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Allergy to transdermal fentanyl resulting in Staphylococcus aureus sepsis and fatal endocarditis with myocardial rupture
+Model MEDMAL-3727; No. of Pages 2
ARTICLE IN PRESS Disponible en ligne sur
ScienceDirect www.sciencedirect.com Médecine et maladies infectieuses xxx (2016) xxx–xxx
Letter to the editor Allergy to transdermal fentanyl resulting in Staphylococcus aureus sepsis and fatal endocarditis with myocardial rupture Allergie au fentanyl transdermique causant un état septique avec staphylocoque doré et endocardite fatale avec rupture du myocarde
Keywords: Staphylococcus aureus; Endocarditis; Cutaneous allergy Mots clés : Staphylococcus aureus ; Endocardite ; Allergie cutanée
Staphylococcus aureus frequently causes sepsis or endocarditis [1]. However, stroke, non-convulsive status epilepticus, multiple organ failure, and death from endocarditis with myocardial rupture during sepsis with S. aureus after allergy to transdermal fentanyl has never been reported. An 88-year-old female patient (height 160 cm, weight 60 kg) presenting with hypertension but otherwise uneventful medical history was admitted for allergic exanthema following transdermal fentanyl administration for coxarthrosis-related pain. The patient received methylprednisolone and diphenhydramine for the allergic reaction and hydromorphone and metamizole for the pain. On day 6 of hospitalization (HD 6), she developed fever and blood cultures were taken. Her condition deteriorated on HD 10. Fever recurred and she developed hypotension, personality change, oculomotor nerve palsy (right side), aphasia, quadriplegia, and pyramidal signs. The results of a cerebral MRI revealed multiple acute and subacute embolic ischemic lesions disseminated over all vascular areas. The results of an ECG showed tachycardia with atrial fibrillation. A non-convulsive status epilepticus was observed on electroencephalography, which resolved with the administration of lorazepam. The results of a transthoracic echocardiography (TTE) showed a slightly thickened aortic valve, moderate aortic insufficiency, and a thickened mitral valve. Valvular vegetations were not observed. Cefotaxime was initiated after a second blood culture. Small-in-size ischemic lesions were attributed to the atrial fibrillation and a therapeutic dose of enoxaparin was added to the treatment regimen. The on-call physicians decided against intensive care measures, such as mechanical ventilation or noradrenalin administration, due to the patient’s age and poor condition. The patient’s status then deteriorated from loss of consciousness to coma, prolonged hypotension, thrombocytopenia, anemia, massive increase of C-reactive protein, elevation of liver
function parameters, and acute renal insufficiency with progressively declining urine production. Cefotaxime was replaced by daptomycin as blood cultures grew S. aureus. The patient died on HD 12 from sepsis with multiple organ failure and without regaining consciousness. The results of the autopsy revealed endocarditis of the mitral valve and rupture of the left ventricular myocardium at the site of the valves. Myocarditis, meningitis, and encephalitis were not observed. Our case patient is interesting for several aspects. First, the origin of S. aureus remains speculative. S. aureus is frequently located on the skin [2]; thus, the portal of entry for bacteremia is the dermis or less likely the teeth, lungs, or kidneys. No other portal of entry was visible or plausible on inspection or instrumental investigations. The lungs and kidneys could not have been the source of infection as pneumonia and urinary infection were not observed. A dental source of the sepsis was excluded based on a normal dental examination. Bacteremia most likely originated from the skin and the growth of S. aureus was boosted by the patient’s immunosuppressed status caused by steroids. Second, embolic stroke was initially regarded to have derived from atrial fibrillation but the autopsy findings challenged this assumption. Embolic