The Use and Effectiveness of Ceftazidime-Avibactam in Real-World Clinical Practice: EZTEAM Study.

INTRODUCTION: Ceftazidime-avibactam has proven activity against multidrug-resistant (MDR) bacteria in clinical trials and real-world studies. This study was conducted to describe the patterns of use of ceftazidime-avibactam (including indications and associated antibiotics), and the effectiveness and safety of ceftazidime-avibactam in real-world clinical practice. METHODS: This non-interventional medical chart review study was conducted in 11 countries across the European and Latin American (LATAM) regions. Consecutive patients treated in clinical practice with at least one dose of ceftazidime-avibactam for an approved indication per country label since 01 January 2018 (or launch date in the country if posterior) were enrolled. Effectiveness analyses were conducted in patients treated with ceftazidime-avibactam for at least 72 h. RESULTS: Of the 569 eligible patients enrolled, 516 (90.7%) were treated for at least 72 h (354 patients from Europe and 162 patients from LATAM); 390 patients (75.7%) had switched from another antibiotic line for Gram-negative coverage. Infection sources were intra-abdominal, urinary, respiratory, bloodstream infections, and other infections (approximately 20% each). K. pneumoniae was the most common microorganism identified in the latest microbiological evaluation before starting ceftazidime-avibactam (59.3%). Two-thirds of microorganisms tested for susceptibility were MDR, of which 89.3% were carbapenem-resistant. The common MDR mechanisms for K. pneumoniae were carbapenemase (33.9%), oxacillinase 48 (25.2%), extended-spectrum beta-lactamase (21.5%), or metallo-beta-lactamase (14.2%) production. Without prior patient exposure, 17 isolates (mostly K. pneumoniae) were resistant to ceftazidime-avibactam. Treatment success was achieved in 77.3% of patients overall (88.3% among patients with urinary infection), regardless of first or second treatment line. In-hospital mortality rate was 23.1%. Adverse events were reported for six of the 569 patients enrolled. CONCLUSION: This study provides important real-world evidence on treatment patterns, effectiveness, and safety of ceftazidime-avibactam in clinical practice through its recruitment in the European and LATAM regions. Ceftazidime-avibactam is one of the antibiotics to consider for treatment of MDR bacteria. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03923426.

Patient perceptions of the re-usable Respimatt® Soft Mist™ inhaler in current users and those switching to the device: A real-world, non-interventional COPD study.

PLAIN LANGUAGE SUMMARY: Inhalers are often used to treat patients with chronic obstructive pulmonary disease (COPD). However, there are many available, which can lead to confusion and poor inhaler technique. It is important for a patient to be happy with their inhaler. This study looked at how patients liked the re-usable Respimat® Soft Mist™ inhaler vs. their previous inhaler. It also asked whether they would be willing to continue using the device at the end of the study period.After 4-6 weeks of using the re-usable device, patients reported that they were happy with the inhaler and most would be willing to carry on using it.Overall, these results show that doctors can prescribe Respimat re-usable to patients, even if the patient has not used the inhaler before.

Risk Factors and Medical Resource Utilization of Respiratory Syncytial Virus, Human Metapneumovirus, and Influenza-Related Hospitalizations in Adults-A Global Study During the 2017-2019 Epidemic Seasons (Hospitalized Acute Respiratory Tract Infection [HARTI] Study).

Background: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza are respiratory pathogens leading to hospitalization in adults. Our understanding of the disease burden is limited to data from single-center or 1-season studies in elderly patients. The HARTI study allows comparison of risk factors for progression to severe disease and medical resources utilization (MRU) during and post-hospitalization in adults diagnosed with influenza, RSV, or hMPV. Methods: This was a prospective global study in adults hospitalized with acute respiratory tract infection (40 centers, 12 countries). Participants with influenza, RSV, or hMPV were enrolled in a substudy and followed for up to 3 months postdischarge. Results: Overall, 366 influenza, 238 RSV, and 100 hMPV-infected participants enrolled in the substudy. RSV participants were older and had greater frequency of risk factors and longer duration of symptoms before hospitalization than influenza participants. The RSV and hMPV groups received more bronchodilators, corticosteroids, and oxygen supplementation. No significant differences in intensive care unit admissions or complications were observed. Readmission occurred in 20%-33% of patients within 3 months postdischarge, with the highest rates for RSV and hMPV. In-hospital death occurred in 2.5% of RSV, 1.6% of influenza, and 2% of hMPV participants. In multivariate analyses, length of stay was independently associated with country, renal disease, and increased age; probability of receiving supplemental oxygen was associated with pathogen (hMPV > RSV > influenza), abnormal chest x-ray, and increased age. Conclusions: Although influenza is more frequent, the HARTI study demonstrates greater frequency of underlying risk factors and MRU for RSV and hMPV vs influenza in hospitalized adults, indicating a need for effective interventions.

