Sean Ong discusses how persistent fever beyond 72 hours emerges as a stronger predictor of mortality in MRSA bacteremia compared to CRP and WBC counts.
Sean Ong
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A post hoc analysis of the CAMERA2 randomized clinical trial has identified persistent fever after 72 hours as a key predictor of increased mortality in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. In contrast, white blood cell (WBC) count and C-reactive protein (CRP) levels did not show the same predictive value.
Published in Open Forum Infectious Diseases, the study analyzed 345 hospitalized patients with MRSA bacteremia, 18.3% of whom died within 90 days. Researchers found that fever (≥38°C) was strongly associated with increased odds of 90-day mortality, particularly starting on day 4 of illness, with the association becoming even stronger as the illness progressed. By day 7, the adjusted odds ratio for mortality was 8.78 (95% CI, 2.78–27.7) compared to 3.7 (95% CI, 1.58–8.67) on day 4. In contrast, CRP and WBC count did not demonstrate a consistent temporal relationship with mortality.
One of the study's authors, Sean Ong, an infectious diseases physician and joint PhD student at the University of Toronto and University of Melbourne, discussed why fever emerged as a more reliable predictor compared to WBC and CRP levels.
“Fever is likely to be a stronger predictor because it is more specific for non-resolving infection or ongoing source control issues,” Ong explained. “Our work shows that patients often defervesce rapidly within 2-3 days if correct treatment is instituted, so persistent fever is highly suggestive that there is an unresolved focus driving ongoing inflammation.”
Unlike fever, CRP and WBC levels are non-specific biomarkers that can remain elevated for extended periods, making them less reliable for monitoring treatment response. Ong further clarified, “WBC and CRP can remain persistently elevated for several days, often beyond a week, making them less reliable in assessing treatment response. We often see patients with persistently elevated WBC or CRP, even though their other clinical parameters are indicative of a good treatment response.”
The study's findings underline the importance of assessing persistent fever in patients with MRSA bacteremia. Ong stressed that fever beyond 72 hours should not be overlooked and should prompt clinicians to conduct a thorough investigation for unresolved sources of infection.
“Persistent fever beyond 72 hours should not be ignored, and a detailed search for ongoing source control issues should be undertaken,” Ong emphasized. He recommended a comprehensive approach, including history-taking, physical examination, and additional diagnostic tools such as echocardiography, CT, MRI, or PET/CT scans of suspicious areas.
Fever lasting beyond 72 hours is a stronger predictor of 90-day mortality in MRSA bacteremia patients than CRP and WBC counts.
Persistent fever suggests unresolved infections or ongoing source control issues, making it a more specific and reliable marker than CRP or WBC.
The findings emphasize the need for clinicians to prioritize persistent fever in risk stratification and consider personalized diagnostic and treatment strategies for MRSA bacteremia
Despite the significant findings, Ong acknowledged certain limitations of the study, including the smaller sample size for patients with available daily CRP or WBC readings. “This limited our ability to combine multiple variables together, such as temperature, CRP, and other patient factors like age and comorbidities,” he said. While he suggested that more sophisticated clinical prediction models could improve risk stratification, Ong cautioned that increased complexity could limit the applicability of these models in real-world clinical settings.
Looking ahead, Ong believes these findings could shape future guidelines for managing MRSA bacteremia. He advocates for a more individualized approach to treatment, which could refine risk stratification strategies.
“Future guidelines should integrate a risk stratification approach to managing patients with MRSA bacteremia, to permit an individualized approach to guide which patients should receive which diagnostic interventions,” Ong stated. He also raised the question of whether the current universal recommendation for echocardiography is necessary for all patients or if low-risk cases could safely omit this procedure.
Ultimately, the study highlights the need to enhance risk assessment tools for MRSA bacteremia. Fever should be prioritized as a key clinical marker, while additional biomarkers should be explored to improve patient stratification and guide treatment decisions.
