Mycobacterium chimaera Infection After Aortic Valve Replacement Presenting With Aortic Dissection and Pseudoaneurysm

Mycobacterium chimaera Infection After Aortic Valve Replacement Presenting With Aortic Dissection... Open Forum Infectious Diseases BRIEF REPORT normal. Transthoracic echocardiogram performed in January Mycobacterium chimaera Infection 2017 at another center was reported as normal. Investigation Aer A ft ortic Valve Replacement for infectious causes including blood cultures, HIV serology, Presenting With Aortic Dissection and viral hepatitis serology, and syphilis serology were negative. A single mycobacterial blood culture was collected and ultim- Pseudoaneurysm ately reported negative after 7 weeks of incubation. 1 1,2 1,2 1,2 3 C. R. O’Neil, G. Taylor, S. Smith, A. M. Joffe, K. Antonation, 1 1 In March 2017, the patient presented to the hospital with a S. Shafran, and D. Kunimoto 1 1-week history of chest pain. He was hemodynamically stable Division of Infectious Diseases, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada; Infection Prevention and Control, Alberta on presentation. Laboratory investigations showed normal com- Health Services, Edmonton, Alberta, Canada; National Microbiology Laboratory, Winnipeg, plete blood count parameters and a slightly elevated troponin Manitoba, Canada I  of 0.07 ug/L (normal being ≤0.02 ug/L). Electrocardiogram showed normal sinus rhythm. Computed tomography of his We present a case of Mycobacterium chimaera infection present- chest revealed a dissection of his ascending aorta with a large ing with aortic dissection and pseudoaneuysm in a 22-year-old man with a past history of aortic valve replacement. Clinicians aortic pseudoaneurysm (Figure 1). He underwent urgent repair should consider M.  chimaera infection in those presenting of his aortic dissection with placement of a prosthetic graft. His with aortic dissection as a late complication of cardiovascular existing mechanical aortic valve was not replaced as transtho- surgery. racic and transesophageal echocardiograms showed no evi- Keywords. aortic dissection; Canada; heater  cooler units; dence of endocarditis or paravalvular abscess. Intraoperative Mycobacterium chimaera. specimens were sent for bacterial and mycobacterial culture. An intraoperative specimen was also submitted for pathologic examination; however, only thrombus was identified. He was CASE discharged with infectious diseases follow-up pending intraop- A 22-year-old man was referred for infectious diseases consult- erative tissue culture results. ation in January 2017. He had a past medical history of a bi- Aer 21  ft days of incubation, intraoperative tissue cultures cuspid aortic valve with mechanical aortic valve replacement at identified a Mycobacterium species ultimately identified as our hospital in June 2015. He reported a 1-year history of inter- Mycobacterium chimaera. e Th isolate was sent to the National mittent drenching night sweats, occurring 1–2  days per week. Microbiology Laboratory (NML; Winnipeg, MB, Canada) for He denied other constitutional symptoms, fever, weight loss, confirmation of identification and whole-genome sequencing. chest pain, or dyspnea. He reported a small pustule on the su- Whole-genome sequencing showed a high degree of related- perior aspect of his sternotomy incision that had resolved with a ness to M.  chimaera isolates from LivaNova 3T Heater Cooler seven-day course of cephalexin 2 months prior to presentation. Units (HCU) used at the University of Alberta Hospital in He was taking warfarin and aspirin. On examination, he looked Edmonton and to publicly available genomes of isolates associ- well with normal vital signs. Cardiorespiratory examination was ated with the HCU outbreak from the United States and Europe unremarkable. There was no evidence of lymphadenopathy or (Supplementary Figure 1). The draft sequence covered >99% of organomegaly. His sternotomy incision was well healed with no the genome with a depth of coverage ~50× as compared with the step deformity or instability. Preliminary investigations showed reference sequence ZUERICH-1 (Accession No. CP015267). The normal complete blood count parameters, electrolytes, cre- HCU used at the time of his original aortic valve replacement in atinine, liver enzymes, and C-reactive protein. Chest x-ray was 2015 could not be confirmed. The total time from cardiovascu- lar surgery to initial clinical presentation was 18.8 months, and Received 26 October 2017; editorial decision 8 January 2018; accepted 15 January 2018. the time from clinical presentation to microbial diagnosis was Correspondence: C.  