Staphylococcus Aureus BacteremiaBACSAFONCT06695832
Adjunctive Fosfomycin for Treatment of Staphylococcus Aureus Bacteraemia
An observational study of Staphylococcus Aureus Bacteremia, run by Hospital Universitari de Bellvitge at 6 sites in 3 countries.
Trial summary
Staphylococcus aureus bacteraemia is a frequent and life-threatening infection, despite current standard antibiotic monotherapy. This study aims to clarify the role of fosfomycin as an adjunctive therapy for improving outcomes in patients with this serious infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Staphylococcus Aureus Bacteremia
- How many people
- 369 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 1 Nov 2024to 31 Jan 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: In the BACSARM trial, 155 adult patients with MRSA bacteraemia were randomised 1:1 to receive daptomycin in combination with fosfomycin or daptomycin alone. In the SAFO trial, 214 adult patients with MSSA bacteraemia were randomised 1:1 to receive cloxacillin in combination with fosfomycin or cloxacillin alone. As this is a pooled analysis of all SAB, all patients included in the intention-to-treat analysis of the BACSARM and SAFO trials will be included in the present study, regardless of their susceptibility to methicillin.
Who may be able to join
- All patients included in the BACSARM and SAFO clinical trials.
Who cannot join
- For both trials: polymicrobial bacteraemia, severe clinical status with expected survival < 24 hours, severe liver disease with Child-Pugh score class C, diagnosis of prosthetic infective endocarditis, allergy or known resistance to study drugs, pregnancy at the time of inclusion, inclusion in another clinical trial.
- For the BACSARM trial: diagnosis of MRSA pneumonia, prior history of eosinophilic pneumonia, use of additional antibiotic therapy with microbiological activity against MRSA.
- For the SAFO trial: prior history of myasthenia gravis, acute SARS-CoV2 infection.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Spain4 sites
Germans Trias i Pujol Research Institute and Hospital (IGTP)
Badalona, Catalonia, 08916
Hospital Clinic de Barcelona
Barcelona, Catalonia, 08036
Hospital de la Santa Creu i Sant Pau
Barcelona, Catalonia, 08041
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Australia1 site
The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity
Melbourne, Victoria, 3000
Canada1 site
Institute of Health Policy, Management and Evaluation, University of Toronto
Toronto, Ontario
About this study
Official title: Adjunctive Fosfomycin for Treatment of Staphylococcus Aureus Bacteraemia: Protocol for a Pooled Post-hoc Analysis of Two Randomised Clinical Trials
Staphylococcus aureus bacteraemia is a frequent and life-threatening infection, despite current standard antibiotic monotherapy. This study aims to clarify the role of fosfomycin as an adjunctive therapy for improving outcomes in patients with this serious infection. Two clinical trials suggested that adjunctive fosfomycin therapy might offer a clinical benefit in certain cases, but the results are inconclusive. We aim to analyse pooled data from these trials in order to identify subgroups of patients that might benefit most from this therapy.
Read the detailed description
Background. Improving outcomes in patients with methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus bacteraemia (SAB) is a critical healthcare goal. Two recent randomised clinical trials (RCTs), the BACSARM trial and the SAFO trial, assessed the efficacy of fosfomycin as an adjunctive therapy for MRSA and MSSA SAB respectively. Although neither trial demonstrated statistically significant differences in their primary endpoints of treatment success and reduced mortality respectively, both studies observed lower rates of persistent bacteraemia in the fosfomycin groups.
Methods. We will perform a post-hoc analysis of pooled individual patient data from the BACSARM and SAFO trials, which will be referred to as the BACSAFO study. The primary exposure of interest is fosfomycin adjunctive therapy, and the primary outcome will be treatment success at 8 weeks, defined as the patient being alive, without signs of relapse, and showing improvement in clinical signs and symptoms. We will use both Bayesian and frequentist methodologies: the Bayesian analysis will use a hierarchical Bayesian log-binomial model, while the frequentist analysis will apply a hierarchical log-binomial model. In addition, we will investigate whether adjunctive fosfomycin is particularly beneficial in specific patient subgroups (created according to age, methicillin resistance, place of acquisition, and complicated bacteraemia status).
