approach claims to also consider polymicrobial interactions influencing antimicrobial susceptibility. Case studies have suggested this approach leads to selection of antibiotics with better efficacy for treating nosocomial pneumonia (71) and chronic relapsing urinary tract infections (72). A recently-published clinical trial in which the AtbFinder system was used in the context of respiratory tract infections in CF patients (35 patients, of which 33 were chronically colonized with Pseudomonas aeruginosa) suggests that antibiotics selected with AtbFinder lead to clearance of P.…”

Section: Alternative Methods For Susceptibility Testingmentioning

confidence: 99%

Biofilm antimicrobial susceptibility testing: where are we and where could we be going?

Coenye

2023

Clin Microbiol Rev

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SUMMARY Our knowledge about the fundamental aspects of biofilm biology, including the mechanisms behind the reduced antimicrobial susceptibility of biofilms, has increased drastically over the last decades. However, this knowledge has so far not been translated into major changes in clinical practice. While the biofilm concept is increasingly on the radar of clinical microbiologists, physicians, and healthcare professionals in general, the standardized tools to study biofilms in the clinical microbiology laboratory are still lacking; one area in which this is particularly obvious is that of antimicrobial susceptibility testing (AST). It is generally accepted that the biofilm lifestyle has a tremendous impact on antibiotic susceptibility, yet AST is typically still carried out with planktonic cells. On top of that, the microenvironment at the site of infection is an important driver for microbial physiology and hence susceptibility; but this is poorly reflected in current AST methods. The goal of this review is to provide an overview of the state of the art concerning biofilm AST and highlight the knowledge gaps in this area. Subsequently, potential ways to improve biofilm-based AST will be discussed. Finally, bottlenecks currently preventing the use of biofilm AST in clinical practice, as well as the steps needed to get past these bottlenecks, will be discussed.

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Section: Alternative Methods For Susceptibility Testingmentioning

confidence: 99%

Biofilm antimicrobial susceptibility testing: where are we and where could we be going?

Coenye

2023

Clin Microbiol Rev

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“…Relapses in infection can often be attributed to flawed antimicrobial susceptibility testing (27)(28)(29)(30). Conventional antimicrobial susceptibility testing methods cannot always predict the efficacy of antibiotic treatment in vivo (27), and do not factor in biofilm or polymicrobial communities (28,30).…”

Section: Introductionmentioning

confidence: 99%

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia

Walsh,

Parmenter,

Bakker

et al. 2024

Preprint

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Defined as a pneumonia occurring after more than 48 hours of mechanical ventilation via an endotracheal tube, ventilator-associated pneumonia results from biofilm formation on the indwelling tube, seeding the patient’s lower airways with pathogenic microbes such asPseudomonas aeruginosa, Klebsiella pneumoniae,andCandida albicans.Currently there is a lack of accuratein vitromodels of ventilator-associated pneumonia development. This greatly limits our understanding of how the in-host environment alters pathogen physiology and the efficacy of ventilator-associated pneumonia prevention or treatment strategies. Here, we showcase a reproducible model that simulates biofilm formation of these pathogens in a host-mimicking environment, and demonstrate that the biofilm matrix produced differs from that observed in standard laboratory growth medium. In our model, pathogens are grown on endotracheal tube segments in the presence of a novel synthetic ventilator airway mucus (SVAM) medium that simulates the in-host environment. Matrix-degrading enzymes and cryo-SEM were employed to characterise the system in terms of biofilm matrix composition and structure, as compared to standard laboratory growth medium. As seen in patients, the biofilms of ventilator-associated pneumonia pathogens in our model either required very high concentrations of antimicrobials for eradication, or could not be eradicated. However, combining matrix-degrading enzymes with antimicrobials greatly improved biofilm eradication of all pathogens. Ourin vitroendotracheal tube (IVETT) model informs on fundamental microbiology in the ventilator-associated pneumonia context, and has broad applicability as a screening platform for antibiofilm measures including the use of matrix-degrading enzymes as antimicrobial adjuvants.ImportanceThe incidence of ventilator-associated pneumonia in mechanically ventilated patients is between 5-40%, increasing to 50-80% in patients suffering from coronavirus disease 2019 (COVID-19). The mortality rate of ventilator-associated pneumonia patients can reach 45%. Treatment of the endotracheal tube biofilms that cause ventilator-associated pneumonia is extremely challenging, with causative organisms able to persist in endotracheal tube biofilm despite appropriate antimicrobial treatment in 56% of ventilator-associated pneumonia patients. Flawed antimicrobial susceptibility testing often means that ventilator-associated pneumonia pathogens are insufficiently treated, resulting in patients experiencing ventilator-associated pneumonia recurrence. Here we present anin vitroendotracheal tube biofilm model that recapitulates key aspects of endotracheal tube biofilms, including dense biofilm growth and elevated antimicrobial tolerance. Thus our biofilm model can be used as a ventilated airway simulating environment, aiding the development of anti-ventilator-associated pneumonia therapies and antimicrobial endotracheal tubes that can one day improve the clinical outcomes of mechanically ventilated patients.

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“…Relapses in infection can often be attributed to flawed antimicrobial susceptibility testing [32][33][34][35]. Conventional antimicrobial susceptibility testing methods cannot always predict the efficacy of antibiotic treatment in vivo [32] and do not factor in biofilm or polymicrobial communities [33,35].…”

Section: Introductionmentioning

confidence: 99%

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia

Walsh,

Parmenter,

Bakker

et al. 2024

Microbiology

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Ventilator-associated pneumonia is defined as pneumonia that develops in a patient who has been on mechanical ventilation for more than 48 hours through an endotracheal tube. It is caused by biofilm formation on the indwelling tube, which introduces pathogenic microbes such as Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans into the patient’s lower airways. Currently, there is a lack of accurate in vitro models of ventilator-associated pneumonia development. This greatly limits our understanding of how the in-host environment alters pathogen physiology and the efficacy of ventilator-associated pneumonia prevention or treatment strategies. Here, we showcase a reproducible model that simulates the biofilm formation of these pathogens in a host-mimicking environment and demonstrate that the biofilm matrix produced differs from that observed in standard laboratory growth medium. In our model, pathogens are grown on endotracheal tube segments in the presence of a novel synthetic ventilated airway mucus medium that simulates the in-host environment. Matrix-degrading enzymes and cryo-scanning electron microscopy were employed to characterize the system in terms of biofilm matrix composition and structure, as compared to standard laboratory growth medium. As seen in patients, the biofilms of ventilator-associated pneumonia pathogens in our model either required very high concentrations of antimicrobials for eradication or could not be eradicated. However, combining matrix-degrading enzymes with antimicrobials greatly improved the biofilm eradication of all pathogens. Our in vitro endotracheal tube model informs on fundamental microbiology in the ventilator-associated pneumonia context and has broad applicability as a screening platform for antibiofilm measures including the use of matrix-degrading enzymes as antimicrobial adjuvants.

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Treatment of chronic relapsing urinary tract infection with antibiotics selected by AtbFinder

Cited by 6 publications

References 5 publications

Biofilm antimicrobial susceptibility testing: where are we and where could we be going?

Biofilm antimicrobial susceptibility testing: where are we and where could we be going?

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia

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