The impact of initial antibiotic treatment failure: real-world insights in patients with complicated, health care-associated intra-abdominal infection.

PURPOSE: The RECOMMEND study (NCT02364284; D4280R00005) assessed the clinical management patterns and treatment outcomes associated with initial antibiotic therapy (IAT; antibiotics administered ≤48 hours post-initiation of antibiotic therapy) for health care-associated infections across five countries. PATIENTS AND METHODS: Data were collected from a retrospective chart review of patients aged ≥18 years with health care-associated complicated intra-abdominal infection (cIAI). Potential risk factors for IAT failure were identified using logistic regression analyses. RESULTS: Of 385 patients with complete IAT data, bacterial pathogens were identified in 270 (70.1%), including Gram-negative isolates in 221 (81.9%) and Gram-positive isolates in 92 (34.1%). Multidrug-resistant (MDR) pathogens were identified in 112 patients (41.5% of patients with a pathogen identified). IAT failure rate was 68.3% and in-hospital mortality rate was 40.8%. Multivariate regression analysis demonstrated three factors to be significantly associated with IAT failure: patients admitted/transferred to the intensive care unit during index hospitalization, isolation of an MDR pathogen and previous treatment with ß-lactam antibiotics. CONCLUSION: We reveal the real-world insights into the high rates of IAT failure and mortality observed among patients with cIAI. These data highlight the challenges associated with choosing IAT, the impact of MDR pathogens on IAT outcomes and the importance of tailoring IAT selection to account for local epidemiology and patient history.

The impact of initial antibiotic treatment failure: Real-world insights in healthcare-associated or nosocomial pneumonia.

OBJECTIVES: To assess real-world treatment patterns and clinical outcomes associated with initial antibiotic therapy (IAT, antibiotics received ≤ 48 h post-initiation of antibiotic therapy), including level of IAT failure, and potential risk factors for IAT failure in healthcare-associated infections. METHODS: Data were obtained from medical records of adult patients hospitalized with healthcare-associated pneumonia (HCAP) and nosocomial pneumonia (NP), including ventilator-associated pneumonia, from 1 July 2013 to 30 June 2014 in Brazil, France, Italy, Russia and Spain during the retrospective, observational study, RECOMMEND (NCT02364284; D4280R00005). Potential risk factors for IAT failure were explored using logistic regression analyses. RESULTS: Mean (standard deviation) age and Deyo-Charlson Comorbidity Score were 66.0 (16.2) years and 2.4 (2.4), respectively (N = 451). Most patients (62.5%) received monotherapy. Mean (standard deviation) duration of IAT was 8.8 (7.2) days. Multidrug-resistant (MDR) pathogens were identified in 52.4% of patients with ≥ 1 pathogen isolated (154/294). IAT failure was recorded in 72.5% of patients and was significantly associated with isolation of a MDR pathogen and country using multivariate analyses. CONCLUSIONS: Real-world data demonstrate the burden of HCAP/NP, with high rates of IAT failure. The association of IAT failure with MDR pathogens highlights the urgent need to understand and account for local prevalence of MDR pathogens when selecting IAT for the management of HCAP/NP.

The impact of initial antibiotic treatment failure: Real-world insights in patients with complicated urinary tract infection.

