Infections with Mycobacterium chimaera and open chest surgery. An unresolved problem

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An unresolved problem" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "317" "paginaFinal" => "323" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Magda Campins Martí, Blanca Borrás Bermejo, Lluis Armadans Gil" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Magda" "apellidos" => "Campins Martí" "email" => array:1 [ 0 => "mcampins@vhebron.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Blanca" "apellidos" => "Borrás Bermejo" ] 2 => array:2 [ "nombre" => "Lluis" "apellidos" => "Armadans Gil" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Preventiva y Epidemiología, Hospital Universitario Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Infecciones por Mycobacterium chimaera y cirugía cardíaca. Un problema no resuelto" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1104 "Ancho" => 1250 "Tamanyo" => 198504 ] ] "descripcion" => array:1 [ "en" => "Image of a normo-hypothermia module." ] ] ] "textoCompleto" => "Mycobacterium chimaera (M. chimaera) is a non-tuberculous mycobacterium of the Mycobacterium avium complex (MAC).<a class="elsevierStyleCrossRef" href="#bib0250">1</a> It is an environmental opportunistic pathogen with great capacity to form biofilms and has slow growth. It is present in water, soil, dust, and is intrinsically resistant to most disinfectants and antibiotics.It was first described in 2004 as a cause of respiratory infection in patients with chronic lung disease and disseminated infection in immunocompromised patients,<a class="elsevierStyleCrossRefs" href="#bib0250">1–3</a> but in general it was considered a low virulence microorganism.The first description of M. chimaera associated with cardiovascular surgery was made in 2011 in Zurich in two patients with disseminated infection and with a history of valvular prosthetic surgery.<a class="elsevierStyleCrossRef" href="#bib0265">4</a> Both isolates belonged to the same clone, with identical molecular pattern, identified with Random Amplification of Polymorphic DNA. The initial epidemiological investigation identified a total of six infection cases, with a latency time from surgery between 1.5 and 3.6 years. M. chimaera was isolated in the hypothermia equipment water circuit and operating room air samples collected while the unit was in operation.<a class="elsevierStyleCrossRef" href="#bib0270">5</a> From 2013 to April 2018, more than 140 cases of severe infection with M. chimaera have been identified in the world, the majority were fatal, and all of them were found in patients who had undergone cardiothoracic surgery.<a class="elsevierStyleCrossRefs" href="#bib0250">1,6–11</a> However, it is possible that more cases will be identified given the long incubation period of this infection.Although the incidence of confirmed cases is small in relation to the large number of patients undergoing extracorporeal cardiac surgery worldwide, the extent of this outbreak is still not well established. This article will review our current knowledge on the infection's epidemiology, transmission mechanisms, clinical manifestations and prevention and control measures.Epidemiology and transmission mechanismsNormo-hypothermia modules, or thermoregulation devices, are sanitary devices that are used in cardiac surgery, thoracic surgery and in oxygenation with extracorporeal membrane.<a class="elsevierStyleCrossRef" href="#bib0305">12</a> They contain two deposits, one is a compartment for cold water and the other for hot water; the water from each compartment is pumped into two or more circuits closed with a heat exchanger: the one that receives cold water is used to cool the liquid in a cardioplegia circuit (whose purpose is to cool the myocardium and minimise its metabolic activity), and the one that receives hot water is used to transfer heat to the patient through a thermal blanket. The design of normo-hypothermia devices prevents the circuit water and the patient's blood from coming into contact, but the circuit is not hermetic. In addition, the device has cooling ventilators that produce a flow of air through grilles located in its frame (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The water temperature may range between 2 and 41°C during surgery. The water circuits in this equipment have ideal environmental conditions for the growth of a great variety of microorganisms: high counts of Legionella pneumophila, other gram-negative bacteria, fungi and non-tuberculous mycobacteria have all been described.<a class="elsevierStyleCrossRefs" href="#bib0305">12–14</a>Although haematogenous infections were described in the 1970s through cardiopulmonary bypass equipment,<a class="elsevierStyleCrossRef" href="#bib0320">15</a> this transmission mechanism is very unlikely, since in modern equipment the leakage of water into the blood has been observed in a much lower frequency of 0.003%.<a class="elsevierStyleCrossRef" href="#bib0325">16</a> In the epidemiological study carried out by Sax et al. with the Zurich outbreak, no nontuberculous mycobacteria were isolated in the blood cultures performed perioperatively in 32 exposed patients.<a class="elsevierStyleCrossRef" href="#bib0270">5</a> Conversely, M. chimaera was detected in the air expelled by the contaminated equipment's ventilator when it was in operation. This phenomenon was confirmed later by Götting et al.,<a class="elsevierStyleCrossRef" href="#bib0285">8</a> in a study carried out in another centre. Indirect evidence of the association between contaminated air in the operating room and the infection was established by an experimental study conducted in a laminar flow operating theatre by Sommerstein et al.<a class="elsevierStyleCrossRef" href="#bib0305">12</a> to demonstrate that the air current generated by the normo-hypothermia device's ventilator interfered with the operating room's air flow and caused an increase in the concentration of particles in the operation site, especially when the air expelled by the ventilator was facing the operation site. Furthermore, M. chimaera was isolated in sedimentation plates located 5m from the device. Transmission to the patient is rare, possibly because a colony-forming unit of M. chimaera emerging from the aerosol generated by the module is placed on the prosthetic material during the intervention, followed by its replication on-site and subsequent dissemination (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Investigations conducted in the first two hospitals that detected cases of infection and contamination of hypothermia equipment did not isolate M. chimaera in the centre's water supply. Both centres used Livanova 3T equipment (Sorin Group, Milan, Italy). Kuehl et al.<a class="elsevierStyleCrossRef" href="#bib0315">14</a> detected M. chimaera in air samples associated with normo-hypothermia modules in that same model, but not in air exposed to other models that were also contaminated by M. chimaera, and they related it to the design of 3T devices: they have two ventilators in the rear that generate air flow horizontally, one of which (the one that cools the upper board's electronic components) is located above the deposit and, therefore, generates a current that drags the aerosols released through the cracks and orifices in that deposit. The composition of M. chimaera's outer membrane is rich in hydrophobic lipids, favouring its accumulation on the surface of water and its concentration in the aerosols, which are extraordinarily high.<a class="elsevierStyleCrossRef" href="#bib0330">17</a>Subsequent investigations confirmed clonal isolate in the majority of infected patients in Switzerland, Germany, Holland, United Kingdom and USA through molecular biology techniques. This indicated a common source of infection. The high degree of similarity of M. chimaera strains isolated in patients and those detected in LivaNova/Sorin normo-hypothermia modules in use, new modules from the same manufacturer not yet distributed and environmental samples from the place of production, indicates that contamination occurred during the manufacture of the devices.