Characteristics of Pseudomonas aeruginosa infection in intensive care unit before (2007-2010) and after (2011-2014) the beginning of an antimicrobial stewardship program.

Objectives: To investigate the factors associated with Pseudomonas aeruginosa isolates in intensive care unit (ICU) before and after an antimicrobial stewardship program. Materials: Monocentric retrospective cohort study. Patients admitted to the ICU in 2007-2014 were included. Characteristics of P. aeruginosa patients were compared to overall ICU population. Clinical and microbiological characteristics of P. aeruginosa patients before (2007-2010) and after (2011-2014) the beginning of the AMP were compared. Results: Overall, 5,263 patients were admitted to the ICU, 274/5,263 (5%) had a P. aeruginosa isolate during their staying. In 2011-2014, the percentage P. aeruginosa isolates reduced (7% vs 4%, P ≤ .0001). Patients with P. aeruginosa had higher rates of in-hospital death (43% vs 20%, P < .0001) than overall ICU population. In 2011-2014, rates of multidrug-resistant (11% vs 2%, P = .0020), fluoroquinolone-resistant (35% vs 12%, P < .0001), and ceftazidime-resistant (23% vs 8%, P = .0009) P. aeruginosa reduced. Treatments by fluoroquinolones (36% vs 4%, P ≤ .0001), carbapenems (27% vs 9%, P = .0002), and third-generation cephalosporins (49% vs 12%, P ≤ .0001) before P. aeruginosa isolation reduced while piperacillin (0% vs 13%, P < .0001) and trimethoprim-sulfamethoxazole (8% vs 26%, P = .0023) increased. Endotracheal intubation reduced in 2011-2014 (61% vs 35%, P < .0001). Fluoroquinolone-resistance was higher in patients who received endotracheal intubation (29% vs 17%, P = .0197). Previous treatment by fluoroquinolones (OR = 2.94, P = .0020) and study period (2007-2010) (OR = 2.07, P = .0462) were the factors associated with fluoroquinolone-resistance at the multivariate analysis. Conclusions: Antibiotic susceptibility in P. aeruginosa isolates was restored after the reduction of endotracheal intubation, fluoroquinolones, carbapenems, and third-generation cephalosporins and the increased use of molecules with a low ecological footprint, as piperacillin and trimethoprim-sulfamethoxazole.

Prescriptions of generic antiretroviral drugs in three healthcare centers in the Paris area, France.

In a retrospective study conducted in three hospitals in Paris, generic antiretroviral accounted for 30.2% of all prescriptions. Tenofovir disoproxil/emtricitabine (TDF/FTC) was the most prescribed generic ART (82.3% of generic prescriptions). Generic ART (gART) was more likely to be prescribed to women, to patients less than 50 years, and with recent HIV diagnosis less than 3 years. Physicians prescribed more gART if they were men, older than 55 years or worked at a university teaching hospital.

Antibiotic prescriptions associated with a diagnosis of acute nasopharyngitis by general practitioners in France.

BACKGROUND: Rhinopharyngitis is a common viral infection that has led to an overuse of prescription drugs. Antibiotics, which are not indicated for this infection, are frequently misused. AIM: The purpose of this study was to describe drug prescriptions for acute rhinopharyngitis diagnoses in the French general practices. DESIGN & SETTING: Retrospective study of 1,067,403 prescriptions issued by 2,637 physicians to 754,476 patients residing in metropolitan France for a diagnosis of nasopharyngitis. METHOD: The data were sourced from the prescription software, Cegedim, for a period spanning from first January 2018 to 31st December 2021 and analysed according to patients and physicians ages. RESULTS: A total of 2,591,584 medications were prescribed by GPs with a median of 3 medications per patient. A total of 171,540 antibiotics were prescribed (16% prescription rates) with amoxicillin being the most frequently prescribed (102,089 prescriptions and 59.5% of antibiotic prescriptions). Amoxicillin prescription increases in extreme age groups (patients less than 9-year-old were prescribed amoxicillin in 18.2% of their visits, those over 80 years-old 10% of the visits, while patients aged 20-29-year-old were prescribed amoxicillin in just 2.9% of their visits), and more prescriptions are issued by older doctors (GPs older than 70 years prescribed antibiotics in 26.4% of the visits vs 3.2% of the visits by GPs aged less than 29 years). CONCLUSION: Nasopharyngitis is frequently a cause of therapeutical over-prescriptions including antibiotics with an antibiotic prescription rate of 16%. Additional research is required to enhance our understanding of the factors linked to drug prescriptions.

