PipEracillin Tazobactam Versus mERoPENem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae (PETERPEN)

Piperacillin Tazobactam Versus Meropenem for Treatment of Bloodstream Infections Caused by Cephalosporin-resistant Enterobacteriaceae- a Non-inferiority Randomized Controlled Trial

Data regarding optimal treatment for extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae blood-stream infection are lacking. Observational studies show conflicting results when comparing treatment with combination beta-lactam-beta-lactamase inhibitor and carbapenems. The investigators aim to evaluate the effect of definitive treatment with meropenem vs. piperacillin-tazobactam on the outcome of patients with bacteremia due to cephalosporin-non-susceptible Enterobacteriaceae. The investigators hypothesize that piperacillin-tazobactam is non-inferior to meropenem.

Inclusion Criteria:

1. Adults (age ≥ 18 years)
2. New onset BSI due to E. coli or Klebsiella spp. in one or more blood cultures associated with evidence of infection.
3. The microorganism will have to be non-susceptible to third generation cephalosporins (ceftriaxone and ceftazidime) and susceptible to both PTZ and meropenem (see microbiological methods).
4. Both community and hospital-acquired bacteremias will be included.
5. We will permit the inclusion of bacteremias due to E. coli or Klebsiella spp. with concomitant growth in blood of skin commensals considered as contaminants.

Exclusion Criteria:

1. More than 72 hr. elapsed since initial blood culture taken, regardless of the time covering antibiotics were started (up to 72 hrs.).

2. Polymicrobial bacteremia. Polymicrobial bacteremia will be defined as either growth of two or more different species of microorganisms in the same blood culture, or growth of different species in two or more separate blood cultures within the same episode.

3. Patients with prior bacteremia or infection that have not completed antimicrobial therapy for the previous infectious episode.

4. Patients with septic shock at the time of enrollment and randomization, defined as at least 2 measurements of systolic blood pressure < 90 mmHg and/or use of vasopressors (dopamine>15μg/kg/min, adrenalin>0.1μg/kg/min, noradrenalin>0.1μg/kg/min, vasopressin any dose) in the 12 hours prior to randomization. In the absence of the use of vasopressors, a systolic blood pressure <90 would need to represent a deviation for the patient's known normal blood pressure.

5. BSI due to specific infections known at the time of randomization:

   1. Endocarditis / endovascular infections
   2. Osteomyelitis (not resected)
   3. Central nervous system infections

6. Allergy to any of the study drugs confirmed by history taken by the investigator

7. Previous enrollment in this trial

8. Concurrent participation in another interventional clinical trial

9. Imminent death (researcher's assessment of expected death within 48 hrs. of recruitment)