Comparison of Cloxacillin and Benzylpenicillin in Penicillin Susceptible S. Aureus Bacteraemia

Phase 4

Recruiting

• Conditions: Staphylococcus Aureus Bacteraemia; Staphylococcal Bacteraemia; Staphylococcus Aureus Bloodstream Infections (BSI; Bacteremia); Staphylococcus (S.) Aureus Infection
• Interventions: Drug: Penicillin G_1200mg; Drug: cloxacillin

• Registration Number: NCT06726395
• Lead Sponsor: Region Skane

Brief Summary

The goal of this study is to investigate if benzylpenicillin is a better treatment option than cloxacillin in patients with penicillin-susceptible Staphylococcus aureus bacteraemia.

Detailed Description

The overall research idea of is a RCT is to test the hypothesis that benzylpenicillin is superior to cloxacillin in the treatment of PSSA bacteraemia.

Population: Adult patients (\>18 years) with PSSA bacteraemia will be eligible for enrolment in the study. Exclusion criteria are allergy to penicillin, inability to give informed consent, and concomitant growth of other clinically significant bacteria in blood cultures. We are planning a nation-wide study.

Intervention: Benzylpenicillin treatment of PSSA bacteraemia will be evaluated. As soon as S. aureus has been identified in blood cultures and the susceptibility testing indicates penicillin susceptibility (Two-three days from start of treatment), patients will be randomized to continue therapy with either cloxacillin or benzylpenicillin. The duration of treatment depends on the type of infection, and details about length of therapy and dosage will be decided by the specific patient diagnosis (i.e., endocarditis, arthritis). Repeated blood cultures and echocardiography are important in the diagnostic work-up of S. aureus bacteraemia and will be included in the study protocol. Patients will also be monitored regarding adverse events, such as liver and renal impairment, rash, diarrhoea, thrombophlebitis et c., and treatment failure, relapse, and mortality.

Control: The study drug (benzylpenicillin) will be compared to cloxacillin, which is the current drug of choice for methicillin susceptible S. aureus in Sweden. Both drugs will be used at clinically recommended doses, with appropriate adjustments for renal impairment if needed. Outcome: Primary outcome is; to be alive for 90 days without any complications. Complications are defined as having any of relapse (90 days after antibiotic finished), need of change or addition of antibiotics due to side effects or treatment failure or adverse events.

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-26
• Study First Submitted QC: 2024-12-05
• Study First Posted: 2024-12-10
• Study Start: 2025-03-10
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-12
• Primary Completion: 2028-04
• Study Completion: 2028-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

Aged ≥18 with penicillin susceptible S. aureus bacteraemia (PSSA), and able to provide written informed consent.

Exclusion Criteria

• allergy to penicillin,

• inability to give informed consent,

• concomitant growth of other clinically significant bacteria in blood cultures

• neutropenia

  -≥ 96h with prior antibiotics

• When the per oral follow up medication can not be flukloxacillin or penicillinV/Amoxicillin (ie prosthetic joint infection)

• Patients in terminal palliation, where death is expected within 7 days.

• Where the treating physician believes cloxacillin is not a first-line treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Benzylpenicillin treatment	Penicillin G_1200mg	-
cloxacillin	cloxacillin	-

Primary Outcome Measures

Name	Time	Method
Survival at 90 days without any treatment complications	From enrollment to 90 days after end of treatment	Complications are defined as having any of; relapse within 90 days after treatment finish, need of change or addition of antibiotics due to side effects or treatment failure or adverse events.

Secondary Outcome Measures

Name	Time	Method
Mortality at 90 days	From enrollment to 90 days after end of treatment	All cause mortality within 90 days from enrollment
Relapse 90 days after end of treatment	From enrollment to 90 days after end of treatment	Relapse with positive culturing from sterile sites or high suscpition of clinical relapse
Cumulative frequency of side effects within 90 days	From enrollment until 90 days.	all side effects registered as a cumulative frequence
Cumulative frequence of change or addition of antibiotic treatment due to sideeffects or treatment failure	from enrollment to end of treatment duration up to 90 days	Every time additional antibiotics or change in antibiotic treatment is made due to either side effects or treatment failure (according to treating doctor)
Decrease of Bacterial DNA in blood samples	From enrollment and first 5 days	Bacterial DNA tested the first 5 days during study treatment.

Trial Locations

Locations (1)

Skånes universitetssjukhus, Region Skåne; 🇸🇪 Lund, Sweden