Exclusive oral antibiotic treatment for hospitalized community-acquired pneumonia: a post-hoc analysis of a randomized clinical trial.

OBJECTIVES: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). METHODS: In this post-hoc analysis of randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the first antibiotic intake, defined as temperature >37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. oral AMC, patients with multi-lobar infection, patients aged ≥65 years old, and patients with CURB65 scores of 3-4). RESULTS: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (aOR) 0.973 (95% CI 0.519-1.823), p 0.932)]. Failure rates at Day 15 were not significantly different among the subgroup populations. DISCUSSION: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT01963442.

Identifying General Practitioners' Antibiotic Prescribing Profiles Based on National Health Reimbursement Data.

Background: Antibiotic selection pressure in human medicine is a significant driver of antibiotic resistance in humans. The primary aspect of antibiotic consumption is associated with general practitioner (GP) prescriptions. We aimed to identify prescriber profiles for targeted antimicrobial stewardship programs using novel indicators. Methods: A cross-sectional study was conducted in 2018 investigating GPs' antibiotic prescriptions in a French department, utilizing the reimbursement database of the national health service. Three antibiotic prescribing indicators were used. Specific targets were established for each indicator to identify the antibiotic prescribers most likely contributing to the emergence of resistance. Results: Over 2018, we had 2,908,977 visits to 784 GPs, leading to 431,549 antibiotic prescriptions. Variations between GPs were shown by the 3 indicators. The median antibiotic prescription rate per visit was 13.6% (interquartile range [IQR], 9.8%-17.7%). Median ratios of the prescriptions of low-impact antibiotics to the prescriptions of high-impact antibiotics and of amoxicillin prescriptions to amoxicillin-clavulanic acid prescriptions were 2.5 (IQR, 1.7-3.7) and 2.94 (IQR, 1.7-5), respectively. We found 163 (21%) high prescribers of antibiotics with 3 distinct patterns: The first group overuses broad-spectrum antibiotics but without an overprescription rate per visit, the second group displays an overprescription rate but no excessive use of broad-spectrum antibiotics, and the third group shows both an overprescription rate and excessive use of broad-spectrum antibiotics. Conclusions: Prescription-based indicators enable the identification of distinct profiles of antibiotic prescribers. This identification may allow for targeted implementation of stewardship programs focused on the specific prescribing patterns of each profile.

One Hundred Explicit Definitions of Potentially Inappropriate Prescriptions of Antibiotics in Hospitalized Older Patients: The Results of an Expert Consensus Study.

BACKGROUND: In geriatrics, explicit criteria for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. OBJECTIVE: To produce an expert consensus on explicit definitions of antibiotic-PIPs for hospitalized older patients. METHODS: We conducted a Delphi survey involving French experts on antibiotic stewardship in hospital settings. During the survey's rounds, the experts gave their opinion on each explicit definition, and could suggest new definitions. Definitions with a 1-to-9 Likert score of between 7 and 9 from at least 75% of the participants were adopted. The results were discussed during consensus meetings after each round. RESULTS: Of the 155 invited experts, 128 (82.6%) participated in the whole survey: 59 (46%) infectious diseases specialists, 45 (35%) geriatricians, and 24 (19%) other specialists. In Round 1, 65 explicit definitions were adopted and 21 new definitions were suggested. In Round 2, 35 other explicit definitions were adopted. The results were validated during consensus meetings (with 44 participants after Round 1, and 54 after Round 2). CONCLUSIONS: The present study is the first to have provided a list of explicit definitions of potentially inappropriate antibiotic prescriptions for hospitalized older patients. It might help to disseminate key messages to prescribers and reduce inappropriate prescriptions of antibiotics.

