Mycobacterium Chimaera: Comparison
Please note this is a comparison between Version 3 by Vivi Li and Version 2 by Matteo Bolcato.

Mycobacterium Chimaera (MC) in recent years has shown a high infectious capacity via the aerosol by operating room equipment and represent a new frontier of medico legal aspect of nosocomila infections

  • medico legal evaluation
  • clinical risk management

Note:All the information in this draft can be edited by authors. And the entry will be online only after authors edit and submit it.

Definition: Mycobacterium chimaera (MC) is of recent origin and belongs to the large family of non-tuberculous mycobacteria. In recent years, it has shown a high infectious capacity via the aerosol produced by operating room equipment, such as heater–cooler units (HCU). The infection has a long latent period and high mortality rate. Genetic and epidemiological studies have shown that there is a clear link between the infection and a specific HCU model manufactured by LivaNova/Sorin. There is, therefore, a strong possibility that contamination occurs during device construction. 

1. Introduction

Mycobacterium chimaera  (MC) belongs to the large family of non-tuberculous mycobacteria (NTM), which are commonly found in the environment, especially in water. This particular type of mycobacterium was only identified in 2004, when Tortoli et al [1] [1] carried out molecular tests and identified particularly aggressive, epidemiological characteristics that led to the proposal of a new taxonomic classification, Mycobacterium chimaera. The term chimaera  is used due to its hybrid characteristics as compared with the more widely known mycobacteria [2,3] [2][3] and similarity to M. avium and M. intracellulare; the name refers to the creature described in Greek mythology composed of the parts of different animals.

In subsequent years, references to MC in the literature from many parts of the world have increased; the mycobacterium has often been found in patients affected by respiratory problems among others, indicating rising dissemination on a global level [4,5,6,7,8,9,10,11,12][4][5][6][7][8][9][10][11][12].

The clinical manifestations of an MC infection can be varied and may include systemic and aspecific signs and symptoms, such as fever, asthenia, easy fatigue, and other more specific symptoms, such as the formation of emboli on cardiac valves or structures involved in surgery. These formations can then embolize and cause neurological, ocular and auditory damage [13,14][13][14]. The infection has a long latent period that can extend even beyond 70 months. On average, patients present with no symptoms until approximately 20 months [15[15][16],16], which makes diagnosis complex. To date, treatment with antimycobacterial drugs [17,18,19][17][18][19] is still uncertain and the mortality rate remains above 50% [20,21,22][20][21][22].

Although MC in water [23] is generally not dangerous to immunocompetent humans, since 2014 it has been indicated as a cause of infection in patients who have undergone heart surgery with exposure to contaminated heater–cooler units (HCU) [24]. Several patients have been affected by MC with a long incubation period following cardio-surgical operations, despite the small surgical opening in the chest [25,26,27,28,29,30][25][26][27][28][29][30].

Epidemiological studies have demonstrated a clear link between the infection and a specific HCU model: the 3T device manufactured by LivaNova/Sorin. In particular, the tests conducted at the manufacturing site revealed that the HCU water tanks and water present in the system pump assembly area were contaminated. Genetic investigations on the strains of MC on environmental and clinical isolates from patients from three different European countries showed almost identical genome sequences [31]. One study on the whole genome sequence of clinical isolates from patients infected with MC who had undergone open-heart surgery in hospitals in the USA showed few single nucleotide polymorphism differences [32]. Apart from this, there are no references in the literature to cases of infection associated with HCU devices produced by manufacturers other than LivaNova. These factors show the high probability that contamination occurs at the manufacturing site before the devices are dispatched to hospitals. The characteristics of MC enable it to lodge on the device and form a biofilm that is particularly resistant to the disinfection protocols in place. The assumption that contamination first begins in the production stage is supported by the fact that no other operating room equipment such as extracorporeal membrane oxygenation (ECMO) devices, though considered a potential source of infection, has been shown to have caused a patient to contract MC, and none of the studies has detected any contamination of the air in the environment [33]. This confirms the hypothesis that HCU contamination occurs during the manufacturing process.

