Pilot RCT of Meropenem Versus Piperacillin-Tazobactam for Definitive Treatment of Bloodstream Infections Caused by AmpC Beta-lactamase Producing Enterobacter Spp., Citrobacter Freundii, Morganella Morganii, Providencia Spp. or Serratia Marcescens. in Low-risk Patients

HREC/14/QRBW/350

Infections of the blood are extremely serious and require intravenous antibiotic treatment. When the infection results from antibiotic resistant bacteria, the choice of antibiotic is an extremely important decision. Some types of bacteria produce enzymes that may inactivate essential antibiotics, related to penicillin, called 'beta-lactams'. Furthermore high level production of these enzymes can occur during therapy and lead to clinical failure, even when an antibiotic appears effective by laboratory testing. However, this risk of this occurring in clinical practice has only been well described in a limited range of antibiotic classes in a type of bacteria called Enterobacter. There is currently uncertainty as to whether a commonly used, and highly effective antibiotic, called piperacillin-tazobactam is subject to the same risk of resistance developing while on treatment. Infections caused by Enterobacter (and other bacteria with similar resistance mechanisms) are often treated with an alternative drug called meropenem (a carbapenem antibiotic), which is effective but has an extremely broad-spectrum of activity. Excessive use of carbapenems is driving further resistance to this antibiotic class - which represent our 'lastline' of antibiotic defence. As such, we need studies to help us see whether alternatives to meropenem are an effective and safe choice. No study has ever directly tested whether these two antibiotics have the same effectiveness for this type of infection. The purpose of this study is to randomly assign patients with blood infection caused by Enterobacter or related bacteria to either meropenem or piperacillin/tazobactam in order to test whether these antibiotics have similar effectiveness.

2015-04-01

2020-12-31

2020-12-31

Completed

Early phase I

100

Inclusion Criteria: * Bloodstream infection with Enterobacter spp., Serratia marcescens, Providencia spp., Morganella morganii or Citrobacter freundii (i.e. likely AmpC-producer), and susceptibility to 3rd generation cephalosporins (i.e. ceftriaxone, cefotaxime or ceftazidime), meropenem and piperacillin-tazobactam from at least one blood culture draw. This will be determined in accordance with laboratory methods and susceptibility breakpoints defined by protocols used in the recruiting site laboratories.. * No more than 72 hours has elapsed since the first positive blood culture collection. * Patient is aged 18 years and over (\>=21y in Singapore). Exclusion Criteria: 1. Patient not expected to survive more than 4 days 2. Patient allergic to a penicillin or a carbapenem 3. 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). 4. Treatment is not with the intent to cure the infection (that is, palliative care is an exclusion). 5. Pregnancy or breast-feeding. 6. Use of concomitant antimicrobials in the first 4 days after enrolment with known activity against Gram-negative bacilli (except trimethoprim/sulphamethoxazole may be continued as Pneumocystis prophylaxis). 7. Severe acute illness as defined by Pitt bacteraemia score of \>4 8. Likely source to be from (proven or suspected at the time of randomisation) the central nervous system, e.g. brain abscess, post-surgical meningitis, shunt infection (due to concerns over CNS penetration of piperacillin/tazobactam)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 100, 'type': 'ESTIMATED'}}

2023-05-10