Antibiotic prescription in ambulatory care for COVID-19 patients: a cohort analysis in four European countries.

OBJECTIVE: To analyse antibiotic prescription rates in ambulatory care for COVID-19 patients by general practitioners (GPs) in four European countries. METHODS: A total of 4,513,955 anonymised electronic prescribing records of 3656 GPs in four European countries were analysed. Diagnosis and prescriptions were retrieved. Antibiotic prescription rates during COVID-19 consultations were analysed and compared between France, the UK, Belgium and Romania. RESULTS: Overall prescription rate was in France and Belgium (6.66 and 7.46%). However, analysing median GP prescribing rates, we found that 33.9% of the GPs in Belgium prescribed antibiotics with a median of 16 prescriptions per 100 COVID-19 consultations, while 55.21% of the GPs in France prescribed a median of 8 antibiotic prescriptions per 100 COVID-19 consultations. Overall antibiotic prescription rates were less in Romania than in the UK (22% vs 32%); however, 73% of the Romanian GPs vs 57% of the British GPs prescribed antibiotics. Depending on the country, the proportion of each type of antibiotic was statistically different, with the proportion of azithromycin being more than 50% of all antibiotics in each country except for the UK where it was less than 1%. CONCLUSION: Both individual GPs prescribing patterns in addition to overall consumption patterns should be analysed in order to implement a tailored antimicrobial stewardship programme. Furthermore, antibiotic prescribing rates in COVID-19 are lower than other respiratory tract infections.

Yellow fever vaccine-associated neurologic and viscerotropic disease: a 10-year case series of the French National Reference Center for Arboviruses with clinical and immunological insights.

BACKGROUND: Immunization against the Yellow fever virus (YFV) with the 17D live-attenuated vaccine is the most effective way to prevent the disease. However, unexpected severe adverse events can occur. They consist in a neurological impairment - neurological disease (YEL-AND), a YF-like illness - viscerotropic disease (YEL-AVD) or anaphylaxis. In this article, we describe the epidemiology, clinical and biological features of YEL-AND and YEL-AVD cases reported to the French National Reference Center for Arboviruses (NRCA) in the past 10 years. METHODS: We conducted a national, retrospective study using the database of the NRCA from June 2012 to June 2022. All patients whose biological samples were sent to the NRCA for detection of YFV by serology and/or RT-qPCR for a suspected vaccine-associated adverse event were included. We collected data by reading medical records and conducted complementary neuro-immunological analysis, followed by a search for autoimmunity against type-1-interferon when samples were available at the NRCA. RESULTS: There were 10 cases of YEL-AND and 2 cases of YEL-AVD reported to the NRCA in the past 10 years, which represented an overall incidence of 0.6 for 100 000 doses. A total of 6/12 cases were previously healthy patients (50%, mean age 31 years), and 4/12 cases had cardiovascular co-morbidities (42%, mean age 56 years). The majority of YEL-AND had a favourable outcome at 6 months of follow up. One YEL-AVD patient passed. In secondary analyses, we evidenced a significant blood cerebrospinal fluid (CSF) barrier dysfunction, without intrathecal synthesis of immunoglobulin and without argument for a neuron damage. We further detected a significant rate of anti-type-1alpha interferon antibodies in 3/10 tested patients (2 YEL-AND and 1 YEL-AVD). CONCLUSION: YEL-AND and YEL-AVD are rare events that can underlie defect in the innate immunity of apparently healthy or mild co-morbid subjects. Outcome was generally favourable in the YEL-AND cases of our series, but still life-threatening or even fatal in the YEL-AVD cases.