Discussion. The BACSAFO study aims to clarify the role of fosfomycin as an adjunctive therapy for improving outcomes in SAB patients. Although previous trials have not demonstrated significant differences in the primary endpoints, the significant reductions in rates of persistent bacteraemia observed suggest that fosfomycin might offer a clinical benefit in certain cases. By analysing pooled data and attempting to identify subgroups that might benefit most, this study has the potential to refine treatment strategies and inform trial design and planning for future RCTs investigating combination antibiotic therapies for SAB.
- Conditions
- Staphylococcus Aureus Bacteremia
- Keywords
- Staphylococcus aureus bacteremia, Fosfomycin, Daptomycin, Cloxacillin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Adjunctive fosfomycin | All patients receiving adjunctive fosfomycin (the combination therapy group). | |
| Standard antibiotic monotherapy group | All patients not receiving fosfomycin, i.e., those receiving daptomycin alone for MRSA bacteraemia or cloxacillin alone for MSSA bacteraemia. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment success at 8 weeks from the time of randomisation
A composite outcome available from the information collected in both trials and based on the fulfilment of all the following criteria:
- Alive at week 8 from the time of randomisation.
- Absence of relapse within 8 weeks after randomisation, defined as isolation of S. aureus in blood cultures after the index blood cultures were cleared.
- Improvement of clinical signs and symptoms as assessed by investigators of the BACSARM and SAFO trials at week 8 from the time of randomisation.
Measured: 8 weeks from the time of randomisation
Secondary outcomes (3)
Persistent bacteraemia
Positive blood cultures for S. aureus at days 3 and 7 from the time of randomisation
Measured: At days 3 and 7 from the time of randomisation
Mortality at days 14, 30 and 60 from the time of randomisation
Mortality at days 14, 30 and 60 from the time of randomisation
Measured: Days 14, 30 and 60 from the time of randomisation
Adverse events leading to treatment discontinuation
Adverse events leading to treatment discontinuation during adjunctive fosfomycin therapy
Measured: During the time that adjunctive fosfomycin therapy was administered
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2024
- Study start1 Nov 2024
- Primary completion31 Jan 2025 (estimated)
- Study completion31 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Staphylococcus Aureus BacteremiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 369 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Universitari de Bellvitge
- Sponsor type
- University, hospital or other
- Collaborators
- Institut d'Investigació Biomèdica de Bellvitge
- Responsible party
- Principal investigator, Francesc Escrihuela-Vidal, Hospital Universitari de Bellvitge
- Investigators
- Jordi Carratalà, Medical Doctor, Principal investigator, Department of Infectious Diseases, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06695832
- Sponsor's protocol ID
- EOM033/24
- Acronym
- BACSAFO
- Status last verified
- Nov 2024
- First submitted
- 18 Nov 2024
- Last updated
- 22 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual data cannot be shared because of privacy restrictions. Raw anonymised data relating to primary and secondary outcomes and safety can be shared upon request to researchers who provide a methodologically reasonable proposal. The request for data can be sent to the corresponding author (J.C.). A period of 18 months after publication of the main study results should elapse before requests are made, so as to allow authors to publish substudies. Interested researchers must obtain the approval of the Bellvitge University Hospital Ethics Committee.
Publications
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. doi: 10.1016/0021-9681(87)90171-8.
PubMed 3558716Chow JW, Yu VL. Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents. 1999 Jan;11(1):7-12. doi: 10.1016/s0924-8579(98)00060-0.
PubMed 10075272Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials - a practical guide with flowcharts. BMC Med Res Methodol. 2017 Dec 6;17(1):162. doi: 10.1186/s12874-017-0442-1.
PubMed 29207961Grillo S, Pujol M, Miro JM, Lopez-Contreras J, Euba G, Gasch O, Boix-Palop L, Garcia-Pais MJ, Perez-Rodriguez MT, Gomez-Zorrilla S, Oriol I, Lopez-Cortes LE, Pedro-Botet ML, San-Juan R, Aguado JM, Gioia F, Iftimie S, Morata L, Jover-Saenz A, Garcia-Pardo G, Loeches B, Izquierdo-Cardenas A, Goikoetxea AJ, Gomila-Grange A, Dietl B, Berbel D, Videla S, Hereu P, Padulles A, Pallares N, Tebe C, Cuervo G, Carratala J; SAFO study group. Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial. Nat Med. 2023 Oct;29(10):2518-2525. doi: 10.1038/s41591-023-02569-0. Epub 2023 Oct 2.
