scholarly journals Quantifying antibiotic impact on within-patient dynamics of extended-spectrum beta-lactamase resistance

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Rene Niehus ◽  
Esther van Kleef ◽  
Yin Mo ◽  
Agata Turlej-Rogacka ◽  
Christine Lammens ◽  
...  

Antibiotic-induced perturbation of the human gut flora is expected to play an important role in mediating the relationship between antibiotic use and the population prevalence of antibiotic resistance in bacteria, but little is known about how antibiotics affect within-host resistance dynamics. Here we develop a data-driven model of the within-host dynamics of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. We use blaCTX-M (the most widespread ESBL gene family) and 16S rRNA (a proxy for bacterial load) abundance data from 833 rectal swabs from 133 ESBL-positive patients followed up in a prospective cohort study in three European hospitals. We find that cefuroxime and ceftriaxone are associated with increased blaCTX-M abundance during treatment (21% and 10% daily increase, respectively), while treatment with meropenem, piperacillin-tazobactam, and oral ciprofloxacin is associated with decreased blaCTX-M (8% daily decrease for all). The model predicts that typical antibiotic exposures can have substantial long-term effects on blaCTX-M carriage duration.

2019 ◽  
Author(s):  
Rene Niehus ◽  
Esther van Kleef ◽  
Mo Yin ◽  
Agata Turlej-Rogacka ◽  
Christine Lammens ◽  
...  

AbstractAntibiotic exposure can perturb the human gut microbiome and cause changes in the within-host abundance of the genetic determinants of drug-resistance in bacteria. Such within-host dynamics are expected to play an important role in mediating the relationship between antibiotic use and persistence of drug-resistance within a host and its prevalence within a population. Developing a quantitative representation of these within-host dynamics is an important step towards a detailed mechanistic understanding of the population-level processes by which antibiotics select for resistance. Here we study extended-spectrum beta-lactamase (ESBL) producing organisms of the Enterobacteriaceae bacterial family. These have been identified as a global public health priority and are resistant to most first-line antibiotics for treatment of Enterobacteriaceae infections.We analyse data from 833 rectal swabs from a prospective longitudinal study in three European countries including 133 ESBL-positive hospitalised patients. Quantitative polymerase chain reaction was used to quantify the abundance of the CTX-M gene family – the most wide-spread ESBL gene family – and the 16S rRNA gene as a proxy for bacterial load. We find strong dynamic heterogeneity in CTX-M abundance that is largely explained by the variable nature of the swab sampling. Using information on time-varying antibiotic treatments, we develop a dynamic Bayesian model to decompose the serial data into observational variation and ecological signal and to quantify the potentially causal antibiotic effects.We find an association of treatment with cefuroxime or ceftriaxone with increased CTX-M abundance (approximately 21% and 10% daily increase, respectively), while treatment with meropenem or piperacillin-tazobactam is associated with decreased CTX-M (approximately 8% daily decrease for both). Despite a potential risk for indirect selection, oral ciprofloxacin is also associated with decreasing CTX-M (approximately 8% decrease per day). Using our dynamic model to make forward stochastic simulations of CTX-M dynamics, we generate testable predictions about antibiotic impacts on duration of carriage. We find that a typical course of cefuroxime or ceftriaxone is expected to more than double a patient’s carriage duration of CTX-M. A typical course of piperacillin-tazobactam or of meropenem – both options to treat hospital acquired infections (HAI) like pneumonia – would reduce CTX-M carriage time relative to ceftriaxone plus amikacin (also an option to treat HAIs) by about 70%. While most antibiotics showed little association with changes in total bacterial abundance, meropenem and piperacillin-tazobactam were associated with decrease in 16S rRNA abundance (3% and 4% daily decrease, respectively).Our study quantifies antibiotic impacts on within-host resistance abundance and resistance carriage, and informs our understanding of how changes in patterns of antibiotic use will affect the prevalence of resistance. This work also provides an analytical framework that can be used more generally to quantify the antibiotic treatment effects on within-host dynamics of determinants of antibiotic resistance using clinical data.