<a class="elsevierStyleCrossRefs" href="#bib0335">18,19</a> A case of M. chimaera infection associated with cardiac surgery with exposure to a module from another manufacturer (Maquet, Rastatt, Germany) contaminated with this mycobacterium has been described; the molecular study identified the hospital's water as the source of contamination.<a class="elsevierStyleCrossRef" href="#bib0340">19</a> Thus, the risk of transmission and infection persists, despite the contamination control of the LivaNova equipment.Clinical manifestations and ways it presents:Infection by M. chimaera after exposure to normo-hypothermia modules’ contaminated aerosols used in cardiopulmonary bypass heart surgery usually presents as constitutional symptoms: fever, night sweats, asthaenia and weight loss.<a class="elsevierStyleCrossRef" href="#bib0345">20</a> Fever of unknown origin is the most common symptom and is present in 80% of cases at the time of diagnosis, according to the largest study published with a series of 30 cases (in the UK).<a class="elsevierStyleCrossRef" href="#bib0350">21</a> Physical examination does not show specific findings, although splenomegaly is present in the majority of patients.Results from laboratory tests are also non-specific, in 70% of cases, isolated lymphopaenia, thrombocytopenia, elevation of liver enzymes with cholestasis and creatinine increase are detected, among others.<a class="elsevierStyleCrossRefs" href="#bib0350">21,22</a>The infection can present as localised (surgical infection), cardiovascular affectation and systemic disease.<a class="elsevierStyleCrossRefs" href="#bib0270">5,6,23</a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the main ways the infection presents. Systemic symptoms usually precede cardiovascular manifestations, which can be severe, in the form of hepatitis, acute renal failure or abscess formation, and are difficult to manage if a diagnosis has not yet been made.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Symptoms may take months, even years, to appear after extracorporeal surgery, with an average of 1.5 years (range 0.1–6.3 years) until the time of diagnosis according to published studies.<a class="elsevierStyleCrossRef" href="#bib0275">6</a>.<a class="elsevierStyleCrossRefs" href="#bib0350">21,23,24</a> A long latency period, its non-specific clinical manifestations, as well as the presence of granulomas in the histopathological study, mean that M. chimaera infections should be considered a differential diagnosis in patients diagnosed with sarcoidosis who have a history of cardiovascular surgery with exposure to normo-hypothermia modules. Sarcoidosis is the most frequently described diagnostic error in these patients.<a class="elsevierStyleCrossRefs" href="#bib0295">10,17,25,26</a>Risk factorsImmunosuppression and especially infection by the human immunodeficiency virus are the classic risk factors of lung disease or disseminated nontuberculous mycobacterial disease. However, this outbreak of M. chimaera occurred in immunocompetent patients, in whom no intrinsic risk factors have been detected associated with an increased risk of acquisition or progression of the disease.Surgeries lasting more than 5h and extracorporeal circulation lasting more than 2h have been associated with an increased risk of infection,<a class="elsevierStyleCrossRef" href="#bib0365">24</a> as has implantation of prosthetic material, due to M. chimaera's ability to form biofilms. Cases have been described in patients without prosthetic material regardless.<a class="elsevierStyleCrossRef" href="#bib0380">27</a>No cases have been documented in health personnel exposed to the aerosols generated by contaminated normo-hypothermia modules in the operating room, which supports the hypothesis that transmission is due to direct contamination in the surgical site.DiagnosisComplementary imaging tests are useful in diagnosis. The most frequent findings in echocardiography are the observation of vegetations, abscesses and valvular regurgitation. Prosthetic valve endocarditis is present in less than 50% of the cases described, which does not rule out cardiac involvement.<a class="elsevierStyleCrossRefs" href="#bib0275">6,21</a> CT scans usually show splenomegaly, pulmonary infiltrates and even aortic root or vascular graft infection, and positron emission tomography shows cardiac disease and peripheral abscesses undetectable in CTs.<a class="elsevierStyleCrossRef" href="#bib0350">21</a>Ocular involvement in the form of choroiditis and uveitis have often been described in these patients. Extension of choroidal lesions seems to be related to the degree of systemic involvement of the disease, which is why serially performing ocular fundus is useful to monitor the evolution and the effectiveness of the treatment.<a class="elsevierStyleCrossRefs" href="#bib0295">10,28</a>A histological study of biopsies of various tissues (hepatic, renal, cutaneous, bone marrow) shows noncaseating granulomas, compatible with systemic connective tissue disease.<a class="elsevierStyleCrossRef" href="#bib0350">21</a>Microbiological diagnosisM. chimaera has been isolated in cardiac tissue and explanted prosthetic valves in patients who have been reoperated for valve replacement and in the autopsies of deceased patients (acid-fast bacilli are observed in wet mount examination), even in those patients without radiological evidence of cardiac tissue or valve prosthesis involvement.<a class="elsevierStyleCrossRef" href="#bib0390">29</a> Blood culture is the most frequent method for diagnosis, and its sensitivity can be increased by taking multiple samples before the start of antibiotic treatment.<a class="elsevierStyleCrossRef" href="#bib0350">21</a> The conventional culture for mycobacteria (blood culture and uroculture) has shown to have a limited diagnostic utility because M. chimaera is a slow-growing mycobacterium that can require up to seven weeks for the culture to be positive.<a class="elsevierStyleCrossRef" href="#bib0275">6</a> Direct identification can be made with the polymerase chain reaction technique and subsequent sequencing or hybridisation of DNA in blood, cardiac tissue, prosthetic material or biopsies.<a class="elsevierStyleCrossRef" href="#bib0395">30</a>There are different commercial kits for the identification of mycobacteria; one example is GenoType®, which consist of a solid-phase hybridisation of 16S, a coding region of the mycobacterial genome.<a class="elsevierStyleCrossRef" href="#bib0400">31</a> The GenoType NTMDR® specifically identifies M. chimaera, but the GenoType CM® and AS® do not differentiate between M. chimaera and Mycobacterium intracellulare (which belong to the MAC complex). As not all laboratories have the capacity to identify M. chimaera, the detection of Mycobacterium intracellulare in a patient with a clinical and epidemiological history of cardiac surgery should lead the professional to consider a diagnosis of M. chimaera infection<a class="elsevierStyleCrossRef" href="#bib0405">32</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>TreatmentWhen diagnosis is not well established, patients usually start treatment with glucocorticoids or other immunosuppressive agents with a slight initial clinical, analytical and radiological improvement, but this actually favours disease progression with greater aggressiveness.<a class="elsevierStyleCrossRef" href="#bib0410">33</a>The combined antibiotic treatment of clarithromycin or azithromycin, rifabutin or rifampicin and ethambutol, with the possibility of adding an intravenous aminoglycoside (amikacin) or a fluoroquinolone (moxifloxacin) is currently the most common. This regimen is recommended by the Infectious Diseases Society of America and the American Thoracic Society for the treatment of disseminated MAC infection,<a class="elsevierStyleCrossRef" href="#bib0415">34</a> but its effectiveness against M. chimaera is unknown.There is no consensus regarding the optimal duration of treatment, although in general long regimens are required because of the difficulty of negativisation of the cultures in some cases. The Infectious Diseases Society of America and the American Thoracic Society<a class="elsevierStyleCrossRef" href="#bib0415">34</a> recommend a minimum treatment time of 12 months for patients not infected with the human immunodeficiency virus who acquire a disseminated MAC disease.Many of the antimicrobial agents are associated with a high percentage of unwanted effects, including liver and kidney damage, spinal toxicity, hearing loss, gastrointestinal upset, hypercalcaemia and lengthening of the QT interval in the electrocardiogram, among others, which sometimes requires suspension or change.Given the capacity of M. chimaera to generate biofilms, as well as the persistent detection of the microorganism in patients despite prolonged antibiotic treatment, some authors suggest that a cure is only possible by removing and replacing the prosthetic material, which in some cases has been related to greater survival.