Clinical and Histopathologic Ocular Findings in Disseminated Mycobacterium chimaera Infection after Cardiothoracic Surgery

doi:10.1016/j.ophtha.2016.09.032

Ophthalmology

Volume 124, Issue 2, February 2017, Pages 178-188

https://doi.org/10.1016/j.ophtha.2016.09.032 Get rights and content

Purpose

To investigate and characterize clinical and histopathologic ocular findings in patients with disseminated infection with Mycobacterium chimaera, a slow-growing nontuberculous mycobacterium (NTM), subsequent to cardiothoracic surgery.

Design

Observational case series.

Participants

Five white patients (10 eyes).

Methods

Analysis of clinical ocular findings, including visual acuity, slit-lamp biomicroscopy, spectral-domain optical coherence tomography (SD OCT), fundus autofluorescence (FAF), and fluorescein angiography/indocyanine green (ICG) angiography findings, of patients with a disseminated M. chimaera infection. Biomicroscopic and multimodal imaging findings were compared with the histopathology of 1 patient.

Main Outcome Measures

Clinical and histopathologic ocular findings of M. chimaera.

Results

The mean age of the 5 male patients, diagnosed with endocarditis or aortic graft infection, was 57.8 years. Clinical ocular findings included anterior and intermediate uveitis, optic disc swelling, and white-yellowish choroidal lesions. Multifocal choroidal lesions were observed bilaterally in all patients and were hyperfluorescent on fluorescein angiography, hypofluorescent on ICG angiography, and correlated with choroidal lesions on SD OCT. The extent of choroidal lesions varied from few in 2 patients to widespread miliary lesions in 3 patients leading to localized choroidal thickening with elevation of the overlying retinal layers. Spectral-domain optical coherence tomography through regressing lesions revealed altered outer retinal layers and choroidal hypertransmission. The ocular findings were correlated with the course of the systemic disease. Patients with few choroidal lesions had a favorable outcome, whereas all patients with widespread chorioretinitis died of systemic complications of M. chimaera infection despite long-term targeted antimicrobial therapy. Ocular tissue was obtained from 1 patient at autopsy. Necropsy of 2 eyes of 1 patient revealed prominent granulomatous lymphohistiocytic choroiditis with giant cells.

Conclusions

M. chimaera infection subsequent to cardiothoracic surgery is a novel entity that has been recently described. It involves multiple organ systems and can cause life-threatening disseminated disease. The ocular manifestations documented using multimodal imaging allow us to use the eye as a window to the systemic infection.

Section snippets

Case Detection

As of February 2015, a total of 6 patients with M. chimaera infection who had undergone cardiothoracic surgery at the Zurich Heart Center were identified. Methods of case identification have been described.4, 9 On the basis of a thorough histopathologic analysis of cardiac tissue in the first patient, M. chimaera could be identified by polymerase chain reaction (PCR).⁴ In the subsequent patients, diagnosis was based on positive mycobacterial tissue cultures, 16SrRNA PCR, or mycobacterial blood

Patient Characteristics

Five white patients (10 eyes) aged between 51 and 65 years were examined. All patients were diagnosed with endocarditis or aortic graft infection with M. chimaera after cardiothoracic surgery with extracorporeal circulation performed in Zurich between June 2008 and May 2012. All patients had serology negative for human immunodeficiency virus. The median duration from cardiac surgery to diagnosis of M. chimaera infection was 20 months (range, 16–42 months). The median duration from cardiac

Discussion

These case series describes the spectrum of ocular manifestations of disseminated M. chimaera infections among patients undergoing heart surgery and presenting with aortic graft infection or prosthetic valve endocarditis.⁵ All patients of this series demonstrated mild or severe bilateral choroidal involvement, with some patients showing a miliary picture as a sign of dissemination of mycobacteria. The extent of choroidal lesions was indicative of the degree of systemic disease control, and the

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Cited by (37)