R. O’Neil, MD, FRCPC, Division of Infectious Diseases, Faculty of 82 days. Susceptibility results performed by microbroth dilution Medicine and Dentistry, 1-124R Clinical Sciences Building, University of Alberta Hospital, are summarized in Supplementary Table 1. 11350 83 Avenue, Edmonton, AB, Canada T6G 2G3 (conar@ualberta.ca). e p Th atient was treated with a combination of azithromycin, Open Forum Infectious Diseases © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases rifabutin, ethambutol, and amikacin. When susceptibility results Society of America. This is an Open Access article distributed under the terms of the Creative were reported, ethambutol was changed to moxifloxacin. The Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any patient was referred for ophthalmologic assessment and was found medium, provided the original work is not altered or transformed in any way, and that the work to have no ocular abnormalities. Therapeutic drug monitoring is properly cited. For commercial re-use, please contact journals.permissions@oup.com DOI: 10.1093/ofid/ofy018 performed at the Infectious Disease Pharmacokinetics Laboratory BRIEF REPORT • OFID • 1 Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy018/4823097 by Ed 'DeepDyve' Gillespie user on 16 March 2018 [4]. Hospital-level contamination of other brands of HCUs (eg, Maquet) with M. chimaera has been described, though these do not appear to be related to the epidemic strain [4]. e e Th arliest described sentinel surgery with subsequent M.  chimaera infection was 2006 [5]. No cases have yet been associated with LivaNova HCUs manufactured aer m ft odifica- tions were made to the manufacturing and maintenance pro- cesses in September 2014. LivaNova holds approximately 70% of the global market share, and the majority of HCUs in clin- ical use were manufactured between 2006 and November 2014. Cardiovascular surgery cannot be performed without HCUs, and existing HCUs cannot be removed from active use without unacceptable disruption in the delivery of cardiovascular sur- gical services. Infection prevention and control and risk miti- Figure  1. Computed tomography of patient with Mycobacterium chimaera in- gation strategies for M.  chimaera have been reviewed in detail fection presenting with aortic dissection with large aortic pseudoaneurysm. *Red arrow indicates false lumen (ie, pseudoaneurysm) of the ascending aorta. elsewhere [5–7]. The precise risk of M.  chimaera infection aer c ft ardiovascular surgery is unknown. A UK national study demonstrated increasing risk of M. chimaera infection aer c ft ar - (Gainesville, FL) confirmed adequate antimicrobial peak concen- diovascular surgery over time peaking at 1 in 2000 in 2014 [3]. trations of rifabutin, azithromycin, and moxifloxacin. Amikacin e Th Centers for Disease Control and Prevention has estimated was discontinued aer 11 w ft eeks of therapy, when subclinical the risk to be 1 in 100 to 1 in 1000 infections per surgery in sites sensorineural hearing loss was noted on screening audiometry. that have already had a case [8]. Ethambutol was thus recommenced. Details of his treatment Patients with M. chimaera infections most oen p ft resent with course are outlined in Supplementary Figure  2. Follow-up oph- nonspecific symptoms such as fatigue, fever, night sweats, and thalmological examination performed aer 12 w ft eeks of therapy weight loss [5, 9]. Local complications such as sternal osteomye- was normal. At the time of manuscript submission, the patient is litis and left ventricular assist device driver site infections have doing well aer 21 w ft eeks of combination therapy. also been described [5]. M. chimaera infection presenting with In November 2016, the infection control department con- aortic dissection has not been previously described. In cases of ducted a retrospective review of all nontuberculous myco- M chimaera infection, physical examination may show lymph- bacteria isolated from patients who underwent open chest adenopathy, organomegaly, or other signs of disseminated in- cardiovascular surgery in Alberta aer J ft anuary 1, 2011. Of fection. Ophthalmologic examination may show choroidal 11 500 patients potentially exposed, we identified no other cases