<a class="elsevierStyleCrossRef" href="#bib0350">21</a>According to most studies, fatality is high, occurring in approximately 50% of cases, and is related to the progression of the infection.<a class="elsevierStyleCrossRefs" href="#bib0275">6,21,24,35,36</a> Some studies have associated a delay in diagnosis and treatment with higher mortality, although the impact of early diagnosis and treatment is still unknown. The majority of patients who survive have a torpid evolution and high pharmacological toxicity.<a class="elsevierStyleCrossRef" href="#bib0365">24</a>Epidemiological investigation of possible casesBoth the European Centre for Disease Control (ECDC) and the US Centers for Disease Control and Prevention recommend that all hospitals using normo-hypothermia modules carry out an active case investigation.<a class="elsevierStyleCrossRefs" href="#bib0395">30,37</a> Based on the information provided by the Microbiology Service regarding the nontuberculous mycobacterial isolates in sterile samples, whether these patients have a history of cardiac surgery with exposure to normo-hypothermia modules within the previous four years should be retrospectively reviewed, and whether they meet the definition of probable or confirmed case should be determined.<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> specifies the criteria for suspicion and confirmation of M. chimaera.Prevention and risk control measuresDisinfection of the normo-hypothermia module circuitsPrior to 2015, the manufacturer of the normo-hypothermia 3-T devices recommended disinfecting the interior of circuits with chlorine derivatives.<a class="elsevierStyleCrossRef" href="#bib0435">38</a> This process included changing the device's water every 15 days, to be replaced with filtered water and 100ml of hydrogen peroxide at 3%; adding 50ml of hydrogen peroxide at 3% to the deposit every five days, and completely disinfecting the circuit every three months by filling the deposit with 420ml sodium hypochlorite at 30% and filtered water and circulating the mixture through the circuit.<a class="elsevierStyleCrossRef" href="#bib0440">39</a> In 2015, after the alert associating infections to cardiac surgery, manufacturers of the 3T modules issued new instructions on disinfection, indicating a weekly replacement of the water in the circuit, adding hydrogen peroxide daily, and completely disinfecting the circuit fortnightly with a peracetic acid and hydrogen peroxide.<a class="elsevierStyleCrossRef" href="#bib0445">40</a>However, these recommendations were insufficient, and contamination by M. chimaera continued.<a class="elsevierStyleCrossRef" href="#bib0310">13</a> Hospitals in Birmingham chose to replace tubes and disinfect the modules twice with peracetic acid and hydrogen peroxide; completely disinfect the circuit with peracetic acid and hydrogen peroxide on a weekly basis, and add 100ml peroxide hydrogen at 3% every day.<a class="elsevierStyleCrossRef" href="#bib0440">39</a> By adopting these measures, the normo-hypothermia module water cultures were negative for M. chimaera and total bacterial counts were below 10cfu/l.<a class="elsevierStyleCrossRef" href="#bib0450">41</a> The University Hospital in Zurich chose to change the module water every day; add hydrogen peroxide, and disinfect every two weeks with peracetic acid and hydrogen peroxide. With this regime, M. chimaera continued to be detected in the water but not in the air emitted by the device.<a class="elsevierStyleCrossRef" href="#bib0445">40</a>Microbiological monitoring of contamination of normo-hypothermic modulesIn response to the first publications on outbreaks of M. chimaera infections associated with cardiac surgery, protocols for the microbiological study of water in the normo-hypothermia module circuits were published.<a class="elsevierStyleCrossRefs" href="#bib0455">42,43</a>The ECDC<a class="elsevierStyleCrossRef" href="#bib0455">42</a> recommended taking periodic samples of the water in the modules and air samples (250–500ml) to study the contamination. Currently, the FDA recommends performing sampling only in case of suspected contamination.<a class="elsevierStyleCrossRef" href="#bib0465">44</a> However, Marra et al.<a class="elsevierStyleCrossRef" href="#bib0345">20</a> recommend not sampling for air or water cultures from normo-hypothermia modules, because there is little information about the sensitivity of these procedures, and because of the possibility of obtaining false negative results (positive and negative results have alternated in certain published studies). Conversely, the result of water culture from modules for mycobacterial investigations may take up to eight weeks from sampling, during which the device may be dispersing microorganisms without control measures being taken. Götting et al.<a class="elsevierStyleCrossRef" href="#bib0285">8</a> have suggested using non-fermenting bacteria counting as an alternative indicator of the microbiological quality of the water in such devices and the risk associated with their use. Recently, Schreiber et al.<a class="elsevierStyleCrossRef" href="#bib0470">45</a> established a limit for the detection of M. chimaera of 1000ml samples processed in Mycobacteria Growth Indicator Tube (MGIT 960, BD) ≥2.4cfu/ml. However, the sensitivity for samples below 50ml was lower (detection limit ≥1.44×104ufc/ml).Containment and relocation of the normo-hypothermia modulesGiven the difficulty in effectively disinfecting the normo-hypothermia modules and the complications of the microbiological study of water, considering all the equipment as potentially contaminated has been suggested.<a class="elsevierStyleCrossRef" href="#bib0345">20</a> The ECDC recommends locating normo-hypothermia devices outside operating rooms.<a class="elsevierStyleCrossRef" href="#bib0475">46</a> However, if it is installed in the surgical waiting room and the door is left ajar to allow the passage of the connection tubes between the module and the cardiopulmonary machine, M. chimaera can be detected in the operating room air when the device is operating.<a class="elsevierStyleCrossRef" href="#bib0285">8</a>Some hospitals have decided to place the module outside the operating room and open a space or hole in the wall to allow the connecting tubing between the module and the cardiopulmonary machine, without this installation affecting the surgery ventilation.<a class="elsevierStyleCrossRefs" href="#bib0345">20,47</a> Another alternative, used in some centres, is to place each module inside a stainless steel container with a conduit in its rear end that connects to the operating room air extraction (the negative pressure attracts the aerosol generated by the normo-hypothermia module ventilators).<a class="elsevierStyleCrossRef" href="#bib0445">40</a>Changes in the design of normo-hypothermia modulesThe Sorin Group, manufacturers of the Livanova 3T module, the brand most associated with M. chimaera infections in the world, has made changes to their equipment to minimise the risk. They installed a vacuum gauge and overflow tube connection to a container suction that must be connected to a vacuum source when the normo-hypothermia module is in operation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The purpose of this device, which must be changed every three days, is to collect the aerosol generated by the device and prevent its dispersion.