Temocillin in ESBL-Enterobacteriaceae Infections

Completed

• Conditions: Infectious Disease
• Interventions: Other: Temocillin

• Registration Number: NCT05413772
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Because of the increasing incidence of infections with multi-drug resistant enterobacteriaceae, we need alternative treatments to spare carbapenems. Temocillin could be an interesting option but its position is only defined for the curative treatment of urinary tract infections. We would like to explore others indications comparing two groups : one using temocillin empirically for treatment or prophylaxis and the second using it in second line whatever the indication is.

Detailed Description

We will retrospectively include every patient who received at least 24 hours of temocillin for the treatment of an extended-spectrum beta-lactamase Enterobacteriaceae (ESBL-E) infection from January to December 2016 in two university hospitals (centres 1 and 2). Each treatment indication will be recorded including off-label prescriptions. Patients will be classified in 2 treatment groups: group 1 received a probabilistic antibiotherapy first (3GC or carbapenem or piperacillin/tazobactam or fluoroquinolones) followed by temocillin as second line treatment. Group 2 was defined by the use of temocillin as first line treatment or as prophylaxis.

Data collection : Clinical, biological and pharmaceutical data will be retrieved from medical chart. The patient's referring physician and/or the department will be contacted for further information on missing data. Remote outcomes will be retrieved either by hospital records if the patient is rehospitalized in the meantime or by contacting directly the patient by phone or e-mail. Demographic characteristics, comorbidities, type and location of infection, treatment, side effects, biological results, follow-up duration, treatment and outcome will be collected. For all antibiotics, doses, route and scheme administration, duration, first, second and third line of antibiotic (after temocillin) will be retrieved from medical chart.

Case definition and outcome: Treatment failure in curative use is defined by the persistence of clinical symptoms 72h after starting the antibiotic and/or clinical worsening leading to a switch to broad-spectrum antibiotic and/or recurrence of initial symptoms and/or identification of the same bacterial species with the same susceptibility pattern as initially observed (same or new location). Treatment failure in prophylactic use is defined by the persistence of the enterobacteria according to the indication of prophylaxis (e.g. urine). All deaths and lost-to-follow-up will be considered as failures (worst case scenario). Treatment success is defined by the absence of failure in the four weeks after treatment. We will use the Sequential Organ Failure Assessment (SOFA) score in predicting mortality in patients with ESBL-E infections included in our study.

Microbiological definitions : The susceptibility of the isolates to temocillin wil be determined by disc diffusion method (Biorad®, Marnes-la-Coquette, France) according to the guidelines of the CA-SFM ("Comité de l'Antibiogramme - Société Française de Microbiologie", Antibiogram Committee - French Society of Microbiology ). The Minimum Inhibitory Concentration (MIC) of temocillin will be determined by E-test (bioMérieux®, Marcy l'Étoile, France) on Mueller-Hinton agar using the manufacturer's instructions. MIC results will be also interpreted according to the 2016 guidelines of the CA-SFM.18

Study Timeline

• Study First Submitted: 2022-01-24
• Study First Submitted QC: 2022-06-07
• Study First Posted: 2022-06-10
• Study Start: 2022-10-20
• Status Verified: 2022-11
• Primary Completion: 2022-11-24
• Study Completion: 2022-11-24
• Last Update Submitted: 2023-02-03
• Last Update Posted: 2023-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Age ≥ 18 years
• All patients who received at least 24 hours of temocillin for the treatment of ESBL enterobacteriaceae infection / colonization from January to December 2016 in the university hospitals of Tenon and Pitié Salpêtrière. All indications, including excluding recommendations.
• Informed and not opposed to the use of their data

Exclusion Criteria

• Patient < 18 years
• Pregnancy
• Refusal to participate
• Multi-resistant bacterial infection not treated with temocillin
• Temocillin resistant bacteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Temocillin received empirically	Temocillin	Temocillin received in probabilistic , in curative context or in preventive use (prophylaxis)
Temocillin received on second line of treatment	Temocillin	Temocillin received second-line therapy in curative context or in preventive use (prophylaxis)

Primary Outcome Measures

Name	Time	Method
Number of patients with failure or success	10 days	Definition of failure: persistence of clinical symptoms 72h after starting the antibiotic and/or clinical worsening (ie : fever, cough, sputum, urinary symptoms, diarrhea...) leading to a switch to broad-spectrum antibiotic and/or recurrence of initial symptoms and/or identification of the same bacterial species, retrieved in collection samples, with the same susceptibility pattern as initially observed (same or new location)

Secondary Outcome Measures

Name	Time	Method
Number of patients with treatment related adverse events as assessed by CTCAE v6.0	28 days	Any side effect described in the medical file : Clostridium difficile colitis, renal failure, rash, for example.; Collection of information in the medical file in order to explore the reason of failure : analyse of others potential failure's causes (other cause of fever for example)

Trial Locations

Locations (2)

Pitié-Salpêtrière University Hospital; 🇫🇷 Paris, France

Tenon University Hospital; 🇫🇷 Paris, France