Utilidad del panel de PCR multiplex en el diagnóstico microbiológico temprano y adecuación antimicrobiana en pacientes críticos con neumonía
Palabras clave:
NEUMONÍA, CUIDADOS CRÍTICOS, TÉCNICAS DE AMPLIFICACIÓN DE ÁCIDO NUCLEICO, PANEL PCR MULTIPLEX, DIAGNÓSTICO MICROBIOLÓGICO RÁPIDO
Resumen
Introducción: el inicio temprano de la antibioticoterapia adecuada en infecciones graves se asocia con reducción de la mortalidad. La identificación precoz del microorganismo es fundamental para realizar un tratamiento dirigido y disminuir la terapéutica inicial inapropiada.
Objetivo: valorar la utilidad de una técnica de biología molecular por amplificación de ácidos nucleicos mediante reacción en cadena de polimerasa en tiempo real para diagnóstico microbiológico temprano y adecuación de la antibioticoterapia en pacientes con neumonías graves.
Metodología: estudio retrospectivo observacional llevado a cabo en la unidad de cuidados intensivos del Hospital Maciel. Se analizaron muestras respiratorias de pacientes con diagnóstico o sospecha de neumonía. Se compararon los resultados microbiológicos obtenidos por técnicas convencionales y por biología molecular multiplex (panel neumonía).
Resultados: se incluyeron 53 muestras obtenidas de 51 pacientes. El multiplex detectó al menos un microorganismo en 38 (71,7%) muestras frente a 30 (56.6%) desarrollos en cultivos tradicionales. La mayoría de las muestras se obtuvieron bajo antibioticoterapia previa (86.8%). El panel neumonía mostró un porcentaje de concordancia positiva combinado de 100% y un porcentaje de concordancia negativa del 94% para la identificación bacteriana en comparación con los métodos microbiológicos tradicionales. En 27 (51%) casos el resultado del panel de neumonía determinó un cambio en la conducta terapéutica.
Conclusiones: la técnica de PCR permite la identificación temprana de microorganismos causantes de neumonía optimizando la terapéutica empírica inicial y racionalizando el uso de antimicrobianos. Un panel negativo aleja el planteo de infección respiratoria a gérmenes habituales y permite considerar diagnósticos diferenciales en cuanto a foco y/o etiología.
Citas
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4) Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, Escobar GJ. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 2017; 196(7):856-63. doi: 10.1164/rccm.201609-1848OC.
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6) Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009; 48(1):1-12. doi: 10.1086/595011.
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9) Bassetti M, Kollef MH, Poulakou G. Principles of antimicrobial stewardship for bacterial and fungal infections in ICU. Intensive Care Med 2017; 43(12):1894-7. doi: 10.1007/s00134-017-4922-x.
10) Bhat N, O’Brien KL, Karron RA, Driscoll AJ, Murdoch DR; Pneumonia Methods Working Group. Use and evaluation of molecular diagnostics for pneumonia etiology studies. Clin Infect Dis 2012; 54(Suppl 2):S153-S158. doi: 10.1093/cid/cir1060.
11) Vincent JL, Brealey D, Libert N, Abidi NE, O’Dwyer M, Zacharowski K, et al. Rapid diagnosis of infection in the critically ill, a multicenter study of molecular detection in bloodstream infections, pneumonia, and sterile site infections. Crit Care Med 2015; 43(11):2283-91. doi: 10.1097/CCM.0000000000001249.
12) Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63(5):e61-e111. doi: 10.1093/cid/ciw353.
13) De Bus L, Denys W, Catteeuw J, Gadeyne B, Vermeulen K, Boelens J, et al. Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients: a retrospective observational study. Intensive Care Med 2016; 42(6):1029-39. doi: 10.1007/s00134-016-4301-z.
14) Bantar C, Curcio D, Jasovich A, Bagnulo H, Arango Á, Bavestrello L, et al. Neumonía aguda adquirida en la comunidad en adultos: actualización de los lineamientos para el tratamiento antimicrobiano inicial basado en la evidencia local del Grupo de Trabajo de Sudamérica (ConsenSur II). Rev Chil Infectol 2010; 27(Supl 1):9-38.
15) Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44(Suppl 2):S27-S72. doi: 10.1086/511159.
16) SATI SATI, COMITE DE INFECTOLOGIA CRITICA. Actualización en neumonía asociada a la ventilación mecánica. Rev Arg Ter Int 2019; 12-9. Disponible en: //revista.sati.org.ar/index.php/MI/article/view/688 [Consulta: 17 agosto 2021].