In order to comprehend the infection mechanism, several studies have been conducted, the results of which show that the exhaust vent from contaminated HCUs can transmit contaminated aerosol to the surgical field by laminar airflow [34]. It has been demonstrated that the probability of NTM infection increases in proportion to the time the patient spends connected to a running HCU; surgeries that exceed 5 hours present a significant risk [35]. These findings suggest that the source of infection is, therefore, the contaminated aerosol that, by means of insufflation, comes into contact with parts of the body exposed during surgery and that MC is able to lodge and create a thin biofilm on body structures, particularly cardiac structures, and manifest over long periods of time [36]

2. Discussion

The dissemination and danger of infections contracted in hospital settings represent a serious public health and medico–legal problem [67,68,69][37][38][39]. In recent decades, there has been an increase in awareness, thereof, due to the social and patient safety implications, an issue that, in Italy, was highlighted by the recent law on the safety of care. This law, no. 24/2017 [70[40][41],71], set forth the need to implement clinical risk management programs in all hospital settings to prevent the occurrence of such infections [72,73][42][43].

Cases of MC infection are particularly difficult and complex for various reasons: a) the time between infection and manifestation of symptoms is extremely long, and the clinical characteristics can vary greatly and are not yet fully understood and described in the literature; b) the characteristics of this particular mycobacterium, the route of infection and the symptomatological presentation are not widely recognized by doctors, who therefore tend not to suspect infection; c) many diagnostic tests for MC are slow and of low sensitivity; a DNA test is needed to confirm identification; d) the hospital infection route is very specific and occurs through routine processes employed within operating rooms; e) elimination of MC biofilms from surfaces by means of routine disinfection procedures poses significant difficulties.

The study of this specific mycobacterium is complex and further microbiological studies are required to be able to fully identify the transmission characteristics thereof and to measure the efficacy of the prevention measures that have been introduced. For the purposes of risk containment, the evidence considered highlights the need to monitor obsolete devices and arrange for replacements, along with the need to position the device outside the operating room using methods to prevent potentially contaminated aerosol from reaching the patient. In addition to these precautions, the use of safe water only in conjunction with uncontaminated devices can protect the patient. However, there is no significant evidence to warrant routine water and air sampling.

From a training perspective, much can be done. Training for all personnel actively involved in operating rooms is essential for ensuring maximum patient safety. Training healthcare professionals involves providing information, on the methods and presentation of MC infections, to all who work in cardiology and cardiac surgery departments, including cardiovascular perfusion technicians, radiology nurses, and technicians practicing in that department, in addition to primary healthcare and internal medicine physicians.

In order to comprehend the true extent of this silent global epidemic, it is essential to develop an organic preventative monitoring system for at-risk patients undergoing cardiac surgery and to conduct retrospective analyses in order to monitor closely patients who have been exposed to the risk of infection.

Identification of cases of infection cannot be left entirely to the ability of doctors; however, comprehensively and thoroughly trained and informed regarding MC, to arrive at a diagnosis from the symptomatology of an individual patient via laboratory tests. MC is an insidious bacterium because it has an aspecific symptomatology, an extremely late manifestation in relation to contact with the host in addition to a completely asymptomatic latent period. An isolated diagnosis of an individual case by an individual doctor is uncertain and, in any case, late as regards the probability of therapeutic success in the specific patient, the identification of the risk and the consequent prevention of other cases originating from the same source.

Since there is increasing evidence of the possibility of HCU contamination from various non-tuberculous mycobacteria, and other opportunistic pathogens and consequent dissemination via aerosol, it is appropriate that monitoring not be limited to MC infection, but extended to all these additional agents.

The general objective of such monitoring is to make a global contribution to the identification of infectious risks connected to the use of electromedical devices in cardiac surgery.

3. Conclusions

From a medico–legal point of view, MC infection represents a new frontier of hospital infection liability in that, not only are the preventative and diagnostic activities of doctors implicated, but also those of the manufacturer. Given this potential twofold liability, litigation involving MC infections requires careful medico–legal analysis, including an evaluation of the quality and timeliness of measures the specific hospital has put in place in view of the recommendations issued by the supervisory boards. It would also be necessary to evaluate on a case-by-case basis whether the manufacturers and Ministry of Health’s recommendations, if applied, were sufficient to counteract the infection effectively and reliably.

New knowledge on the topic of infections associated with electromedical apparatus has clear repercussions on both clinical risk management in regards to risk identification and elimination, and on medico–legal evaluations on healthcare liability, particularly in the context of reconstructing the causal link of infections with long incubation periods and modest clinical manifestations.

