printable versionBest anthrax treatment: rapid diagnosis, antibiotics
BY SARA SELIS
FBI agents check for anthrax contamination in 2001.
When spores sent through the mail in 2001 caused 11 people to contract anthrax—killing five of them—infectious disease experts noted that the death rate was substantially lower than the historical mortality rate, which approached 100 percent. Many assumed that access to modern intensive care units and more powerful antibiotics made the difference.
But after completing the most comprehensive review of anthrax cases ever conducted, researchers at the Veterans Affairs Palo Alto Health Care System and the School of Medicine have found that what most likely saved lives from the various anthrax mailings in September 2001 was not advanced hospital care: It was rapid diagnosis and antibiotic treatment in the first few days of symptoms.
The researchers found that once anthrax progresses to its advanced stage, typically four days after initial symptoms, patients are almost certain to die, even if they receive the best care modern medicine can offer. They also found that drainage of fluid from around the lungs is strongly associated with survival.
The study findings, published in the Feb. 21 issue of Annals of Internal Medicine, underscore the importance of detecting anthrax early, educating medical personnel about its symptoms and treatment and ensuring efficient distribution systems that can deliver antibiotics to patients within hours of a bioterrorist attack. The findings also indicate that bioterrorism response stockpiles should include ample supplies of chest tubes used to perform fluid drainage—an intervention that has received relatively little attention in bioterrorism planning.
"Even with our modern intensive care, once you've reached the advanced stage of this disease, you're probably going to die. That's why it's crucial to start antibiotics within the first few days," said lead author Jon-Erik Holty, MD, a fellow in pulmonary and critical-care medicine, who did the research during a fellowship at the VA-Palo Alto.
What makes early treatment so challenging is that anthrax is difficult to diagnose. Its early symptoms mimic the flu, and even in the later stages there is no quick, definitive test for it. For this reason, Holty said, "Doctors in the ER need to have a high degree of suspicion. They need to ask questions and notice patterns: Are a lot of patients getting flu symptoms in the summer? Is there a group of patients with these symptoms who were all in the same place?"
Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. "It's one of the main agents we're worried about for bioterrorism, because it's available, it can be weaponized and it can do a spectacular amount of damage in a short period of time," said study senior author Douglas Owens, MD, a senior investigator at the VA-Palo Alto and an associate professor of medicine at the Center for Health Policy/Center for Primary Care and Outcomes Research at Stanford. A few grams of anthrax spores could kill thousands of people within a week.
Anthrax progresses in two phases: the initial (prodomal) phase, lasting about four days, produces flu-like symptoms including cough, fever and chills; the advanced (fulminant) phase, causes respiratory distress and shock.
While previous studies have examined up to 40 anthrax cases, this one obtained reports of 82 confirmed cases of inhalational anthrax in 15 countries from 1900 to 2005. The researchers sought to determine how patient characteristics, type of treatment given and the timing of treatment affect the course of the disease. They also aimed to compare the 2001 cases with the previous ones.
The study found that the overall death rate was 85 percent, but for patients who progressed to the fulminant phase, it was 97 percent, even among those who received care in a hospital ICU.
Timely antibiotic treatment was the key to patients' survival. When antibiotics were begun within two days of initial symptoms, approximately 20 percent of patients died. When treatment was begun at four days, mortality was about 58 percent. At six days it was nearly 80 percent. Multi-drug regimens were found to be more effective than single-drug regimens. Among the anthrax patients who survived, 80 percent had fluid drained from around their lungs, a procedure known as pleural fluid drainage.
Comparing the 2001 anthrax cases with all others previously reported, researchers found that the 2001 patients were more likely to have started antibiotics during the prodromal phase, to have used multi-drug treatments and to have received pleural fluid drainage. Probably as a result, these patients were less likely to have progressed to the fulminant phase and to have died.