<a class="elsevierStyleCrossRef" href="#bib0485">48</a>ConclusionsThe outbreak of M. chimaera infections associated with contaminated normo-hypothermia modules in patients undergoing cardiac surgery has been a cause of concern and a major challenge in infection control programmes in hospitals around the world.Despite having a low incidence rate and non-specific clinical symptoms, it is a disabling disease, that is difficult to manage and which has a high mortality. It is therefore necessary to maintain high diagnostic suspicion in all those patients with compatible symptoms, history of cardiac surgery with extracorporeal circulation and detection of a MAC complex mycobacterium. Diagnostic confirmation may require that the sample be referred to a laboratory with the capacity to identify M. chimaera.The combined antibiotic treatment of clarithromycin or azithromycin, rifabutin or rifampicin and ethambutol, with the possibility of adding an intravenous aminoglycoside or a fluoroquinolone is currently the most common.Given the difficulty of decontaminating the normo-hypothermia modules and the complications of the microbiological study of water, considering all the equipment as potentially contaminated has been suggested. Currently recommended prevention measures include locating the devices outside the operating room and following the manufacturer's recommendations for disinfection and containment of aerosols.Risk prevention and mitigation measures were only implemented three years ago, since the mechanism of transmission has been known, so we expect more cases to be diagnosed in the near future due to the long latency period of the infection.When a M. chimaera infection related to the use of normo-hypothermia modules is confirmed, an investigation of the possible source of transmission should be carried out, and the case should be declared to the Public Health authorities.Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1178790" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1100245" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1178789" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1100244" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Epidemiology and transmission mechanisms" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Clinical manifestations and ways it presents:" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Risk factors" ] ] ] 6 => array:3 [ "identificador" => "sec0020" "titulo" => "Diagnosis" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Microbiological diagnosis" ] ] ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Treatment" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Epidemiological investigation of possible cases" ] 9 => array:3 [ "identificador" => "sec0040" "titulo" => "Prevention and risk control measures" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Disinfection of the normo-hypothermia module circuits" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Microbiological monitoring of contamination of normo-hypothermic modules" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Containment and relocation of the normo-hypothermia modules" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Changes in the design of normo-hypothermia modules" ] ] ] 10 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-08-03" "fechaAceptado" => "2018-10-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1100245" "palabras" => array:6 [ 0 => "Mycobacterium chimaera" 1 => "Cardiothoracic surgery" 2 => "Normo-hypothermia modules" 3 => "Outbreak" 4 => "Infection" 5 => "Prevention and control" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1100244" "palabras" => array:6 [ 0 => "Mycobacterium chimaera" 1 => "Cirugía cardíaca" 2 => "Módulos de normo-hipotermia" 3 => "Brote" 4 => "infección" 5 => "Prevención y control" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "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." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "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." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Campins Martí M, Borrás Bermejo B, Armadans Gil L. Infecciones por Mycobacterium chimaera y cirugía cardíaca. Un problema no resuelto. Med Clin (Barc). 2019;152:317–323." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1104 "Ancho" => 1250 "Tamanyo" => 198504 ] ] "descripcion" => array:1 [ "en" => "Image of a normo-hypothermia module." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 998 "Ancho" => 2500 "Tamanyo" => 154617 ] ] "descripcion" => array:1 [ "en" => "Transmission mechanism of Mycobacterium chimaera related to normo-hypothermia modules used during cardiac surgery." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Adapted from Sax et al.<a class="elsevierStyleCrossRef" href="#bib0270">5</a> and Allen et al.<a class="elsevierStyleCrossRef" href="#bib0360">23</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Localised infection \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Cardiovascular involvement \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Disseminated disease \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Surgical wound infection (sternotomy or donor saphenous vein resection area) Retrosternal abscess Mediastinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Endocarditis on prosthetic valve Vascular graft infection Myocarditis Paraprosthetic abscesses Pseudoaneurysms Aortic dissection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bacteremia Spondylodiscitis and osteoarthritis Uveitis, chorioretinitis Pneumonitis Cholestatic hepatitis Nephritis Cerebral vasculitis Splenomegaly and hepatomegaly Lung, kidney, spleen, brain embolism. Noncaseating granulomas in liver, spleen, bone marrow and skin \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2008653.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Ways the Mycobacterium chimaera disease presents." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Adapted from Köhler et al.<a class="elsevierStyleCrossRef" href="#bib0275">6</a> and Allen et al.<a class="elsevierStyleCrossRef" href="#bib0490">49</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Suspicion of new case</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Exposure criteria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Patient with a history of cardiovascular surgery that used normo-hypothermia module (increased risk if there is insertion of prosthetic material) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clinical criteria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fever of unknown origin Endocarditis on prosthetic valve Vascular graft infection Sternotomy infection Mediastinitis Disseminated infection Sarcoidosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Microbiological criteria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Haemoculture+M. chimaera CRP+M. chimaera in heart tissue or another invasive sample (biopsy, prosthetic material, pacemaker, etc.) CRP+M. avium complex in invasive sample \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Histopathological criteria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Detection of non-caseating granulomas in biopsy (skin, bone marrow, etc.) and/or foamy macrophages with or without resistant acid-fast bacilli in cardiac tissue or next to prosthetic material \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Exclusion criteria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conventional cultures negative Other causes of culture-negative endocarditis: Coxiella, Bartonella, Brucella, Tropheryma whipplei, Mycoplasma, Chlamydia, Legionella, etc. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2008654.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Suspicion and confirmation of Mycobacterium chimaera disease criteria." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:49 [ 0 => array:3 [ "identificador" => "bib0250" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium chimaera sp. nov" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. 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Infections with Mycobacterium chimaera and open chest surgery. An unresolved problem

Infecciones por Mycobacterium chimaera y cirugía cardíaca. Un problema no resuelto

Magda Campins Martí

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mcampins@vhebron.net

Corresponding author.