Knowledge of recommended antibiotic treatments for community-acquired infections in general medical practice: a cross-sectional study in Occitanie region, France.

To assess and analyse the knowledge of recommended antibiotic treatments, focusing on the appropriate drugs and treatment durations for the most common community-acquired infections in general medical practice in Occitanie region, France. A web-based survey was conducted over a 3-month period, from October, 2018 to January, 2019. All participants answered directly through the online platform. For the analysis of overtreatment risk, a score based system was adopted and two scores were produced: the duration score and the treatment score. 413 general practitioners completed the survey. The overall rate of concordance with guidelines in terms of both drug choice and treatment length was 2974/4956 (60%) answers. Diseases with at least 70% good answers included cystitis, group A streptococcal pharyngitis, and bacterial superficial skin infections. Diseases with fewer than 50% good answers included pyelonephritis, dog bite wounds, and community-acquired pneumonia in patients aged ≥ 65 years. Factors associated with the risk of overtreatment were age > 40 years, country setting and hospital employment. Knowledge of treatment durations is satisfactory with 60% of recommendations being met. However, varying levels were observed according to different diseases. This study highlighted a very high rate of adherence when recommendations were clear. In contrast, low levels of adherence were observed when recommendations were ambiguous or when conflicting guidelines existed.

Updated mortality and causes of death in 2020-2021 in people with HIV: a multicenter study in France.

OBJECTIVE: The aim of this study was to assess updated mortality and causes of death in people with HIV (PWH) in France. DESIGN AND METHODS: We analyzed all deaths in PWH followed up between January 1, 2020, and December 31, 2021, in 11 hospitals in the Paris region. We described the characteristics and causes of death among deceased PWH, and evaluated the incidence of mortality and associated risk factors using a multivariate logistic regression. RESULTS: Of the 12 942 patients followed in 2020--2021, 202 deaths occurred. Mean annual incidence of death [95% confidence interval (95% CI)] was 7.8 per 1000 PWH (6.3-9.5). Forty-seven patients (23%) died from non-AIDS nonviral hepatitis (NANH)-related malignancies, 38 (19%) from non-AIDS infections (including 21 cases of COVID-19), 20 (10%) from AIDS, 19 (9%) from cardiovascular diseases (CVD), 17 (8.4%) from other causes, six (3%) from liver diseases, and five (2.5%) from suicides/violent deaths. The cause of death was unknown in 50 (24.7%) patients. Risks factors for death were age [adjusted odds ratio (aOR) 1.93; 1.66-2.25 by additional decade), AIDS history (2.23; 1.61-3.09), low CD4 + cell count (1.95; 1.36-2.78 for 200-500 cells/µl and 5.76; 3.65-9.08 for ≤200 versus > 500 cells/µl), and viral load more than 50 copies/ml (2.03; 1.33-3.08), both at last visit. CONCLUSION: NANH malignancies remained in 2020-2021 the first cause of death. COVID-19 accounted for more than half of the mortality related to non-AIDS infections over the period. Aging, AIDS history, and a poorer viro-immunological control were associated with death.

Fatal neonatal listeriosis following L. monocytogenes horizontal transmission highlights neonatal susceptibility to orally acquired listeriosis.

We report a case of fulminant fatal neonatal listeriosis due to horizontal transmission of Listeria monocytogenes (Lm) in a neonatal double room. Genomic analyses reveal a close genetic relationship between clinical isolates, supporting cross-contamination. Oral inoculation experiments in adult and neonatal mice show that neonates are susceptible to a low Lm inoculum and that this susceptibility results from the immaturity of the neonatal gut microbiota. Infected neonates should therefore be isolated for as long as they shed Lm in their feces to avoid horizontal transmission and its dire consequences.

Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review.