Advanced Cardiovascular Imaging for the Diagnosis of Mycobacterium chimaera Prosthetic Valve Infective Endocarditis After Open-heart Surgery: A Contemporary Systematic Review
2022, Current Problems in Cardiology
Citation Excerpt :
Due to the challenging nature of diagnosis, M chimaera infection should be considered in cases of suspected “sarcoidosis” with granulomatous inflammation of organs in patients with prior median sternotomy. Ophthalmology evaluation is a very sensitive tool in disseminated infections (associated with PVIE), as chorioretinitis is almost always identified by fundoscopy.7 Atypical presentations of disease with associated granulomatous changes in patients with prior cardiac surgery should also trigger a high level of suspicion for M chimaera infection, as it has been described as a cause of rare conditions, such as granulomatous interstitial nephritis (GIN).8
Mycobacterium chimaera is an opportunistic and emerging pathogen, which has been recognized to cause prosthetic valve infective endocarditis and disseminated infection following open-chest cardiac surgery with certain contaminated heater-cooler systems. Diagnostic evaluation of suspected prosthetic valve infective endocarditis due to M chimaera is challenging and requires a very high index of suspicion. This systematic review aims to evaluate prosthetic valve infective endocarditis due to M chimaera. Based on the current literature review, transesophageal echocardiography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography are the most common imaging modalities used to establish the diagnosis. Based on 22 published cases, the reported cases of M chimaera endocarditis have occurred almost entirely in males. Within this cohort, the patients developed endocarditis on average 2.7 years after exposure to contaminated heater-cooler systems during cardiac surgery. M chimaera infection is associated with significant morbidity and mortality.
Ocular manifestations of disseminated Mycobacterium chimaera infection after cardiothoracic surgery
2022, Canadian Journal of Ophthalmology
Citation Excerpt :
Choroidal neovascularization has been reported in 2 patients with M. chimaera infection and has been suggested to be a late complication of this disease.13,21 In an ocular histopathologic analysis of these lesions, 1 affected subject revealed local choroidal inflammation consisting of granulomatous and nongranulomatous, patchy lymphohistiocytic infiltration and is consistent with our findings.12 These ocular lymphohistiocytic and granulomatous changes suggest that M. chimaera had a direct effect on choroidal tissue.
To describe the ocular manifestations of disseminated Mycobacterium chimaera infection after cardiothoracic surgery.
Retrospective, observational case series.
Patients with disseminated M. chimaera infection treated at the University of Alberta Hospital and Royal Alexandra Hospital in Edmonton, Alberta, Canada.
Seven patients (14 eyes) with systemic M. chimaera infection after aortic graft and/or valvular surgeries were reviewed for ocular involvement. Cases were identified based on histopathologic analysis of cardiac tissue, repeat positive mycobacterial blood cultures, and cerebrospinal fluid analysis. Clinical ocular findings, fundus autofluorescence, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and autopsy results are described.
The mean age of our patients was 63 years (range, 22–76 years). Aortic graft and/or valvular surgeries were performed between June 2015 and April 2016. The mean duration from surgery to diagnosis of infection was 27 months (range, 19–36 months). All patients exhibited white-yellowish choroidal lesions. Bilateral, multifocal choroiditis was observed in 6 patients (12 eyes), who died of disseminated M. chimaera infection despite aggressive, multiagent antimicrobial therapy. One patient had a solitary, white-yellow choroidal lesion in the left eye only. Choroidal lesions were hyperfluorescent on late-phase fluorescein angiography and corresponded to localized choroidal thickening and retinal elevation on SD-OCT.
M. chimaera infection after cardiothoracic surgery can cause life-threatening disease involving multiple organ systems. Ocular involvement is an important and possibly early clinical finding, with good correlation to systemic disease severity. Ophthalmological assessment and multimodal imaging may aid in early diagnosis and can be used to monitor disease progression.
Décrire les manifestations oculaires d'une infection à Mycobacterium chimaera disséminée au décours d'une chirurgie cardiothoracique.
Étude rétrospective d'observation portant sur une série de cas.
Patients qui présentaient une infection à M. chimaera disséminée et qui ont été soignés à l'Hôpital de l'Université de l'Alberta et à l'Hôpital Royal Alexandra, à Edmonton (Alberta, Canada).