PubMed 37783969Pujol M, Miro JM, Shaw E, Aguado JM, San-Juan R, Puig-Asensio M, Pigrau C, Calbo E, Montejo M, Rodriguez-Alvarez R, Garcia-Pais MJ, Pintado V, Escudero-Sanchez R, Lopez-Contreras J, Morata L, Montero M, Andres M, Pasquau J, Arenas MD, Padilla B, Murillas J, Jover-Saenz A, Lopez-Cortes LE, Garcia-Pardo G, Gasch O, Videla S, Hereu P, Tebe C, Pallares N, Sanllorente M, Dominguez MA, Camara J, Ferrer A, Padulles A, Cuervo G, Carratala J; MRSA Bacteremia (BACSARM) Trial Investigators. Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial. Clin Infect Dis. 2021 May 4;72(9):1517-1525. doi: 10.1093/cid/ciaa1081.
PubMed 32725216Garcia-de-la-Maria C, Gasch O, Castaneda X, Garcia-Gonzalez J, Soy D, Canas MA, Ambrosioni J, Almela M, Pericas JM, Tellez A, Falces C, Hernandez-Meneses M, Sandoval E, Quintana E, Vidal B, Tolosana JM, Fuster D, Llopis J, Moreno A, Marco F, Miro JM; Hospital Clinic Endocarditis Study Group. Cloxacillin or fosfomycin plus daptomycin combinations are more active than cloxacillin monotherapy or combined with gentamicin against MSSA in a rabbit model of experimental endocarditis. J Antimicrob Chemother. 2020 Dec 1;75(12):3586-3592. doi: 10.1093/jac/dkaa354.
PubMed 32853336Kastoris AC, Rafailidis PI, Vouloumanou EK, Gkegkes ID, Falagas ME. Synergy of fosfomycin with other antibiotics for Gram-positive and Gram-negative bacteria. Eur J Clin Pharmacol. 2010 Apr;66(4):359-68. doi: 10.1007/s00228-010-0794-5. Epub 2010 Feb 26.
PubMed 20186407Garcia-de-la-Maria C, Gasch O, Garcia-Gonzalez J, Soy D, Shaw E, Ambrosioni J, Almela M, Pericas JM, Tellez A, Falces C, Hernandez-Meneses M, Sandoval E, Quintana E, Vidal B, Tolosana JM, Fuster D, Llopis J, Pujol M, Moreno A, Marco F, Miro JM. The Combination of Daptomycin and Fosfomycin Has Synergistic, Potent, and Rapid Bactericidal Activity against Methicillin-Resistant Staphylococcus aureus in a Rabbit Model of Experimental Endocarditis. Antimicrob Agents Chemother. 2018 May 25;62(6):e02633-17. doi: 10.1128/AAC.02633-17. Print 2018 Jun.
PubMed 29610194Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4.
PubMed 21208910Paul M, Zemer-Wassercug N, Talker O, Lishtzinsky Y, Lev B, Samra Z, Leibovici L, Bishara J. Are all beta-lactams similarly effective in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia? Clin Microbiol Infect. 2011 Oct;17(10):1581-6. doi: 10.1111/j.1469-0691.2010.03425.x. Epub 2010 Dec 14.
PubMed 21073629GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. Lancet. 2024 Sep 28;404(10459):1199-1226. doi: 10.1016/S0140-6736(24)01867-1. Epub 2024 Sep 16.
PubMed 39299261Gasch O, Camoez M, Dominguez MA, Padilla B, Pintado V, Almirante B, Molina J, Lopez-Medrano F, Ruiz E, Martinez JA, Bereciartua E, Rodriguez-Lopez F, Fernandez-Mazarrasa C, Goenaga MA, Benito N, Rodriguez-Bano J, Espejo E, Pujol M; REIPI/GEIH Study Groups. Predictive factors for mortality in patients with methicillin-resistant Staphylococcus aureus bloodstream infection: impact on outcome of host, microorganism and therapy. Clin Microbiol Infect. 2013 Nov;19(11):1049-57. doi: 10.1111/1469-0691.12108. Epub 2013 Jan 17.