lesions or uveitis in patients with disseminated disease [10]. of M. chimaera infection. As of the date of manuscript accept- Patients with disseminated disease may have laboratory abnor- ance (January 2018), two additional cases of M. chimaera in- malities such as elevated inflammatory markers (eg, C-reactive fection have been identified in patients who have undergone protein), cytopenias, and elevated liver enzymes [7]. Which cardiovascular surgery at our institution. patients should be investigated and which diagnostic investi- gations should be carried out on suspect patients is not clear DISCUSSION [7]. In our case, a single mycobacterial blood culture collected In 2013, Achermann and colleagues reported 2 cases of M. chi- prior to surgery was negative. Even in patients with dissemi- maera infection that were related by random amplification of nated infection, mycobacterial blood cultures may be nega- polymorphic DNA–polymerase chain reaction [1]. Preliminary tive [9]. Histopathology of biopsy specimens characteristically investigations did not identify a nosocomial link. The follow-up shows noncaseating granulomatous inflammation that is rarely outbreak investigation identified what has now been recog- acid-fast bacilli stain–positive. A  number of reported cases nized as a global outbreak of M. chimaera infections associated have been misdiagnosed as sarcoidosis or other inflammatory with contaminated LivaNova 3T HCUs used in cardiothor- conditions and received immunosuppression prior to the diag- acic surgery [2]. Subsequent investigations have demonstrated nosis of M.  chimaera infection [5, 9]. The median time from that M.  chimaera isolated from HCUs can be aerosolized and cardiovascular surgery to presentation is 17 months, though the spread to the environment via the exhaust fan, resulting in longest lag time described is 6 years [5, 7]. Clearly, pending fur- airborne transmission to the patient [2, 3]. Whole-genome ther research, clinicians should consider broadly investigating sequencing has demonstrated that globally distributed clin- patients with previous cardiac surgery presenting with a wide ical cases are genetically similar, suggesting a common-source range of symptoms within the at-risk time frame to avoid miss- outbreak involving the manufacturing of LivaNova 3T HCUs ing patients with M. chimaera infection. 2 • OFID • BRIEF REPORT Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy018/4823097 by Ed 'DeepDyve' Gillespie user on 16 March 2018 Supplementary Data Optimal treatment of M.  chimaera infections has not been Supplementary materials are available at Open Forum Infectious Diseases established. Mycobacterium chimaera is genetically related to online. Consisting of data provided by the authors to benefit the reader, Mycobacterium avium complex [11], and therefore, treatment of the posted materials are not copyedited and are the sole responsibility of M. chimaera infection might be expected to be similar to treatment the authors, so questions or comments should be addressed to the corre- sponding author. of M.  avium complex infection. The American Thoracic Society/ Infectious Diseases Society of America guidelines for disseminated Acknowledgements M. avium complex infection recommend a macrolide (clarithromy- e a Th uthors gratefully acknowledge the patient who provided written con- cin or azithromycin) and ethambutol with or without rifabutin [12]. sent for publication of this case report. The authors also acknowledge the Susceptibility testing, other than for clarithromycin, is not recom- microbiologists and technologists at the Provincial Laboratory for Public Health, Edmonton, AB, Canada, and the National Microbiology Laboratory, mended for treatment-naïve patients as there is a lack of correlation Winnipeg, MB, Canada. Note that the opinions expressed within do not between in vitro susceptibility and clinical outcomes. However, it is represent the opinions of the Public Health Agency of Canada or the unknown whether this is true for M. chimaera. Susceptibility results Government of Canada. Financial support. This work was unfunded. are presented here as it is expected that results will be similar for all Potential conifl cts of interest. All authors: no reported conflicts of strains in this clonal outbreak, barring antibiotic exposure and sub- interest. All authors have submitted the ICMJE Form for Disclosure of sequent development of resistance. For