On a examiné 7 patients (14 yeux) qui présentaient une infection à M. chimaera généralisée après une greffe d'aorte et/ou une chirurgie valvulaire pour vérifier la présence d'une atteinte oculaire. Les cas ont été identifiés grâce à l'analyse histopathologique du tissu cardiaque, à de multiples cultures sanguines qui faisaient état de la présence de la mycobactérie et à l'analyse du liquide céphalorachidien. Sont ainsi décrits les résultats de l'examen clinique oculaire, de l'autofluorescence du fond d’œil, de l'angiographie à la fluorescéine, de la tomographie par cohérence optique en domaine spectral (SD-OCT, pour spectral domain optical coherence tomography) et de l'autopsie.
L’âge moyen de nos patients était de 63 ans (fourchette : 22–76 ans). Les interventions (greffe de l'aorte et/ou chirurgie valvulaire) ont eu lieu entre juin 2015 et avril 2016. Le délai moyen entre l'intervention et le diagnostic de l'infection était de 27 mois (fourchette : 19–36 mois). Tous les patients présentaient des lésions choroïdiennes blanc-jaunâtre. On a observé, chez 6 patients (12 yeux), une choroïdite bilatérale multifocale; ces derniers sont décédés d'une infection à M. chimaera disséminée en dépit d'un traitement antimicrobien énergique reposant sur de nombreux médicaments. Un patient présentait une lésion choroïdienne blanc-jaunâtre unique dans l’œil gauche. Les lésions choroïdiennes étaient hyperfluorescentes selon la phase tardive de l'angiographie à la fluorescéine et correspondaient à un épaississement localisé de la choroïde et à une élévation rétinienne selon la SD-OCT.
L'infection à M. chimaera après une chirurgie cardiothoracique peut entraîner des complications à risque mortel intéressant de nombreux systèmes organiques. L'atteinte oculaire est une caractéristique clinique importante – peut-être même précoce – qui offre une bonne corrélation avec la gravité de l'atteinte systémique. L'examen ophtalmologique et l'imagerie multimodale peuvent donc contribuer à l’établissement d'un diagnostic précoce et servir à la surveillance de l’évolution de l'infection.
Clinical and Multimodal Imaging Findings in Disseminated Mycobacterium Chimaera
2021, Ophthalmology Retina
Citation Excerpt :
Finally, the ophthalmologist should be aware that choroidal neovascularization is a rare, late complication of disseminated M. chimaera infection that has been reported in only 1 other case.9 Osteomyelitis resulting from disseminated M. chimaera infection has been reported independently in 4 patients with disseminated disease.8,17–19 In the first reported case series of ocular M. chimaera infection by Zweifel et al,8 1 of the reported 5 patients demonstrated vertebral osteomyelitis.
To characterize the ophthalmic clinical and multimodal imaging findings of disseminated Mycobacterium chimaera infection after cardiothoracic surgery.
Observational case series.
Four patients (8 eyes) with disseminated M. chimaera infection.
Patients were evaluated with biomicroscopy, OCT and OCT angiography, fundus autofluorescence, and fluorescein and indocyanine green angiography.
Clinical and multimodal imaging findings of patients with disseminated M. chimaera infection.
All 4 patients were white men with a mean age of 65.5 years (range, 60–75 years) who had aortic valve or root infection, or both, with M. chimaera diagnosed by culture, gene sequencing, or both. All 4 patients demonstrated bilateral choroidal lesions on funduscopy and evidence of osteomyelitis by imaging, culture analysis, or both at the time of ocular diagnosis. Indocyanine green and OCT angiography revealed numerous additional subclinical choroidal lesions and were used to track disease response to therapy. Fluorescein angiography and fundus autofluorescence were useful in determining lesion age and activity. All patients were treated with 3- or 4-drug antimycobacterial therapy. Three underwent revision of cardiothoracic surgery with removal of infected graft. One patient went on to demonstrate progressive ocular disease that was noted before each of his surgical revisions. Two patients showed improvement in ocular and systemic disease, however one of them developed a choroidal neovascular membrane. The final patient was a single encounter whose clinical and imaging findings showed longstanding inactive disease.
Ophthalmologists should be aware of the systemic and ocular findings of this rare life-threatening disease. Multimodal imaging is useful in corroborating a diagnosis of ocular M. chimaera and particularly in evaluating patient response to therapy, because choroidal activity seems to mimic systemic activity. Treating physicians should be aware of the co-occurrence of choroiditis and osteomyelitis. Choroidal neovascular membrane can also be a late complication of this disease.