, Blanca Borrás Bermejo, Lluis Armadans Gil

Servicio de Medicina Preventiva y Epidemiología, Hospital Universitario Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Mycobacterium chimaera &#40;M&#46; chimaera&#41;</span> is a non-tuberculous mycobacterium of the <span class="elsevierStyleItalic">Mycobacterium avium complex</span> &#40;MAC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">1</span></a> It is an environmental opportunistic pathogen with great capacity to form biofilms and has slow growth&#46; It is present in water&#44; soil&#44; dust&#44; and is intrinsically resistant to most disinfectants and antibiotics&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">It was first described in 2004 as a cause of respiratory infection in patients with chronic lung disease and disseminated infection in immunocompromised patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">1&#8211;3</span></a> but in general it was considered a low virulence microorganism&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The first description of <span class="elsevierStyleItalic">M&#46; chimaera</span> associated with cardiovascular surgery was made in 2011 in Zurich in two patients with disseminated infection and with a history of valvular prosthetic surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">4</span></a> Both isolates belonged to the same clone&#44; with identical molecular pattern&#44; identified with Random Amplification of Polymorphic DNA&#46; The initial epidemiological investigation identified a total of six infection cases&#44; with a latency time from surgery between 1&#46;5 and 3&#46;6 years&#46; <span class="elsevierStyleItalic">M&#46; chimaera</span> was isolated in the hypothermia equipment water circuit and operating room air samples collected while the unit was in operation&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">5</span></a> From 2013 to April 2018&#44; more than 140 cases of severe infection with <span class="elsevierStyleItalic">M&#46; chimaera</span> have been identified in the world&#44; the majority were fatal&#44; and all of them were found in patients who had undergone cardiothoracic surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">1&#44;6&#8211;11</span></a> However&#44; it is possible that more cases will be identified given the long incubation period of this infection&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Although the incidence of confirmed cases is small in relation to the large number of patients undergoing extracorporeal cardiac surgery worldwide&#44; the extent of this outbreak is still not well established&#46; This article will review our current knowledge on the infection&#39;s epidemiology&#44; transmission mechanisms&#44; clinical manifestations and prevention and control measures&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Epidemiology and transmission mechanisms</span><p id="par0025" class="elsevierStylePara elsevierViewall">Normo-hypothermia modules&#44; or thermoregulation devices&#44; are sanitary devices that are used in cardiac surgery&#44; thoracic surgery and in oxygenation with extracorporeal membrane&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">12</span></a> They contain two deposits&#44; one is a compartment for cold water and the other for hot water&#59; the water from each compartment is pumped into two or more circuits closed with a heat exchanger&#58; the one that receives cold water is used to cool the liquid in a cardioplegia circuit &#40;whose purpose is to cool the myocardium and minimise its metabolic activity&#41;&#44; and the one that receives hot water is used to transfer heat to the patient through a thermal blanket&#46; The design of normo-hypothermia devices prevents the circuit water and the patient&#39;s blood from coming into contact&#44; but the circuit is not hermetic&#46; In addition&#44; the device has cooling ventilators that produce a flow of air through grilles located in its frame &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The water temperature may range between 2 and 41<span class="elsevierStyleHsp" style=""></span>&#176;<span class="elsevierStyleSmallCaps">C</span> during surgery&#46; The water circuits in this equipment have ideal environmental conditions for the growth of a great variety of microorganisms&#58; high counts of <span class="elsevierStyleItalic">Legionella pneumophila</span>&#44; other gram-negative bacteria&#44; fungi and non-tuberculous mycobacteria have all been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">12&#8211;14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Although haematogenous infections were described in the 1970s through cardiopulmonary bypass equipment&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">15</span></a> this transmission mechanism is very unlikely&#44; since in modern equipment the leakage of water into the blood has been observed in a much lower frequency of 0&#46;003&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">16</span></a> In the epidemiological study carried out by Sax et al&#46; with the Zurich outbreak&#44; no nontuberculous mycobacteria were isolated in the blood cultures performed perioperatively in 32 exposed patients&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">5</span></a> Conversely&#44; <span class="elsevierStyleItalic">M&#46; chimaera</span> was detected in the air expelled by the contaminated equipment&#39;s ventilator when it was in operation&#46; This phenomenon was confirmed later by G&#246;tting et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">8</span></a> in a study carried out in another centre&#46; Indirect evidence of the association between contaminated air in the operating room and the infection was established by an experimental study conducted in a laminar flow operating theatre by Sommerstein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">12</span></a> to demonstrate that the air current generated by the normo-hypothermia device&#39;s ventilator interfered with the operating room&#39;s air flow and caused an increase in the concentration of particles in the operation site&#44; especially when the air expelled by the ventilator was facing the operation site&#46; Furthermore&#44; <span class="elsevierStyleItalic">M&#46; chimaera</span> was isolated in sedimentation plates located 5<span class="elsevierStyleHsp" style=""></span>m from the device&#46; Transmission to the patient is rare&#44; possibly because a colony-forming unit of <span class="elsevierStyleItalic">M&#46; chimaera</span> emerging from the aerosol generated by the module is placed on the prosthetic material during the intervention&#44; followed by its replication on-site and subsequent dissemination &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Investigations conducted in the first two hospitals that detected cases of infection and contamination of hypothermia equipment did not isolate <span class="elsevierStyleItalic">M&#46; chimaera</span> in the centre&#39;s water supply&#46; Both centres used Livanova 3<span class="elsevierStyleHsp" style=""></span>T equipment &#40;Sorin Group&#44; Milan&#44; Italy&#41;&#46; Kuehl et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">14</span></a> detected <span class="elsevierStyleItalic">M&#46; chimaera</span> in air samples associated with normo-hypothermia modules in that same model&#44; but not in air exposed to other models that were also contaminated by <span class="elsevierStyleItalic">M&#46; chimaera</span>&#44; and they related it to the design of 3<span class="elsevierStyleHsp" style=""></span>T devices&#58; they have two ventilators in the rear that generate air flow horizontally&#44; one of which &#40;the one that cools the upper board&#39;s electronic components&#41; is located above the deposit and&#44; therefore&#44; generates a current that drags the aerosols released through the cracks and orifices in that deposit&#46; The composition of <span class="elsevierStyleItalic">M&#46; chimaera</span>&#39;s outer membrane is rich in hydrophobic lipids&#44; favouring its accumulation on the surface of water and its concentration in the aerosols&#44; which are extraordinarily high&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">17</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Subsequent investigations confirmed clonal isolate in the majority of infected patients in Switzerland&#44; Germany&#44; Holland&#44; United Kingdom and USA through molecular biology techniques&#46; This indicated a common source of infection&#46; The high degree of similarity of <span class="elsevierStyleItalic">M&#46; chimaera</span> strains isolated in patients and those detected in LivaNova&#47;Sorin normo-hypothermia modules in use&#44; new modules from the same manufacturer not yet distributed and environmental samples from the place of production&#44; indicates that contamination occurred during the manufacture of the devices&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">18&#44;19</span></a> A case of <span class="elsevierStyleItalic">M&#46; chimaera</span> infection associated with cardiac surgery with exposure to a module from another manufacturer &#40;Maquet&#44; Rastatt&#44; Germany&#41; contaminated with this mycobacterium has been described&#59; the molecular study identified the hospital&#39;s water as the source of contamination&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">19</span></a> Thus&#44; the risk of transmission and infection persists&#44; despite the contamination control of the LivaNova equipment&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical manifestations and ways it presents&#58;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Infection by <span class="elsevierStyleItalic">M&#46; chimaera</span> after exposure to normo-hypothermia modules&#8217; contaminated aerosols used in