The high cost of failed empiric drug therapy

The high cost of failed empiric drug therapy

Even complicated skin infections turn deadly

Failure of initial antibiotic therapy is a well-known cause of morbidity and mortality in infections such as ventilator-associated pneumonia. However, the damage doesn’t stop there. Inappropriate antibiotic empiric therapy can be a surprisingly costly — and sometimes deadly — consequence even for less serious infections.

For example, the failure of initial intravenous antibiotic therapy in hospital patients with complicated skin and skin-structure infections (cSSSIs) may cost the U.S. health care system more than $800 million each year and result in increased patient deaths, says David J. Weber, MD, medical director of hospital epidemiology for the University of North Carolina Health Care System in Chapel Hill. Weber estimates that more than 168,000 patients each year may fail the initial regular course of treatment for cSSSIs.

More than 700,000 patients are hospitalized annually in the United States with a primary diagnosis of cSSSI. Initial IV antibiotic therapy for these patients often is the regular course of treatment.

"Our study looked at something that does not lead to many deaths — skin and soft tissue infections — but we did show an increase in survival," he says. "The mortality rate for patients with appropriate initial therapy was .4%. However, fatal infections rose to 1.2% if the initial regimen was wrong. "They may not sound like much, it’s only .8%," he says. "But approximately 700,000 people are admitted each year with this infection in the United States."

Indeed, patients experiencing initial antibiotic treatment failure were three times more likely to die in the hospital than patients whose therapy did not fail. In addition, the patients whose therapy failed required hospitalization for twice the length of stay as the other patients, or an additional 4.3 days of antibiotic therapy and hospitalization.

The additional antibiotic therapy also resulted in a doubling of the cost of the patients’ treatment, or an additional $4,778 in inpatient charges. "The results of this study are alarming," Weber says. "They clearly demonstrate the harmful consequences of not selecting the right antibiotic for patients presenting with these serious infections."

Why is failed empiric therapy a continuing problem? One explanation is that physicians are not aware of the drug susceptibility profiles of pathogens in their own communities.

"It’s not like lung cancer," Webber says. "We don’t treat lung cancer different in San Francisco and New Orleans. You need to know your own community’s and institution’s organisms and what the susceptibilities are. It’s a little harder to apply [general prescribing] rules. You may be in a city where 40% of the skin and soft tissue [infections] are community-associated methicillin-resistant Staphylococcus aureus. Another place a few miles away may have only a 5% [proportion of MRSA infections]."

Diagnostic tests may not be available, meaning a built-in lag of several days waiting for culture results. In addition to new antibiotics coming on-line, infectious disease physicians must be aware of which old drugs are losing efficacy, he adds.

"The bugs develop resistance, so what you were using 15 years ago may be totally wrong now," he says. "It’s complicated. There are a lot of different drugs and a lot of different combinations. I’m continually amazed when you look at the list of what people are actually using, how many times people are giving drugs that truly aren’t the right drug for that syndrome or using multiple drugs that are overlapping in their efficacy and do not make sense to combine."

The large, multi-hospital study found that 24% of the 23,846 patients studied experienced failure of their initial IV antibiotic therapy. Webber presented the data recently in San Francisco at the 2005 Meeting of the Infectious Disease Society of America.

"This study demonstrates the need within the medical community for additional antibiotic therapy options for treating complicated skin infections," he says. "Physicians need antibiotics that provide coverage for a broad spectrum of infections in order to ensure better patient outcomes."

Patients in the study were treated primarily for cellulitis or post-operative wound infections and received either cefazolin, vancomycin, ampicillin-sulbactam, ceftriaxone, or vancomycin and piperacillin-tazobactam as initial therapy. Initial therapy failure occurred if a patient received any other IV antibiotics on the third day in the hospital or any day thereafter, or if the patient underwent drainage-debridement on the third day in the hospital or any day thereafter.