Antibiotic Resistance and the Risk of Recurrent Bacteremia

Woudt, Sjoukje H S; Greeff, Sabine C. de; Schoffelen, Annelot F.; Bonten, Marc J. M.; Stuart, J. W. T. Cohen; Weersink, A. J. L.; Vandenbroucke-Grauls, Christina M. J. E.; Visser, Caroline E.; Ogtrop, M L van; Kaersenhout, D J; Scholing, Maarten; Hees, B.C. van; Keulen, P. H. J. van; Kluytmans, Jan; Kraan, E.M.; Mattsson, Eva; Sebens, F.W.; Jong, Ellen de; Frénay, H.M.E.; Maraha, B.; Griethuysen, A. J. van; Silvis, Welmoed; Demeulemeester, A. A.; Wintermans, B.B.; Trijp, M. van; Ott, Alewijn; Arends, Jan P.; Kampinga, Greetje A.; Veenendaal, Dick; Hol, C.; Brauwer, E.I.G.B. De; Stals, Frans; Bakker, L. J.; Dorigo-Zetsma, J. W.; Ridwan, Ben U.; Zeijl, J.H. van; Bernards, A.T.; Erkens-Hulshof, Sandra; Jongh, B. M. De; Vlaminckx, Bart J. M.; Nabuurs-Franssen, Marrigje H.; Kuipers, Saskia; Diederen, Bram M. W.; Melles∗, Damian C.; Rijn, M. van; Dinant, Sander; Pontesilli, O.; Man, Peter de; Vaessen, Norbert; Hall, Michael; Elzakker, Erika P. M. van; Muller, Anouk E.; Renders, Nicole H. M.; Dam, D W van; Buiting, A. G. M.; Vlek, A. L. M.; Deege, Marjolein P D; Frakking, Florine N. J.; Overdevest, Ilse; Bosboom, Ron; Trienekens, T. A. M.; Voorn, G. Paul; Ruijs, G. J. H. M.; Wolfhagen, M. J. H. M.; Alblas, Jacques B. H.; Kuil, Wieke Altorf-van der; Blijboom, L.; Groenendijk, S. R.; Heereveld, J. van; Hertroys, R.; Monen, Jos; Notermans, Daan W.; Reuland, E.A.; Triest, M.I. van; Wielders, Cornelia C H

doi:10.1093/cid/cix1076

Cited by 16 publications

(12 citation statements)

References 16 publications

(14 reference statements)

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“…This is noteworthy as extended-spectrum cephalosporin resistance increased in U.S. hospitals from 5.46% to 12.97% between 2009 and 2016 ( 28 ). In addition, a recent Dutch study found that resistance to third-generation cephalosporins in Enterobacteriaceae is a significant risk factor for recurrence in bloodstream infections ( 29 ). The shared relative prevalence of the 12 most common O-antigen serotypes between BSI and UTI strains is consistent with the association between strains responsible for sepsis and strains sourced from urinary tract infections ( 30 – 33 ).…”

Section: Discussionmentioning

confidence: 99%

Preclinical Immunogenicity and Efficacy of Optimized O25b O-Antigen Glycoconjugates To Prevent MDR ST131 E. coli Infections

Chorro

Chu

et al. 2022

Infect Immun

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Multivalent O-antigen polysaccharide glycoconjugate vaccines are under development to prevent invasive infections caused by pathogenic Enterobacteriaceae . Sequence type 131 (ST131) Escherichia coli of serotype O25b has emerged as the predominant lineage causing invasive multidrug-resistant extraintestinal pathogenic E. coli (ExPEC) infections. We observed the prevalence of E. coli O25b ST131 among a contemporary collection of isolates from U.S. bloodstream infections from 2013 to 2016 ( n = 444) and global urinary tract infections from 2014 to 2017 ( n = 102) to be 25% and 24%, respectively.

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Section: Discussionmentioning

confidence: 99%

Preclinical Immunogenicity and Efficacy of Optimized O25b O-Antigen Glycoconjugates To Prevent MDR ST131 E. coli Infections

Chorro

Chu

et al. 2022

Infect Immun

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“…Nevertheless, only one of them included a limited number of cases of bloodstream infections produced by P . aeruginosa (BSI-PA), and thus the question on the efficacy of short treatments remains open for this microorganism, whose ability to produce relapsing infections and breakthrough antibiotic resistance is superior to other Gram-negative bacteria [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Hitherto, three randomized trials have confirmed the non-inferiority of 7-day courses of antibiotics compared to 14-day schemes for non-complicated bacteremic infections produced by Gram-negative bacilli [9][10][11]. Nevertheless, only one of them included a limited number of cases of bloodstream infections produced by P. aeruginosa (BSI-PA), and thus the question on the efficacy of short treatments remains open for this microorganism, whose ability to produce relapsing infections and breakthrough antibiotic resistance is superior to other Gram-negative bacteria [12,13].…”