References

  1. Tortoli, E.; Rindi, L.; Garcia, M.J.; Chiaradonna, P.; Dei, R.; Garzelli, C.; Kroppenstedt, R.M.; Lari, N.; Mattei, R.; Mariottini, A.; et al. Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium chimaera sp. nov. Int. J. Syst. Evol. Microbiol. 2004, 54, 1277–1285.
  2. Boyle, D.P.; Zembower, T.R.; Reddy, S.; Qi, C. Comparison of clinical features, virulence, and relapse among Mycobacterium avium complex species. Am. J. Respir. Crit. Care Med. 2015, 191, 1310–1317.
  3. Schweickert, B.; Goldenberg, O.; Richter, E.; Göbel, U.B.; Petrich, A.; Buchholz, P.; Moter, A. Occurrence and clinical relevance of Mycobacterium chimaera sp. nov., Germany. Emerg. Infect. Dis. 2008, 14, 1443–1446.
  4. Van Ingen, J.; Hoefsloot, W.; Buijtels, P.C.A.M.; Tortoli, E.; Supply, P.; Dekhuijzen, P.N.R.; Boeree, M.J.; Van Soolingen, D. Characterization of a novel variant of Mycobacterium chimaera. J. Med. Microbiol. 2012, 61, 1234–1239.
  5. Wallace, R.J.; Iakhiaeva, E.; Williams, M.D.; Brown-Elliott, B.A.; Vasireddy, S.; Vasireddy, R.; Lande, L.; Peterson, D.D.; Sawicki, J.; Kwait, R.; et al. Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Mycobacterium avium complex respiratory disease. J. Clin. Microbiol. 2013, 51, 1747–1752.
  6. Durnez, L.; Eddyani, M.; Mgode, G.F.; Katakweba, A.; Katholi, C.R.; Machang’U, R.R.; Kazwala, R.R.; Portaels, F.; Leirs, H. First detection of mycobacteria in African rodents and insectivores, using stratified pool screening. Appl. Environ. Microbiol. 2007, 74, 768–773.
  7. Bills, N.D.; Hinrichs, S.H.; Aden, T.A.; Wickert, R.S.; Iwen, P.C. Molecular identification of Mycobacterium chimaera as a cause of infection in a patient with chronic obstructive pulmonary disease. Diagn. Microbiol. Infect. Dis. 2009, 63, 292–295.
  8. Cohen-Bacrie, S.; David, M.; Le Bel, N.S.; Dubus, J.-C.; Rolain, J.-M.; Drancourt, M. Mycobacterium chimaera pulmonary infection complicating cystic fibrosis: A case report. J. Med. Case Rep. 2011, 5, 473.
  9. Larcher, R.; Lounnas, M.; Dumont, Y.; Michon, A.-L.; Bonzon, L.; Chiron, R.; Carriere, C.; Klouche, K.; Godreuil, S. Mycobacterium chimaera pulmonary disease in cystic fibrosis patients, France, 2010–2017. Emerg. Infect. Dis. 2019, 25, 611–613.
  10. Liu, G.; Chen, S.-T.; Yu, X.; Li, Y.-X.; Ling, Y.; Dong, L.-L.; Zheng, S.-H.; Huang, H.-R. Bacteriological and virulence study of a Mycobacterium chimaera isolate from a patient in China. Antonie Leeuwenhoek 2015, 107, 901–909.
  11. Honda, J.R.; Hasan, N.A.; Davidson, R.M.; Williams, M.D.; Epperson, L.E.; Reynolds, P.R.; Smith, T.; Iakhiaeva, E.; Bankowski, M.J.; Wallace, R.J.; et al. Environmental nontuberculous mycobacteria in the Hawaiian Islands. PLoS Neglected Trop. Dis. 2016, 10, e0005068.
  12. Soetaert, K.; Vluggen, C.; André, E.; Vanhoof, R.; Vanfleteren, B.; Mathys, V. Frequency of Mycobacterium chimaera among Belgian patients, 2015. J. Med. Microbiol. 2016, 65, 1307–1310.
  13. Lau, D.; Cooper, R.; Chen, J.; Sim, V.L.; McCombe, J.A.; Tyrrell, G.J.; Bhargava, R.; Adam, B.; Chapman, E.; Croxen, M.A.; et al. Mycobacterium chimaera encephalitis post-cardiac surgery: A new syndrome. Clin. Infect. Dis. 2019, 70, 692–695.
  14. Zweifel, S.A.; Mihic-Probst, D.; Curcio, C.A.; Barthelmes, D.; Thielken, A.; Keller, P.M.; Hasse, B.; Böni, C. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Ophthalmology 2017, 124, 178–188.
