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).

BACKGROUND: Antibiotic resistance is increasing among urinary pathogens, resulting in worse clinical and economic outcomes. We analysed factors associated with antibiotic-resistant bacteria (ARB) in patients hospitalized for urinary tract infection, using the comprehensive French national claims database. METHODS: Hospitalized urinary tract infections were identified from 2015 to 2017. Cases (due to ARB) were matched to controls (without ARB) according to year, age, sex, infection, and bacterium. Healthcare-associated (HCAI) and community-acquired (CAI) infections were analysed separately; logistic regressions were stratified by sex. RESULTS: From 9460 cases identified, 6468 CAIs and 2855 HCAIs were matched with controls. Over a 12-months window, the risk increased when exposure occurred within the last 3 months. The following risk factors were identified: antibiotic exposure, with an OR reaching 3.6 [2.8-4.5] for men with CAI, mostly associated with broad-spectrum antibiotics; surgical procedure on urinary tract (OR 2.0 [1.5-2.6] for women with HCAI and 1.3 [1.1-1.6] for men with CAI); stay in intensive care unit > 7 days (OR 1.7 [1.2-2.6] for men with HCAI). Studied co-morbidities had no impact on ARB. CONCLUSIONS: This study points out the critical window of 3 months for antibiotic exposure, confirms the impact of broad-spectrum antibiotic consumption on ARB, and supports the importance of prevention during urological procedures, and long intensive care unit stays.

Impact of a medication reconciliation care bundle at hospital discharge on continuity of care: A randomised controlled trial.

OBJECTIVE: To compare the impact of a care bundle including medication reconciliation at discharge by a pharmacist versus standard of care, on continuity of therapeutic changes between hospital and primary care and outcome of patients, within 1 month after discharge. METHODS: Randomised controlled trial in 120 adult patients with at least one chronic disease and three current medications before admission, hospitalised in an infectious disease department of a tertiary hospital and discharged home. Patients were randomly assigned (1:1) to receive a discharge care bundle including medication reconciliation, counselling session and documentation transfer to primary care physician (PCP) (intervention group) or standard of care (control group). Primary outcome was the proportion of in-hospital prescription changes, not maintained by the PCP, 1 month after discharge. Secondary outcome measures included the proportion of patients experiencing early PCP's consultation, hospital readmissions or adverse reactions within 1-month postdischarge and cost of discharge prescriptions. RESULTS: Baseline characteristics were comparable between the two groups. One month after discharge, the proportion of in-hospital prescription changes, not maintained by the PCP, was 11% in the intervention group versus 24% in the control group (P = .007). The median delay before PCP's consultation was longer in the intervention group (30.5 vs 19.5 days, P = .013), there were fewer patients readmitted to hospital (3.4% vs 20.7%, P = .009, odds ratio (OR) = 0.13 [0.02-0.53]) and fewer patients who suffered from adverse drug reaction (7.0% vs 22.8%, P = .04, OR = 0.26 [0.07-0.78]). CONCLUSION: This care bundle resulted in the reduction of treatment changes between hospital discharge and primary care.

Costs and Outcomes of 1-year post-discharge care trajectories of patients admitted with infection due to antibiotic-resistant bacteria.

BACKGROUND: The impact of antibiotic resistance (AMR) on initial hospital management has been extensively studied but its consequences after hospital discharge remain largely unknown. We aimed to analyze hospital care trajectories, cumulative length of hospital stays (c-LOS) and associated costs of care over a 1-year period after hospitalization with incident AMR infection. METHOD: All incident bacterial infection-related hospitalizations occurring from January 1, 2015, to December 31, 2015 and recorded in the French national health data information system were extracted. Bacterial resistance ICD-10 codes determined six infection status. Inpatient and outpatient care consumption and associated costs were studied. The impact of resistance on c-LOS was estimated using a Poisson regression. A sequence analysis through optimal matching method was conducted to identify hospital trajectories along with an extrapolation. FINDING: Of the 73,244 patients selected, 15.9% had AMR infection, thus providing 58,286 incident AMR infections after extrapolation. c-LOS was significantly longer for infections with resistant bacteria, reaching 20.4 days and 2.9 additional days IC95%[2.6; 3.2] for skin and soft tissue infections. An estimated 29,793 (51.1%) patients had hospital readmission within the following year, for a total cost of €675 million. Five post-discharge trajectories were identified: Post-hospitalization mainly at home (68.4% of patients); Transition to home from rehabilitation care (12.3%); Early death (<3 months) (9.7%); Late death (7.4%), and Long-term hospitalization (2.2%). INTERPRETATION: AMR has an impact on patients' c-LOS stay beyond the initial hospitalization. Half of patients hospitalized due to AMR are readmitted to hospital within the ensuing year, along five different trajectories. FUNDING: French Ministry of health.