2020 ◽  
Author(s):  
Nicholas Haddad ◽  
Joanna Abi Ghosn

Abstract Background: ESBL-PE are emerging worldwide. This study assesses the effect of contact precaution (CP) on ESBL-PE-colonization rates among nurses in 3 hospitals in Beirut, where ESBL is endemic, to define risk factors for colonization, and evaluate the ongoing use of CP to prevent ESBL-PE transmission to healthy nurses. Methods: Cross-sectional, non-randomized study completed in three hospitals. Hospital 1 required CP, Hospital 2 recently stopped CP, and Hospital 3 had stopped it 3 years previously. Questionnaires and stool-collection containers were distributed to all patient care nurses in those 3 hospitals. Returned samples were tested using agar dilution technique. Results: 269 of 733 nurses volunteered; 140 met inclusion criteria (no recent hospitalization, antibiotic use, known ESBL-PE colonization). 15% were ESBL-positive. Compared to nurses from Hospital 3, nurses from Hospital 1 were 59% less likely to be colonized, while nurses from Hospital 2 were 62% more likely to be colonized. Discussion: In hospitals where CP is ongoing for ESBL-positive patients, transmission to nursing staff was reduced. Additionally, a work experience of 2-4 years increased the odds of ESBL-PE colonization in comparison with longer nursing experience. HIGHLIGHTS : • We examined the impact of contact precautions (CP) for Extended spectrum beta-lactamase- producing Enterobacteriaceae (ESBL-PE) colonized patients on rates of ESBL-PE colonization in nursing staff. • We found significantly decreased rates of colonization in nurses from a hospital utilizing CP, and significantly increased rates of colonization among nurses from a hospital that recently • discontinued CP, compared with nurses from a hospital that had discontinued CP 3 years previously. • Findings suggest that contact precaution may be required to prevent ESBL-PE transmission from patients to nursing staff.


2015 ◽  
Vol 20 (36) ◽  
Author(s):  
Isabelle Arnaud ◽  
Sylvie Maugat ◽  
Vincent Jarlier ◽  
Pascal Astagneau ◽  
◽  
...  

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are a major focus of multidrug-resistant organisms (MRO) surveillance programmes in France. To describe the temporal and geographical trends of these pathogens, we conducted an epidemiological study based on data extracted from the nationwide MRO surveillance network from 2009 to 2013. During this time, the incidence of ESBL-E infections in French hospitals increased by 73%, from 0.35 to 0.60 per 1,000 patient days (PD) (p < 0.001) and ESBL-E bacteraemia by 77%, from 0.03 to 0.05 per 1,000 PD (p < 0.001). The incidence of ESBL-E infections was higher in intensive-care units (1.62 to 2.44 per 1,000 PD (p < 0.001)) than in recovery and long-term care facilities (0.20 to 0.31 per 1,000 PD (p < 0.001)). Escherichia coli was the most frequent extended-spectrum beta-lactamase-producing (ESBL) pathogen, representing 59% (26,238/44,425) of all ESBL isolates, followed by Klebsiella pneumoniae (20%; 8,856/44,425) in 2013. The most frequent infection was urinary tract infection, for all species. The incidence of ESBL-E varied by region but showed an upward trend overall. Reinforcement of control measures for halting the spread of such MRO is crucial.


BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e023859 ◽  
Author(s):  
Yin Mo ◽  
Ivan Seah ◽  
Pei Shi Priscillia Lye ◽  
Xiang Lee Jamie Kee ◽  
Kien Yee Michael Wong ◽  
...  

ObjectivesTo study the correlation between knowledge, attitude and practices (KAP) of antibiotic consumption with epidemiology and molecular characteristics of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) carriage, in order to identify modifiable factors and public health interventions to reduce prevalence of multidrug-resistant organism colonisation in the community.DesignCross-sectional questionnaire of KAP towards antibiotic use and collection of stool samples or rectal swabs. ESBL-PE isolates obtained underwent whole genome sequencing to identify resistance genes.SettingA densely populated community in Singapore.ParticipantsThere were 693 healthy community-dwelling questionnaire respondents. Out of which, 305 provided stool samples or rectal swabs.ResultsThe overall knowledge of antibiotic use was poor (mean score 4.6/10, IQR 3.0–6.0). 80 participants (80/305, 26.2%) carried at least one ESBL-PE isolate. The most common ESBL-PE was Escherichia coli sequence type 131 carrying CTX-M type beta-lactamases (11/71, 15.5%). Living overseas for >1 year (OR 3.3, 95% CI 1.6 to 6.9) but not short-term travel, recent hospitalisation or antibiotic intake was associated with ESBL-PE carriage. Interestingly, higher knowledge scores (OR 2.0, 95% CI 1.03 to 3.9) and having no leftover antibiotics (OR 2.4, 95% CI 1.2 to 4.9) were independent factors associated with ESBL-PE carriage in the multivariate logistic regression model.ConclusionsWhile the role of trans-border transmission of antimicrobial resistance is well known, we may have to examine the current recommendation that all antibiotics courses have to be completed. Clinical trials to determine the optimum duration of treatment for common infections are critically important.


2015 ◽  
Vol 9 (4) ◽  
pp. 150-156
Author(s):  
NADHYA NUR FITRI ◽  
◽  
MUSOFA RUSLI ◽  
MANIK RETNO WAHYUNITISARI ◽  
◽  
...  

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