cardiopulmonary bypass heart surgery usually presents as constitutional symptoms&#58; fever&#44; night sweats&#44; asthaenia and weight loss&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">20</span></a> Fever of unknown origin is the most common symptom and is present in 80&#37; of cases at the time of diagnosis&#44; according to the largest study published with a series of 30 cases &#40;in the UK&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">21</span></a> Physical examination does not show specific findings&#44; although splenomegaly is present in the majority of patients&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Results from laboratory tests are also non-specific&#44; in 70&#37; of cases&#44; isolated lymphopaenia&#44; thrombocytopenia&#44; elevation of liver enzymes with cholestasis and creatinine increase are detected&#44; among others&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The infection can present as localised &#40;surgical infection&#41;&#44; cardiovascular affectation and systemic disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">5&#44;6&#44;23</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the main ways the infection presents&#46; Systemic symptoms usually precede cardiovascular manifestations&#44; which can be severe&#44; in the form of hepatitis&#44; acute renal failure or abscess formation&#44; and are difficult to manage if a diagnosis has not yet been made&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Symptoms may take months&#44; even years&#44; to appear after extracorporeal surgery&#44; with an average of 1&#46;5 years &#40;range 0&#46;1&#8211;6&#46;3 years&#41; until the time of diagnosis according to published studies&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#46;</span><a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">21&#44;23&#44;24</span></a> A long latency period&#44; its non-specific clinical manifestations&#44; as well as the presence of granulomas in the histopathological study&#44; mean that <span class="elsevierStyleItalic">M&#46; chimaera</span> infections should be considered a differential diagnosis in patients diagnosed with sarcoidosis who have a history of cardiovascular surgery with exposure to normo-hypothermia modules&#46; Sarcoidosis is the most frequently described diagnostic error in these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">10&#44;17&#44;25&#44;26</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Risk factors</span><p id="par0070" class="elsevierStylePara elsevierViewall">Immunosuppression and especially infection by the human immunodeficiency virus are the classic risk factors of lung disease or disseminated nontuberculous mycobacterial disease&#46; However&#44; this outbreak of <span class="elsevierStyleItalic">M&#46; chimaera</span> occurred in immunocompetent patients&#44; in whom no intrinsic risk factors have been detected associated with an increased risk of acquisition or progression of the disease&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Surgeries lasting more than 5<span class="elsevierStyleHsp" style=""></span>h and extracorporeal circulation lasting more than 2<span class="elsevierStyleHsp" style=""></span>h have been associated with an increased risk of infection&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">24</span></a> as has implantation of prosthetic material&#44; due to <span class="elsevierStyleItalic">M&#46; chimaera&#39;s</span> ability to form biofilms&#46; Cases have been described in patients without prosthetic material regardless&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">27</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">No cases have been documented in health personnel exposed to the aerosols generated by contaminated normo-hypothermia modules in the operating room&#44; which supports the hypothesis that transmission is due to direct contamination in the surgical site&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Diagnosis</span><p id="par0085" class="elsevierStylePara elsevierViewall">Complementary imaging tests are useful in diagnosis&#46; The most frequent findings in echocardiography are the observation of vegetations&#44; abscesses and valvular regurgitation&#46; Prosthetic valve endocarditis is present in less than 50&#37; of the cases described&#44; which does not rule out cardiac involvement&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">6&#44;21</span></a> CT scans usually show splenomegaly&#44; pulmonary infiltrates and even aortic root or vascular graft infection&#44; and positron emission tomography shows cardiac disease and peripheral abscesses undetectable in CTs&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">21</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Ocular involvement in the form of choroiditis and uveitis have often been described in these patients&#46; Extension of choroidal lesions seems to be related to the degree of systemic involvement of the disease&#44; which is why serially performing ocular fundus is useful to monitor the evolution and the effectiveness of the treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">10&#44;28</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">A histological study of biopsies of various tissues &#40;hepatic&#44; renal&#44; cutaneous&#44; bone marrow&#41; shows noncaseating granulomas&#44; compatible with systemic connective tissue disease&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">21</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Microbiological diagnosis</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">M&#46; chimaera</span> has been isolated in cardiac tissue and explanted prosthetic valves in patients who have been reoperated for valve replacement and in the autopsies of deceased patients &#40;acid-fast bacilli are observed in wet mount examination&#41;&#44; even in those patients without radiological evidence of cardiac tissue or valve prosthesis involvement&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">29</span></a> Blood culture is the most frequent method for diagnosis&#44; and its sensitivity can be increased by taking multiple samples before the start of antibiotic treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">21</span></a> The conventional culture for mycobacteria &#40;blood culture and uroculture&#41; has shown to have a limited diagnostic utility because <span class="elsevierStyleItalic">M&#46; chimaera is</span> a slow-growing mycobacterium that can require up to seven weeks for the culture to be positive&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">6</span></a> Direct identification can be made with the polymerase chain reaction technique and subsequent sequencing or hybridisation of DNA in blood&#44; cardiac tissue&#44; prosthetic material or biopsies&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">30</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">There are different commercial kits for the identification of mycobacteria&#59; one example is <span class="elsevierStyleItalic">GenoType</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">&#174;</span></span>&#44; which consist of a solid-phase hybridisation of 16S&#44; a coding region of the mycobacterial genome&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">31</span></a> The GenoType NTMDR<span class="elsevierStyleSup">&#174;</span> specifically identifies <span class="elsevierStyleItalic">M&#46; chimaera</span>&#44; but the GenoType CM<span class="elsevierStyleSup">&#174;</span> and AS<span class="elsevierStyleSup">&#174;</span> do not differentiate between <span class="elsevierStyleItalic">M&#46; chimaera</span> and <span class="elsevierStyleItalic">Mycobacterium intracellulare</span> &#40;which belong to the MAC complex&#41;&#46; As not all laboratories have the capacity to identify <span class="elsevierStyleItalic">M&#46; chimaera</span>&#44; the detection of <span class="elsevierStyleItalic">Mycobacterium intracellulare</span> in a patient with a clinical and epidemiological history of cardiac surgery should lead the professional to consider a diagnosis of <span class="elsevierStyleItalic">M</span>&#46; <span class="elsevierStyleItalic">chimaera</span> infection<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">32</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Treatment</span><p id="par0110" class="elsevierStylePara elsevierViewall">When diagnosis is not well established&#44; patients usually start treatment with glucocorticoids or other immunosuppressive agents with a slight initial clinical&#44; analytical and radiological improvement&#44; but this actually favours disease progression with greater aggressiveness&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">33</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The combined antibiotic treatment of clarithromycin or azithromycin&#44; rifabutin or rifampicin and ethambutol&#44; with the possibility of adding an intravenous aminoglycoside &#40;amikacin&#41; or a fluoroquinolone &#40;moxifloxacin&#41; is currently the most common&#46; This regimen is recommended by the Infectious Diseases Society of America and the American Thoracic Society for the treatment of disseminated MAC infection&#44;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">34</span></a> but its effectiveness against <span class="elsevierStyleItalic">M&#46; chimaera</span> is unknown&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">There is no consensus regarding the optimal duration of treatment&#44; although in general long regimens are required because of the difficulty of negativisation of the cultures in some cases&#46; The Infectious Diseases Society of America and the American Thoracic Society<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">34</span></a> recommend a minimum treatment time of 12 months for