OBJECTIVES: RECOMMEND (NCT02364284; D4280R00005) assessed treatment patterns and outcomes associated with initial antibiotic therapy (IAT; antibiotics received <48 h post-initiation of antibiotic therapy) in healthcare-associated infections across five countries. METHODS: Data from medical records of hospitalized patients aged ≥18 years with healthcare-associated complicated urinary tract infections (cUTI) are presented. Univariate and multivariate logistic regression analyses identified potential risk factors associated with IAT failure. RESULTS: Mean (SD) age was 68.7 (17.4) years (n = 408). In patients with microbiological documentation (357/408), Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were most common (47.1%, 21.6% and 11.8%, respectively); 46.1% of patients had a multidrug resistant (MDR) pathogen isolated. Most patients received monotherapy IAT (72.5%). Mean IAT duration was 7.8 days. IAT failure, in-hospital mortality, and mortality 30-day post-discharge were 54.4%, 35.0% and 37.3%, respectively. IAT failure was associated with age, Deyo-Charlson comorbidity score, country, MDR status and ICU admission in the univariate analysis; and country and age in the multivariate analysis. CONCLUSIONS: This study provides real-world insights into the high rates of IAT failure and morbidity observed in patients with cUTI. Further study is imperative to understand the epidemiology of cUTI, support appropriate IAT selection and management, and reduce the burden of this disease.

Disease status, costs and quality of life of patients with rheumatoid arthritis in France: the ECO-PR Study.

OBJECTIVE: To investigate resource consumption and quality of life (utility) in a sample of patients covering the full spectrum of the disease, modalities of patient management and geographic areas. METHODS: Information on demographics, disease parameters, work capacity and resource consumption (in the past 1, 3 or 12 months depending on the resource) was collected in an anonymous mail survey from all members of a national patient association (ANDAR). Results are presented for the sample and by level of functional capacity, in 2005 euro. RESULTS: 1487 patients were included in the analysis (response rate 49%). Mean age was 62.7 years and 83.5% of respondents were female. Mean disease duration was 18 years; mean HAQ was 1.42; fatigue and pain ranked 5.6 and 4.8 on a scale between 0 and 10, respectively. Of patients below 60 years, 34% had taken early retirement due to RA, and only 15% of patients with a HAQ of 2 or higher were working. Productivity losses were estimated at 5076 euro, of which indemnity payments covered 1944 euro. Direct health care costs were 11,757 euro in the societal perspective and 9216 euro in the perspective of the national health insurance. Direct non-medical costs (including informal care) were 4857 euro and 136 euro respectively. Costs to society increased from 9400 euro in mild disease to 40,700 euro in severe disease, and to public payers from 6000 euro to 19,000 euro. Utility decreased simultaneously from 0.80 to 0.06. CONCLUSION: The study confirms overall findings in other studies in other countries, and provides the first estimate of all costs by disease severity in France.

Cost-effectiveness of once-daily treatment with calcipotriol/betamethasone dipropionate followed by calcipotriol alone compared with tacalcitol in the treatment of Psoriasis vulgaris.

BACKGROUND: Daivobet is a once-daily treatment of psoriasis vulgaris containing betamethasone dipropionate and calcipotriol in a new ointment vehicle. OBJECTIVE: To assess the cost-effectiveness of once-daily treatment with Daivobet (4 weeks) followed by calcipotriol (4 weeks) compared to tacalcitol (8 weeks). METHODS: Resource utilization was assessed within a double-blind 8-week clinical trial (all treatments for psoriasis, adverse events and concomitant dermatological medication), estimated from the French societal perspective. RESULTS: Total direct medical costs for psoriasis were comparable (Daivobet: EUR 107.53 and tacalcitol EUR 113.50) despite a higher acquisition cost for Daivobet. The probability of > or =75% reduction in the Psoriasis Area and Severity Index (effectiveness criterion) was 46.6% with Daivobet and 13.9% with tacalcitol at 4 weeks, and 44.6 and 23.8%, respectively, at 8 weeks (both: p < 0.001). Over 8 weeks, Daivobet was almost twice as cost-effective as tacalcitol (EUR 241.22 per successful treatment vs. EUR 476.70); this result was robust to sensitivity assumptions. CONCLUSION: Daivobet is more effective and less costly than tacalcitol for treating psoriasis.