M.  chimaera infections, the Potential Conflicts of Interest. Conflicts that the editors consider relevant to combination of a rifamycin (rifabutin or rifampin), ethambutol, and a the content of the manuscript have been disclosed. macrolide is the most commonly described regimen in the literature [5, 9]. However, it should be noted that the combination of clarithro- References 1. Achermann Y, Rössle M, Hoffmann M, et  al. Prosthetic valve endocarditis and mycin and rifampin may result in subtherapeutic levels of clarithro- bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol 2013; mycin [12]. A combination of antimicrobial therapy and removal of 51:1769–73. 2. Sax H, Bloemberg G, Hasse B, et  al. Prolonged outbreak of Mycobacterium chi- prosthetic material should be considered when feasible. er Th e are no maera infection after open-chest heart surgery. Clin Infect Dis 2015; 61:67–75. data on reinfection rates for newly placed prosthetic devices. Patients 3. Chand M, Lamagni T, Kranzer K, et  al. Insidious risk of severe Mycobacterium failing initial therapy or those patients in whom surgical source con- chimaera infection in cardiac surgery patients. Clin Infect Dis 2017; 64:335–42. 4. van Ingen J, Kohl TA, Kranzer K, et al. Global outbreak of severe Mycobacterium trol cannot be achieved may benefit from the addition of moxifloxa- chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet cin and/or intravenous amikacin [9]. Optimal treatment duration in Infect Dis 2017; 17:p1003–41. 5. Marra AR, Diekema DJ, Edmond MB. Mycobacterium chimaera infections associ- patients with disseminated disease or those with retained prosthetic ated with contaminated heater-cooler devices for cardiac surgery: outbreak man- devices has not been established. The crude mortality rate of reported agement. Clin Infect Dis 2017; 65:669–74. 6. Sommerstein R, Schreiber PW, Diekema DJ, et al. Mycobacterium chimaera out- cases is approximately 50% [7]. Cure has been achieved for patients break associated with heater-cooler devices: piecing the puzzle together. Infect with limited disease (eg, sternal osteomyelitis) treated with surgical Control Hosp Epidemiol 2017; 38:103–8. 7. Ogunremi T, Taylor G, Johnston L, et  al. Mycobacterium chimaera infections debridement and prolonged antimicrobials [5]. in post-operative patients exposed to heater-cooler devices: An overview. Can Commun Dis Rep 2017; 43:107–13. 8. CDC Advises Hospitals to Alert Patients at Risk from Contaminated Heater- CONCLUSIONS Cooler Devices Used during Cardiac Surgery [press release]. Atlanta, GA: Office of Public Health Preparedness and Response, Centers for Disease Control and We report the first case of M. chimaera infection associated with Prevention; October 13, 2016. https://emergency.cdc.gov/han/han00397.asp. the global HCU outbreak in Western Canada. To our knowledge, Accessed August 30, 2017. this is also the first description of M. chimaera infection present- 9. Kohler P, Kuster SP, Bloemberg G, et  al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections ing with aortic dissection. Our case also highlights the challenge subsequent to open heart surgery. Eur Heart J 2015; 36:2745–53. in making the diagnosis, especially when patients do not have 10. Zweifel SA, Mihic-Probst D, Curcio CA, et al. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic disseminated disease or clinically apparent localized infection surgery. Ophthalmology 2017; 124:178–88. such as sternal osteomyelitis. M. chimaera infections will remain 11. Tortoli E, Rindi L, Garcia MJ, et al. Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium difficult to diagnose given the long incubation period and typi- chimaera sp. nov. Int J Syst Evol Microbiol 2004; 54:1277–85. cally nonspecific presentation. Vigilance is necessary to identify 12. Griffith DE, Aksamit T, Brown-Elliott BA, et  al; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of patients potentially at risk, and we would advise clinicians to con- America. An official ATS/IDSA statement: diagnosis, treatment, and prevention sider M. chimaera infection in those patients with previous aortic of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; surgery presenting with aortic dissection or pseudoaneurysm. 175:367–416. 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Mycobacterium chimaera Infection After Aortic Valve Replacement Presenting With Aortic Dissection and Pseudoaneurysm