Trends in Antibiotic Consumption and Resistance in France Over 20 Years: Large and Continuous Efforts but Contrasting Results.

BACKGROUND: Antimicrobial resistance (AMR) is a serious threat to humanity. This paper describes the French efforts made since 2001 and presents data on antimicrobial consumption (AC) and AMR. METHODS: We gathered all data on AC and AMR recorded since 2001 from different national agencies, transferred on a regular basis to standardized European data on AC and resistance in both humans and animals. RESULTS: After a large information campaign implemented in France from 2001 to 2005 in humans, AC in the community decreased significantly (18% to 34% according to the calculation method used). It remained at the same level from 2005 to 2010 and increased again from 2010 to 2018 (8%). Contrasting results were observed for AMR. The resistance of Staphylococcus aureus decreased significantly. For gram-negative bacilli, the results were variable according to the microorganism. The resistance of Enterobacteriaceae to third-generation cephalosporins increased, remaining moderate for Escherichia coli (12% in 2017) but reaching 35% in the same year for Klebsiella pneumoniae. Resistance to carbapenems in those 2 microorganisms remained below 1%. Both global AC and resistance to most antibiotics decreased significantly in animals. CONCLUSIONS: Antibiotic consumption decreased significantly in France after a large public campaign from 2001 to 2005, but this positive effect was temporary. The effect on AMR varied according to the specific microorganism: The effect was very impressive for gram-positive cocci, variable for gram-negative bacilli, and moderate for E. coli, but that for K. pneumoniae was of concern. The consumption of and resistance to antibiotics decreased significantly in animals.

Early mechanical ventilation in patients with Guillain-Barré syndrome at high risk of respiratory failure: a randomized trial.

INTRODUCTION: About 30% of patients with Guillain-Barré syndrome become ventilator dependent, of whom roughly 75% develop pneumonia. This trial aimed at assessing the impact of early mechanical ventilation (EMV) on pneumonia occurrence in GBS patients. We hypothesize that EMV will reduce the incidence of pneumonia. METHODS: This was a single centre, open-label, randomized controlled trial performed on two parallel groups. 50 intensive care unit adults admitted for Guillain-Barré syndrome and at risk for acute respiratory failure. Patients were randomized to early mechanical ventilation via face-mask or endotracheal intubation owing to the presence or absence of impaired swallowing (experimental arm), or to conventional care (control arm). The primary outcome was the incidence of pneumonia up to intensive care unit discharge (or 90 days, pending of which occurred first). FINDINGS: Twenty-five patients were randomized in each group. There was no significant difference between groups for the incidence of pneumonia (10/25 (40%) vs 9/25 (36%), P = 1). There was no significant difference between groups for the time to onset of pneumonia (P = 0.50, Gray test). During follow-up, there were 16/25 (64%) mechanically ventilated patients in the control group, and 25/25 (100%) in the experimental arm (P < 000·1). The time on ventilator was non-significantly shorter in the experimental arm (14 [7; 29] versus 21.5 [17.3; 35.5], P = 0.10). There were no significant differences between groups for length of hospital stay, neurological scores, the proportion of patients who needed tracheostomy, in-hospital death, or any serious adverse events. CONCLUSIONS: In the present study including adults with Guillain-Barré syndrome at high risk of respiratory failure, we did not observe a prevention of pneumonia with early mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov under the number NCT00167622. Registered 9 September 2005, https://clinicaltrials.gov/ct2/show/NCT00167622?cond=Guillain-Barre+Syndrome&cntry=FR&draw=2&rank=1.

Testing the repatriated for SARS-Cov2: Should laboratory-based quarantine replace traditional quarantine?

BACKGROUND: An ongoing epidemic of respiratory diseases caused by a novel coronavirus (COVID 2019, SARS-CoV2) started in Wuhan, Hubei, in China at the end of December 2019. The French government decided to repatriate the 337 French nationals living in Wuhan and place them in quarantine in their home country. We decided to test them all for SARS-Cov2 twice in order to reduce anxiety among the population and decision-makers. METHODS: We investigated the presence of SARS-CoV-19 in asymptomatic carriers by testing all repatriated patients within the first 24 h of their arrival in France and at day 5. Viral RNA was extracted from pooled nasal and oropharyngeal swab fluids or sputum in the absence of nasal/oropharyngeal swabs. Detection of SARS-CoV-2 RNA was then carried out using several real-time reverse transcription (RT)-PCR assays. RESULTS: We tested 337 passengers at day 0 and day 5. All the tests for SARS-CoV2 were negative. By optimising the sampling process, sending samples sequentially and reducing the time-scale for biological analysis, we were able to test the samples within 5 h (including sampling, shipment and biological tests). CONCLUSION: Optimising our procedures reduces anxiety and reassures the population and decision makers.

