Efficacy of temocillin against MDR Enterobacterales: a retrospective cohort study.

OBJECTIVES: EUCAST recently advised against temocillin use, except for non-serious urinary tract infections (UTI) caused by Escherichia coli, Klebsiella spp. (except Klebsiella aerogenes) and Proteus mirabilis (EKP) treated with a dose of 2 g q8h. We aimed to analyse our practice in the context of a larger temocillin use in France. PATIENTS AND METHODS: All ≥3 day temocillin prescriptions from 2016 to 2019 were reviewed, with reference to French recommendations and a susceptibility breakpoint of 8 mg/L. The primary outcome was early clinical failure (antibiotic switch, relapse or death within 10 days after the completion of antibiotic treatment). RESULTS: Overall, 153 cases were analysed: 123 cases of UTI (80.4%) and 133 cases of monomicrobial infection with Enterobacterales (86.9%). A total of 160 Enterobacterales were isolated, comprising 108 (67.5%) ESBL producers and 30 (20.7%) non-EKP species. The rate of early clinical failure was 9.2% and was significantly lower for UTI compared with non-UTI (4.9% versus 26.7%, P = 0.001) and for sepsis compared with severe sepsis or septic shock (6.2% versus 25%, P = 0.011). It was not different between 2 g q12h and 2 g q8h doses (10% versus 7.4%, P = 0.81) and between EKP and other Enterobacterales (8.7% versus 14.3%, P = 0.41). CONCLUSIONS: EUCAST recommendations on urinary isolates seem to be too restrictive. Our data support the efficacy of temocillin at a dose of 2 g q12h to treat patients with non-severe complicated UTI caused by MDR Enterobacterales with an MIC of ≤8 mg/L, whatever the species.

Risk factors of vitamin K antagonist overcoagulation. A case-control study in unselected patients referred to an emergency department.

The aims of this case-control study were to identify in vitamin K antagonist (VKA)-treated unselected patients, factors associated with international normalised ratio (INR) values: (i) greater than 6.0.; and (ii) ranging from 4.0 to 6.0 complicated with bleeding. We also assessed VKA-related morbidity in these patients. During a two-month period, 4,188 consecutive and unselected patients were referred to our Emergency Department. At admission, the medical records of each patient and two age- and sex-matched controls were reviewed for: both duration and indication of VKA therapy, previous medical history of VKA-related haemorrhage, underlying co-morbidities, concomitant medications other than VKA, duration of hospitalization and deaths' causes. Of these 4,188 subjects, 50 case-patients (1.19%) were identified; both case-patients and controls did not differ as regards indications and patterns of VKA therapy. Interestingly, two-thirds of case-patients were women, suggesting that female gender may be a risk factor of VKA over-coagulation onset. We identified the following risk factors of VKA over-coagulation: previous medical history of INR levels over therapeutic range, therapy with antibiotics, amiodarone and proton pump inhibitors, as well as fever. A total of 88% of case-patients were hospitalized; mean duration of patients' hospitalization was seven days [range: 1-56 days]; no patient died from major bleeding. Our study underscores that it is of utmost importance to consider the strength of indication before starting VKA therapy, as this therapy has been responsible for as high as 1.19% of admissions in unselected subjects referred to an Emergency Department. Our data therefore suggest that internists should be aware of VKA-related high morbidity, particularly in situations at risk of VKA over-coagulation.