stroke most likely resulted from endocarditis [3], but atrial fibrillation cannot be ruled out as the cause. Embolic stroke might also have resulted from disseminated intravascular coagulation syndrome. An argument for such a scenario is that failure of other organs, such as kidneys or the liver, simultaneously occurred. Literature data most frequently attribute embolic stroke associated with endocarditis to endocarditis [4]. Third, TTE did not reveal endocarditis despite good image quality. Thrombus on the valve may have disappeared before or vegetations could have been too small to be visible. Endocarditis would probably not have been observed on transesophageal echocardiography (TEE) even though it is usually easier to detect endocarditis on TEE than TTE [5]. Only one vegetation was observed on the mitral valve during autopsy. Fourth, the cause of myocardial rupture remains elusive. The authors of previous reports mentioned that endocarditis may be complicated by abscess formation, [6] which itself may be complicated by myocardial rupture. Although rupture has occasionally been reported in association with S. aureus endocarditis [7], its occurrence seems to be quite rare. One may also hypothesize that the rupture resulted from bacteremia-induced myocarditis, although this scenario has only been observed on very rare occasions. An argument standing against myocarditis is that it was not observed on autopsy. It is also possible that
http://dx.doi.org/10.1016/j.medmal.2016.03.006 0399-077X/© 2016 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Finsterer J, Dumser M. Allergy to transdermal fentanyl resulting in Staphylococcus aureus sepsis and fatal endocarditis with myocardial rupture. Med Mal Infect (2016), http://dx.doi.org/10.1016/j.medmal.2016.03.006
+Model MEDMAL-3727; No. of Pages 2 2
ARTICLE IN PRESS Letter to the editor / Médecine et maladies infectieuses xxx (2016) xxx–xxx
the patient experienced acute myocardial infarction and that the rupture resulted from consecutive necrosis. However, there was no indication for myocardial ischemia or coronary heart disease on autopsy. Our case patient indicates that treating allergic exanthema with steroids may lead to sepsis with S. aureus, multiple organ failure, and death. Bacteremia from immunosuppression may favor endocarditis, which may go undetected on TTE. TEE should be performed in patients presenting with sepsis and embolic stroke, and in the absence of vegetations on TTE.
[3] [4]
[5]
[6]
Ethical standards The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Funding The authors did not receive any funding. Disclosure of interest The authors declare that they have no competing interest. References [1] Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, Kirby A, Tilley R, Török ME, et al. Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis 2011;11:208–22. [2] Yamamoto T, Yodogawa K, Wakita S, Ogano M, Tokita M, Miyagi Y, et al. Recurrent prosthetic valve endocarditis caused by Staphylococcus
[7]
aureus colonizing skin lesions in severe atopic dermatitis. Intern Med 2007;46:571–3. Tisdell J, Smith TW, Muehlschlegel S. Multiple septic brain emboli in infectious endocarditis. Arch Neurol 2012;69:1206–7. Okazaki S, Yoshioka D, Sakaguchi M, Sawa Y, Mochizuki H, Kitagawa K. Acute ischemic brain lesions in infective endocarditis: incidence, related factors, and postoperative outcome. Cerebrovasc Dis 2013;35: 155–62. Incani A, Hair C, Purnell P, O’Brien DP, Cheng AC, Appelbe A, et al. Staphylococcus aureus bacteraemia: evaluation of the role of transoesophageal echocardiography in identifying clinically unsuspected endocarditis. Eur J Clin Microbiol Infect Dis 2013;32:1003–8. Dahl A, Hansen TF, Bruun NE. Staphylococcus aureus endocarditis with fast development of aortic root abscess despite relevant antibiotics. Heart Lung 2013;42:72–3. Furui M, Ohashi T, Yoshida T, Oka F, Hirai Y, Ohyoshi N, et al. Ventricular septal perforation caused by right-sided infective endocarditis associated with giant vegetation. Ann Thorac Surg 2010;89:959–61.