Early Detection of Public Health Emergencies of International Concern through Undiagnosed Disease Reports in ProMED-Mail.

We conducted a retrospective analysis of all reports in ProMED-mail that were initially classified as undiagnosed diseases during 2007-2018. We identified 371 cases reported in ProMED-mail; 34% were later diagnosed. ProMED-mail could be used to supplement other undiagnosed disease surveillance systems worldwide.

Efficacy of cotrimoxazole (Sulfamethoxazole-Trimethoprim) as a salvage therapy for the treatment of bone and joint infections (BJIs).

INTRODUCTION: Cotrimoxazole (Sulfamethoxazole-Trimethoprim, SXT) has interesting characteristics for the treatment of bone and joint infection (BJI): a broad spectrum of activity with adequate bone diffusion and oral and intravenous formulations. However, its efficacy and safety in BJIs are poorly documented and its use remains limited. METHODS: We conducted a retrospective study in 2 reference centers for BJIs from 2013 to 2018 among patients treated with SXT for a BJI. Data were collected from patient's medical charts. Outcomes and adverse events were evaluated at day (D)7, D45 and D90. RESULTS: We analyzed 51 patients with a mean age of 60 ± 20 (SD) years of which 76% presented with an orthopedic device infection (ODI). Gram-negative bacilli (GNB) were involved in 47% of BJIs (n = 24). Moreover, they were often polymicrobial infections (41%). Doses of SXT ranged from 800/160mg bid (61%; n = 31) to 800/160mg tid (39%; n = 20). Median SXT treatment duration was 45 days (IQR 40-45). SXT was part of a dual therapy in 84% of patients (n = 43), associated mainly with fluoroquinolones (n = 17) or rifampicin (n = 14). Outcome was favorable at D7 in 98% (n = 50), at D45 in 88.2% (n = 45) and at D90 in 78.4% (n = 40). The second agent combined with SXT was not an independent factor of favorable outcome (p = 0.97). Adverse events were reported in 8% (n = 4) of patients, with a median of 21 days (IQR 20-30) from SXT initiation and led to discontinuation (n = 3). CONCLUSION: SXT appears to be effective for treatment of BJIs as a salvage therapy, even in GNB or polymicrobial infection, including ODI. Further data are needed to confirm SXT efficacy as an alternative oral regimen in BJIs.

Eosinopenia as a marker of diagnosis and prognostic to distinguish bacterial from aseptic meningitis in pediatrics.

Procalcitonin (PCT) has proven its efficacy to distinguish bacterial from aseptic meningitis in children. Nevertheless, its use in routine is limited by its cost and availability, especially in low- and middle-income countries. It is now acknowledged that eosinopenia is a marker of infection and/or severity of the systemic inflammatory response. Although no study ever demonstrated that eosinopenia could differentiate bacterial from viral infection, we decided to conduct a study concerning meningitis in children. This bicentric and retrospective study was conducted between January 2012 and October 2018, in children hospitalized for meningitis. The white blood cell was systematically gathered at the admission to evaluate the eosinophil count. Characteristic data were compared between 2 groups: documented bacterial meningitis (DBP) and aseptic meningitis which includes documented viral meningitis (DVM) and non-documented meningitis (ND). Among 190 patients admitted for meningitis, 151 were analyzed, including DBM (n = 45), DVM (n = 73), and ND (n = 33) meningitis. Groups were comparable. Mean age was 33 ± 48 months with a sex ratio of 1.6. Mean of eosinophil count was 15 ± 34/mm3 in the DBM group versus 132 ± 167/mm3 for the aseptic meningitis group (p < 0.0001). Best threshold for the diagnosis of bacterial meningitis was an eosinophil count < 5/mm3 with a sensitivity of 80% and specificity of 73% and a likelihood ratio of 2.9. Eosinopenia seems to be a reliable and non-invasive marker of bacterial meningitis in pediatrics. The absence of extra cost makes it very interesting in low- and middle-income countries or when usual biomarkers such as PCT are unavailable.

Evaluation in general practice of the patient's feelings about a recent hospitalization and isolation for a multidrug-resistant infection.

