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Article ; Online: Determinants of worldwide antibiotic resistance dynamics across drug-bacterium pairs: a multivariable spatial-temporal analysis using ATLAS.

Rahbe, Eve / Watier, Laurence / Guillemot, Didier / Glaser, Philippe / Opatowski, Lulla

The Lancet. Planetary health

2023 Volume 7, Issue 7, Page(s) e547–e557

Abstract: Background: Antibiotic resistance (ABR) is a major concern for global health. However, factors driving its emergence and dissemination are not fully understood. Identification of such factors is crucial to explain heterogeneity in ABR rates observed ... ...

Abstract	Background: Antibiotic resistance (ABR) is a major concern for global health. However, factors driving its emergence and dissemination are not fully understood. Identification of such factors is crucial to explain heterogeneity in ABR rates observed across space, time, and species and antibiotics. Methods: We analysed count data of clinical isolates from 51 countries over 2006-19 for thirteen drug-bacterium pairs taken from the ATLAS database. We characterised ABR spatial and temporal patterns and used a mixed-effect negative binomial model, accounting for country-year dependences with random effects, to investigate associations with potential drivers, including antibiotic sales, economic and health indicators, meteorological data, population density, and tourism. Findings: ABR patterns were strongly country and drug-bacterium pair dependent. In 2019, median ABR rates ranged from 6·3% (IQR 19·7% [0·5-20·2]) for carbapenem-resistant Klebsiella pneumoniae to 80·7% (41·8% [50·4-92·2]) for fluoroquinolone-resistant Acinetobacter baumannii, with heterogeneity across countries. From 2006 to 2019, carbapenem resistance increased in more than 60% of investigated countries; no global trend was observed for other resistances. Multivariable analyses identified significant associations of ABR with country-level selecting antibiotic sales, but only in fluoroquinolone-resistant-Escherichia coli, fluoroquinolone-resistant-Pseudomonas aeruginosa, and carbapenem-resistant-A baumannii. We also found a correlation between temperature and resistance in Enterobacteriaceae and with the health system quality for all drug-bacterium pairs except Enterococci and Streptococcus pneumoniae pairs. Despite wide consideration of possible explanatory variables, drug-bacterium pair ABR rates still showed unexplained spatial random effects variance. Interpretation: Our findings reflect the diversity of mechanisms driving global antibiotic resistance across pathogens and stress the need for tailored interventions to tackle bacterial resistance. Funding: Independent research Pfizer Global Medical Grant and ANR Labex IBEID.
MeSH term(s)	Drug Resistance, Microbial ; Anti-Bacterial Agents/pharmacology ; Carbapenems ; Commerce ; Escherichia coli ; Fluoroquinolones
Chemical Substances	Anti-Bacterial Agents ; Carbapenems ; Fluoroquinolones
Language	English
Publishing date	2023-03-21
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2542-5196
ISSN (online)	2542-5196
DOI	10.1016/S2542-5196(23)00127-4
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Article ; Online: Care pathways of sepsis survivors: sequelae, mortality and use of healthcare services in France, 2015-2018.

Pandolfi, Fanny / Brun-Buisson, Christian / Guillemot, Didier / Watier, Laurence

Critical care (London, England)

2023 Volume 27, Issue 1, Page(s) 438

Abstract: Background: Individuals who survive sepsis are at high risk of chronic sequelae, resulting in significant health-economic costs. Several studies have focused on aspects of healthcare pathways of sepsis survivors but comprehensive, longitudinal overview ... ...