Section: Introductionmentioning

confidence: 99%

Study protocol for a randomized clinical trial to assess 7 versus 14-days of treatment for Pseudomonas aeruginosa bloodstream infections (SHORTEN-2 trial)

et al. 2022

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Background Research priorities in Antimicrobial Stewardship (AMS) have rapidly evolved in the last decade. The need for a more efficient use of antimicrobials have fueled plenty of studies to define the optimal duration for antibiotic treatments, and yet, there still are large areas of uncertainty in common clinical scenarios. Pseudomonas aeruginosa has been pointed as a priority for clinical research, but it has been unattended by most randomized trials tackling the effectiveness of short treatments. The study protocol of the SHORTEN-2 trial is presented as a practical example of new ways to approach common obstacles for clinical research in AMS. Objective To determine whether a 7-day course of antibiotics is superior to 14-day schemes for treating bloodstream infections by P. aeruginosa (BSI-PA). Methods A superiority, open-label, randomized controlled trial will be performed across 30 Spanish hospitals. Adult patients with uncomplicated BSI-PA will be randomized to receive a 7 versus 14-day course of any active antibiotic. The primary endpoint will be the probability for the 7-day group of achieving better outcomes than the control group, assessing altogether clinical effectiveness, severe adverse events, and antibiotic exposure through a DOOR/RADAR analysis. Main secondary endpoints include treatment failure, BSI-PA relapses, and mortality. A superiority design was set for the primary endpoint and non-inferiority for treatment failure, resulting in a sample size of 304 patients. Conclusions SHORTEN-2 trial aligns with some of the priorities for clinical research in AMS. The implementation of several methodological innovations allowed overcoming common obstacles, like feasible sample sizes or measuring the clinical impact and unintended effects. Trial registration EudraCt: 2021-003847-10; ClinicalTrials.gov: NCT05210439.

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“…The ability of pathogenic bacteria to survive therapeutic intervention is quickly becoming a major medical crisis of the modern world, where the emergence of multidrug resistance amongst Gram-positive and -negative bacteria have rendered conventional antimicrobials inept (Frieri et al 2017). Several resistance mechanisms have been recognised within bacterial populations including immunosuppression of the host, evasion of immune response by the pathogen and ineffectiveness of antibiotic therapies (Woudt et al 2018). Persister cells are a survival mechanism exhibited by bacteria, during the exponential growth phase, in response to a range of adverse environmental conditions (Fisher et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Persister cells: formation, resuscitation and combative therapies

2021

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Persister cells, or superfits, have been strongly implicated in the recalcitrance and recurrence of chronic bacterial infection through the dormant (metabolically reduced) phenotype they display and the tolerance to antimicrobial agents this dormancy grants them. The complex biochemical events that lead to the formation of persister cells are not completely understood, though much research has linked the degradation of type II toxin/antitoxin systems and reduced cellular ATP levels to the rise in stress response molecules (where (p)ppGpp is of particular interest), which induce this dormant state. The equally complex mechanism of resuscitation is initiated by the cells’ ability to sense nutrient availability via chemotaxis systems. Levels of secondary messenger proteins (i.e., cAMP) within the cell are reduced to allow the resuscitation of ribosomes, by ribosomal resuscitation factor HflX, to reinstate protein synthesis and, therefore, growth to re-populate. Techniques of superfit eradication utilise one, or more, of three approaches (i) direct killing, (ii) re-sensitising persister cells to conventional antimicrobials, or (iii) prevention of persister formation though few laboratory findings have been translated to clinical practice. This work will outline current findings in the field with a critical approach, where possible.

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Antibiotic Resistance and the Risk of Recurrent Bacteremia

Abstract: Antibiotic nonsusceptibility was consistently associated with higher risks of recurrent bacteremia, but the estimated number of additional recurrent episodes in the Netherlands (40 per year) was rather limited.

Cited by 16 publications

References 16 publications

Preclinical Immunogenicity and Efficacy of Optimized O25b O-Antigen Glycoconjugates To Prevent MDR ST131 E. coli Infections

Preclinical Immunogenicity and Efficacy of Optimized O25b O-Antigen Glycoconjugates To Prevent MDR ST131 E. coli Infections

Study protocol for a randomized clinical trial to assess 7 versus 14-days of treatment for Pseudomonas aeruginosa bloodstream infections (SHORTEN-2 trial)

Persister cells: formation, resuscitation and combative therapies

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