17) Douglas IS. Pulmonary infections in critical/intensive care - rapid diagnosis and optimizing antimicrobial usage. Curr Opin Pulm Med 2017; 23(3):198-203. doi: 10.1097/MCP.0000000000000366.
18) Banerjee R, Teng CB, Cunningham SA, Ihde SM, Steckelberg JM, Moriarty JP, et al. Randomized trial of rapid multiplex polymerase chain reaction-based blood culture identification and susceptibility testing. Clin Infect Dis 2015; 61(7):1071-80. doi: 10.1093/cid/civ447.
19) Peiffer-Smadja N, Bouadma L, Mathy V, Allouche K, Patrier J, Reboul M, et al. Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia. Crit Care 2020; 24(1):366. doi: 10.1186/s13054-020-03067-2.
20) Lee SH, Ruan SY, Pan SC, Lee TF, Chien JY, Hsueh PR. Performance of a multiplex PCR pneumonia panel for the identification of respiratory pathogens and the main determinants of resistance from the lower respiratory tract specimens of adult patients in intensive care units. J Microbiol Immunol Infect 2019; 52(6):920-8. doi: 10.1016/j.jmii.2019.10.009.
21) Buchan BW, Windham S, Balada-Llasat JM, Leber A, Harrington A, Relich R, et al. Practical comparison of the biofire filmarray pneumonia panel to routine diagnostic methods and potential impact on antimicrobial stewardship in adult hospitalized patients with lower respiratory tract infections. J Clin Microbiol 2020; 58(7):e00135-20. doi: 10.1128/JCM.00135-20.
22) Yugueros-Marcos J, Barraud O, Iannello A, Ploy MC, Ginocchio C, Rogatcheva M, et al. New molecular semi-quantification tool provides reliable microbiological evidence for pulmonary infection. Intensive Care Med 2018; 44(12):2302-4. doi: 10.1007/s00134-018-5417-0.
23) Organización Panamericana de Salud. Informe de situación de Influenza. Actualización regional. Disponible en: https://www.paho.org/es/informe-situacion-influenza. [Consulta: 3 setiembre 2021].
24) Garau J, Baquero F, Pérez-Trallero E, Pérez JL, Martín-Sánchez AM, García-Rey C, et al.; NACER Group. Factors impacting on length of stay and mortality of community-acquired pneumonia. Clin Microbiol Infect 2008; 14(4):322-9. doi: 10.1111/j.1469-0691.2007.01915.x.
25) Monard C, Pehlivan J, Auger G, Alviset S, Tran Dinh A, Duquaire P, et al.; ADAPT study group. Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia. Crit Care 2020; 24(1):434. doi: 10.1186/s13054-020-03114-y.
26) Cawcutt K, Kalil AC. Pneumonia with bacterial and viral coinfection. Curr Opin Crit Care 2017; 23(5):385-90. doi: 10.1097/MCC.0000000000000435.
27) Fernández Dorado F, Garro Pau, coords.; Sociedad Catalana de Medicina Intensiva. Conferencia de experto de la SOCMIC 2015: neumonía vírica en el ámbito de la medicina intensiva. Barcelona: Edika Med, 2015.
28) González F, Verga F, Albornoz H, Burghi G, Galiana A, Barbato M. Viral low tract respiratory infection in the intensive care unit. (Resumo do trabalho científico apresentado no XIII Congresso Mundial de Medicina Intensiva. Rio de Janeiro, Brasil: 8-11 nov 2017). Rev Bras Ter Intensiva 2017; (Supl 1):S3.
29) Murdoch DR. How recent advances in molecular tests could impact the diagnosis of pneumonia. Expert Rev Mol Diag 2016; 16(5):533-40. doi: 10.1586/14737159.2016.1156536.
30) Gastli N, Loubinoux J, Daragon M, Lavigne JP, Saint-Sardos P, Pailhoriès H, et al. Multicentric evaluation of BioFire FilmArray Pneumonia Panel for rapid bacteriological documentation of pneumonia. Clin Microbiol Infect 2021; 27(9):1308-14. doi: 10.1016/j.cmi.2020.11.014.