BACKGROUND: Isolation precautions used against multidrug-resistant (MDR) organisms are responsible for many emotional side effects. We evaluated patient's feeling after a hospitalization for an MDR infection. METHODS: We conducted a qualitative study that included 11 interviews from August 2017 to June 2018. We used phenomenology and verbatim transcription analysis was performed using NVivo software. Patients reported mainly negative feelings. Among them, 4 main themes were expressed: a desire to "be free from carriage," self-questioning regarding its nosocomial origin, the reduction of the therapeutic arsenal, and the expression of many fears especially relapse. RESULTS: For most of the participants (n = 6/11), the type of bacteria that colonized their digestive tract was precisely known including the MDR characteristics of the infection. Participants were convinced that the infection was strongly linked to the hospital and considered it as nosocomial that led to anxiety, especially regarding the origin of the infection and the absence of formal source of infection. CONCLUSIONS: MDR infections are negatively impacting patient's lived experience even after hospital discharge, partly owing to prior implementation of isolation precautions. We need to improve communication between specialists and general practitioners to reassure the patient and his surroundings regarding the anxiety resulting from such hospitalization.

Emergency management of chlorine gas exposure - a systematic review.

INTRODUCTION: Chlorine exposure can lead to pulmonary obstruction, reactive airway dysfunction syndrome, acute respiratory distress syndrome and, rarely, death. OBJECTIVE: We performed a systematic review of published animal and human data regarding the management of chlorine exposure. METHODS: Three databases were searched from 2007 to 2017 using the following keywords "("chlorine gas" OR "chlorine-induced" OR" chlorine-exposed") AND ("therapy" OR "treatment" OR "post-exposure")". Forty-five relevant papers were found: 22 animal studies, 6 reviews, 19 case reports and 1 human randomized controlled study. General management: Once the casualty has been removed from the source of exposure and adequately decontaminated, chlorine-exposed patients should receive supportive care. Humidified oxygen: If dyspnea and hypoxemia are present, humidified oxygen should be administered. Inhaled bronchodilators: The use of nebulized or inhaled bronchodilators to counteract bronchoconstriction is standard therapy, and the combination of ipratropium bromide with beta2-agonists effectively reversed bronchoconstriction, airway irritation and increased airway resistance in experimental studies. Inhaled sodium bicarbonate: In a randomized controlled trial, humidified oxygen, intravenous prednisolone and inhaled salbutamol were compared with nebulized sodium bicarbonate. The only additional benefit of sodium bicarbonate was to increase the forced expiratory volume in one second, 2 and 4 h after administration. Corticosteroids: Dexamethasone 100 mg/kg intraperitoneally (IP) reduced lung edema when given within 1 h of chlorine inhalation and when administered within 6 h significantly decreased (p < 0.01) the leukocyte count in the bronchoalveolar lavage (BAL). As corticosteroids were never given alone in clinical studies, it is impossible to assess whether they had an additional beneficial effect. Antioxidants: An ascorbic acid/deferoxamine combination (equivalent to 100 mg/kg and 15 mg/kg, respectively) was administered intramuscularly 1 h after chlorine exposure, then every 12 h up to 60 h, then as an aerosol, and produced a significant reduction (p < 0.05) in BAL leukocytes and a significant reduction (p < 0.007) in mortality at 72 h. The single clinical case reported was uninterpretable. Sodium nitrite: Sodium nitrite 10 mg/kg intramuscularly (IM), 30 min post-chlorine exposure in mice and rabbits significantly reduced (p < 0.01) the number of leukocytes and the protein concentration in BAL and completely reversed mortality in rabbits and decreased mortality by about 50% in mice. No clinical studies have reported the use of sodium nitrite. Dimethylthiourea: Dimethylthiourea 100 mg/kg IP significantly decreased (p < 0.05) lymphocytes and neutrophils in BAL fluid 24 h after chlorine exposure in experimental studies. No clinical studies have been undertaken. AEOL 10150: Administration of AEOL10150 5 mg/kg IP at 1 h and 9 h post-chlorine exposure reduced significantly the neutrophil (p < 0.001) and macrophage (p < 0.05) bronchoalveolar cell counts. Transient receptor potential vanilloid 4 (TRPV4): IM or IP TRPV4 reduced significantly (p < 0.001) bronchoalveolar neutrophil and macrophage counts to baseline at 24 h. No clinical studies have been performed. Reparixin and triptolide: In experimental studies, triptolide 100-1000 µg/kg IP 1 h post-exposure caused a significant decrease (p < 0.001) in bronchoalveolar neutrophils, whereas reparixin 15 mg/kg IP 1 h post-exposure produced no benefit. Rolipram: Nanoemulsion formulated rolipram administered intramuscularly returned airway resistance to baseline. Rolipram (40%)/poly(lactic-co-glycolic acid) (60%) 0.36 mg/mouse given intramuscularly 1 h post-exposure significantly reduced (p < 0.05) extravascular lung water by 20% at t + 6 h. Prophylactic antibiotics: Studies in patients have failed to demonstrate benefit. Sevoflurane: Sevoflurane has been used in one intubated patient in addition to beta2-agonists. Although the peak inspiratory pressure was decreased after 60 min, the role of sevofluorine is not known. CONCLUSIONS: Various therapies seem promising based on animal studies or case reports. However, these recommendations are based on low-level quality data. A systematic list of outcomes to monitor and improve may help to design optimal therapeutic protocols to manage chlorine-exposed patients.