patients not infected with the human immunodeficiency virus who acquire a disseminated MAC disease&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Many of the antimicrobial agents are associated with a high percentage of unwanted effects&#44; including liver and kidney damage&#44; spinal toxicity&#44; hearing loss&#44; gastrointestinal upset&#44; hypercalcaemia and lengthening of the QT interval in the electrocardiogram&#44; among others&#44; which sometimes requires suspension or change&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Given the capacity of <span class="elsevierStyleItalic">M&#46; chimaera</span> to generate biofilms&#44; as well as the persistent detection of the microorganism in patients despite prolonged antibiotic treatment&#44; some authors suggest that a cure is only possible by removing and replacing the prosthetic material&#44; which in some cases has been related to greater survival&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">21</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">According to most studies&#44; fatality is high&#44; occurring in approximately 50&#37; of cases&#44; and is related to the progression of the infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">6&#44;21&#44;24&#44;35&#44;36</span></a> Some studies have associated a delay in diagnosis and treatment with higher mortality&#44; although the impact of early diagnosis and treatment is still unknown&#46; The majority of patients who survive have a torpid evolution and high pharmacological toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Epidemiological investigation of possible cases</span><p id="par0140" class="elsevierStylePara elsevierViewall">Both the <span class="elsevierStyleItalic">European Centre for</span> Disease Control &#40;ECDC&#41; and the US Centers for Disease Control and Prevention recommend that all hospitals using normo-hypothermia modules carry out an active case investigation&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">30&#44;37</span></a> Based on the information provided by the Microbiology Service regarding the nontuberculous mycobacterial isolates in sterile samples&#44; whether these patients have a history of cardiac surgery with exposure to normo-hypothermia modules within the previous four years should be retrospectively reviewed&#44; and whether they meet the definition of probable or confirmed case should be determined&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> specifies the criteria for suspicion and confirmation of <span class="elsevierStyleItalic">M&#46; chimaera&#46;</span></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Prevention and risk control measures</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Disinfection of the normo-hypothermia module circuits</span><p id="par0150" class="elsevierStylePara elsevierViewall">Prior to 2015&#44; the manufacturer of the normo-hypothermia 3-T devices recommended disinfecting the interior of circuits with chlorine derivatives&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">38</span></a> This process included changing the device&#39;s water every 15 days&#44; to be replaced with filtered water and 100<span class="elsevierStyleHsp" style=""></span>ml of hydrogen peroxide at 3&#37;&#59; adding 50<span class="elsevierStyleHsp" style=""></span>ml of hydrogen peroxide at 3&#37; to the deposit every five days&#44; and completely disinfecting the circuit every three months by filling the deposit with 420<span class="elsevierStyleHsp" style=""></span>ml sodium hypochlorite at 30&#37; and filtered water and circulating the mixture through the circuit&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">39</span></a> In 2015&#44; after the alert associating infections to cardiac surgery&#44; manufacturers of the 3<span class="elsevierStyleHsp" style=""></span>T modules issued new instructions on disinfection&#44; indicating a weekly replacement of the water in the circuit&#44; adding hydrogen peroxide daily&#44; and completely disinfecting the circuit fortnightly with a peracetic acid and hydrogen peroxide&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">40</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">However&#44; these recommendations were insufficient&#44; and contamination by <span class="elsevierStyleItalic">M&#46; chimaera</span> continued&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">13</span></a> Hospitals in Birmingham chose to replace tubes and disinfect the modules twice with peracetic acid and hydrogen peroxide&#59; completely disinfect the circuit with peracetic acid and hydrogen peroxide on a weekly basis&#44; and add 100<span class="elsevierStyleHsp" style=""></span>ml peroxide hydrogen at 3&#37; every day&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">39</span></a> By adopting these measures&#44; the normo-hypothermia module water cultures were negative for <span class="elsevierStyleItalic">M&#46; chimaera</span> and total bacterial counts were below 10<span class="elsevierStyleHsp" style=""></span>cfu&#47;l&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">41</span></a> The University Hospital in Zurich chose to change the module water every day&#59; add hydrogen peroxide&#44; and disinfect every two weeks with peracetic acid and hydrogen peroxide&#46; With this regime&#44; <span class="elsevierStyleItalic">M&#46; chimaera</span> continued to be detected in the water but not in the air emitted by the device&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">40</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Microbiological monitoring of contamination of normo-hypothermic modules</span><p id="par0160" class="elsevierStylePara elsevierViewall">In response to the first publications on outbreaks of <span class="elsevierStyleItalic">M&#46; chimaera</span> infections associated with cardiac surgery&#44; protocols for the microbiological study of water in the normo-hypothermia module circuits were published&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">42&#44;43</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The ECDC<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">42</span></a> recommended taking periodic samples of the water in the modules and air samples &#40;250&#8211;500<span class="elsevierStyleHsp" style=""></span>ml&#41; to study the contamination&#46; Currently&#44; the FDA recommends performing sampling only in case of suspected contamination&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">44</span></a> However&#44; Marra et al&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">20</span></a> recommend not sampling for air or water cultures from normo-hypothermia modules&#44; because there is little information about the sensitivity of these procedures&#44; and because of the possibility of obtaining false negative results &#40;positive and negative results have alternated in certain published studies&#41;&#46; Conversely&#44; the result of water culture from modules for mycobacterial investigations may take up to eight weeks from sampling&#44; during which the device may be dispersing microorganisms without control measures being taken&#46; G&#246;tting et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">8</span></a> have suggested using non-fermenting bacteria counting as an alternative indicator of the microbiological quality of the water in such devices and the risk associated with their use&#46; Recently&#44; Schreiber et al&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">45</span></a> established a limit for the detection of <span class="elsevierStyleItalic">M&#46; chimaera</span> of 1000<span class="elsevierStyleHsp" style=""></span>ml samples processed in Mycobacteria Growth Indicator Tube &#40;MGIT 960&#44; BD&#41; &#8805;2&#46;4<span class="elsevierStyleHsp" style=""></span>cfu&#47;ml&#46; However&#44; the sensitivity for samples below 50<span class="elsevierStyleHsp" style=""></span>ml was lower &#40;detection limit &#8805;1&#46;44<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">4</span><span class="elsevierStyleHsp" style=""></span>ufc&#47;ml&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Containment and relocation of the normo-hypothermia modules</span><p id="par0170" class="elsevierStylePara elsevierViewall">Given the difficulty in effectively disinfecting the normo-hypothermia modules and the complications of the microbiological study of water&#44; considering all the equipment as potentially contaminated has been suggested&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">20</span></a> The ECDC recommends locating normo-hypothermia devices outside operating rooms&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">46</span></a> However&#44; if it is installed in the surgical waiting room and the door is left ajar to allow the passage of the connection tubes between the module and the cardiopulmonary machine&#44; <span class="elsevierStyleItalic">M&#46; chimaera</span> can be detected in the operating room air when the device is operating&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">8</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Some hospitals have decided to place the module outside the operating room and open a space or hole in the wall to allow the connecting tubing between the module and the cardiopulmonary machine&#44; without this installation affecting the surgery ventilation&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">20&#44;47</span></a> Another alternative&#44; used in some centres&#44; is to place each module inside a stainless steel container with a conduit in its rear end that connects to the operating room air extraction &#40;the negative pressure attracts the aerosol generated by the normo-hypothermia module ventilators&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">40</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Changes