31) Ginocchio CC, Garcia-Mondragon C, Mauerhofer B, Rindlisbacher C; EME Evaluation Program Collaborative. Multinational evaluation of the BioFire® FilmArray® Pneumonia plus Panel as compared to standard of care testing. Eur J Clin Microbiol Infect Dis 2021; 40(8):1609-22. doi: 10.1007/s10096-021-04195-5.
32) Driscoll AJ, Deloria Knoll M, Hammitt LL, Baggett HC, Brooks WA, Feikin DR, et al. The effect of antibiotic exposure and specimen volume on the detection of bacterial pathogens in children with pneumonia. Clin Infect Dis 2017; 64(Suppl 3):S368-S377. doi: 10.1093/cid/cix101.
33) Rand KH, Beal SG, Rivera K, Allen B, Payton T, Lipori GP. Hourly effect of pretreatment with iv antibiotics on blood culture positivity rate in emergency department patients. Open Forum Infect Dis 2019; 6(5):ofz179. doi: 10.1093/ofid/ofz179.
34) Bauer KA, West JE, Balada-Llasat JM, Pancholi P, Stevenson KB, et al. An antimicrobial stewardship program’s impact with rapid polymerase chain reaction methicillin-resistant Staphylococcus aureus/S. aureus blood culture test in patients with S. aureus bacteremia. Clin Infect Dis 2010; 51(9):1074-80. doi: 10.1086/656623.
35) Walker T, Dumadag S, Lee CJ, Lee SH, Bender JM, Cupo Abbott J, et al. Clinical impact of laboratory implementation of verigene bc-gn microarray-based assay for detection of Gram-negative bacteria in positive blood cultures. J Clin Microbiol 2016; 54(7):1789-96. doi: 10.1128/JCM.00376-16.
36) Murphy CN, Fowler R, Balada-Llasat JM, Carroll A, Stone H, Akerele O, et al. Multicenter evaluation of the Biofire FilmArray Pneumonia/pneumonia Plus Panel for detection and quantification of agents of lower respiratory tract infection. J Clin Microbiol 2020; 58(7):e00128-20. doi: 10.1128/JCM.00128-20.
37) Leone M, Malavieille F, Papazian L, Meyssignac B, Cassir N, Textoris J, et al. Routine use of Staphylococcus aureus rapid diagnostic test in patients with suspected ventilator-associated pneumonia. Crit Care 2013; 17(4):R170. doi: 10.1186/cc12849.
38) Timsit JF, Bassetti M, Cremer O, Daikos G, de Waele J, Kallil A, et al. Rationalizing antimicrobial therapy in the ICU: a narrative review. Intensive Care Med 2019; 45(2):172-89. doi: 10.1007/s00134-019-05520-5.
2) Barbier F, Andremont A, Wolff M, Bouadma L. Hospital-acquired pneumonia and ventilator-associated pneumonia: recent advances in epidemiology and management. Curr Opin Pulm Med 2013; 19(3):216-28. doi: 10.1097/MCP.0b013e32835f27be.
3) Zilberberg MD, Shorr AF, Micek ST, Vazquez-Guillamet C, Kollef MH. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care 2014; 18(6):596. doi: 10.1186/s13054-014-0596-8.
4) Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, Escobar GJ. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 2017; 196(7):856-63. doi: 10.1164/rccm.201609-1848OC.
5) Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9.
6) Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009; 48(1):1-12. doi: 10.1086/595011.
7) Bassetti M, De Waele JJ, Eggimann P, Garnacho-Montero J, Kahlmeter G, Menichetti F, et al. Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria. Intensive Care Med 2015; 41(5):776-95. doi: 10.1007/s00134-015-3719-z.
8) Kollef MH, Bassetti M, Francois B, Burnham J, Dimopoulos G, Garnacho-Montero J, et al. The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship. Intensive Care Med 2017; 43(9):1187-97. doi: 10.1007/s00134-017-4682-7.
9) Bassetti M, Kollef MH, Poulakou G. Principles of antimicrobial stewardship for bacterial and fungal infections in ICU. Intensive Care Med 2017; 43(12):1894-7. doi: 10.1007/s00134-017-4922-x.
10) Bhat N, O’Brien KL, Karron RA, Driscoll AJ, Murdoch DR; Pneumonia Methods Working Group. Use and evaluation of molecular diagnostics for pneumonia etiology studies. Clin Infect Dis 2012; 54(Suppl 2):S153-S158. doi: 10.1093/cid/cir1060.
