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.

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.

Discontinuing ß-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial.

BACKGROUND: Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of ß-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. METHODS: We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with ß-lactam therapy were randomly assigned (1:1) to receive ß-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. FINDINGS: Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of ß-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or ß-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the ß-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0-84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the ß-lactam group (between-group difference of 9·42%, 95% CI -0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the ß-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI -0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the ß-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the ß-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the ß-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). INTERPRETATION: Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing ß-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. FUNDING: French Ministry of Health.

Extreme gonococcal susceptibility associated with acquired complement deficiency secondary to hypocomplementemic urticarial vasculitis and systemic lupus erythematosus.

Gonococcal infection is rarely associated with septic shock. We describe a recurrent case of septic shock related to disseminated gonococcemia in a patient with systemic lupus erythematosus and hypocomplementemic urticarial vasculitis, and discuss the implication of profound acquired complement deficiency secondary to these auto-immune diseases. This case raises the question of systematic antibioprophylaxis in patients with acquired complement deficiency.

Streptococcal and enterococcal endocarditis: time for individualized antibiotherapy?

Recommendations for the treatment of streptococcal and enterococcal endocarditis are based on old efficacy studies, but the starting doses have never been reassessed and are associated with significant adverse events. Based on data from other serious infections, we suggest that maintaining a concentration of ß-lactams higher than 4-6 times the responsible bacteria MIC 100% of the time in the heart of the vegetation would be a pertinent therapeutic objective. The data point to a diffusion gradient of ß-lactams in the vegetation. Yet, so far as is known, the ratio of antibiotic concentration at steady state between plasma and vegetation cannot be completely determined. Answering this crucial question would make it possible for each patient to have a targeted ß-lactam plasma concentration, according to the MIC for the responsible bacteria. This would lead the way to personalized antibiotherapy and allow a safe switch to oral medication.

Trimethoprim-sulfamethoxazole as de-escalation in ventilator-associated pneumonia: a cohort study subanalysis.

PURPOSE: This is a subanalysis of a previous study which compared the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) with all other regimens for treatment of ventilator-associated pneumonia (VAP). Aim of the current study was to focus on the effectiveness of a strategy based on TMP-SMX as de-escalation from ß-lactam including regimens. METHODS: Retrospective cohort study including patients who were hospitalized for VAP from 2011 to 2019. Patients were distributed in two groups: NO SWITCH TO TMP-SMX group, including patients who received ß-lactams for all treatment duration, and SWITCH TO TMP-SMX group, which included patients who switched to TMP-SMX from a ß-lactam including regimen after microbiology diagnosis. Three clinical outcomes were analyzed: mortality at 30 days from the start of the antibiotic treatment (T30), mortality at the end of treatment (EoT), and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. RESULTS: Overall, 70 patients were included in the current study, 32/70 (45.7%) in NO SWITCH TO TMP-SMX group and 38/70 (54.3%) in SWITCH TO TMP-SMX group, 37/70 (52.8%) had been already included in the previous study. No significant differences in clinical outcomes and patient's characteristics were found when the two groups were compared. CONCLUSIONS: De-escalation to TMP-SMX for VAP treatment was not associated with higher mortality at EoT and T30 than standard treatment with ß-lactam. Monotherapy with TMP-SMX as de-escalation from broad-spectrum empirical regimens is a ß-lactam sparing strategy worthy to be further investigated in either multicenter cohort studies or randomized clinical trials.

Mycobacterium bovis infection of an aortobifemoral bypass graft with Streptococcus intermedius superinfection after intravesical bacillus Calmette-Guérin immunotherapy for bladder cancer.

BACKGROUND: The Bacillus Calmette-Guerin (BCG) is a life-attenuated form of Mycobacterium bovis widely used as immunotherapy for localized bladder cancer. Adverse reactions to intravesical BCG instillations are rare. CASE: We describe a 70-year-old man with a history of an aortobifemoral bypass graft, placement of a synthetic mesh for treatment of a ventral hernia and, most recently, superficial bladder cancer treated with BCG therapy. Ten months after his final intravesical BCG instillation, he complained of fever and asthenia. After 12 months of investigation, he was diagnosed with Mycobacterium bovis infection of his aortobifemoral bypass graft and abdominal mesh, with Streptococcus intermedius superinfection. The bypass graft was excised and replaced with an in situ arterial allograft, the abdominal mesh was removed, and treatment started with amoxicillin, isoniazid, rifampicin and ethambutol. Several additional vascular interventions were needed for allograft degradation, but 12 months after the final procedure, outcome was good. DISCUSSION AND CONCLUSIONS: Among 35 cases of mycotic aneurysm reported after BCG therapy in the last 10 years, only one involved a vascular prosthesis. Surgical repair of such aneurysms using prosthetic grafts is commonly performed, associated with anti-mycobacterial treatment. Prognosis is poor with mortality of 14% (4/35) and a 26% rate of aneurysm recurrence under treatment (9/35).

A Retrospective Study on Amoxicillin Susceptibility in Severe Haemophilus influenzae Pneumonia.