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Open Forum Infectious Diseases BRIEF REPORT normal. Transthoracic echocardiogram performed in January Mycobacterium chimaera Infection 2017 at another center was reported as normal. Investigation Aer A ft ortic Valve Replacement for infectious causes including blood cultures, HIV serology, Presenting With Aortic Dissection and viral hepatitis serology, and syphilis serology were negative. A single mycobacterial blood culture was collected and ultim- Pseudoaneurysm ately reported negative after 7 weeks of incubation. 1 1,2 1,2 1,2 3 C. R. O’Neil, G. Taylor, S. Smith, A. M. Joffe, K. Antonation, 1 1 In March 2017, the patient presented to the hospital with a S. Shafran, and D. Kunimoto 1 1-week history of chest pain. He was hemodynamically stable Division of Infectious Diseases, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada; Infection Prevention and Control, Alberta on presentation. Laboratory investigations showed normal com- Health Services, Edmonton, Alberta, Canada; National Microbiology Laboratory, Winnipeg, plete blood count parameters and a slightly elevated troponin Manitoba, Canada I  of 0.07 ug/L (normal being ≤0.02 ug/L). Electrocardiogram showed normal sinus rhythm. Computed tomography of his We present a case of Mycobacterium chimaera infection present- chest revealed a dissection of his ascending aorta with a large ing with aortic dissection and pseudoaneuysm in a 22-year-old man with a past history of aortic valve replacement. Clinicians aortic pseudoaneurysm (Figure 1). He underwent urgent repair should consider M.  chimaera infection in those presenting of his aortic dissection with placement of a prosthetic graft. His with aortic dissection as a late complication of cardiovascular existing mechanical aortic valve was not replaced as transtho- surgery. racic and transesophageal echocardiograms showed no evi- Keywords. aortic dissection; Canada; heater  cooler units; dence of endocarditis or paravalvular abscess. Intraoperative Mycobacterium chimaera. specimens were sent for bacterial and mycobacterial culture. An intraoperative specimen was also submitted for pathologic examination; however, only thrombus was identified. He was CASE discharged with infectious diseases follow-up pending intraop- A 22-year-old man was referred for infectious diseases consult- erative tissue culture results. ation in January 2017. He had a past medical history of a bi- Aer 21  ft days of incubation, intraoperative tissue cultures cuspid aortic valve with mechanical aortic valve replacement at identified a Mycobacterium species ultimately identified as our hospital in June 2015. He reported a 1-year history of inter- Mycobacterium chimaera. e Th isolate was sent to the National mittent drenching night sweats, occurring 1–2  days per week. Microbiology Laboratory (NML; Winnipeg, MB, Canada) for He denied other constitutional symptoms, fever, weight loss, confirmation of identification and whole-genome sequencing. chest pain, or dyspnea. He reported a small pustule on the su- Whole-genome sequencing showed a high degree of related- perior aspect of his sternotomy incision that had resolved with a ness to M.  chimaera isolates from LivaNova 3T Heater Cooler seven-day course of cephalexin 2 months prior to presentation. Units (HCU) used at the University of Alberta Hospital in He was taking warfarin and aspirin. On examination, he looked Edmonton and to publicly available genomes of isolates associ- well with normal vital signs. Cardiorespiratory examination was ated with the HCU outbreak from the United States and Europe unremarkable. There was no evidence of lymphadenopathy or (Supplementary Figure 1). The draft sequence covered >99% of organomegaly. His sternotomy incision was well healed with no the genome with a depth of coverage ~50× as compared with the step deformity or instability. Preliminary investigations showed reference sequence ZUERICH-1 (Accession No. CP015267). The normal complete blood count parameters, electrolytes, cre- HCU used at the time of his original aortic valve replacement in atinine, liver enzymes, and C-reactive protein. Chest x-ray was 2015 could not be confirmed. The total time from cardiovascu- lar surgery to initial clinical presentation was 18.8 months, and Received 26 October 2017; editorial decision 8 January 2018; accepted 15 January 2018. the time from clinical presentation to microbial diagnosis was Correspondence: C.  