11) Vincent JL, Brealey D, Libert N, Abidi NE, O’Dwyer M, Zacharowski K, et al. Rapid diagnosis of infection in the critically ill, a multicenter study of molecular detection in bloodstream infections, pneumonia, and sterile site infections. Crit Care Med 2015; 43(11):2283-91. doi: 10.1097/CCM.0000000000001249.
12) Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63(5):e61-e111. doi: 10.1093/cid/ciw353.
13) De Bus L, Denys W, Catteeuw J, Gadeyne B, Vermeulen K, Boelens J, et al. Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients: a retrospective observational study. Intensive Care Med 2016; 42(6):1029-39. doi: 10.1007/s00134-016-4301-z.
14) Bantar C, Curcio D, Jasovich A, Bagnulo H, Arango Á, Bavestrello L, et al. Neumonía aguda adquirida en la comunidad en adultos: actualización de los lineamientos para el tratamiento antimicrobiano inicial basado en la evidencia local del Grupo de Trabajo de Sudamérica (ConsenSur II). Rev Chil Infectol 2010; 27(Supl 1):9-38.
15) Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44(Suppl 2):S27-S72. doi: 10.1086/511159.
16) SATI SATI, COMITE DE INFECTOLOGIA CRITICA. Actualización en neumonía asociada a la ventilación mecánica. Rev Arg Ter Int 2019; 12-9. Disponible en: //revista.sati.org.ar/index.php/MI/article/view/688 [Consulta: 17 agosto 2021].
17) Douglas IS. Pulmonary infections in critical/intensive care - rapid diagnosis and optimizing antimicrobial usage. Curr Opin Pulm Med 2017; 23(3):198-203. doi: 10.1097/MCP.0000000000000366.
18) Banerjee R, Teng CB, Cunningham SA, Ihde SM, Steckelberg JM, Moriarty JP, et al. Randomized trial of rapid multiplex polymerase chain reaction-based blood culture identification and susceptibility testing. Clin Infect Dis 2015; 61(7):1071-80. doi: 10.1093/cid/civ447.
19) Peiffer-Smadja N, Bouadma L, Mathy V, Allouche K, Patrier J, Reboul M, et al. Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia. Crit Care 2020; 24(1):366. doi: 10.1186/s13054-020-03067-2.
20) Lee SH, Ruan SY, Pan SC, Lee TF, Chien JY, Hsueh PR. Performance of a multiplex PCR pneumonia panel for the identification of respiratory pathogens and the main determinants of resistance from the lower respiratory tract specimens of adult patients in intensive care units. J Microbiol Immunol Infect 2019; 52(6):920-8. doi: 10.1016/j.jmii.2019.10.009.
21) Buchan BW, Windham S, Balada-Llasat JM, Leber A, Harrington A, Relich R, et al. Practical comparison of the biofire filmarray pneumonia panel to routine diagnostic methods and potential impact on antimicrobial stewardship in adult hospitalized patients with lower respiratory tract infections. J Clin Microbiol 2020; 58(7):e00135-20. doi: 10.1128/JCM.00135-20.
22) Yugueros-Marcos J, Barraud O, Iannello A, Ploy MC, Ginocchio C, Rogatcheva M, et al. New molecular semi-quantification tool provides reliable microbiological evidence for pulmonary infection. Intensive Care Med 2018; 44(12):2302-4. doi: 10.1007/s00134-018-5417-0.
23) Organización Panamericana de Salud. Informe de situación de Influenza. Actualización regional. Disponible en: https://www.paho.org/es/informe-situacion-influenza. [Consulta: 3 setiembre 2021].
24) Garau J, Baquero F, Pérez-Trallero E, Pérez JL, Martín-Sánchez AM, García-Rey C, et al.; NACER Group. Factors impacting on length of stay and mortality of community-acquired pneumonia. Clin Microbiol Infect 2008; 14(4):322-9. doi: 10.1111/j.1469-0691.2007.01915.x.
25) Monard C, Pehlivan J, Auger G, Alviset S, Tran Dinh A, Duquaire P, et al.; ADAPT study group. Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia. Crit Care 2020; 24(1):434. doi: 10.1186/s13054-020-03114-y.
26) Cawcutt K, Kalil AC. Pneumonia with bacterial and viral coinfection. Curr Opin Crit Care 2017; 23(5):385-90. doi: 10.1097/MCC.0000000000000435.
