Penicillin Against Flucloxacillin Treatment Evaluation

• Status: Unknown status
• Trial end date: 2020-07-01
• Target enrollment: 0
• Participant gender: All

Summary

There is theroretical superiority with benzylpenicillin over orther anti-staphylococcal penicillins (ASP) for treatment of penicillin susceptible S. aureus (PSSA) infections due to a lower MIC distribution when compared with ASPs active against PSSA, combined with the ability to obtain higher levels of free non-protein-bound plasma drug concentrations. Although the data to support this theoretical advantage is limited, many clinicians in Australia (and worldwide) use benzylpenicillin for therapy in this situation despite many international guidelines cautioning against this. This uncertainty is significant given that 1) S. aureus bacteraemia (SAB) is associated with a high mortality and significant morbidity, 2) S. aureus is one of the most common organisms isolated from blood cultures, 3) SAB is the most common reason for consultation with an Infectious Disease specialist (which itself has been shown to improve outcomes) and 4) a significant proportion (up to 20%) of SAB isolates in Australia will be reported as susceptible to penicillin, a proportion which appears to be increasing over the past 10 years in Australia and internationally.

Given the frequency of PSSA and the associated morbidity and mortality related to SABs in general, a definitive study to determine the optimal therapy for PSSA is required. In a recent survey of Infectious Diseases Physicians and Clinical Microbiologists in Australasia, 87% of respondents were willing to randomise patients to either benzylpenicillin or flucloxacillin for a clinical trial, whist 71% responded that they would switch therapy from flucloxacillin to benzylpenicillin for treatment of PSSA BSIs in clinical practice (unpublished data).

Therefore, the investigators see the opportunity to determine the feasibility of a definitive study comparing benzylpenicillin against flucloxacillin (or other ASP) for treatment of PSSA bloodstream infections.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The University of Queensland
• Treatments: Floxacillin; Penicillin G; Penicillin G Benzathine; Penicillin G Procaine; Penicillins

Criteria

Inclusion Criteria:

• Bloodstream infection with Staphylococcus aureus susceptible to penicillin and negative for penicillinase by phenotypic methods.

• No more than 72 hours has elapsed since the first positive blood culture was drawn

• Patient is aged 18 years and over

• The patient or approved proxy is able to provide informed consent

Exclusion Criteria:

• Patient with a recorded allergy to penicillin including:

1. Hypersensitivity type reaction

2. Stephens-Johnson syndrome

3. Rash

4. Urticaria

• Contraindications based upon other recorded allergies, such as gastrointestinal upset, will be at the discretion of the treating clinician

• Patient with significant polymicrobial bacteraemia (skin contaminants excepted)

• Treated with non-curative intent

• Pregnancy or breast-feeding

• Patient currently receiving concomitant antimicrobials with activity against S. aureus which cannot be ceased or substituted.