Mycobacterium Chimaera: Clinical and medico-legal considerations starting from a case of sudden acoustic damage
2020, Legal Medicine
Mycobacterium Chimaera is a microorganism that can cause nosocomial infections particularly in patients undergoing cardiac surgery. The specific case presented herein shows an original clinical presentation of the infection: sudden unilateral deafness as a result of septic embolization. Medico-legal experts appointed by the court in a civil liability dispute analyzed the case and submitted their expert opinion. This article analyzes the peculiar and innovative aspect of professional liability that can be attributed to the healthcare facility and the manufacturer of the equipment used in the operating room from a medical-legal point of view.
International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass
2020, Journal of Hospital Infection
Citation Excerpt :
Extracorporeal circulation provides a bloodless field for surgery and maintains vital organ perfusion. M. chimaera has caused disseminated infections following a variety of open-chest surgeries with CPB, including placement of prosthetic heart valves, prosthetic aortic grafts, and mechanical circulatory support devices [3,7] with a proclivity for ocular involvement [5,15] and granulomatous inflammation in multiple organs in some cases that prompted an initial misdiagnosis of sarcoidosis [3,14,15,29]. Infections following on-pump coronary artery bypass graft (CABG) have also been rarely reported [9,30].
Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.
Infections with Mycobacterium chimaera and open chest surgery. An unresolved problem
2019, Medicina Clinica
Mycobacterium chimaera (M. chimaera) es una micobacteria no tuberculosa del complejo Mycobacterium avium complex. Desde 2013 hasta abril de 2018 se han identificado más de 140 casos de infección grave por M. chimaera, todos ellos en pacientes sometidos a cirugía cardiotorácica con circulación extracorpórea.
Las investigaciones epidemiológicas han mostrado que la mayoría de las infecciones tienen una fuente común: módulos de normo-hipotermia contaminados. Estos aparatos poseen en su interior un circuito de agua y ventiladores de enfriamiento que producen un aerosol, que puede contener M. chimaera, contaminar el aire del quirófano y transmitirse al paciente.
La sintomatología clínica puede tardar meses, incluso años, en aparecer tras la cirugía extracorpórea, con una media de 1,5 años, y en general se presenta en forma de síntomas constitucionales. La sarcoidosis es la entidad descrita con mayor frecuencia como error diagnóstico en estos pacientes, por lo que es necesario mantener una elevada sospecha diagnóstica en todos aquellos pacientes con antecedente de cirugía cardíaca con circulación extracorpórea.
Mycobacterium chimaera (M. chimaera) is a non-tuberculous mycobacterium of the Mycobacterium avium complex. Between 2013 and April 2018, more than 140 cases of severe infection have been identified, all of them in patients who had undergone cardiothoracic surgery with extracorporeal circulation.
The epidemiological investigations have shown that the majority of infections have a common source: contaminated normo-hypothermia modules. These devices have a water circuit inside and cooling fans that produce an aerosol, which can be contaminated with M. chimaera, and disperse it into the air in the operating room.
The clinical symptoms can take months, even years to appear after the extracorporeal surgery, with an average of 1.5 years. Sarcoidosis is the most frequently described entity as a misdiagnosis in these patients, so it is necessary to maintain a high diagnostic suspicion in all patients with a history of cardiac surgery with extracorporeal circulation.

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: Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

: This study was performed within the framework of the Vascular Graft Cohort Study supported by the Swiss National Science Foundation (grant no. 32473B_163132). Supported by the University of Zurich (P.M.K.).

: Author Contributions:

: Conception and design: Zweifel

: Data collection: Zweifel, Mihic-Probst, Thielken, Böni, Keller

: Analysis and interpretation: Zweifel, Mihic-Probst, Curcio, Barthelmes, Hasse, Böni, Keller

: Obtained funding: Not applicable

: Overall responsibility: Zweifel, Mihic-Probst, Hasse

^∗: B.H. and C.B. contributed equally to this work (co–senior author).

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Original articleClinical and Histopathologic Ocular Findings in Disseminated Mycobacterium chimaera Infection after Cardiothoracic Surgery