R. O’Neil, MD, FRCPC, Division of Infectious Diseases, Faculty of 82 days. Susceptibility results performed by microbroth dilution Medicine and Dentistry, 1-124R Clinical Sciences Building, University of Alberta Hospital, are summarized in Supplementary Table 1. 11350 83 Avenue, Edmonton, AB, Canada T6G 2G3 (conar@ualberta.ca). e p Th atient was treated with a combination of azithromycin, Open Forum Infectious Diseases © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases rifabutin, ethambutol, and amikacin. When susceptibility results Society of America. This is an Open Access article distributed under the terms of the Creative were reported, ethambutol was changed to moxifloxacin. The Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any patient was referred for ophthalmologic assessment and was found medium, provided the original work is not altered or transformed in any way, and that the work to have no ocular abnormalities. Therapeutic drug monitoring is properly cited. For commercial re-use, please contact journals.permissions@oup.com DOI: 10.1093/ofid/ofy018 performed at the Infectious Disease Pharmacokinetics Laboratory BRIEF REPORT • OFID • 1 Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy018/4823097 by Ed 'DeepDyve' Gillespie user on 16 March 2018 [4]. Hospital-level contamination of other brands of HCUs (eg, Maquet) with M. chimaera has been described, though these do not appear to be related to the epidemic strain [4]. e e Th arliest described sentinel surgery with subsequent M.  chimaera infection was 2006 [5]. No cases have yet been associated with LivaNova HCUs manufactured aer m ft odifica- tions were made to the manufacturing and maintenance pro- cesses in September 2014. LivaNova holds approximately 70% of the global market share, and the majority of HCUs in clin- ical use were manufactured between 2006 and November 2014. Cardiovascular surgery cannot be performed without HCUs, and existing HCUs cannot be removed from active use without unacceptable disruption in the delivery of cardiovascular sur- gical services. Infection prevention and control and risk miti- Figure  1. Computed tomography of patient with Mycobacterium chimaera in- gation strategies for M.  chimaera have been reviewed in detail fection presenting with aortic dissection with large aortic pseudoaneurysm. *Red arrow indicates false lumen (ie, pseudoaneurysm) of the ascending aorta. elsewhere [5–7]. The precise risk of M.  chimaera infection aer c ft ardiovascular surgery is unknown. A UK national study demonstrated increasing risk of M. chimaera infection aer c ft ar - (Gainesville, FL) confirmed adequate antimicrobial peak concen- diovascular surgery over time peaking at 1 in 2000 in 2014 [3]. trations of rifabutin, azithromycin, and moxifloxacin. Amikacin e Th Centers for Disease Control and Prevention has estimated was discontinued aer 11 w ft eeks of therapy, when subclinical the risk to be 1 in 100 to 1 in 1000 infections per surgery in sites sensorineural hearing loss was noted on screening audiometry. that have already had a case [8]. Ethambutol was thus recommenced. Details of his treatment Patients with M. chimaera infections most oen p ft resent with course are outlined in Supplementary Figure  2. Follow-up oph- nonspecific symptoms such as fatigue, fever, night sweats, and thalmological examination performed aer 12 w ft eeks of therapy weight loss [5, 9]. Local complications such as sternal osteomye- was normal. At the time of manuscript submission, the patient is litis and left ventricular assist device driver site infections have doing well aer 21 w ft eeks of combination therapy. also been described [5]. M. chimaera infection presenting with In November 2016, the infection control department con- aortic dissection has not been previously described. In cases of ducted a retrospective review of all nontuberculous myco- M chimaera infection, physical examination may show lymph- bacteria isolated from patients who underwent open chest adenopathy, organomegaly, or other signs of disseminated in- cardiovascular surgery in Alberta aer J ft anuary 1, 2011. Of fection. Ophthalmologic examination may show choroidal 11 500 patients potentially exposed, we identified no other cases lesions or uveitis in patients with disseminated disease [10]. of M. chimaera infection. As of the date of manuscript accept- Patients with disseminated disease may have