  15. Lecorche, E.; De Ponfilly, G.P.; Mougari, F.; Benmansour, H.; Poisnel, E.; Janvier, F.; Cambau, E. disseminated Mycobacterium chimaera following open-heart surgery, the heater-cooler unit worldwide outbreak: Case report and minireview. Front. Med. 2020, 7.
  16. Chand, M.; Lamagni, T.; Kranzer, K.; Hedge, J.; Moore, G.; Parks, S.; Collins, S.; Elias, C.D.O.; Ahmed, N.; Brown, T.; et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin. Infect. Dis. 2016, 64, 335–342.
  17. Maurer, F.P.; Pohle, P.; Kernbach, M.; Sievert, D.; Hillemann, R.; Rupp, J.; Hombach, M.; Kranzer, K. Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium-intracellulare complex. Clin. Microbiol. Infect. 2019, 25, 379.
  18. Griffith, D.E.; Aksamit, T.; Brown-Elliott, B.A.; Catanzaro, A.; Daley, C.; Gordin, F.; Holland, S.M.; Horsburgh, R.; Huitt, G.; Iademarco, M.F.; et al. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am. J. Respir. Crit. Care Med. 2007, 175, 367–416.
  19. Overton, K.; Mennon, V.; Mothobi, N.; Neild, B.; Martinez, E.; Masters, J.; Grant, P.; Akhunji, Z.; Su, W.-Y.; Torda, A.; et al. Cluster of invasive Mycobacteria chimaera infections following cardiac surgery demonstrating novel clinical features and risks of aortic valve replacement. Intern. Med. J. 2018, 48, 1514–1520.
  20. Kasperbauer, S.H.; Daley, C.L. Mycobacterium chimaera infections related to the heater-cooler unit outbreak: A guide to diagnosis and management. Clin. Infect. Dis. 2018, 68, 1244–1250.
  21. Schreiber, P.W.; Sax, H. Mycobacterium chimaera infections associated with heater-cooler units in cardiac surgery. Curr. Opin. Infect. Dis. 2017, 30, 388–394.
  22. Scriven, J.E.; Scobie, A.; Verlander, N.Q.; Houston, A.; Collyns, T.; Čajić, V.; Kon, O.M.; Mitchell, T.; Rahama, O.; Robinson, A.; et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: Clinical features and outcome of the first 30 cases. Clin. Microbiol. Infect. 2018, 24, 1164–1170.
  23. Falkinham, J.O.; Norton, C.D.; Lechevallier, M.W. Factors influencing numbers of Mycobacterium avium, Mycobacterium intracellulare, and other mycobacteria in drinking water distribution systems. Appl. Environ. Microbiol. 2001, 67, 1225–1231.
  24. Kohler, P.; Kuster, S.P.; Bloemberg, G.; Schulthess, B.; Frank, M.; Tanner, F.C.; Rössle, M.; Böni, C.; Falk, V.; Wilhelm, M.J.; et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur. Hear. J. 2015, 36, 2745–2753.
  25. Sax, H.; Bloemberg, G.; Hasse, B.; Sommerstein, R.; Kohler, P.; Achermann, Y.; Rössle, M.; Falk, V.; Kuster, S.P.; Böttger, E.C.; et al. Prolonged outbreak of Mycobacterium chimaera infection after open-chest heart surgery. Clin. Infect. Dis. 2015, 61, 67–75.
  26. Achermann, Y.; Rössle, M.; Hoffmann, M.; Deggim, V.; Kuster, S.; Zimmermann, D.R.; Bloemberg, G.; Hombach, M.; Hasse, B. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J. Clin. Microbiol. 2013, 51, 1769–1773.
  27. Acosta, F.; Pérez-Lago, L.; Serrano, M.R.; Marín, M.; Kohl, T.A.; Lozano, N.; Niemann, S.; Valerio, M.; Olmedo, M.; Pérez-Granda, M.J.; et al. Fast update of undetected Mycobacterium chimaera infections to reveal unsuspected cases. J. Hosp. Infect. 2018, 100, 451–455.
  28. Williamson, D.A.; Howden, B.; Stinear, T. Mycobacterium chimaera spread from heating and cooling units in heart surgery. New Engl. J. Med. 2017, 376, 600–602. [Google Scholar] [CrossRef]
  29. Bursle, E.; Playford, E.G.; Coulter, C.; Griffin, P. First Australian case of disseminated Mycobacterium chimaera infection post-cardiothoracic surgery. Infect. Dis. Heal. 2017, 22, 1–5.