Abstract	Background: Individuals who survive sepsis are at high risk of chronic sequelae, resulting in significant health-economic costs. Several studies have focused on aspects of healthcare pathways of sepsis survivors but comprehensive, longitudinal overview of their pathways of care are scarce. The aim of this retrospective, longitudinal cohort study is to identify sepsis survivor profiles based on their healthcare pathways and describe their healthcare consumption and costs over the 3 years following their index hospitalization. Methods: The data were extracted from the French National Hospital Discharge Database. The study population included all patients above 15 years old, with bacterial sepsis, who survived an incident hospitalization in an acute care facility in 2015. To identify survivor profiles, state sequence and clustering analyses were conducted over the year following the index hospitalization. For each profile, patient characteristics and their index hospital stay and sequelae were described, as well as use of care and its associated monetary costs, both pre- and post-sepsis. Results: New medical (79.2%), psychological (26.9%) and cognitive (18.5%) impairments were identified post-sepsis, and 65.3% of survivors were rehospitalized in acute care. Cumulative mortality reached 36.6% by 3 years post-sepsis. The total medical cost increased by 856 million € in the year post-sepsis. Five patient clusters were identified: home (65.6% of patients), early death (12.9%), late death (6.8%), short-term rehabilitation (11.3%) and long-term rehabilitation (3.3%). Survivors with early and late death clusters had high rates of cancer and primary bacteremia and experienced more hospital-at-home care post-sepsis. Survivors in short- or long-term rehabilitation clusters were older, with higher percentage of septic shock than those coming back home, and had high rates of multiple site infections and higher rates of new psychological and cognitive impairment. Conclusions: Over three years post-sepsis, different profiles of sepsis survivors were identified with different mortality rates, sequels and healthcare services usage and cost. This study confirmed the importance of sepsis burden and suggests that strategies of post-discharge care, in accordance with patient profile, should be further tested in order to reduce sepsis burden.
MeSH term(s)	Humans ; Adolescent ; Longitudinal Studies ; Retrospective Studies ; Aftercare ; Critical Pathways ; Patient Discharge ; Sepsis ; Health Care Costs ; Survivors
Language	English
Publishing date	2023-11-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-023-04726-w
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Article: From Pathophysiological Hypotheses to Case-Control Study Design: Resistance from Antibiotic Exposure in Community-Onset Infections.

Abbara, Salam / Guillemot, Didier / Brun-Buisson, Christian / Watier, Laurence

Antibiotics (Basel, Switzerland)

2022 Volume 11, Issue 2

Abstract: Antimicrobial resistance is a global public health concern, at least partly due to the misuse of antibiotics. The increasing prevalence of antibiotic-resistant infections in the community has shifted at-risk populations into the general population. ... ...

Abstract	Antimicrobial resistance is a global public health concern, at least partly due to the misuse of antibiotics. The increasing prevalence of antibiotic-resistant infections in the community has shifted at-risk populations into the general population. Numerous case-control studies attempt to better understand the link between antibiotic use and antibiotic-resistant community-onset infections. We review the designs of such studies, focusing on community-onset bloodstream and urinary tract infections. We highlight their methodological heterogeneity in the key points related to the antibiotic exposure, the population and design. We show the impact of this heterogeneity on study results, through the example of extended-spectrum β-lactamases producing Enterobacteriaceae. Finally, we emphasize the need for the greater standardization of such studies and discuss how the definition of a pathophysiological hypothesis specific to the bacteria-resistance pair studied is an important prerequisite to clarify the design of future studies.
Language	English
Publishing date	2022-02-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics11020201
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Article: Outpatient Antibiotic Prescriptions in France: Patients and Providers Characteristics and Impact of the COVID-19 Pandemic.

Bara, Wilfried / Brun-Buisson, Christian / Coignard, Bruno / Watier, Laurence

Antibiotics (Basel, Switzerland)

2022 Volume 11, Issue 5

Abstract: In France, despite several successive plans to control antimicrobial resistance, antibiotic use remains high in the outpatient setting. This study aims to better understand outpatient antibiotic use and prescription in order to identify tailored targets ... ...

Abstract	In France, despite several successive plans to control antimicrobial resistance, antibiotic use remains high in the outpatient setting. This study aims to better understand outpatient antibiotic use and prescription in order to identify tailored targets for future public health actions. Using data from the French National Health Data System, we described and compared the individual characteristics of patients with and without an antibiotic prescription. The prescribed antibiotics (ATC-J01) were detailed and compared between 2019 and 2020. Antibiotic prescribing indicators that take prescriber activity into account were estimated and compared. Patients who were female, advanced age, and the presence of comorbidities were associated with antibiotic prescriptions. The overall prescription rate was estimated at 134 per 1000 consultations and 326 per 1000 patients seen in 2019. General practitioners (GPs), dentists and paediatricians were associated with 78.0%, 12.2% and 2.2% of antibiotic prescriptions, respectively, with high prescription rates (391, 447, and 313 p. 1000 patients seen, respectively). In comparison with 2019, this rate decreased in 2020 for paediatricians (-30.4%) and GPs (-17.9%) whereas it increased among dentists (+17.9%). The reduction was twice as high among the male prescribers than among their female counterparts (-26.6 and -12.0, respectively). The reduction in prescriptions observed in 2020 (-18.2%) was more marked in children (-35.8%) but less so among individuals ≥65 years (-13.1%) and those with comorbidities (-12.5%). The decrease in penicillin prescriptions represents 67.3% of the overall reduction observed in 2020. The heterogeneous decrease in prescriptions by age and antibiotic class could be explained by the impact of COVID-19 control measures on the spread of respiratory viruses; thus, a substantial proportion of the prescriptions avoided in 2020 is likely inappropriate, particularly among children. In order to keep the rate of prescriptions comparable to that observed in 2020, male prescribers, paediatricians and GPs should be encouraged to maintain that level, while a campaign to raise awareness of the appropriate use of antibiotics should be aimed at dentists in particular.
Language	English
Publishing date	2022-05-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics11050643
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Article ; Online: Trends in bacterial sepsis incidence and mortality in France between 2015 and 2019 based on National Health Data System (Système National des données de Santé (SNDS)): a retrospective observational study.

