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Antistaphylococcal penicillins vs. cefazolin in the treatment of methicillin-susceptible Staphylococcus aureus infective endocarditis: a quasi-experimental monocentre study

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Abstract

Whether cefazolin is as effective and safer than antistaphylococcal penicillins (ASPs) for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) is still debated in the absence of a randomized controlled trial. In this quasi-experimental study, we aimed to assess the effectiveness and safety of these two treatments in MSSA-IE, using the ASPs nationwide shortage in April 2016 as a unique opportunity to overcome the indication bias associated with observational studies. In this single-centre study, we compared patients with Duke-Li definite MSSA-IE treated with ASPs from January 2015 to March 2016 versus those treated with cefazolin from April 2016 to December 2018, when ASPs were not available. Effectiveness outcome was 90-day all-cause mortality. Safety outcomes included significant decrease in GFR and significant increase in serum liver enzymes. Logrank test was used to compare survival rates. Of 73 patients with MSSA-IE, 35 and 38 were treated with ASPs and cefazolin, respectively. Baseline patients’ characteristics (demography, native or prosthetic valve IE, clinical characteristics, cardiac and septic complications) were similar between groups. Ninety-day all-cause mortality was 28.6% and 21.1%, in patients treated with ASPs and cefazolin, respectively (logrank p = 0.5727). There was no difference between groups for incident renal or liver toxicity events: acute kidney injury 45.7% vs. 44.7% (p = 0.933), increased ALT 5.7% vs. 13.2% (p = 0.432), bilirubin increase 5.7% vs. 10.5% (p = 0.676), in ASPs vs. cefazolin groups, respectively. In this quasi-experimental, effectiveness and safety did not statistically differ between ASPs and cefazolin for MSSA-IE treatment.

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Data and materials availability

The datasets generated during and/or analysed during the current study are not publicly available due to restrictions by the French law, but are available from the last author on reasonable request at the following email address: n.agrinier@chru-nancy.fr.

Code availability

Not applicable.

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Acknowledgements

We would like to acknowledge the entire ObservatoireEI team.

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Authors and Affiliations

  1. Infectious and Tropical Diseases, CHRU-Nancy, Université de Lorraine, 54000, Nancy, France

    B. Lefèvre, B. Hoen, F. Goehringer, E. Jeanmaire & S. Hénard

  2. APEMAC, Université de Lorraine, 54000, Nancy, France

    B. Lefèvre & N. Agrinier

  3. Service Maladies Infectieuses Et Tropicales, Bâtiment Des Spécialités Médicales, Hôpitaux de Brabois, Centre Hospitalier Régional Universitaire de Nancy, Route de Morvan, 54511, Vandœuvre-Lès-Nancy Cedex, France

    B. Lefèvre

  4. INSERM, CIC-EC, Epidémiologie clinique, CHRU-Nancy, 54000, Nancy, France

    W. Ngueyon Sime & N. Agrinier

  5. Service de Microbiologie, CHRU-Nancy, 54000, Nancy, France

    N. Aissa & C. Alauzet

  6. SIMPA, Université de Lorraine, 54000, Nancy, France

    C. Alauzet

  7. Cardiology, CHRU-Nancy, 54000, Nancy, France

    L. Filippetti & C. Selton-Suty

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for AEPEI study group (Association pour l’Etude et la Prévention de l’Endocardite Infectieuse)

Contributions

Personal contribution for the conception and design of the study (BL, BH, FG, NAg), acquisition of data (BL, BH, FG, NA, CA, EJ, SH, LF, CSS), analysis and interpretation of data (BL, BH, WNS, NAg), drafting the article or revising it critically for important intellectual content (BL, BH, WNS, NAg) and final approval of the version to be submitted (BL, BH, FG, NA, WNS, NA, CA, EJ, SH, LF, CSS, NAg).

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Correspondence to B. Lefèvre.

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This study complies with the principles outlined in the Declaration of Helsinki. ObservatoireEI (NCT03272724) was authorized by the Commission Nationale de l’Informatique et des Libertés (CNIL).

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Patients were informed of the study and individual consent was waived, in accordance with French legal standards.

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Lefèvre, B., Hoen, B., Goehringer, F. et al. Antistaphylococcal penicillins vs. cefazolin in the treatment of methicillin-susceptible Staphylococcus aureus infective endocarditis: a quasi-experimental monocentre study. Eur J Clin Microbiol Infect Dis 40, 2605–2616 (2021). https://doi.org/10.1007/s10096-021-04313-3

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