No randomised controlled trials (RCTs) have yet been performed comparing different treatment options for AmpC or ESBL-producing Enterobacteriaceae. During the last 10 years we have seen an exponentially increasing rate of carbapenem resistance worldwide. We need data from well-designed RCTs to guide clinicians in the treatment of antibiotic resistant Gram-negative infections. We face a situation where a commonly used antibiotic for these infections (meropenem) may be driving carbapenem resistance. For this reason, we are seeking to compare a carbapenem-sparing regimen with a carbapenem for the treatment of these infections.
The study is a multi-centre study. The study population will be drawn from any patient admitted to hospital with a blood culture positive for third generation cephalosporin non-susceptible E. coli or Klebsiella. There will be no restrictions on race, gender or ethnicity. Minors (aged <18y) have been excluded both to simplify the consent procedure and since the response to infection in children may be different than in adults (for instance, shorter duration of therapy is commonly used).
Eligible patients will be identified by liaison with the microbiology laboratory. A research team member will call the microbiology laboratory on a daily basis to identify any patient above 18 years of age who has blood culture positive for third generation cephalosporin non-susceptible E. coli or Klebsiella .
a. Bloodstream infection with E. coli or Klebsiella spp. with proven non-susceptibility to third generation cephalosporins and susceptibility to meropenem and piperacillin-tazobactam from at least one blood culture draw.
b. No more than 72 hours has elapsed since the first positive blood culture collection.
c. Patient is aged 18 years and over
d. The patient or approved proxy is able to provide informed consent
a. Patient not expected to survive more than 4 days
b. Patient allergic to a penicillin or a carbapenem
c. Patient with significant polymicrobial bacteraemia (that is, a Gram positive skin contaminant in one set of blood cultures is not regarded as significant polymicrobial bacteraemia).
d. Treatment is not with the intent to cure the infection (that is, palliative care is an exclusion).
e. Pregnancy or breast-feeding.
f. Use of concomitant antimicrobials in the first 4 days after enrolment with known activity against Gram-negative bacilli