in the design of normo-hypothermia modules</span><p id="par0180" class="elsevierStylePara elsevierViewall">The Sorin Group&#44; manufacturers of the Livanova 3<span class="elsevierStyleHsp" style=""></span>T module&#44; the brand most associated with <span class="elsevierStyleItalic">M&#46; chimaera</span> infections in the world&#44; has made changes to their equipment to minimise the risk&#46; They installed a vacuum gauge and overflow tube connection to a container suction that must be connected to a vacuum source when the normo-hypothermia module is in operation &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The purpose of this device&#44; which must be changed every three days&#44; is to collect the aerosol generated by the device and prevent its dispersion&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">48</span></a></p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0185" class="elsevierStylePara elsevierViewall">The outbreak of <span class="elsevierStyleItalic">M&#46; chimaera</span> infections associated with contaminated normo-hypothermia modules in patients undergoing cardiac surgery has been a cause of concern and a major challenge in infection control programmes in hospitals around the world&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Despite having a low incidence rate and non-specific clinical symptoms&#44; it is a disabling disease&#44; that is difficult to manage and which has a high mortality&#46; It is therefore necessary to maintain high diagnostic suspicion in all those patients with compatible symptoms&#44; history of cardiac surgery with extracorporeal circulation and detection of a MAC complex mycobacterium&#46; Diagnostic confirmation may require that the sample be referred to a laboratory with the capacity to identify <span class="elsevierStyleItalic">M&#46; chimaera</span>&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The combined antibiotic treatment of clarithromycin or azithromycin&#44; rifabutin or rifampicin and ethambutol&#44; with the possibility of adding an intravenous aminoglycoside or a fluoroquinolone is currently the most common&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Given the difficulty of decontaminating the normo-hypothermia modules and the complications of the microbiological study of water&#44; considering all the equipment as potentially contaminated has been suggested&#46; Currently recommended prevention measures include locating the devices outside the operating room and following the manufacturer&#39;s recommendations for disinfection and containment of aerosols&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Risk prevention and mitigation measures were only implemented three years ago&#44; since the mechanism of transmission has been known&#44; so we expect more cases to be diagnosed in the near future due to the long latency period of the infection&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">When a <span class="elsevierStyleItalic">M&#46; chimaera</span> infection related to the use of normo-hypothermia modules is confirmed&#44; an investigation of the possible source of transmission should be carried out&#44; and the case should be declared to the Public Health authorities&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interest</span><p id="par0215" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Mycobacterium chimaera &#40;M&#46; chimaera&#41;</span> is a non-tuberculous mycobacterium of the <span class="elsevierStyleItalic">Mycobacterium avium complex</span>&#46; Between 2013 and April 2018&#44; more than 140 cases of severe infection have been identified&#44; all of them in patients who had undergone cardiothoracic surgery with extracorporeal circulation&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The epidemiological investigations have shown that the majority of infections have a common source&#58; contaminated normo-hypothermia modules&#46; These devices have a water circuit inside and cooling fans that produce an aerosol&#44; which can be contaminated with <span class="elsevierStyleItalic">M&#46; chimaera</span>&#44; and disperse it into the air in the operating room&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The clinical symptoms can take months&#44; even years to appear after the extracorporeal surgery&#44; with an average of 1&#46;5 years&#46; Sarcoidosis is the most frequently described entity as a misdiagnosis in these patients&#44; so it is necessary to maintain a high diagnostic suspicion in all patients with a history of cardiac surgery with extracorporeal circulation&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Mycobacterium chimaera &#40;M&#46; chimaera&#41;</span> es una micobacteria no tuberculosa del complejo <span class="elsevierStyleItalic">Mycobacterium avium complex</span>&#46; Desde 2013 hasta abril de 2018 se han identificado m&#225;s de 140 casos de infecci&#243;n grave por <span class="elsevierStyleItalic">M&#46; chimaera</span>&#44; todos ellos en pacientes sometidos a cirug&#237;a cardiotor&#225;cica con circulaci&#243;n extracorp&#243;rea&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Las investigaciones epidemiol&#243;gicas han mostrado que la mayor&#237;a de las infecciones tienen una fuente com&#250;n&#58; m&#243;dulos de normo-hipotermia contaminados&#46; Estos aparatos poseen en su interior un circuito de agua y ventiladores de enfriamiento que producen un aerosol&#44; que puede contener <span class="elsevierStyleItalic">M&#46; chimaera</span>&#44; contaminar el aire del quir&#243;fano y transmitirse al paciente&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La sintomatolog&#237;a cl&#237;nica puede tardar meses&#44; incluso a&#241;os&#44; en aparecer tras la cirug&#237;a extracorp&#243;rea&#44; con una media de 1&#44;5 a&#241;os&#44; y en general se presenta en forma de s&#237;ntomas constitucionales&#46; La sarcoidosis es la entidad descrita con mayor frecuencia como error diagn&#243;stico en estos pacientes&#44; por lo que es necesario mantener una elevada sospecha diagn&#243;stica en todos aquellos pacientes con antecedente de cirug&#237;a card&#237;aca con circulaci&#243;n extracorp&#243;rea&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Campins Mart&#237; M&#44; Borr&#225;s Bermejo B&#44; Armadans Gil L&#46; Infecciones por <span class="elsevierStyleItalic">Mycobacterium chimaera</span> y cirug&#237;a card&#237;aca&#46; Un problema no resuelto&#46; Med Clin &#40;Barc&#41;&#46; 2019&#59;152&#58;317&#8211;323&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Localised infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Cardiovascular involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Disseminated disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Surgical wound infection &#40;sternotomy or donor saphenous vein resection area&#41;<br>Retrosternal abscess<br>Mediastinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Endocarditis on prosthetic valve<br>Vascular graft infection<br>Myocarditis<br>Paraprosthetic abscesses<br>Pseudoaneurysms<br>Aortic dissection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bacteremia<br>Spondylodiscitis and osteoarthritis<br>Uveitis&#44; chorioretinitis<br>Pneumonitis<br>Cholestatic hepatitis<br>Nephritis<br>Cerebral vasculitis<br>Splenomegaly and hepatomegaly<br>Lung&#44; kidney&#44; spleen&#44; brain embolism&#46;<br>Noncaseating granulomas in liver&#44; spleen&#44; bone marrow and skin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Adapted from K&#246;hler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">6</span></a> and Allen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">49</span></a></p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Suspicion of new case</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Exposure criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patient with a history of cardiovascular surgery that used normo-hypothermia module &#40;increased risk if there is insertion of prosthetic material&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clinical criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fever of unknown origin<br>Endocarditis on prosthetic valve<br>Vascular graft infection<br>Sternotomy infection<br>Mediastinitis<br>Disseminated infection<br>Sarcoidosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Microbiological criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Haemoculture<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">M&#46; chimaera</span><br>CRP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">M&#46; chimaera</span> in heart tissue or another invasive sample &#40;biopsy&#44; prosthetic material&#44; pacemaker&#44; etc&#46;&#41;<br>CRP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">M&#46; avium complex</span> in invasive sample&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Histopathological criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Detection of non-caseating granulomas in biopsy &#40;skin&#44; bone marrow&#44; etc&#46;&#41; and&#47;or foamy macrophages with or without resistant acid-fast bacilli in cardiac tissue or next to prosthetic material&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Exclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conventional cultures negative<br>Other causes of culture-negative endocarditis&#58; <span class="elsevierStyleItalic">Coxiella&#44; Bartonella&#44; Brucella&#44; Tropheryma whipplei&#44; Mycoplasma&#44; Chlamydia&#44; Legionella</span>&#44; etc&#46;&nbsp;\t\t\t\t\t\t\n
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      "titulo" => "References"
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Article information

ISSN: 23870206
Original language: English

DOI:10.1016/j.medcle.2019.02.006

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