Pandolfi, Fanny / Guillemot, Didier / Watier, Laurence / Brun-Buisson, Christian

BMJ open

2022 Volume 12, Issue 5, Page(s) e058205

Abstract: Objective: This study aims to provide a case definition of sepsis of presumed bacterial aetiology based on 10th revision of the International Classification of Diseases (ICD-10) codes, to assess trends in sepsis incidence and mortality between 2015 and ... ...

Abstract	Objective: This study aims to provide a case definition of sepsis of presumed bacterial aetiology based on 10th revision of the International Classification of Diseases (ICD-10) codes, to assess trends in sepsis incidence and mortality between 2015 and 2019 in France, and to describe the characteristics of affected patients and hospital stays. Design: Nationwide, population-based, retrospective observational study. Setting: Metropolitan France between 2015 and 2019. Participants: Between 2015 and 2019, 1 224 433 patients with sepsis of presumed bacterial aetiology were selected from the French National Hospital Discharge Database (Programme de Médicalisation des Systèmes d'Information) and were identified from corresponding ICD-10 codes for explicit sepsis or implicit sepsis. Main outcomes measures: Annual overall and age-specific and gender-specific incidence and 95% CI, as well as trends in sepsis incidence and mortality, were estimated. Comorbidities, length of hospital stay and outcomes were described. Results: The sex-standardised and age-standardised incidence per 100 000 (95% CI) increased from 357 (356.0 to 359.0) in 2015 to 403 (401.9 to 405.0) in 2019 and remained higher for males compared with females. Children under 1 year and patients over 75 years consistently had the highest incidence. The most common comorbidities were cancer and chronic heart failure. The median hospital length of stay was 12 days. Most patients came from home, but only half returned home after their hospital stay and approximately 15% were discharged to long-term care. In-hospital mortality was about 25% and declined along the study period. Conclusions: Medico-administrative databases can be used to provide nationwide estimates of the in-hospital burden of bacterial sepsis. The results confirm the high burden of sepsis in France. These data should be complemented by estimating the additional burden associated with fungal and viral infections during the COVID-19 pandemic.
MeSH term(s)	COVID-19 ; Child ; Databases, Factual ; Female ; France/epidemiology ; Humans ; Incidence ; Male ; Pandemics ; Retrospective Studies ; Sepsis/epidemiology
Language	English
Publishing date	2022-05-24
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2021-058205
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Article ; Online: One-year hospital readmission for recurrent sepsis: associated risk factors and impact on 1-year mortality-a French nationwide study.

Pandolfi, Fanny / Brun-Buisson, Christian / Guillemot, Didier / Watier, Laurence

Critical care (London, England)

2022 Volume 26, Issue 1, Page(s) 371

Abstract: Background: Sepsis is a complex health condition, leading to long-term morbidity and mortality. Understanding the risk factors for recurrent sepsis, as well as its impact on mid- and long-term mortality among other risk factors, is essential to improve ... ...

