There was no difference in 90-day all-cause mortality in patients with methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) treated with cefazolin vs antistaphylococcal penicillins (ASP), according to study results published in Clinical Microbiology and Infection.

In this post hoc retrospective analysis of a prospective observational cohort study conducted at university hospitals in France, researchers compared 90-day mortality and other clinical outcomes among patients with MSSA IE treated with cefazolin vs ASP (oxacillin or cloxacillin).

Of the 210 patients (median age, 65 years; 72.9% men) included in the final analysis, 53 (25.2%) were in the cefazolin group and 157 (74.8%) were in the ASP group. There were no differences between the 2 groups in terms of demographics, comorbidities, site of endocarditis, existence of an IE-related lesion, initiation of treatment, and duration of treatment.

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At 90 days, there was no significant difference in all-cause mortality among patients in either treatment group (24.5% vs 28.7%; P =.561). After adjustment for potential confounding factors, 90-day all-cause mortality remained the same between the 2 groups (adjusted odds ratio [aOR], 1.2; 95% CI, 0.49-2.91; P =.681).

Similar to findings in the univariate analysis, multivariate analysis showed that the following factors were associated with significantly increased 90-day all-cause mortality:

  • Age (aOR, 1.06; 95% CI, 1.03-1.09; P <.001);
  • Charlson comorbidity index (aOR, 1.18; 95% CI, 1.02-1.36; P =.023);
  • Cerebral embolism (aOR, 2.83; 95% CI, 1.33-6.14; P =.007); and
  • Intensive care unit admission (aOR, 4.16; 95% CI, 1.89-9.59; P =.001).

Treatment outcomes between the 2 groups yielded no significant difference in terms of length of hospitalization, 90-day unplanned valvular operations, duration of bacteremia, development of embolic events, relapse, and 1-year all-cause mortality. There was a statistically significant increase in premature treatment discontinuation due to adverse events among patients in the ASP group compared with those in the cefazolin group (8.3% vs 0%; P =.042).

The study was limited by its small sample size, especially in the cefazolin group. In addition, cefazolin is currently not recommended as first-line treatment for patients with IE, and the researchers did not evaluate the frequency of the cefazolin inoculum effect.

Given the concerns about the use of cefazolin, “additional randomized interventional studies are needed to assess which antistaphylococcal β-lactam should be considered as a first-line antibiotic in IE,” concluded the researchers.


Lecomte R, Bourreau A, Deschanvres C, et al. Comparative outcomes of cefazolin versus antistaphylococcal penicillins in methicillin-susceptible Staphylococcus aureus infective endocarditis: a post hoc analysis of a prospective multicentre French cohort study. Clin Microbiol Infect. 2021;27(7):1015-1021. doi:10.1016/j.cmi.2020.08.044