A Payer Perspective of the Hospital Inpatient Additional Care Costs of Antimicrobial Resistance in France: A Matched Case-Control Study.

BACKGROUND AND OBJECTIVE: Antimicrobial resistance (AMR) has become one of the biggest threats to global public health given its association with mortality, morbidity and cost of health care. However, little is known on the economic burden of hospitalization attributable to AMR from a public health insurance perspective. We assessed the excess costs to the French public health insurance system attributable to AMR infections in hospitals. METHODS: Bacterial infectious disease-related hospitalizations were extracted from the National health data information system for all stays occurring in 2015. Bacterial infections, strains, and microbial resistance were identified by specific French ICD-10 codes. Information about health care expenditure, co-morbidities and demographic characteristics (i.e. gender, age) are provided. We used a matched case-control approach to determine the excess of reimbursements paid to stays with AMR compared to stays with an infection without resistance. Cases and controls were matched on gender, age, Charlson comorbidity index, category of infection, infection as principal diagnosis (two classes), microorganism and hospital status. The overall AMR cost was extrapolated to stays with AMR and excluded from the sample (multiple infections), and a second extrapolation was performed to consider stays with unknown resistance status. RESULTS: The final sample included 52,921 matched-pairs (98.2% cases). Our results suggest that AMR overall cost reached EUR109.3 million in France with a mean of EUR1103 per stay; extrapolation to the entire database shows that the overall cost could potentially reach EUR287.1 million if all cases would be identified. The mean excess length of hospital stay attributable to AMR was estimated at 1.6 days. CONCLUSION: AMR causes substantial cost burden in France for the public health insurance. Our study confirms the need to reinforce programs to prevent AMR infection and thereby reduce their economic burden.

Germs of thrones - spontaneous decolonization of Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) in Western Europe: is this myth or reality?

Background: In France, Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) are considered as Extensively Drug-Resistant (XDR) bacteria. Their management requires reinforcement of hospital's hygiene policies, and currently there is few consistent data concerning the spontaneous decolonization in XDR colonized patients. Our aim is to study the natural history of decolonization of XDR carriers over time in a hospital setting in a low prevalence country. Material and methods: Retrospective multicenter study over 2 years (2015-2016) in 2 different tertiary care hospital sites and units having an agreement for permanent cohorting of such XDR carriers. We gathered the type of microorganisms, risk factors for colonization and rectal swabs from patient's follow-up. We also evaluated patient care considering isolation precautions. Results: We included 125 patients, aged 63+/-19y, including 72.8% of CRE (n = 91), 24.8% of VRE (n = 31) and 2.4% (n = 3) co-colonized with CRE and VRE. CRE were mainly E. coli (n = 54), K. pneumoniae (n = 51) and E. cloacae (n = 6). Mechanisms of resistance were mainly OXA-48 (n = 69), NDM-1 (n = 11), OXA-232 (n = 8) and KPC (n = 3).Prior antibiotic therapy was reported in 38.4% (n = 48) of cases. Conversely, 17.6% (n = 22) received antibiotics during follow-up.Spontaneous decolonization occurred within the first 30 days in 16.4% (n = 19/116) of cases and up to 48.2% after day-90 with a median follow-up of 96 days (0-974).We estimated that XDR carriage was associated with a larger care burden in 13.6% (n = 17) of cases, especially due to a prolongation of hospitalization of 32.5 days (15-300). Conclusions: Our study shows that spontaneous decolonization is increasing over time (up to 48.2%). We can regret that only few patients underwent screening after 1 year, emphasizing the need for more monitoring and prospective studies.