A 60-year-old woman was admitted to our hospital because of immobilizing lumbar back pain and elevated inflammatory markers in blood tests. Spine infection was suspected, and after obtaining blood cultures, the patient was treated empirical therapy with ceftriaxone (2 g once daily). Growth of Gram-positive cocci was detected in all blood culture samples. Antimicrobial treatment was switched to amoxicillin/clavulanate (2.2 g every 4 h on days 3 and 4 of hospitalization), and then streamlined to flucloxacillin (2 g every 4 h) after identification of methicillin-susceptible S. aureus. Despite 2 MRI scans, a PET-CT scan, an anti-granulocyte scintigraphy and several transesophageal echocardiographies, the source of bacteremia was not identified. On day 6, blood cultures were still positive for S. aureus. Thus, persistent S. aureus bacteremia without identified source was postulated. In parallel, acute kidney injury developed. Because of persistent bacteremia and renal impairment, antimicrobial treatment was switched to a combination therapy with daptomycin (10 mg/kg body weight) and ceftriaxone (2 g once daily) . Shortly after completion of the first daptomycin administration (60 min infusion), the patient developed lip and tongue swelling and dyspnea. After adrenaline inhalation and intravenous administration of clemastine and methylprednisolone, symptoms and findings resolved. No skin eruption or diffuse lymphadenopathy was noted in clinical examinations, and results of laboratory investigations showed no elevated eosinophil counts, atypical lymphocytosis or increased serum alanine aminotransferase. Thus, the differential diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) appeared unlikely, and a diagnosis of acute angioedema was made.
Antibiotic therapy was switched to vancomycin and continued for 4 weeks. Doses were adapted according to the gradually recovering renal function, and monitored by vancomycin trough levels in serum. Blood cultures showed no growth on day 9 and results remained negative on day 12. The further clinical course was favorable.
The workup of the case included investigations into the cause of angioedema and renal failure. The timely occurrence of the latter and the histopathological characteristics of the kidney biopsy result were consistent with acute interstitial nephritis . High-dose beta-lactam exposure during the first 4–6 days of hospitalization was considered the most likely cause.
After intermittent hemodialysis (days 10–19) and corticosteroid treatment, renal function values returned to normal on the day of discharge (day 32).
A detailed review of the drug charts strongly suggested a timely association between angioedema and daptomycin. The role of other compounds (nonsteroidal anti-inflammatory drugs, opioids) in causing direct histamine release or immunoglobulin E (IgE)-mediated reaction was also reviewed. These compounds were repeatedly challenged without an obvious clinical reaction. Because no similar case was previously described in the literature, the differential diagnosis included a more commonly known reaction to ceftriaxone, although exposure to ceftriaxone in the preceding week spoke against such a reaction. Also, the workup of the patient’s history revealed that she was exposed to 1st and 2nd generation cephalosporins in the previous years without any notable reaction. Daptomycin re-exposure was considered in the intensive care unit (ICU). An intradermal test (IDT) was performed first. The results were positive for daptomycin (5 mg/mL, wheal diameter 5 mm after 20 min), but negative for ceftriaxone (2 mg/mL). One healthy control produced no reaction to IDT with daptomycin at the same concentration. Acute angioedema shortly after daptomycin infusion and the positive IDT result suggested an immediate hypersensitivity reaction to daptomycin. Informed consent was obtained from the patient for being included in this case report.