PubMed 23331461Kuehl R, Morata L, Boeing C, Subirana I, Seifert H, Rieg S, Kern WV, Kim HB, Kim ES, Liao CH, Tilley R, Lopez-Cortes LE, Llewelyn MJ, Fowler VG, Thwaites G, Cisneros JM, Scarborough M, Nsutebu E, Gurgui Ferrer M, Perez JL, Barlow G, Hopkins S, Ternavasio-de la Vega HG, Torok ME, Wilson P, Kaasch AJ, Soriano A; International Staphylococcus aureus collaboration study group and the ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis. Defining persistent Staphylococcus aureus bacteraemia: secondary analysis of a prospective cohort study. Lancet Infect Dis. 2020 Dec;20(12):1409-1417. doi: 10.1016/S1473-3099(20)30447-3. Epub 2020 Aug 4.
PubMed 32763194Minejima E, Mai N, Bui N, Mert M, Mack WJ, She RC, Nieberg P, Spellberg B, Wong-Beringer A. Defining the Breakpoint Duration of Staphylococcus aureus Bacteremia Predictive of Poor Outcomes. Clin Infect Dis. 2020 Feb 3;70(4):566-573. doi: 10.1093/cid/ciz257.
PubMed 30949675Inagaki K, Lucar J, Blackshear C, Hobbs CV. Methicillin-susceptible and Methicillin-resistant Staphylococcus aureus Bacteremia: Nationwide Estimates of 30-Day Readmission, In-hospital Mortality, Length of Stay, and Cost in the United States. Clin Infect Dis. 2019 Nov 27;69(12):2112-2118. doi: 10.1093/cid/ciz123.
PubMed 30753447
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Fosfomycin for Treatment of Staphylococcus Aureus Bacteraemia: Protocol for a Pooled Post-hoc Analysis of Two Randomised Clinical Trials
- ClinicalTrials.gov ID
- NCT06695832
- Acronym / sponsor ID
- BACSAFO / EOM033/24
- Conditions
- Staphylococcus Aureus Bacteremia
- Keywords
- Staphylococcus aureus bacteremia, Fosfomycin, Daptomycin, Cloxacillin
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 369 participants (actual)
- Lead sponsor
- Hospital Universitari de BellvitgeUniversity, hospital or other
- Collaborators
- Institut d'Investigació Biomèdica de Bellvitge
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 31 Jan 2025 (estimated)
- Study completion
- 31 Jan 2025 (estimated)
- First posted
- 19 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Staphylococcus aureus bacteraemia is a frequent and life-threatening infection, despite current standard antibiotic monotherapy. This study aims to clarify the role of fosfomycin as an adjunctive therapy for improving outcomes in patients with this serious infection. Two clinical trials suggested that adjunctive fosfomycin therapy might offer a clinical benefit in certain cases, but the results are inconclusive. We aim to analyse pooled data from these trials in order to identify subgroups of patients that might benefit most from this therapy.
Detailed description
Background. Improving outcomes in patients with methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus bacteraemia (SAB) is a critical healthcare goal. Two recent randomised clinical trials (RCTs), the BACSARM trial and the SAFO trial, assessed the efficacy of fosfomycin as an adjunctive therapy for MRSA and MSSA SAB respectively. Although neither trial demonstrated statistically significant differences in their primary endpoints of treatment success and reduced mortality respectively, both studies observed lower rates of persistent bacteraemia in the fosfomycin groups.
Methods. We will perform a post-hoc analysis of pooled individual patient data from the BACSARM and SAFO trials, which will be referred to as the BACSAFO study. The primary exposure of interest is fosfomycin adjunctive therapy, and the primary outcome will be treatment success at 8 weeks, defined as the patient being alive, without signs of relapse, and showing improvement in clinical signs and symptoms. We will use both Bayesian and frequentist methodologies: the Bayesian analysis will use a hierarchical Bayesian log-binomial model, while the frequentist analysis will apply a hierarchical log-binomial model. In addition, we will investigate whether adjunctive fosfomycin is particularly beneficial in specific patient subgroups (created according to age, methicillin resistance, place of acquisition, and complicated bacteraemia status).