laboratory abnor- ance (January 2018), two additional cases of M. chimaera in- malities such as elevated inflammatory markers (eg, C-reactive fection have been identified in patients who have undergone protein), cytopenias, and elevated liver enzymes [7]. Which cardiovascular surgery at our institution. patients should be investigated and which diagnostic investi- gations should be carried out on suspect patients is not clear DISCUSSION [7]. In our case, a single mycobacterial blood culture collected In 2013, Achermann and colleagues reported 2 cases of M. chi- prior to surgery was negative. Even in patients with dissemi- maera infection that were related by random amplification of nated infection, mycobacterial blood cultures may be nega- polymorphic DNA–polymerase chain reaction [1]. Preliminary tive [9]. Histopathology of biopsy specimens characteristically investigations did not identify a nosocomial link. The follow-up shows noncaseating granulomatous inflammation that is rarely outbreak investigation identified what has now been recog- acid-fast bacilli stain–positive. A  number of reported cases nized as a global outbreak of M. chimaera infections associated have been misdiagnosed as sarcoidosis or other inflammatory with contaminated LivaNova 3T HCUs used in cardiothor- conditions and received immunosuppression prior to the diag- acic surgery [2]. Subsequent investigations have demonstrated nosis of M.  chimaera infection [5, 9]. The median time from that M.  chimaera isolated from HCUs can be aerosolized and cardiovascular surgery to presentation is 17 months, though the spread to the environment via the exhaust fan, resulting in longest lag time described is 6 years [5, 7]. Clearly, pending fur- airborne transmission to the patient [2, 3]. Whole-genome ther research, clinicians should consider broadly investigating sequencing has demonstrated that globally distributed clin- patients with previous cardiac surgery presenting with a wide ical cases are genetically similar, suggesting a common-source range of symptoms within the at-risk time frame to avoid miss- outbreak involving the manufacturing of LivaNova 3T HCUs ing patients with M. chimaera infection. 2 • OFID • BRIEF REPORT Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy018/4823097 by Ed 'DeepDyve' Gillespie user on 16 March 2018 Supplementary Data Optimal treatment of M.  chimaera infections has not been Supplementary materials are available at Open Forum Infectious Diseases established. Mycobacterium chimaera is genetically related to online. Consisting of data provided by the authors to benefit the reader, Mycobacterium avium complex [11], and therefore, treatment of the posted materials are not copyedited and are the sole responsibility of M. chimaera infection might be expected to be similar to treatment the authors, so questions or comments should be addressed to the corre- sponding author. of M.  avium complex infection. The American Thoracic Society/ Infectious Diseases Society of America guidelines for disseminated Acknowledgements M. avium complex infection recommend a macrolide (clarithromy- e a Th uthors gratefully acknowledge the patient who provided written con- cin or azithromycin) and ethambutol with or without rifabutin [12]. sent for publication of this case report. The authors also acknowledge the Susceptibility testing, other than for clarithromycin, is not recom- microbiologists and technologists at the Provincial Laboratory for Public Health, Edmonton, AB, Canada, and the National Microbiology Laboratory, mended for treatment-naïve patients as there is a lack of correlation Winnipeg, MB, Canada. Note that the opinions expressed within do not between in vitro susceptibility and clinical outcomes. However, it is represent the opinions of the Public Health Agency of Canada or the unknown whether this is true for M. chimaera. Susceptibility results Government of Canada. Financial support. This work was unfunded. are presented here as it is expected that results will be similar for all Potential conifl cts of interest. All authors: no reported conflicts of strains in this clonal outbreak, barring antibiotic exposure and sub- interest. All authors have submitted the ICMJE Form for Disclosure of sequent development of resistance. For M.  chimaera infections, the Potential Conflicts of Interest. Conflicts that the editors consider relevant to combination of a rifamycin (rifabutin or rifampin), ethambutol, and a the content of the manuscript have been disclosed. macrolide is the most commonly described regimen in the literature [5, 9]. However, it should be noted that the combination of clarithro- References 1. Achermann Y, Rössle M, Hoffmann M, et  al. Prosthetic valve endocarditis and mycin and rifampin may result in subtherapeutic levels of clarithro- bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol 2013; mycin [12]. A combination of antimicrobial therapy and removal of 51:1769–73. 