INTRODUCTION: Antimicrobial resistance is a major healthcare issue responsible for a large number of deaths. Many reviews identified that PKPD data are in favor of the use of continuous infusion, and we wanted to review clinical data results in order to optimize our clinical practice. METHODOLOGY: We reviewed Medline for existing literature comparing continuous or extended infusion to intermittent infusion of betalactams. RESULTS: In clinical studies, continuous infusion is as good as intermittent infusion. In the subset group of critically ill patients or those with an infection due to an organism with high MIC, a continuous infusion was associated with better clinical response. CONCLUSIONS: Clinical data appear to confirm those of PK/PD to use a continuous infusion in severely ill patients or those infected by an organism with an elevated MIC, as it is associated with higher survival rates. In other cases, it may allow for a decrease in antibiotic daily dosage, thereby contributing to a decrease in overall costs.

Infectious disease hotlines to provide advice to general practitioners: a prospective study.

BACKGROUND: Telephone hotlines in infectious diseases (ID) are part of antimicrobial stewardship programs designed to provide support and expertise in ID and to control antibiotic resistance. The aim of the study was to characterize the activity of the ID hotlines and estimate their usefulness for general practitioners (GPs). METHODS: This was a multicenter prospective observational study in different French regions. ID teams involved in antimicrobial stewardship with a hotline for GPs were asked to record their advice from April 2019 to June 2022. In these regions, all GPs were informed of the ID hotline's operating procedures. The main outcome was usage rate of the hotlines by GPs. RESULTS: Ten volunteer ID teams collected 4138 requests for advice from 2171 GPs. The proportion of GPs using the hotline varied pronouncedly by region, from 54% in the Isere department, to less than 1% in departments with the lowest usage. These differences were associated with the number of physicians in ID teams and with the age of the hotline. These results highlighted the value of working time as a means of ensuring the permanence of expertise. The main reasons for calling were: a diagnostic question (44%); choice of antibiotic (31%). The ID specialist provided advice on antibiotic therapy (43%) or a proposal for specialized consultation or hospitalization (11%). CONCLUSIONS: ID hotlines could help to strengthen cooperation between primary care and hospital medicine. However, the deployment and perpetuation of this activity require reflection concerning its institutional and financial support.

Prescription of antibiotics by general practitioners for patients with a diagnosis of SARS- CoV-2 infection: Analysis of an electronic French health record.

OBJECTIVE: To define the factors associated with overprescription of antibiotics by general practitioners (GPs) for patients diagnosed with COVID-19 during the first wave of the pandemic. METHODS: Anonymised electronic prescribing records of 1370 GPs were analysed. Diagnosis and prescriptions were retrieved. The initiation rate by GP for 2020 was compared with 2017-2019. Prescribing habits of GPs who initiated antibiotics for > 10% of COVID-19 patients were compared with those who did not. Regional differences in prescribing habits of GPs who had consulted at least one COVID-19 patient were also analysed. RESULTS: For the March-April 2020 period, GPs who initiated antibiotics for > 10% of COVID-19 patients had more consultations than those who did not. They also more frequently prescribed antibiotics for non-COVID-19 patients consulting with rhinitis and broad-spectrum antibiotics for treating cystitis. Finally, GPs in the Île-de-France region saw more COVID-19 patients and more frequently initiated antibiotics. General practitioners in southern France had a higher but non-significant ratio of azithromycin initiation rate over total antibiotic initiation rate. CONCLUSION: This study identified a subset of GPs with overprescribing profiles for COVID-19 and other viral infections; they also tended to prescribe broad-spectrum antibiotics for a long duration. There were also regional differences concerning antibiotic initiation rates and the ratio of azithromycin prescribed. It will be necessary to evaluate the evolution of prescribing practices during subsequent waves.

Factors associated with delay in seeking healthcare for imported malaria: a retrospective study in a French hospital.