Abstract	Background: Sepsis is a complex health condition, leading to long-term morbidity and mortality. Understanding the risk factors for recurrent sepsis, as well as its impact on mid- and long-term mortality among other risk factors, is essential to improve patient survival. Methods: A risk factor analysis, based on French nationwide medico-administrative data, was conducted on a cohort of patients above 15 years old, hospitalized with an incident sepsis in metropolitan France between 1st January 2018 and 31st December 2018 and who survived their index hospitalization. Two main analyses, focusing on outcomes occurring 1-year post-discharge, were conducted: a first one to assess risk factors for recurrent sepsis and a second to assess risk factors for mortality. Results: Of the 178017 patients surviving an incident sepsis episode in 2018 and included in this study, 22.3% died during the 1-year period from discharge and 73.8% had at least one hospital readmission in acute care, among which 18.1% were associated with recurrent sepsis. Patients aged between 56 and 75, patients with cancer and renal disease, with a long index hospital stay or with mediastinal or cardiac infection had the highest odds of recurrent sepsis. One-year mortality was higher for patients with hospital readmission for recurrent sepsis (aOR 2.93; 99% CI 2.78-3.09). Among all comorbidities, patients with cancer (aOR 4.35; 99% CI 4.19-4.52) and dementia (aOR 2.02; 99% CI 1.90-2.15) had the highest odds of 1-year mortality. Conclusion: Hospital readmission for recurrent sepsis is one of the most important risk factors for 1-year mortality of septic patients, along with age and comorbidities. Our study suggests that recurrent sepsis, as well as modifiable or non-modifiable other risk factors identified, should be considered in order to improve patient care pathway and survival.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Adolescent ; Patient Readmission ; Aftercare ; Patient Discharge ; Risk Factors ; Sepsis/therapy
Language	English
Publishing date	2022-11-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-022-04212-9
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Article ; Online: Antimicrobial Resistance as Risk Factor for Recurrent Bacteremia after Staphylococcus aureus, Escherichia coli, or Klebsiella spp. Community-Onset Bacteremia.

Abbara, Salam / Guillemot, Didier / Smith, David R M / El Oualydy, Salma / Kos, Maeva / Poret, Cécile / Breant, Stéphane / Brun-Buisson, Christian / Watier, Laurence

Emerging infectious diseases

2024 Volume 30, Issue 5, Page(s) 974–983

Abstract: We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized ... ...

Abstract	We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017-2019. We assessed risk factors of 1-year recurrence using Fine-Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32-6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50-3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting.
MeSH term(s)	Humans ; Bacteremia/microbiology ; Bacteremia/epidemiology ; Klebsiella/drug effects ; Klebsiella/genetics ; Male ; Risk Factors ; Escherichia coli/drug effects ; Female ; Community-Acquired Infections/microbiology ; Community-Acquired Infections/epidemiology ; Middle Aged ; Aged ; Recurrence ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Staphylococcus aureus/drug effects ; Staphylococcus aureus/genetics ; Staphylococcal Infections/epidemiology ; Staphylococcal Infections/microbiology ; Escherichia coli Infections/epidemiology ; Escherichia coli Infections/microbiology ; Escherichia coli Infections/drug therapy ; Klebsiella Infections/epidemiology ; Klebsiella Infections/microbiology ; Klebsiella Infections/drug therapy ; Drug Resistance, Bacterial ; Adult ; France/epidemiology
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid3005.231555
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Article: Strategy for systematic review of observational studies and meta-analysis modelling of risk factors for sporadic foodborne diseases

Gonzales-Barron, Ursula / Thébault, Anne / Kooh, Pauline / Watier, Laurence / Sanaa, Moez / Cadavez, Vasco

Microbial risk analysis. 2019 July 22,

2019

Abstract: In order to design effective public health strategies, and, in particular, effective food safety interventions to reduce the burden of foodborne disease, the most important sources of enteric illnesses should be identified. Both case-control and cohort ... ...

