A release from the academy explains that delirium causes mental confusion that may be accompanied by hallucinations and agitation. Medications are often the cause of delirium, but antibiotics are not necessarily the first medications doctors may suspect.

The release quotes author Shamik Bhattacharyya, MD, of Harvard Medical School and Brigham and Women’s Hospital in Boston, Mass., and a member of the American Academy of Neurology, as saying, “People who have delirium are more likely to have other complications, go into a nursing home instead of going home after being in the hospital and are more likely to die than people who do not develop delirium. Any efforts we can make to help identify the cause of delirium have the potential to be greatly beneficial.”

For the study, researchers reviewed all available scientific reports and found case reports on 391 patients, over seven decades, who were given antibiotics and later developed delirium and other brain problems. A total of 54 different antibiotics were involved, from 12 different classes of antibiotics ranging from commonly used antibiotics such as sulfonamides and ciprofloxacin to intravenous antibiotics such as cefepime and penicillin.

About 47 percent had delusions or hallucinations, 14 percent had seizures, 15 percent had involuntary muscle twitching and 5 percent had loss of control of body movements. Plus, EEG, a test that detects electrical activity in the brain, was abnormal in 70 percent of the cases. 25 percent of the people who developed delirium had kidney failure.

The researchers identified three types of delirium and other brain problems related to antibiotics.

Type 1 was characterized by seizures and most often associated with penicillin and cephalosporins. Type 2 was marked by symptoms of psychosis and associated with procaine penicillin, sulfonamides, fluoroquinolones and macrolides. Both Type 1 and Type 2 had a quick onset of symptoms, within days. Once antibiotics were stopped, symptoms also stopped within days.

Type 3 was characterized by abnormal brain scans and impaired muscle coordination and other signs of brain dysfunction, and was only associated with the drug metronidazole. The beginning of noticeable symptoms took weeks instead of days. Symptoms also took longer to go away once the antibiotic was stopped.

Bhattacharyya noted that all of the patients had an active infection that could not be ruled out as the cause of the delirium and other brain problems. A scale used to determine whether side effects can be attributed to a drug found that the association was possible in most cases. When infections that affected the central nervous system were not included, the association was probable.

“More research is needed, but these antibiotics should be considered as a possible cause of delirium,” said Bhattacharyya. “Recognition of different patterns of toxicity could lead to a quicker diagnosis and hopefully prevent of some of the negative consequences for people with delirium and other brain problems.”

A release from Johns Hopkins quotes one of the study’s authors, Robert Stevens, M.D., a specialist in critical care and an associate professor at the Johns Hopkins University School of Medicine, as saying, “Every patient who develops delirium will on average remain in the hospital at least one day longer. if you’re admitted to the intensive care unit and you develop brain dysfunction, your risk of not surviving your hospital stay is doubled.”

The release notes that physicians and nurses working in intensive care have long been aware that a significant percentage of their patients develop delirium, a type of brain dysfunction characterized by a sudden onset, fluctuating symptoms, inattention, and confusion. However, this study establishes the most definitive link between delirium in the ICU and poor outcomes.

Stevens led an interdisciplinary team of colleagues who sifted through 10,000 published reports before selecting 42 studies that met their specific criteria. For instance, they weeded out any studies that included patients with head injuries, strokes or other neurological disorders to obtain a more precise estimate of delirium in ICU patients. That left Stevens and his team with 16,595 patients, of which 5,280 — or 32 percent — had confirmed cases of delirium as measured by established screening protocols. They conducted a meta-analysis, which found that delirium was associated with a twofold increase in hospital mortality even after adjusting for severity of illness.

One of the best known causes of delirium is medications given to ICU patients, such as sedatives. For instance, benzodiazepine, which is commonly administered to patients to help them calm down and sleep, may paradoxically lead to disorientation and confusion. The goal moving forward, Stevens says, should be to reduce or eliminate the use of such potentially harmful medications, particularly among higher risk populations, such as the elderly and individuals with dementia. Nighttime interruptions should also be kept to a minimum to ensure that patients get a good night’s rest without sedatives.

Other causes of delirium, however, might be harder to address. According to the inflammatory hypothesis, illnesses occurring outside the brain, such as severe pneumonia, can lead secondarily to inflammation in the brain. Another theory posits that delirium is linked to changes in the flow of blood to the brain, sometimes resulting in strokes that are not recognized as such. Intriguingly, Stevens’ review also showed that among patients who develop delirium, the risk of long-term cognitive decline increases by 20 to 30 percent.

“We’re seeing that even though you may have a very severe illness or injury and you’re lucky enough to survive, you’re still not quite out of the woods,” Stevens says. “We need to think about the measures we can put into place to decrease these long-term burdens.”