J. Finsterer ∗ Krankenanstalt Rudolfstiftung, Vienna, Austria M. Dumser Institute of Pathology, Krankenanstalt Rudolfstiftung, Vienna, Austria ∗ Corresponding
author. Postfach 20, 1180 Vienna, Austria, Europe. E-mail address: [email protected] (J. Finsterer) Received 25 February 2016 Received in revised form 1st March 2016 Accepted 17 March 2016
Please cite this article in press as: Finsterer J, Dumser M. Allergy to transdermal fentanyl resulting in Staphylococcus aureus sepsis and fatal endocarditis with myocardial rupture. Med Mal Infect (2016), http://dx.doi.org/10.1016/j.medmal.2016.03.006
ARTICLE IN PRESS Disponible en ligne sur
ScienceDirect www.sciencedirect.com Médecine et maladies infectieuses xxx (2016) xxx–xxx
Letter to the editor Allergy to transdermal fentanyl resulting in Staphylococcus aureus sepsis and fatal endocarditis with myocardial rupture Allergie au fentanyl transdermique causant un état septique avec staphylocoque doré et endocardite fatale avec rupture du myocarde
Keywords: Staphylococcus aureus; Endocarditis; Cutaneous allergy Mots clés : Staphylococcus aureus ; Endocardite ; Allergie cutanée
Staphylococcus aureus frequently causes sepsis or endocarditis [1]. However, stroke, non-convulsive status epilepticus, multiple organ failure, and death from endocarditis with myocardial rupture during sepsis with S. aureus after allergy to transdermal fentanyl has never been reported. An 88-year-old female patient (height 160 cm, weight 60 kg) presenting with hypertension but otherwise uneventful medical history was admitted for allergic exanthema following transdermal fentanyl administration for coxarthrosis-related pain. The patient received methylprednisolone and diphenhydramine for the allergic reaction and hydromorphone and metamizole for the pain. On day 6 of hospitalization (HD 6), she developed fever and blood cultures were taken. Her condition deteriorated on HD 10. Fever recurred and she developed hypotension, personality change, oculomotor nerve palsy (right side), aphasia, quadriplegia, and pyramidal signs. The results of a cerebral MRI revealed multiple acute and subacute embolic ischemic lesions disseminated over all vascular areas. The results of an ECG showed tachycardia with atrial fibrillation. A non-convulsive status epilepticus was observed on electroencephalography, which resolved with the administration of lorazepam. The results of a transthoracic echocardiography (TTE) showed a slightly thickened aortic valve, moderate aortic insufficiency, and a thickened mitral valve. Valvular vegetations were not observed. Cefotaxime was initiated after a second blood culture. Small-in-size ischemic lesions were attributed to the atrial fibrillation and a therapeutic dose of enoxaparin was added to the treatment regimen. The on-call physicians decided against intensive care measures, such as mechanical ventilation or noradrenalin administration, due to the patient’s age and poor condition. The patient’s status then deteriorated from loss of consciousness to coma, prolonged hypotension, thrombocytopenia, anemia, massive increase of C-reactive protein, elevation of liver
function parameters, and acute renal insufficiency with progressively declining urine production. Cefotaxime was replaced by daptomycin as blood cultures grew S. aureus. The patient died on HD 12 from sepsis with multiple organ failure and without regaining consciousness. The results of the autopsy revealed endocarditis of the mitral valve and rupture of the left ventricular myocardium at the site of the valves. Myocarditis, meningitis, and encephalitis were not observed. Our case patient is interesting for several aspects. First, the origin of S. aureus remains speculative. S. aureus is frequently located on the skin [2]; thus, the portal of entry for bacteremia is the dermis or less likely the teeth, lungs, or kidneys. No other portal of entry was visible or plausible on inspection or instrumental investigations. The lungs and kidneys could not have been the source of infection as pneumonia and urinary infection were not observed. A dental source of the sepsis was excluded based on a normal dental examination. Bacteremia most likely originated from the skin and the growth of S. aureus was boosted by the patient’s immunosuppressed status caused by steroids. Second, embolic stroke was initially regarded to have derived from atrial fibrillation but the autopsy findings challenged this assumption. Embolic stroke most likely resulted from endocarditis [3], but atrial fibrillation cannot be ruled out as