USC Research Finds Persistent Growth of Staph in Bloodstream for Three Days or Longer Portends Poor Outcomes

A new USC study shows that staph bloodstream infections persisting for three days or more after treatment started mark a significant risk for complications, prolonged hospitalization and death, underscoring the need for future studies to find diagnostic biomarkers and new treatment strategies.

More people die from Staphylococcus aureus (S. aureus) bloodstream infections each year than from AIDS, tuberculosis and hepatitis combined. Like those diseases, S. aureus can be successfully treated, but a significant proportion of patients have persistent growth of the bacterium in their blood for days despite receiving standard antibiotic treatment. Controversy exists as to how long is too long before clinicians need to alter management approach.

New research from a team led by USC School of Pharmacy faculty members Emi Minejima and Annie Wong-Beringer may clarify that debate. The investigators conducted the largest study to date comparing risk factors and outcomes by duration of S. aureus in the blood among 884 hospitalized adults. Their findings challenged the Infectious Diseases Society of America’s current guidelines, which call for alternative management if blood cultures remain positive for staph up to seven days.

“We found that three days of persistent bacteria in the blood was the most significant duration to differentiate survival versus death,” says Wong-Beringer, professor of clinical pharmacy and associate dean for research and graduate education. “Each day of persistent growth of S. aureus in the bloodstream past the initial blood culture was associated with a 16 percent increase in the risk of death.”

Source Control Matters

Importantly, the research found that source control — procedures performed to remove an infected catheter or device or to drain an abscess, undertaken to eliminate the source of infection — is more important than which specific antibiotics are used as long as the antibiotics are active against the infected bacterium.

“For too long, the guidelines and physicians in practice have focused on trying to tweak antibiotic regimens, hoping one regimen might be magically better at improving outcomes than others,” says co-author Brad Spellberg, infectious diseases specialist and chief medical officer of Los Angeles County+USC (LAC+USC) Medical Center. “But what this study finds is that the key is source control, not which antibiotics are used.”

With the largest study populations of its kind, the research spanned three university-affiliated medical centers to focus on 884 adult patients with S. aureus. Patients were grouped by whether the infection’s duration was considered short (up to two days), intermediate (three to seven days) or prolonged (more than seven days).

According to the authors, the study findings led to new hypotheses that differences in underlying biology of the infected host and/or virulence of the bacterial strain may contribute to persistent growth of the bacterium in the blood. Current research in the Wong-Beringer Lab is directed at elucidating the contribution of host immune response and virulence of the bacterial strain to persistent growth of staph in the bloodstream of infected patients. Until new biological targets to improve treatment success are identified, these findings support the use of bacterial clearance from blood by day three as an important target to prompt clinicians to search for and remove the source of infection.

“Prospective clinical trials on antibiotic treatment of staph bloodstream infection should consider clearance of blood by day three as an important study endpoint,” says Minejima, lead author and assistant professor of clinical pharmacy.

The study has vast potential ramifications. Each day about 1 in 31 hospital patients suffers a healthcare-associated infection, according to the Centers for Disease Control and Prevention. Among those at greater risk are people with weakened immune systems or who have undergone certain medical procedures or have intravenous lines or other medical devices inserted in their bodies.

The study’s authors are affiliated with the USC School of Pharmacy, LAC+USC Medical Center, Keck School of Medicine at USC, and Huntington Hospital’s departments of Medicine-Infectious Diseases, Pharmacy, and Clinical Laboratory.

USC’s Wong-Beringer is the senior and corresponding author of the study. Other authors include Emi Minejima, Nikki Mai, Nancy Bui, Melissa Mert, Wendy Mack, Rosemary C. She, Paul Nieberg and Brad Spellberg of LAC+USC.

The study was supported by National Institutes of Health/National Center for Advancing Translational Science grants (UL1TR001855, UL1TR000130) and by the USC School of Pharmacy. Technical support was provided by Huntington Hospital, LAC+USC Medical Center and Keck Hospital of USC.