INTRODUCTION: Treatment of Haemophilus influenzae (Hi) pneumonia is on concern because resistance to amoxicillin is largely diffused. This study describes the evolution of resistance to amoxicillin and amoxicillin/clavulanic acid (AMC) in Hi isolates and characteristics of patients with Hi severe pneumonia. METHODS: A monocentric retrospective observational study including patients from 2008 to 2017 with severe pneumonia hospitalized in ICU. Evolution of amoxicillin and AMC susceptibility was showed. Characteristics of patients with Hi pneumonia were compared to characteristics of patients with Streptococcus pneumoniae (Sp) pneumonia, as reference. Risk factors for amoxicillin resistance in Hi were investigated. RESULTS: Overall, 113 patients with Hi and 132 with Sp pneumonia were included. The percentages of AMC resistance among Hi strains decreased over the years (from 10% in 2008-2009 to 0% in 2016-2017) while resistance to amoxicillin remained stable at 20%. Also, percentages of Sp resistant strains for amoxicillin decreased over years (from 25% to 3%). Patients with Hi pneumonia experienced higher prevalence of bronchitis (18% vs. 8%, p=0.02, chronic obstructive pulmonary disease (43% vs. 30% p=0.03), HAP (18% vs. 7%, p=0.01, ventilator-associated pneumonia (27% vs. 17%, p=0.04, and longer duration of mechanical ventilation (8 days vs. 6 days, p=0.04) than patients with Sp pneumonia. Patients with Sp pneumonia had more frequently local complications than patients with Hi pneumonia (17% vs. 7%, p=0.03). De-escalation of antibiotics was more frequent in patients with Sp than in patients with Hi (67% vs. 53%, p=0.03). No risk factors were associated with amoxicillin resistance among patients with Hi pneumonia. CONCLUSIONS: Amoxicillin resistance was stable over time, but no risk factors were detected. AMC resistance was extremely low, suggesting that AMC could be used for empiric treatment of Hi pneumonia, as well as other molecules, namely, cephalosporins. Patients with Hi pneumonia had more pulmonary comorbidities and severe diseases than patients with Sp pneumonia.

Evolution of haemostatic parameters and risk of bleeding during treatment with cefazolin.

In 2017, five cases of severe haemorrhages during treatment with cefazolin occurred in France. The aim of this study was to assess the risk of haemorrhage related to treatment with cefazolin by evaluating haemostatic parameters and bleeding events. A retrospective study was conducted from January 2016 to December 2017. Two populations were analysed: (i) overall population, which included all patients treated with cefazolin during this period and (ii) coagulation study population, which included all patients treated with cefazolin with available coagulation parameters (activated partial thromboplastin time (aPTT) and international normalised ratio (INR) at baseline and at the end of treatment or EoT). Values of either aPTT or INR at baseline and at EoT were compared. Cases of severe haemorrhages were reported and correlated with values of aPTT and INR. Overall, 132 patients received cefazolin and 59/132 (45%) were included in the coagulation study group. A significant increase of median aPTT was observed from baseline to EoT (39.5 and 44.3 sec; p = 0.004, respectively). Overall, severe haemorrhage occurred in 7/132 (5%) patients. Coagulation parameters were available in three of them, and no correlation was observed between bleeding events and aPTT increase. This study showed that bleeding is probably more frequent than ever reported before during cefazolin treatment. The significant increase of aPTT observed during cefazolin treatment was not correlated with risk of haemorrhage. Further studies are needed to explore the possible physio-pathological pathways behind the modification of haemostatic parameters and risk of haemorrhage.

Trimetoprim-sulfametoxazole in ventilator-associated pneumonia: a cohort study.

To evaluate the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) for treatment of ventilator-associated pneumonia (VAP). A retrospective cohort study including patients with VAP from 2011 to 2017. Two groups were analysed: TMP-SMX group, including patients who had received TMP-SMX (as first-line and as de-escalation), and No-TMP-SMX group, including patients who had not received TMP-SMX treatment. Primary clinical outcome was mortality at 30 days from starting the antibiotic treatment (T30). Secondary outcomes were mortality at end of treatment (EoT), day survival at T30, and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit. Eighty cases of VAP were included and devised into two groups: No-TMP-SMX (31/80; 39%) and TMP-SMX (49/80; 61%). Univariate analysis showed no significant differences were found when the TMP-SMX group was compared with the No-TMP-SMX group, except for frequency of male gender (p = 0.025). No significant statistical correlations between mortality at T30 and individual factors were detected by the multivariate model. No cases of either severe allergy or Clostridium difficile disease were reported in the TMP-SMX and No-TMP-SMX groups. TMP-SMX treatment was not associated with higher mortality at EoT and T30 in comparison with the No-TMP-SMX group. TMP-SMX had a good safety profile, in terms of ecology (acquisition of MDR bacteria and Clostridium difficile disease) and clinical management (no allergy events).

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.

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.

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.

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.

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.

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.

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.

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.