Abstract	In order to design effective public health strategies, and, in particular, effective food safety interventions to reduce the burden of foodborne disease, the most important sources of enteric illnesses should be identified. Both case-control and cohort observational studies have for long been powerful approaches among epidemiologists to investigate the association of exposure and illness. In the literature, there are numerous case-control and cohort studies reporting results on risk factors and routes of transmission of sporadic foodborne infections. The objective of this article is to describe, in depth, the strategies implemented for systematic review and meta-analysis of the associations between multiple risk factors and eleven food and waterborne diseases, namely, non-typhoidal salmonellosis, campylobacteriosis, Shiga-toxin E. coli infection, listeriosis, yersiniosis, toxoplasmosis, norovirus infection, hepatitis A, hepatitis E, cryptosporidiosis and giardiasis. First, this article describes the procedures of systematic searches in five bibliographic engines, screening of relevance and assessment of methodological quality according to pre-set criteria. It proceeds with the explanation of a broad data categorisation scheme established to hierarchically group the risk factors into travel, host-specific factors and pathways of exposure (i.e., person-to-person, animal, environment and food routes), with views to harmonising and supporting the integration of outcomes from studies investigating a variety of potential determinants of disease. Next, the article describes the four meta-analysis models that were devised in order to calculate: (i) overall odds-ratios of acquiring the disease due to a specific risk factor by geographical region; (ii) overall odds-ratios of acquiring the disease from the different risk factors; (iii) overall risks of disease from consumption of ready-to-eat and barbecued foods; and (iv) overall effects of food handling (i.e., consuming food in raw, undercooked or unwashed state) and food preparation setting (i.e., eating food prepared outside the home) on risk of disease. The procedures for sensitivity analysis and removal of any influential and potentially-biased odds-ratio; and two methods for publication bias assessment are outlined. Finally, details are given on deviations from the standard risk categorisation scheme for specific foodborne hazards.
Keywords	Escherichia coli ; Norovirus ; Shiga toxin ; animals ; campylobacteriosis ; cohort studies ; cryptosporidiosis ; food handling ; food safety ; foodborne illness ; giardiasis ; hepatitis A ; hepatitis E ; host specificity ; ingestion ; listeriosis ; meta-analysis ; models ; observational studies ; odds ratio ; public health ; ready-to-eat foods ; risk analysis ; risk factors ; salmonellosis ; screening ; systematic review ; toxoplasmosis ; travel ; waterborne diseases ; yersiniosis
Language	English
Dates of publication	2019-0722
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ISSN	2352-3522
DOI	10.1016/j.mran.2019.07.003
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Estimation of exposure-attributable fractions from time series: A simulation study.

Cheysson, Felix / Vibet, Marie-Anne / Guillemot, Didier / Watier, Laurence

Statistics in medicine

2018 Volume 37, Issue 24, Page(s) 3437–3454

Abstract: Burden analysis in public health often involves the estimation of exposure-attributable fractions from observed time series. When the entire population is exposed, the association between the exposure and outcome must be carefully modelled before the ... ...

Abstract	Burden analysis in public health often involves the estimation of exposure-attributable fractions from observed time series. When the entire population is exposed, the association between the exposure and outcome must be carefully modelled before the attributable fractions can be estimated. This article derives asymptotic convergences for the estimation of attributable fractions for commonly used time series models (ARMAX, Poisson, negative binomial, and Serfling), using for the most part the delta method. For the Poisson regression, the estimation of the attributable fraction is achieved by a Monte Carlo algorithm, taking into account both an estimation and a prediction error. A simulation study compares these estimations in the case of an epidemic exposure and highlights the importance of thorough analysis of the data: When the outcome is generated under an additive model, the additive models are satisfactory, and the multiplicative models are poor, and vice versa. However, the Serfling model performs poorly in all cases. Of note, a misspecification in the form or delay of the association between the exposure and the outcome leads to mediocre estimation of the attributable fraction. An application to the fraction of French outpatient antibiotic use attributable to influenza between 2003 and 2010 illustrates the asymptotic convergences. This study suggests that the Serfling model should be avoided when estimating attributable fractions while the model of choice should be selected after careful investigation of the association between the exposure and outcome.
MeSH term(s)	Algorithms ; Anti-Bacterial Agents/therapeutic use ; Bias ; Biostatistics ; Computer Simulation ; Epidemics/statistics & numerical data ; France/epidemiology ; Humans ; Influenza, Human/drug therapy ; Influenza, Human/epidemiology ; Models, Statistical ; Monte Carlo Method ; Poisson Distribution ; Prescription Drug Overuse/statistics & numerical data ; Regression Analysis ; Risk Factors ; Time Factors
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2018-06-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.7818
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Article ; Online: Correction to: Antibiotic prescriptions and risk factors for antimicrobial resistance in patients hospitalized with urinary tract infection: a matched case-control study using the French health insurance database (SNDS).

Opatowski, Marion / Brun-Buisson, Christian / Touat, Mehdi / Salomon, Jérôme / Guillemot, Didier / Tuppin, Philippe / Watier, Laurence

BMC infectious diseases

2021 Volume 21, Issue 1, Page(s) 615

Language	English
Publishing date	2021-06-29
Publishing country	England
Document type	Published Erratum
ISSN	1471-2334
ISSN (online)	1471-2334
DOI	10.1186/s12879-021-06329-8
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