Temocillin vs Meropenem for the Targeted Treatment of Bacteraemia Resistant to Third Gen Cephalosporins

The objective of the trial is to demonstrate the non-inferiority of temocillin (2g each 8 hours, intravenous) to carbapenems (meropenem 1g each 8 hours, intravenous) in terms of efficacy and safety in the targeted treatment of bacteraemia due to Enterobacteriaceae resistant to third-generation cephalosporins, and therefore provide evidence for the use of temocillin in these infections.

The duration of treatment will be between 7 and 14 days. From the 5th day of intravenous treatment, the sequential oral treatment is permitted if the patient meets appropriate conditions.

Inclusion criteria

• Adult patients with monomicrobial bacteremia due to Enterobacteriaceae showing resistance to cefotaxime, ceftriaxone (MIC >2 mg/L) and/or ceftazidime (MIC >4 mg/L), and sensible to temocillin (MIC ≤8 mg/L, except in bacteremia only of urinary origin, for which the criterion is MIC ≤16 mg/L ) and meropenem (MIC ≤2 mg/L).

Patients with polymicrobial bacteremia caused by more than one Enterobacteriaceae species may also be included, provided at least one of them is resistant to third-generation cephalosporins, and both are susceptible to meropenem and temocillin.

• Duration of intravenous treatment is planned to be at least 4 days from randomization, or 3 days if the empirical treatment prior to randomization was active.
• The patient signed informed consent form.
• Potentially fertile patients must have a negative pregnancy test.

Exclusion criteria

• <18 years
• Pregnancy
• Breastfeeding
• Terminal condition, with life expectancy of less than 30 days, or palliative care , such that no actions will be taken to control the source of infection if necessary. Patients receiving palliative care with a life expectancy greater than 30 days may be included if source control is not necessary or, if necessary, will be carried out.
• Allergy to betalactams
• Polymicrobial bacteraemia (except when the other microorganism is considered a contaminant, (e.g. coagulase-negative staphylococci or diphtheroids in a single blood culture, or in cases where more than one Enterobacteriaceae species is isolated, provided that at least one isolate is resistant to third-generation cephalosporins and both are susceptible to meropenem and temocillin).
• Infections typically needing prolonged >14 days of therapy (e.g., endocarditis, prosthetic joint infection, vascular graft infection, empyema, chronic prostatitis) or meningitis. Patients who initially do not have a confirmed diagnosis of these infections may be included; if the diagnosis is made subsequently, the patient may be kept in the trial at the discretion of the investigator, establishing the duration of treatment that he considers necessary.
• Active empirical treatment> 96 hours after initial blood culture extraction
• Delay in inclusion> 48 h
• Recruited in another clinical trial with active treatment
• Peritoneal dialysis or continuous hemofiltration