  30. Sommerstein, R.; Schreiber, P.W.; Diekema, D.J.; Edmond, M.B.; Hasse, B.; Marschall, J.; Sax, H. Mycobacterium chimaera outbreak associated with heater-cooler devices: Piecing the puzzle together. Infect. Control. Hosp. Epidemiol. 2016, 38, 103–108.
  31. Haller, S.; Höller, C.; Jacobshagen, A.; Hamouda, O.; Abu Sin, M.; Monnet, D.L.; Plachouras, D.; Eckmanns, T. Contamination during production of heater-cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: Results of an outbreak investigation in Germany, April 2015 to February 2016. Eurosurveillance 2016, 21.
  32. Perkins, K.M.; Lawsin, A.; Hasan, N.A.; Strong, M.; Halpin, A.L.; Rodger, R.R.; Moulton-Meissner, H.; Crist, M.B.; Schwartz, S.; Marders, J.; et al. Notes from the field: Mycobacterium chimaera contamination of heater-cooler devices used in cardiac surgery-United States. MMWR. Morb. Mortal. Wkly. Rep. 2016, 65, 1117–1118.
  33. Trudzinski, F.C.; Schlotthauer, U.; Kamp, A.; Hennemann, K.; Muellenbach, R.M.; Reischl, U.; Gärtner, B.; Wilkens, H.; Bals, R.; Herrmann, M.; et al. Clinical implications of Mycobacterium chimaera detection in thermoregulatory devices used for extracorporeal membrane oxygenation (ECMO), Germany, 2015 to 2016. Eurosurveillance 2016, 21, 30398.
  34. Götting, T.; Klassen, S.; Jonas, D.; Benk, C.; Serr, A.; Wagner, D.; Ebner, W. Heater-cooler units: Contamination of crucial devices in cardiothoracic surgery. J. Hosp. Infect. 2016, 93, 223–228.
  35. Lyman, M.M.; Grigg, C.; Kinsey, C.B.; Keckler, M.S.; Moulton-Meissner, H.; Cooper, E.; Soe, M.M.; Noble-Wang, J.; Longenberger, A.; Walker, S.R.; et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater-cooler devices1. Emerg. Infect. Dis. 2017, 23, 796–805.
  36. Sommerstein, R.; Rüegg, C.; Kohler, P.; Bloemberg, G.; Kuster, S.P.; Sax, H. Transmission of Mycobacterium chimaera from heater-cooler units during cardiac surgery despite an ultraclean air ventilation system. Emerg. Infect. Dis. 2016, 22, 1008–1013.
  37. Gatto, V.; Scopetti, M.; La Russa, R.; Santurro, A.; Cipolloni, L.; Viola, R.V.; Di Sanzo, M.; Frati, P.; Fineschi, V. Advanced loss eventuality assessment and technical estimates: An integrated approach for management of healthcare-associated infections. Curr. Pharm. Biotechnol. 2019, 20, 625–634.
  38. Giraldi, G.; Montesano, M.; Napoli, C.; Frati, P.; La Russa, R.; Santurro, A.; Scopetti, M.; Orsi, G.B. Healthcare-associated infections due to multidrug-resistant organisms: A surveillance study on extra hospital stay and direct costs. Curr. Pharm. Biotechnol. 2019, 20, 643–652.
  39. La Russa, R.; Finesch, V.; Di Sanzo, M.; Gatto, V.; Santurro, A.; Martini, G.; Scopetti, M.; Frati, P. Personalized medicine and adverse drug reactions: The experience of an italian teaching hospital. Curr. Pharm. Biotechnol. 2017, 18, 274–281.
  40. Bellandi, T.; Tartaglia, R.; Sheikh, A.; Donaldson, L. Italy recognises patient safety as a fundamental right. BMJ 2017, 357, j2277.
  41. Bolcato, M.; Russo, M.; Rodriguez, D.; Aprile, A. Patient blood management implementation in light of new Italian laws on patient’s safety. Transfus. Apher. Sci. 2020, 59, 102811.
  42. Bolcato, M.; Russo, M.; Trentino, K.; Isbister, J.; Rodriguez, D.; Aprile, A. Patient blood management: The best approach to transfusion medicine risk management. Transfus. Apher. Sci. 2020, 59, 102779.
  43. Bolcato, M.; Fassina, G.; Rodriguez, D.; Russo, M.; Aprile, A. The contribution of legal medicine in clinical risk management. BMC Health Serv. Res. 2019, 19, 1–6.
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