2. Sax H, Bloemberg G, Hasse B, et  al. Prolonged outbreak of Mycobacterium chi- prosthetic material should be considered when feasible. er Th e are no maera infection after open-chest heart surgery. Clin Infect Dis 2015; 61:67–75. data on reinfection rates for newly placed prosthetic devices. Patients 3. Chand M, Lamagni T, Kranzer K, et  al. Insidious risk of severe Mycobacterium failing initial therapy or those patients in whom surgical source con- chimaera infection in cardiac surgery patients. Clin Infect Dis 2017; 64:335–42. 4. van Ingen J, Kohl TA, Kranzer K, et al. Global outbreak of severe Mycobacterium trol cannot be achieved may benefit from the addition of moxifloxa- chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet cin and/or intravenous amikacin [9]. Optimal treatment duration in Infect Dis 2017; 17:p1003–41. 5. Marra AR, Diekema DJ, Edmond MB. Mycobacterium chimaera infections associ- patients with disseminated disease or those with retained prosthetic ated with contaminated heater-cooler devices for cardiac surgery: outbreak man- devices has not been established. The crude mortality rate of reported agement. Clin Infect Dis 2017; 65:669–74. 6. Sommerstein R, Schreiber PW, Diekema DJ, et al. Mycobacterium chimaera out- cases is approximately 50% [7]. Cure has been achieved for patients break associated with heater-cooler devices: piecing the puzzle together. Infect with limited disease (eg, sternal osteomyelitis) treated with surgical Control Hosp Epidemiol 2017; 38:103–8. 7. Ogunremi T, Taylor G, Johnston L, et  al. Mycobacterium chimaera infections debridement and prolonged antimicrobials [5]. in post-operative patients exposed to heater-cooler devices: An overview. Can Commun Dis Rep 2017; 43:107–13. 8. CDC Advises Hospitals to Alert Patients at Risk from Contaminated Heater- CONCLUSIONS Cooler Devices Used during Cardiac Surgery [press release]. Atlanta, GA: Office of Public Health Preparedness and Response, Centers for Disease Control and We report the first case of M. chimaera infection associated with Prevention; October 13, 2016. https://emergency.cdc.gov/han/han00397.asp. the global HCU outbreak in Western Canada. To our knowledge, Accessed August 30, 2017. this is also the first description of M. chimaera infection present- 9. Kohler P, Kuster SP, Bloemberg G, et  al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections ing with aortic dissection. Our case also highlights the challenge subsequent to open heart surgery. Eur Heart J 2015; 36:2745–53. in making the diagnosis, especially when patients do not have 10. Zweifel SA, Mihic-Probst D, Curcio CA, et al. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic disseminated disease or clinically apparent localized infection surgery. Ophthalmology 2017; 124:178–88. such as sternal osteomyelitis. M. chimaera infections will remain 11. Tortoli E, Rindi L, Garcia MJ, et al. Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium difficult to diagnose given the long incubation period and typi- chimaera sp. nov. Int J Syst Evol Microbiol 2004; 54:1277–85. cally nonspecific presentation. Vigilance is necessary to identify 12. Griffith DE, Aksamit T, Brown-Elliott BA, et  al; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of patients potentially at risk, and we would advise clinicians to con- America. An official ATS/IDSA statement: diagnosis, treatment, and prevention sider M. chimaera infection in those patients with previous aortic of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; surgery presenting with aortic dissection or pseudoaneurysm. 175:367–416. BRIEF REPORT • OFID • 3 Downloaded from https://academic.oup.com/ofid/article-abstract/5/2/ofy018/4823097 by Ed 'DeepDyve' Gillespie user on 16 March 2018

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Open Forum Infectious DiseasesOxford University Press

Published: Feb 1, 2018

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