In Reply We agree with Schmajuk and Yazdany that adverse events occur in a small fraction of patients using trimethoprim-sulfamethoxazole, as they pointed out in response to our recent Teachable Moment.1 However, at doses used for Pneumocystis pneumonia (PCP) prophylaxis, the drug combination is generally well tolerated, and gastrointestinal and cutaneous adverse effects, such as nausea and rash, occur in only 3% to 5% of patients.2,3 In HIV-uninfected patients, most of the adverse reactions (eg, nausea, vomiting, skin rash, pruritus) are not severe and resolve with discontinuation of the drug; this is in contrast to the 25% to 50% of HIV-infected patients who experience adverse effects (eg, neutropenia, anaphylaxis, toxic dermatologic reactions), which are more likely to be severe.4,5 Hyperkalemia, which can be life-threatening, has most commonly occurred in HIV-infected patients receiving high doses (trimethoprim, 20 mg/kg/d, and sulfamethoxazole, 100 mg/kg/d) for PCP treatment.4 Additionally, it is well known that the trimethoprim-sulfamethoxazole–induced creatinine increase is most often reflective of decreased tubular secretion and not an actual decline in glomerular filtration rate. It should also be noted that the risk of serious adverse effects with trimethoprim-sulfamethoxazole is not dissimilar to many other antibiotics.2
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LoPiccolo J, Mehta SA, Lipson EJ. Further Lessons in Pneumocystis Pneumonia Prophylaxis—Reply. JAMA Intern Med. 2018;178(11):1566–1567. doi:10.1001/jamainternmed.2018.5933
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