data analyses from the eu - core registry consisting of 6075 patients indicate that daptomycin is relatively safe and well tolerated , even at high doses ( > 6  mg / kg / day ) . serious adverse events possibly related to daptomycin occurred in 2% of patients , but hypersensitivity reactions were rare . these registry data are important , in particular when facing a previously undescribed adverse event to a compound . here 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 ) . 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 . 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 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 46  days of hospitalization was considered the most likely cause . after intermittent hemodialysis ( days 1019 ) 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 ) the results were positive for daptomycin ( 5  mg / ml , wheal diameter 5  mm after 20  min ) , but negative for ceftriaxone ( 2  mg / ml ) . acute angioedema shortly after daptomycin infusion and the positive idt result suggested an immediate hypersensitivity reaction to daptomycin . to the best of our knowledge , this is the first report of angioedema after daptomycin exposure . a literature review identified only three published cases of immediate - type hypersensitivity reactions to daptomycin . bagwell et al .   reported a 24-year - old woman with multiple antibiotic allergies . she had experienced hypersensitivity reactions to daptomycin previously , and after re - exposure , pruritus and shortness of breath developed . metz and thyagarajan described a 33-year - old man who did not tolerate vancomycin because of a diffuse urticarial eruption . after the third daptomycin administration , he developed a generalized urticarial rash ( no lip or tongue swelling or shortness of breath ) . his symptoms improved with diphenhydramine , but the urticarial rash returned after each subsequent dose . on the basis of the reported patient history , it is unclear whether this reaction was ige mediated or nonspecific ( e.g. , mast cell activation ) . the third case illustrates desensitization to ceftaroline in a 32-year - old woman with multiple allergies , including anaphylaxis to daptomycin ( not further specified ) . in contrast to these cases , our patient had no known allergy , and angioedema developed acutely after the first dose . daptomycin was first approved by the us food and drug administration ( fda ) in september 2003 . after the hallmark study on daptomycin for s. aureus bacteremia and endocarditis was published in 2006 , numerous safety data on this agent became available [ 3 , 1013 ] . in addition to known adverse events ( e.g. , myotoxicity ) , an association of daptomycin with eosinophilic pneumonia has been raised through an fda drug safety communication . moreover , rare clinical manifestations such as acute generalized exanthematous pustulosis and drug rash with eosinophilia and systemic symptoms have been reported . anaphylaxis and angioedema are labeled as reactions of unknown frequency and causality [ 1 , 2 ] . worldwide , 72 immediate - type hypersensitivity reactions to daptomycin have been reported to who pharmacovigilance centers . in 20 of these cases , the reaction occurred on the first day of daptomycin treatment . in the present case , the more frequently reported association of beta - lactams with hypersensitivity reactions   and the lack of a similar case report associated with daptomycin were misleading . when performing an idt , a procedure with sequent dilutions we performed the idt in the icu with a 10 dilution of the original vial concentration ( 50  mg / ml ) and all necessary precautions were taken in case emergency treatment was needed . as done in our investigations , healthy volunteers with or without previous exposure to the drug can be used as negative controls to evaluate nonspecific skin reaction . although one healthy control may be insufficient to draw firm conclusions , the idt result and a negative control was a helpful tool  together with the clinical observation and detailed time analyses of drug application  in pointing towards a daptomycin - associated hypersensitivity reaction . because of the clinical circumstances , no in vitro testing with specific ige level measurements to daptomycin could be performed , and no tryptase was measured . although , in our view , ige - mediated reaction is likely , it can not be ascertained . nevertheless , clinicians should be aware that daptomycin can cause immediate - type hypersensitivity reactions . our case report indicates that acute angioedema can be triggered by daptomycin , even upon first administration . v. gisler , s. mller , l. mller , l. jrg - walther and p. sendi have nothing to disclose . this article is distributed under the terms of the creative commons attribution - noncommercial 4.0 international license ( http://creativecommons.org/licenses/by-nc/4.0/ ) , which permits any noncommercial use , distribution , and reproduction in any medium , provided you give appropriate credit to the original author(s ) and the source , provide a link to the creative commons license , and indicate if changes were made .
introductiondaptomycin is a cyclic lipopeptide antibiotic , frequently administered for staphylococcus aureus bloodstream infections . 
 numerous studies have shown that daptomycin is relatively safe and well tolerated . 
 serious adverse events possibly related to this antimicrobial compound are rare . 
 we report a case of acute angioedema triggered by daptomycin.case reporta 60-year - old woman with s. aureus bacteremia without identified source was treated intravenously with high - dose beta - lactams at our institution . because s. aureus bacteremia persisted on day 6 , and in parallel , acute kidney injury developed , antimicrobial treatment was switched to a combination therapy with daptomycin and ceftriaxone . shortly after completion of the first daptomycin administration , the patient developed lip and tongue swelling and dyspnea . 
 acute angioedema was clinically evident . 
 antibiotic therapy was switched to vancomycin , and the further clinical course was favorable . 
 an intradermal test showed a significant wheal diameter for daptomycin , but negative results for ceftriaxone.conclusionthe association with daptomycin in this case is either probable or certain . 
 clinicians should be aware that daptomycin can cause immediate - type hypersensitivity reactions , including acute angioedema , even upon first administration .