More severe reactions include hemolytic anemia, neutropenia, and thrombocytopenia. “For a lot of these, we don't know what the mechanism is. They may be antibody mediated, and certainly these reactions demand our attention.
In terms of management, the timing and character of previous reactions is important.
“Reactions late in the course are less likely to be IgE mediated. If the child previously had an idiopathic, nonpruritic late rash, you can consider giving the drug in the future,” said Dr. Stechenberg.
In patients with a history of immediate reactions or more severe late reactions, such as Stevens-Johnson syndrome, you wouldn't rechallenge with the same drug, she said.
▸ Vancomycin. Most families think vancomycin hypersensitivity is an allergy. It's really a rate-dependent infusion reaction, said Dr. Stechenberg. It often happens on the first dose, which is different from anaphylaxis, and the rash is more likely to be a diffuse erythema, often on the upper trunk, face, and neck.
The package insert states that the drug infusion shouldn't exceed 1 g over an hour. “Sometimes we have to modify that, but if there's a mild reaction, the best thing is to just stop the infusion and wait a short period, then restart at a slower rate,” she said.
“If there's a moderate reaction, one might want to treat with diphenhydramine and allow the symptoms to subside, then use a much longer rate.”
In patients with severe reactions, “you might have to use an alternate drug,” she said.
▸ Clindamycin. “The biggest issue with this drug is diarrhea. It's often mild and self-limited, which you can treat through.
“When it persists and is more severe, we worry about Clostridium difficile, which can have a wide range of presentations,” Dr. Stechenberg said. The diagnosis of C. difficile can be made by enzyme immunoassays in most hospital labs, she said, noting, however, that “the fly in the ointment with C. difficile is that kids up to 1 year of age will often have asymptomatic C. difficile, so they will test positive by toxin assay.
“The occurrence of diarrheal disease [with antibiotic treatment] may be unrelated.”
The first line of treatment for C. difficile is to stop the drug. “In 20%–25% of patients, this is all you need to do,” Dr. Stechenberg said.
If symptoms persist, “try oral metronidazole. We try not to use oral vancomycin because of concerns about vancomycin-resistant enterococcus, but for patients who can't tolerate or fail metronidazole, oral vancomycin is an option,” she said.
Another option is linezolid, but it is expensive and has been associated with thrombocytopenia in adults.
▸ Trim/sulfa. This broad-spectrum antibiotic “has been around for a long time, but it has new life in the therapy of methicillin-resistant staph aureus,” said Dr. Stechenberg.
It has a reputation as a drug that can cause a rash because a lot of HIV patients who took it developed rashes. In the general population, however, the incidence of rash is fairly low, she said.
“In kids with HIV, we do see fixed drug eruptions in the same area of the body, and [so] we do talk to families about the possibility of rash.”
Trim/sulfa (trimethoprim/sulfamethoxazole) is not recommended for use in infants younger than 2 months because it displaces bilirubin from albumin binding sites, she said.
▸ Azithromycin. The most common reaction with this drug is gastrointestinal upset. “These are side effects, not allergy. Some people just cannot tolerate macrolides,” Dr. Stechenberg noted.
Although rash is uncommon with azithromycin, “when it does occur, it lasts for a long time.
One of the nice things about this drug is that treatment is only for 5 days because it stays in the body for a long time, but that means when there's rash, it will persist,” she said.
▸ Doxycycline. Concerns about tooth staining “have led to a magic cutoff age of 8–9 years old for doxycycline, after the eruption of maxillary central incisors,” said Dr. Stechenberg.
“In reality, tooth staining results from multiple courses of the drug over long periods. When we're using it as a drug of choice for children younger than 8 years, we're treating for 5–7 days for specific indications.”
Photosensitivity dermatitis also is a concern with doxycycline, but this can be prevented with anticipatory guidance regarding the use of broad-spectrum sunscreen and sun avoidance, she said.
▸ Fluoroquinolones. Pediatricians have been reluctant to use these in children, because they have been linked with cartilage damage in animal and adult studies and because of resistance concerns, especially in pneumococcus, said Dr. Stechenberg.