Anaphylactic-like reaction from trimethoprim-sulfamethoxazole in a patient with AIDS

Abstract

We report a patient with AIDS who had an anaphylactic-like reaction from trimethoprim-sulfamethoxazole. Clinical suspicion of anaphylaxis should be considered in patients presenting with fever, hypotension, eosinophilia, rash, flushing or pulmonary infiltrates after initial exposure and re-exposure to the medication. This case highlights the need for healthcare professionals to be reminded of the association between this unusual antibiotic reaction resembling sepsis and HIV disease.

Keywords

Trimethoprim-sulfamethoxazole anaphylaxis sepsis adverse drug reaction HIV AIDS

Case presentation

A 36-year-old Hispanic transgender woman sought medical attention at our emergency department with a one-day history of fever, nausea, vomiting, headache and diarrhoea. She denied any recent travel, unusual food consumption, animal exposure or sick contacts. Further history revealed that our patient had been hospitalised and discharged two months previously at our facility with septic shock. The day before hospitalisation, she was placed on a three-day course of trimethoprim-sulfamethoxazole (TMP-SMX) for a urinary tract infection. Infectious aetiology of her condition was not identified, but a screening test for human immunodeficiency virus (HIV) was positive. Two months after hospital discharge, she presented to the infectious disease clinic at our facility for evaluation and treatment of acquired immunodeficiency syndrome (AIDS) with a CD4 absolute count of 24 cells/mm³ (12%) and a HIV RNA viral load of 114,372 copies/mL. She did not receive highly active antiretroviral therapy due to no health insurance coverage. She had no known drug allergies and was placed on TMP-SMX (one double-strength 160/800 mg tablet every day) and azithromycin (two 600 mg tablets every week) for Pneumocystis jiroveci, Toxoplasma gondii and Mycobacterium avium prophylaxis. After taking her first dose of TMP-SMX the following day at 11:00 a.m., a drug reaction occurred within 60 min in which our patient promptly arrived without ambulance transportation at our emergency department for medical treatment. No other medications, including azithromycin or hormone therapy, were taken by the patient prior to the TMP-SMX dose.

Initial vital signs in the emergency department at 12:50 p.m. were temperature of 40.1°C, heart rate of 156/min, respiratory rate of 19/min, oxygen saturation of 95%, and systolic/diastolic blood pressure of 72/23 mm of mercury. On examination, she had a toxic appearance and was diaphoretic. There was severe flushing of the face, and no rash was seen. Significant abnormal laboratory studies on admission revealed creatinine of 1.69 (0.6–1.3) mg/dL and lactate of 4.3 (0.4–2.0) mEq/L. Aggressive intravenous fluid hydration, vasopressor medications and intravenous hydrocortisone were initiated for suspected septic shock. An anaphylactic reaction to TMP-SMX was not suspected by the emergency room personnel. Collection of a serum tryptase level and administration of intramuscular epinephrine were not performed. Blood and urine cultures were collected in the emergency department before antibiotic administration. Additional samples of blood and urine were collected for screening of sexually transmitted, fungal, viral and mycobacterial infections. Empiric antibiotic treatments with vancomycin, piperacillin-tazobactam, gentamicin and fluconazole were initiated. Radiological studies with chest radiograph and computed tomography of the brain, chest, abdomen and pelvis were unremarkable. All cultures and additional laboratory tests were negative for infection. Eosinophilia was noted on the third day of hospitalisation at 12.8% (0–7.0) cells/mL. Alanine aminotransferase and aspartate aminotransferase levels were not elevated during hospitalisation. An infectious disease specialist was consulted and suspected an anaphylactic-like reaction to TMP-SMX. With intravenous fluid hydration and supportive medical care, our patient made a full recovery after three days in the hospital.

Discussion

TMP-SMX is commonly prescribed for prophylaxis against opportunistic infections in patients with AIDS. Adverse reactions to TMP-SMX, such as rash, transaminitis, leukopenia and thrombocytopenia, are common. These can occur in 65% of HIV-positive patients compared with only 12% of patients with other immunosuppressive diseases.¹ The presenting and pertinent demographic and clinical characteristics of prior published case reports of anaphylactic reactions from TMP-SMX are shown in Table 1.^1–9 These cases depict a life-threatening reaction associated with TMP-SMX usage in patients with HIV and AIDS. The condition can resemble the clinical presentations of sepsis and may not be recognised and reported by healthcare professionals. A reaction can occur within 0.5 to 12 h after administration and is usually associated with re-exposure and prior reaction to the medication. Interestingly, there are no published case reports of female patients which merits further exploration to assess any gender-specific underlying risk factors. All cases fully recovered within a few days after supportive medical care and discontinuation of the antibiotic. The most important and intriguing findings of our case are the lack of rash and pulmonary infiltrates on presentation and the identification of TMP-SMX induced anaphylactic-like reaction on first hospitalisation. The re-exposure to TMP-SMX with recurrence of a similar anaphylactic event confirms that the drug was the cause. Our case differed from classic anaphylaxis in that there was no respiratory involvement.⁹ Only one of the prior published cases reported a similar presentation.² In addition, our patient exhibited fever, eosinophilia and organ involvement with acute renal failure that can be associated with Drug Reaction with Eosinophilia and Systemic Symptom syndrome.¹⁰ Although its exact mechanism is not known, this drug-induced reaction may be caused by higher levels of IgE and tumor necrosis factor in patients with AIDS.^5–7 Immune IgE-mediated drug hypersensitivity (Type I) reaction to antibiotics such as TMP-SMX can induce an anaphylactic reaction.¹¹ Clinical suspicion of anaphylaxis from TMP-SMX should be considered in patients presenting with fever, hypotension, eosinophilia, rash, flushing or pulmonary infiltrates after initial exposure and re-exposure to this drug.

Table 1.

Demographic and clinical characteristics of trimethoprim-sulfamethoxazole anaphylactic reactions in patients with HIV and AIDS.

Age (y)	Gender	Prior TMP-SMX use	Prior TMP-SMX use with reaction	Onset (hrs) of reaction	T⁰ (°C)	Blood pressure (mmHg)	Rash	Eosinophilia	Chest radiograph with infiltrates
31	M	Y	Y	4	40	Low	N	NR	N
46	M	Y	N	Few	40	60/40	Y	Y	Y
28	M	Y	N	0.5	40	70/40	Y	NR	Y
34	M	Y	Y	0.5	41	60/28	Y	NR	Y
28	M	N	N	Few	39	Low	Y	Y	Y
38	M	N	N	12	39	Low	Y	Y	Y
46	M	Y	N	4	40	60/40	N	NR	Y
34	M	Y	Y	1	39	80/40	Y	NR	Y
22	M	Y	Y	4	40	Low	Y	NR	Y
44	M	Y	Y	0.5	40	80/50	Y	NR	Y
38	M	Y	N	Few	39	95/54	Y	NR	Y
33	M	N	N	Few	40	84/45	Y	NR	N
38	M	Y	Y	1	40	75/34	Y	NR	Y

y: years; hrs: hours; T⁰: temperature; M: male; Y: Yes; N: No; NR: not reported.

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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