the cause. Embolic stroke might also have resulted from disseminated intravascular coagulation syndrome. An argument for such a scenario is that failure of other organs, such as kidneys or the liver, simultaneously occurred. Literature data most frequently attribute embolic stroke associated with endocarditis to endocarditis [4]. Third, TTE did not reveal endocarditis despite good image quality. Thrombus on the valve may have disappeared before or vegetations could have been too small to be visible. Endocarditis would probably not have been observed on transesophageal echocardiography (TEE) even though it is usually easier to detect endocarditis on TEE than TTE [5]. Only one vegetation was observed on the mitral valve during autopsy. Fourth, the cause of myocardial rupture remains elusive. The authors of previous reports mentioned that endocarditis may be complicated by abscess formation, [6] which itself may be complicated by myocardial rupture. Although rupture has occasionally been reported in association with S. aureus endocarditis [7], its occurrence seems to be quite rare. One may also hypothesize that the rupture resulted from bacteremia-induced myocarditis, although this scenario has only been observed on very rare occasions. An argument standing against myocarditis is that it was not observed on autopsy. It is also possible that
http://dx.doi.org/10.1016/j.medmal.2016.03.006 0399-077X/© 2016 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Finsterer J, Dumser M. Allergy to transdermal fentanyl resulting in Staphylococcus aureus sepsis and fatal endocarditis with myocardial rupture. Med Mal Infect (2016), http://dx.doi.org/10.1016/j.medmal.2016.03.006
+Model MEDMAL-3727; No. of Pages 2 2
ARTICLE IN PRESS Letter to the editor / Médecine et maladies infectieuses xxx (2016) xxx–xxx
the patient experienced acute myocardial infarction and that the rupture resulted from consecutive necrosis. However, there was no indication for myocardial ischemia or coronary heart disease on autopsy. Our case patient indicates that treating allergic exanthema with steroids may lead to sepsis with S. aureus, multiple organ failure, and death. Bacteremia from immunosuppression may favor endocarditis, which may go undetected on TTE. TEE should be performed in patients presenting with sepsis and embolic stroke, and in the absence of vegetations on TTE.
[3] [4]
[5]
[6]
Ethical standards The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Funding The authors did not receive any funding. Disclosure of interest The authors declare that they have no competing interest. References [1] Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, Kirby A, Tilley R, Török ME, et al. Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis 2011;11:208–22. [2] Yamamoto T, Yodogawa K, Wakita S, Ogano M, Tokita M, Miyagi Y, et al. Recurrent prosthetic valve endocarditis caused by Staphylococcus
[7]
aureus colonizing skin lesions in severe atopic dermatitis. Intern Med 2007;46:571–3. Tisdell J, Smith TW, Muehlschlegel S. Multiple septic brain emboli in infectious endocarditis. Arch Neurol 2012;69:1206–7. Okazaki S, Yoshioka D, Sakaguchi M, Sawa Y, Mochizuki H, Kitagawa K. Acute ischemic brain lesions in infective endocarditis: incidence, related factors, and postoperative outcome. Cerebrovasc Dis 2013;35: 155–62. Incani A, Hair C, Purnell P, O’Brien DP, Cheng AC, Appelbe A, et al. Staphylococcus aureus bacteraemia: evaluation of the role of transoesophageal echocardiography in identifying clinically unsuspected endocarditis. Eur J Clin Microbiol Infect Dis 2013;32:1003–8. Dahl A, Hansen TF, Bruun NE. Staphylococcus aureus endocarditis with fast development of aortic root abscess despite relevant antibiotics. Heart Lung 2013;42:72–3. Furui M, Ohashi T, Yoshida T, Oka F, Hirai Y, Ohyoshi N, et al. Ventricular septal perforation caused by right-sided infective endocarditis associated with giant vegetation. Ann Thorac Surg 2010;89:959–61.
J. Finsterer ∗ Krankenanstalt Rudolfstiftung, Vienna, Austria M. Dumser Institute of Pathology, Krankenanstalt Rudolfstiftung, Vienna, Austria ∗ Corresponding
author. Postfach 20, 1180 Vienna, Austria, Europe. E-mail address: [email protected] (J. Finsterer) Received 25 February 2016 Received in revised form 1st March 2016 Accepted 17 March 2016
Please cite this article in press as: Finsterer J, Dumser M. Allergy to transdermal fentanyl resulting in Staphylococcus aureus sepsis and fatal endocarditis with myocardial rupture. Med Mal Infect (2016), http://dx.doi.org/10.1016/j.medmal.2016.03.006