27) Fernández Dorado F, Garro Pau, coords.; Sociedad Catalana de Medicina Intensiva. Conferencia de experto de la SOCMIC 2015: neumonía vírica en el ámbito de la medicina intensiva. Barcelona: Edika Med, 2015.
28) González F, Verga F, Albornoz H, Burghi G, Galiana A, Barbato M. Viral low tract respiratory infection in the intensive care unit. (Resumo do trabalho científico apresentado no XIII Congresso Mundial de Medicina Intensiva. Rio de Janeiro, Brasil: 8-11 nov 2017). Rev Bras Ter Intensiva 2017; (Supl 1):S3.
29) Murdoch DR. How recent advances in molecular tests could impact the diagnosis of pneumonia. Expert Rev Mol Diag 2016; 16(5):533-40. doi: 10.1586/14737159.2016.1156536.
30) Gastli N, Loubinoux J, Daragon M, Lavigne JP, Saint-Sardos P, Pailhoriès H, et al. Multicentric evaluation of BioFire FilmArray Pneumonia Panel for rapid bacteriological documentation of pneumonia. Clin Microbiol Infect 2021; 27(9):1308-14. doi: 10.1016/j.cmi.2020.11.014.
31) Ginocchio CC, Garcia-Mondragon C, Mauerhofer B, Rindlisbacher C; EME Evaluation Program Collaborative. Multinational evaluation of the BioFire® FilmArray® Pneumonia plus Panel as compared to standard of care testing. Eur J Clin Microbiol Infect Dis 2021; 40(8):1609-22. doi: 10.1007/s10096-021-04195-5.
32) Driscoll AJ, Deloria Knoll M, Hammitt LL, Baggett HC, Brooks WA, Feikin DR, et al. The effect of antibiotic exposure and specimen volume on the detection of bacterial pathogens in children with pneumonia. Clin Infect Dis 2017; 64(Suppl 3):S368-S377. doi: 10.1093/cid/cix101.
33) Rand KH, Beal SG, Rivera K, Allen B, Payton T, Lipori GP. Hourly effect of pretreatment with iv antibiotics on blood culture positivity rate in emergency department patients. Open Forum Infect Dis 2019; 6(5):ofz179. doi: 10.1093/ofid/ofz179.
34) Bauer KA, West JE, Balada-Llasat JM, Pancholi P, Stevenson KB, et al. An antimicrobial stewardship program’s impact with rapid polymerase chain reaction methicillin-resistant Staphylococcus aureus/S. aureus blood culture test in patients with S. aureus bacteremia. Clin Infect Dis 2010; 51(9):1074-80. doi: 10.1086/656623.
35) Walker T, Dumadag S, Lee CJ, Lee SH, Bender JM, Cupo Abbott J, et al. Clinical impact of laboratory implementation of verigene bc-gn microarray-based assay for detection of Gram-negative bacteria in positive blood cultures. J Clin Microbiol 2016; 54(7):1789-96. doi: 10.1128/JCM.00376-16.
36) Murphy CN, Fowler R, Balada-Llasat JM, Carroll A, Stone H, Akerele O, et al. Multicenter evaluation of the Biofire FilmArray Pneumonia/pneumonia Plus Panel for detection and quantification of agents of lower respiratory tract infection. J Clin Microbiol 2020; 58(7):e00128-20. doi: 10.1128/JCM.00128-20.
37) Leone M, Malavieille F, Papazian L, Meyssignac B, Cassir N, Textoris J, et al. Routine use of Staphylococcus aureus rapid diagnostic test in patients with suspected ventilator-associated pneumonia. Crit Care 2013; 17(4):R170. doi: 10.1186/cc12849.
38) Timsit JF, Bassetti M, Cremer O, Daikos G, de Waele J, Kallil A, et al. Rationalizing antimicrobial therapy in the ICU: a narrative review. Intensive Care Med 2019; 45(2):172-89. doi: 10.1007/s00134-019-05520-5.
Publicado
2022-06-13
Cómo citar
1.
Mauro S, Verga F, Galiana A, Vieytes M, Godino M, Barbato M. Utilidad del panel de PCR multiplex en el diagnóstico microbiológico temprano y adecuación antimicrobiana en pacientes críticos con neumonía. Rev. Méd. Urug. [Internet]. 13 de junio de 2022 [citado 22 de diciembre de 2024];38(2):e38204. Disponible en: https://www2.rmu.org.uy/ojsrmu311/index.php/rmu/article/view/885
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