BOSTON — The recent finding that adverse reactions to antimicrobial agents cause more than 142,000 emergency department visits per year in the United States, and that the highest rate occurs in children under 1 year of age should be a wake-up call to pediatric health care providers to exercise caution when pulling out the prescription pad.
Dr. Barbara W. Stechenberg gave this warning at the annual meeting of the American Academy of Pediatrics.
The study used nationally representative surveillance data to estimate the rates of adverse events associated with systemic antibiotics and compared the results by antibiotic class, specific drug, and type of adverse event (Clin. Infect. Dis. 2008;47:735–43).
Approximately half of the emergency department visits attributable to antimicrobial adverse events were for reactions to penicillins and half were for reactions to multiple other agents, according to researchers Dr. Nadine Shehab and her associates at the Centers for Disease Control and Prevention.
Although infants younger than 1 year accounted for only 6% of the emergency department visits, after controlling for prescription frequency, “the rate of visits [for antimicrobial-related adverse events] was highest in this age group,” said Dr. Stechenberg, director of pediatric infectious diseases at Baystate Medical Center in Springfield, Mass.
“Clearly, adverse reactions to antimicrobials are a huge issue. [These findings] remind us to consider certain underlying principles before we prescribe antibiotics to our patients.”
First, ask yourself whether the patient really needs the therapy, “because no therapy is often safer than any therapy,” she said.
“Next, name the bug before you choose the drug, so you can use the narrowest spectrum, least toxic drug possible,” Dr. Stechenberg advised.
The majority of adverse reactions seen in the above study—approximately 80%—were allergic reactions, ranging from rash to anaphylaxis, and the rest were toxicity related.
With respect to allergic reactions, said Dr. Stechenberg, “the ones we worry about the most, particularly with penicillins and cephalosporins, are the IgE-mediated reactions which occur fairly early in the course of antibiotic therapy, but a lot of what we see—most of the maculopapular and morbilliform rashes—are non-IgE mediated.”
With respect to toxic reactions, “most toxicity that we see is related to giving a dose of antibiotic that is above what the particular host can manage. Sometimes it's the wrong dose or the decimal is in the wrong place, but a lot of times it's related to impaired metabolism: The host child has renal dysfunction or liver dysfunction and is not able to metabolize the drug appropriately.”
Other adverse reactions are side effects. “Many patients report stomachaches with erythromycin, for example. Side effects are not IgE mediated or related to toxic levels. They just happen,” said Dr. Stechenberg. “This is a reason why taking a thorough history is very important.”
Adverse reactions associated with genetic issues occasionally arise. In HIV patients, for example, “we know that people metabolize INH [isoniazid] differently. People who are slow metabolizers may accumulate INH and develop neuropathy,” she said.
Finally, underlying diseases also can contribute to antibiotic adverse reactions, Dr. Stechenberg noted.
“Cystic fibrosis patients are more likely to have allergic reactions than other patients, which may be related to the hyperactivity of their immune system. The same is true with HIV patients.”
An awareness of the types of adverse reactions that can occur with different antimicrobial agents is critical to management of them, Dr. Stechenberg stressed.
The following are some of the important points to consider with respect to different drug classes and specific drug reactions.
▸ Penicillins. “Penicillins are generally very safe. There is very little dose-related toxicity because of the wide dose range,” said Dr. Stechenberg.
Regarding allergies, “studies have shown that the true incidence of penicillin allergies among patients who report them is only about 10% [as determined by skin testing]. This doesn't mean that they're not going to have a nonimmediate reaction to penicillin, but it does make you feel more comfortable about the risk of anaphylaxis, which is very uncommon,” she commented.
When immediate reactions to β-lactams, especially penicillins, do occur, they are often IgE mediated and typically present as urticaria. The more severe reactions include bronchospasm or hypertension, she said.
“Most [IgE-mediated reactions] occur within the first 15–20 minutes, the vast majority in the first hour, but about 5% occur after the first hour, which is important to remember as you think about rechallenging someone with penicillin.”
Among the late reactions to penicillins—which usually occur after 72 hours, often 5–10 days into the course of therapy—are maculopapular rashes and morbilliform rashes, often on the extremities, she said.