A large study of patients hospitalized for pneumonia suggests that a treatment strategy designed to account for patients with antibiotic-resistant infections should be reconsidered.
The study, published this week in the JAMA Internal Medicine, found that pneumonia patients who received empirical broad-spectrum antibiotics had a higher risk of death compared with those who received standard antibiotic therapy. They also had a higher risk of kidney injury, along with C. difficile and other secondary infections.
The authors of the study say the findings are a good example of how efforts to improve clinical outcomes for patients can sometimes lead clinicians to adopt practices that aren't backed by solid evidence. In the case of pneumonia, concerns about possible infection with resistant organisms like methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa has led to a strategy of early broad-spectrum antibiotics for certain patients.
"The underlying assumption of this approach is that the benefit of more potent antibiotics during the empirical phase exceeds the harms," they write. "Our study questions this assumption."
The strategy goes back to the 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America for treatment of adults who have community-acquired pneumonia (CAP). Those guidelines recommended that pneumonia patients who lived in nursing homes or had been in the hospital in the previous 90 days should be labeled as having healthcare-associated pneumonia (HCAP) and treated empirically with broad-spectrum antibiotics like vancomycin or piperacillin-tazobactam to cover for the possibility that the pneumonia was caused by MRSA or Pseudomonas.
Subsequently, a 2015 study of patients in the Department of Veterans Affairs (VA) healthcare system found that, after those guidelines were published, a substantial shift in treatment of CAP patients occurred, with the proportion of vancomycin prescribing rising from 16 percent in 2006 to 31 percent in 2010 and piperacillin-tazobactam prescribing jumping from 16 percent to 27 percent. This shift occurred even though less than 5 percent of patients in the study had resistant bacteria detected.
But it's unclear which patients, and how many, are benefiting from the use of more potent antibiotics.
To get a better sense of how empiric broad-spectrum therapy is affecting clinical outcomes in CAP patients, a team led by investigators from the VA Salt Lake City Health Care System and the University of Utah conducted a retrospective cohort study of all CAP hospitalizations in the VA health care system from 2008 through 2013.
They specifically looked at the 30-day mortality rate associated with three empirical treatment regimens: standard antibiotics alone, standard antibiotics plus anti-MRSA therapy, and anti-MRSA therapy without standard antibiotics. Secondary outcomes included development of kidney injury and secondary infections with C. difficile, vancomycin-resistant Enterococcus species, or gram-negative bacteria.
Of the 88,605 CAP patients analyzed in the study, empirical anti-MRSA antibiotics were administered to 33,632 (38 percent), with 13,528 receiving empirical anti-MRSA therapy with standard antibiotics and 20,104 receiving anti-MRSA therapy without standard antibiotics. The 30-day all-cause mortality rate was 10 percent (8,929 patients). Only 2 percent of the patients (2,154) had MRSA detected by clinical culture.
After adjusting for comorbidities and other patient characteristics that might affect treatment regimens and risk of 30-day mortality, the analysis found that empirical anti-MRSA treatment plus standard therapy was significantly associated with greater 30-day mortality compared with standard therapy alone, as was anti-MRSA treatment with non-standard therapy
