Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study.

Background: Temocillin is a ß-lactam that is not hydrolysed by ESBLs. Objectives: To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Methods: Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Results: Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ±â€Š15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were Escherichia coli (49.6%), Klebsiella pneumoniae (44.2%) and Enterobacter cloacae (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5-358.2) and neurological disease (aOR 5.3, 95% CI 1.5-18.6). Conclusions: The main use of temocillin was UTI due to ESBL-producing E. coli and K. pneumoniae, with a favourable clinical outcome. The main risk factor for failure was neurological disease.

Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study.

BACKGROUND: The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. MATERIAL AND METHODS: A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3-5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. RESULTS: Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80-1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%). CONCLUSION: In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.

Enzyme therapy in Fabry disease: severe adverse events associated with anti-agalsidase cross-reactive IgG antibodies.

AIMS: To report a severe adverse event related to enzyme replacement therapy with agalsidase in an hemizygous male patient treated for Fabry disease. METHODS: Retrospective analysis of clinical, radiological and biochemical data in a patient who suffered adverse events related to both agalsidase alfa and agalsidase beta treatments. RESULTS: A hemizygous male patient was first treated for Fabry disease with agalsidase alfa. After more than 1 year of therapy, infusion-related symptoms necessitated systemic steroids and antihistaminic therapy. Decline in kidney function prompted a switch for agalsidase beta. Anaphylactoid shock occurred after the second infusion. No serum IgE antibodies were disclosed. Skin-test reactivity to agalsidase beta was negative. Following a published rechallenge infusion protocol, agalsidase beta was reintroduced, leading to a second anaphylactoid shock episode. Enzyme replacement therapy was stopped and the patient was treated with symptomatic therapy only. This case was referred to the pharmacovigilance department. CONCLUSION: The negativity of immunological tests (specific anti-agalsidase IgE antibodies and skin tests) does not rule out the risk of repeated anaphylactoid shock following agalsidase infusion.

Medication reconciliation: a prospective study in an internal medicine unit.

BACKGROUND: Medication reconciliation has proved its effectiveness at improving drug-prescription safety. This study was undertaken to assess the impact of an intervention aimed at decreasing the discrepancies between a patient's usual treatment(s) and medications prescribed at admission. METHODS: Our study was conducted from November 2010 to May 2011. Discrepancies between home medication( s) and drugs prescribed to every patient aged C65 years, transferred from the Emergency Department and hospitalized in the Internal Medicine Unit, were analyzed. RESULTS: During this 6-month period, 170 patients were prospectively included, with a total of 1,515 medicines reconciled. The unintentional discrepancy rate declined from 4.3 to 0.9 % after the intervention. The main sources of discrepancies concerned alimentary tract and metabolism (25.7 %), cardiovascular (24 %), and nervous system drugs (19.4 %). CONCLUSIONS: The results of this study demonstrated that acquisition of patients' medication history is often incomplete or incorrect. Pharmacists seem to be especially well suited to help medical teams rectify this situation. However, the cost effectiveness of this intervention needs further assessment.

Gemcitabine plus oxaliplatin (GEMOX) combined with cetuximab in patients with progressive advanced stage hepatocellular carcinoma: results of a multicenter phase 2 study.

BACKGROUND: The authors conducted a phase 2 trial of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with the gemcitabine plus oxaliplatin (GEMOX) regimen in patients with documented progressive hepatocellular carcinoma (HCC). METHODS: Forty-five untreated patients with advanced-stage progressive HCC were prospectively enrolled. Treatment consisted of cetuximab at a dose of 400 mg/m2 initially then 250 mg/m2 weekly, plus gemcitabine at a dose of 1000 mg/m2 on Day 1 and oxaliplatin at a dose of 100 mg/m2 on Day 2, every 2 weeks. Treatment was continued until disease progression, unacceptable toxicity, or patient refusal. RESULTS: Overall, 306 cycles were administered. Grade 3 to 4 hematologic toxicity consisted of thrombocytopenia (24%), neutropenia (20%), and anemia (4%). Grade 3 oxaliplatin-induced neurotoxicity occurred in 5 patients (11%) and grade 3 cutaneous toxicity in 7 patients (16%). There were no treatment-related deaths. The confirmed response rate was 20% and disease stabilization was obtained in 40% of patients. The median progression-free and overall survival times were 4.7 months and 9.5 months, respectively. The 1-year survival rate was 40%. CONCLUSIONS: In poor-prognosis patients with progressive advanced-stage HCC, the GEMOX-cetuximab combination appears to be active and to have manageable toxicity. A comparative randomized trial is now being planned.