BACKGROUND: Delayed treatment is associated with a higher risk of severe malaria. In malaria-endemic areas, the main factors associated with delay in seeking healthcare are low educational level and traditional beliefs. In imported malaria, determinants of delay in seeking healthcare are currently unknown. METHODS: We studied all patients presenting with malaria, from 1 January 2017 to 14 February 2022, in the hospital of Melun, France. Demographic and medical data were recorded for all patients, and socio-professional data were recorded for a subgroup of hospitalized adults. Relative-risks and 95% confidence intervals were determined using univariate analysis by cross-tabulation. RESULTS: There were 234 patients included, all travelling from Africa. Among them, 218 (93%) were infected with P. falciparum, 77 (33%) had severe malaria, 26 (11%) were <18 years old and 81 were included during the SARS-CoV-2 pandemic. There were 135 hospitalized adults (58% of all patients). The median time to hospital admission (THA) , defined by the period from onset of symptoms to arrival at hospital, was 3 days (IQR = 2-5). A THA ≥3 days tended to be more frequent in travellers visiting friends and relatives (VFR; RR = 1.44, 95% CI = [1.0-2.05], P = 0.06), while it was less frequent in children and teenagers (RR = 0.58, 95% CI = [0.39-0.84], P = 0.01). Gender, African background, unemployment, living alone and absence of referring physician were not associated with delay in seeking healthcare. Consulting during the SARS-CoV-2 pandemic was neither associated with a longer THA nor with a higher rate of severe malaria. CONCLUSION: In contrast to an endemic area, socio-economic factors did not impact on delay in seeking healthcare in imported malaria. Prevention should focus on VFR subjects, who tend to consult later than other travellers.

The Production of Antibiotics Must Be Reoriented: Repositioning Old Narrow-Spectrum Antibiotics, Developing New Microbiome-Sparing Antibiotics.

The development of broad-spectrum antibiotics to control multidrug-resistant bacteria is an outdated business model. This strategy has led to the introduction of highly effective antibiotics, but their widespread use has contributed to the emergence of even broader antibiotic resistance. In a strategy to combat antimicrobial resistance, we believe that the use of narrow-spectrum antibiotics should be promoted. This should involve both the repositioning of old antibiotics and the reorientation of research and development towards new narrow-spectrum antibiotics with a low ecological impact. These antibiotics could be prescribed for common conditions such as sore throats and cystitis, which account for the bulk of antibiotic use in humans. Narrow-spectrum, targeted, microbiome-sparing antibiotics could help control antibiotic resistance while being economically sustainable. Their development and production should be supported by governments, which would ultimately benefit from reduced health care costs.

Advocacy for Responsible Antibiotic Production and Use.

Antibiotic-resistant bacteria have become one of humankind's major challenges, as testified by the UN's Call to Action on Antimicrobial Resistance in 2021. Our knowledge of the underlying processes of antibiotic resistance is steadily improving. Beyond the inappropriate use of antimicrobials in human medicine, other causes have been identified, raising ethical issues and requiring an approach to the problem from a "One Health" perspective. Indeed, it is now clear that the two main issues regarding the subject of antibiotics are their misuse in the global food industry and their method of production, both leading to the emergence and spread of bacterial resistance.

Association of high SARS-CoV-2 RNAemia with diabetes and mortality in critically ill COVID-19 patients.

It has been suggested that during the period of respiratory worsening of severe COVID-19 patients, viral replication plays a less important role than inflammation. Using the droplet-based digital PCR (ddPCR) for precise quantification of plasma SARS-CoV-2 viral load (SARS-CoV-2 RNAemia), we investigated the relationship between plasma viral load, comorbidities, and mortality of 122 critically ill COVID-19 patients. SARS-CoV-2 RNAemia was detected by ddPCR in 90 (74%) patients, ranging from 70 to 213,152 copies per mL. A high (>1 000 copies/ml) or very high (>10,000 copies/ml) SARS-Cov-2 RNAemia was observed in 46 patients (38%), of which 26 were diabetic. Diabetes was independently associated with a higher SARS-CoV-2 RNAemia. In multivariable logistic regression models, SARS-CoV-2 RNAemia was strongly and independently associated with day-60 mortality. Early initiation of antiviral therapies might be considered in COVID-19 critically ill patients with high RNAemia.