Which Antibiotics Are Most Associated With Encephalopathy?

Antibiotics remain an underdiagnosed cause of encephalopathy
Antibiotics remain an underdiagnosed cause of encephalopathy

VANCOUVER, BC—The "most comprehensive clinical description of antibiotic-associated encephalopathy" has found that "different antibiotics likely have varying patterns of toxicity," a review presented at the 68th AAN Annual Meeting has found.

"Antibiotics are an underdiagnosed cause of encephalopathy," reported Shamik Bhattacharyya, MD, MS, of Massachusetts General Hospital, Brigham & Women's Hospital, and Harvard Medical School, Boston, MA, and colleagues. "In critically ill patients, cefepime use, for example, was associated with encephalopathy in 15% of patients," and the condition remains difficult to diagnose due to unclear clinical features.

The researchers retrieved 292 articles from PubMed describing 391 patients. The articles were retrieved using the search terms for individual antibiotics as well as “encephalopathy,” “confusion,” “delirium,” “seizure,” “neuropathy,” “neurotoxicity,” “mania,” “hallucination,” or “psychosis” from beginning of indexing to October 2013.

The number of reports for each antibiotic was as follows: penicillins, 73 (penicillin G procaine, penicillin, other); cephalosporins, 68 (cefepime, ceftazidime, and other); antimycobacterials, 65 (isoniazid, other); quinolones, 63 (ciprofloxacin, ofloxacin, other); macrolides, 54 (clarithromycin, other); metronidazole, 29; and sulfonamides, 29 (trimethoprim-sulfamethoxazole, other).

Data from these studies showed that cephalosporins were prescribed more frequently in older adults (median age, 66 years), leading to renal insufficiency in 72%.

Among patients with prior psychiatric history, macrolides were prescribed most frequently in 20% of the studies.

Penicillins were associated with psychosis in 54%, seizures in 16%, and myoclonus in 27% of the studies, while cephalosporins were identified in 34%, non-convulsive seizures in 57%, and myoclonus in 40%.

For the anti-mycobacterial isoniazid, median days to toxicity was 21 (range, 1–360), and median days to resolution, 5 (range, 1–180).

Psychosis was reported as being associated with the quinolones in 67% of the studies and with the sulfonamides in 68%.

Metronidazole was associated with cerebellar toxicity in 48% of the studies, with a median of 19 days to toxicity (range, 1–180) and median days to resolution, 13 (range, 1–365).

"Recognition of different clinical phenotypes will aid in more prompt recognition of toxicity and change in therapy," he concluded.

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