Discussion. The BACSAFO study aims to clarify the role of fosfomycin as an adjunctive therapy for improving outcomes in SAB patients. Although previous trials have not demonstrated significant differences in the primary endpoints, the significant reductions in rates of persistent bacteraemia observed suggest that fosfomycin might offer a clinical benefit in certain cases. By analysing pooled data and attempting to identify subgroups that might benefit most, this study has the potential to refine treatment strategies and inform trial design and planning for future RCTs investigating combination antibiotic therapies for SAB.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adjunctive fosfomycin | – | –All patients receiving adjunctive fosfomycin (the combination therapy group). |
| Standard antibiotic monotherapy group | – | –All patients not receiving fosfomycin, i.e., those receiving daptomycin alone for MRSA bacteraemia or cloxacillin alone for MSSA bacteraemia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- In the BACSARM trial, 155 adult patients with MRSA bacteraemia were randomised 1:1 to receive daptomycin in combination with fosfomycin or daptomycin alone. In the SAFO trial, 214 adult patients with MSSA bacteraemia were randomised 1:1 to receive cloxacillin in combination with fosfomycin or cloxacillin alone. As this is a pooled analysis of all SAB, all patients included in the intention-to-treat analysis of the BACSARM and SAFO trials will be included in the present study, regardless of their susceptibility to methicillin.
Key inclusion criteria (1 listed)
- All patients included in the BACSARM and SAFO clinical trials.
Key exclusion criteria (3 listed)
- For both trials: polymicrobial bacteraemia, severe clinical status with expected survival < 24 hours, severe liver disease with Child-Pugh score class C, diagnosis of prosthetic infective endocarditis, allergy or known resistance to study drugs, pregnancy at the time of inclusion, inclusion in another clinical trial.
- For the BACSARM trial: diagnosis of MRSA pneumonia, prior history of eosinophilic pneumonia, use of additional antibiotic therapy with microbiological activity against MRSA.
- For the SAFO trial: prior history of myasthenia gravis, acute SARS-CoV2 infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Treatment success at 8 weeks from the time of randomisation
Time frame: 8 weeks from the time of randomisation
A composite outcome available from the information collected in both trials and based on the fulfilment of all the following criteria: * Alive at week 8 from the time of randomisation. * Absence of relapse within 8 weeks after randomisation, defined as isolation of S. aureus in blood cultures after the index blood cultures were cleared. * Improvement of clinical signs and symptoms as assessed by investigators of the BACSARM and SAFO trials at week 8 from the time of randomisation.
3 secondary outcomes
Persistent bacteraemia
Time frame: At days 3 and 7 from the time of randomisation
Mortality at days 14, 30 and 60 from the time of randomisation
Time frame: Days 14, 30 and 60 from the time of randomisation
Adverse events leading to treatment discontinuation
Time frame: During the time that adjunctive fosfomycin therapy was administered
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Background: PubMed 3558716Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. doi: 10.1016/0021-9681(87)90171-8.
- Background: PubMed 10075272Chow JW, Yu VL. Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents. 1999 Jan;11(1):7-12. doi: 10.1016/s0924-8579(98)00060-0.
- Background: PubMed 29207961Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials - a practical guide with flowcharts. BMC Med Res Methodol. 2017 Dec 6;17(1):162. doi: 10.1186/s12874-017-0442-1.
- Background: PubMed 37783969Grillo S, Pujol M, Miro JM, Lopez-Contreras J, Euba G, Gasch O, Boix-Palop L, Garcia-Pais MJ, Perez-Rodriguez MT, Gomez-Zorrilla S, Oriol I, Lopez-Cortes LE, Pedro-Botet ML, San-Juan R, Aguado JM, Gioia F, Iftimie S, Morata L, Jover-Saenz A, Garcia-Pardo G, Loeches B, Izquierdo-Cardenas A, Goikoetxea AJ, Gomila-Grange A, Dietl B, Berbel D, Videla S, Hereu P, Padulles A, Pallares N, Tebe C, Cuervo G, Carratala J; SAFO study group. Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial. Nat Med. 2023 Oct;29(10):2518-2525. doi: 10.1038/s41591-023-02569-0. Epub 2023 Oct 2.
- Background: PubMed 32725216Pujol M, Miro JM, Shaw E, Aguado JM, San-Juan R, Puig-Asensio M, Pigrau C, Calbo E, Montejo M, Rodriguez-Alvarez R, Garcia-Pais MJ, Pintado V, Escudero-Sanchez R, Lopez-Contreras J, Morata L, Montero M, Andres M, Pasquau J, Arenas MD, Padilla B, Murillas J, Jover-Saenz A, Lopez-Cortes LE, Garcia-Pardo G, Gasch O, Videla S, Hereu P, Tebe C, Pallares N, Sanllorente M, Dominguez MA, Camara J, Ferrer A, Padulles A, Cuervo G, Carratala J; MRSA Bacteremia (BACSARM) Trial Investigators. Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial. Clin Infect Dis. 2021 May 4;72(9):1517-1525. doi: 10.1093/cid/ciaa1081.
- Background: PubMed 32853336Garcia-de-la-Maria C, Gasch O, Castaneda X, Garcia-Gonzalez J, Soy D, Canas MA, Ambrosioni J, Almela M, Pericas JM, Tellez A, Falces C, Hernandez-Meneses M, Sandoval E, Quintana E, Vidal B, Tolosana JM, Fuster D, Llopis J, Moreno A, Marco F, Miro JM; Hospital Clinic Endocarditis Study Group. Cloxacillin or fosfomycin plus daptomycin combinations are more active than cloxacillin monotherapy or combined with gentamicin against MSSA in a rabbit model of experimental endocarditis. J Antimicrob Chemother. 2020 Dec 1;75(12):3586-3592. doi: 10.1093/jac/dkaa354.
- Background: PubMed 20186407Kastoris AC, Rafailidis PI, Vouloumanou EK, Gkegkes ID, Falagas ME. Synergy of fosfomycin with other antibiotics for Gram-positive and Gram-negative bacteria. Eur J Clin Pharmacol. 2010 Apr;66(4):359-68. doi: 10.1007/s00228-010-0794-5. Epub 2010 Feb 26.
- Background: PubMed 29610194Garcia-de-la-Maria C, Gasch O, Garcia-Gonzalez J, Soy D, Shaw E, Ambrosioni J, Almela M, Pericas JM, Tellez A, Falces C, Hernandez-Meneses M, Sandoval E, Quintana E, Vidal B, Tolosana JM, Fuster D, Llopis J, Pujol M, Moreno A, Marco F, Miro JM. The Combination of Daptomycin and Fosfomycin Has Synergistic, Potent, and Rapid Bactericidal Activity against Methicillin-Resistant Staphylococcus aureus in a Rabbit Model of Experimental Endocarditis. Antimicrob Agents Chemother. 2018 May 25;62(6):e02633-17. doi: 10.1128/AAC.02633-17. Print 2018 Jun.
- Background: PubMed 21208910Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4.
- Background: PubMed 21073629Paul M, Zemer-Wassercug N, Talker O, Lishtzinsky Y, Lev B, Samra Z, Leibovici L, Bishara J. Are all beta-lactams similarly effective in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia? Clin Microbiol Infect. 2011 Oct;17(10):1581-6. doi: 10.1111/j.1469-0691.2010.03425.x. Epub 2010 Dec 14.
- Background: PubMed 39299261GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. Lancet. 2024 Sep 28;404(10459):1199-1226. doi: 10.1016/S0140-6736(24)01867-1. Epub 2024 Sep 16.
- Background: PubMed 23331461Gasch O, Camoez M, Dominguez MA, Padilla B, Pintado V, Almirante B, Molina J, Lopez-Medrano F, Ruiz E, Martinez JA, Bereciartua E, Rodriguez-Lopez F, Fernandez-Mazarrasa C, Goenaga MA, Benito N, Rodriguez-Bano J, Espejo E, Pujol M; REIPI/GEIH Study Groups. Predictive factors for mortality in patients with methicillin-resistant Staphylococcus aureus bloodstream infection: impact on outcome of host, microorganism and therapy. Clin Microbiol Infect. 2013 Nov;19(11):1049-57. doi: 10.1111/1469-0691.12108. Epub 2013 Jan 17.
- Individual participant dataSharing planned: Yes. Individual data cannot be shared because of privacy restrictions. Raw anonymised data relating to primary and secondary outcomes and safety can be shared upon request to researchers who provide a methodologically reasonable proposal. The request for data can be sent to the corresponding author (J.C.). A period of 18 months after publication of the main study results should elapse before requests are made, so as to allow authors to publish substudies. Interested researchers must obtain the approval of the Bellvitge University Hospital Ethics Committee.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jordi Carratalà, Medical Doctor principal investigator
Department of Infectious Diseases, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Staphylococcus Aureus Bacteremia, run by Hospital Universitari de Bellvitge at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Spain, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment success at 8 weeks from the time of randomisation (time frame: 8 weeks from the time of randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06695832, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2024.