A randomised controlled trial of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDITOF-MS) versus conventional microbiological methods for identifying pathogens: Impact on optimal antimicrobial therapy of invasive bacterial and fungal infections in Vietnam

Behzad Nadjm, Vu Quoc Dat, James I Campbell, Vu Tien Viet Dung, Alessandro Torre, Nguyen Thi Cam Tu, Ninh Thi Thanh Van, Dao Tuyet Trinh, Nguyen Phu Huong Lan, Nguyen Vu Trung, Nguyen Thi Thuy Hang, Le Thi Hoi, Stephen Baker, Marcel Wolbers, Nguyen Van Vinh Chau, Nguyen Van Kinh, Guy E Thwaites, H Rogier van Doorn, Heiman F L Wertheim, Behzad Nadjm, Vu Quoc Dat, James I Campbell, Vu Tien Viet Dung, Alessandro Torre, Nguyen Thi Cam Tu, Ninh Thi Thanh Van, Dao Tuyet Trinh, Nguyen Phu Huong Lan, Nguyen Vu Trung, Nguyen Thi Thuy Hang, Le Thi Hoi, Stephen Baker, Marcel Wolbers, Nguyen Van Vinh Chau, Nguyen Van Kinh, Guy E Thwaites, H Rogier van Doorn, Heiman F L Wertheim

Abstract

Objectives: We assessed the impact of MALDITOF-MS on the timeliness of optimal antimicrobial therapy through a parallel-arm randomised controlled trial in two hospitals in Vietnam.

Methods: We recruited patients with a pathogen (bacterial or fungal) cultured from a normally sterile sample. Samples were randomly assigned (1:1) to identification by MALDITOF-MS or conventional diagnostics. The primary outcome was the proportion on optimal antimicrobial therapy within 24 h of positive culture, determined by a blinded independent review committee. Trial registered at ClinicalTrials.gov (NCT02306330).

Results: Among 1005 randomised patients, pathogens were isolated from 628 (326 intervention, 302 control), with 377 excluded as likely contaminants or discharged/died before positive culture. Most isolates were cultured from blood (421/628, 67.0%). The proportion receiving optimal antimicrobial therapy within 24 h (the primary outcome) or 48 h of growth was not significantly different between MALDITOF-MS and control arms (135/326, 41.4% vs 120/302, 39.7%; Adjusted Odds ration (AOR) 1.17, p = 0.40 and 151/326, 46.3% vs 141/302, 46.7%; AOR 1.05 p = 0.79, respectively).

Conclusions: MALDITOF-MS, in the absence of an antimicrobial stewardship programme, did not improve the proportion on optimal antimicrobial therapy at 24 or 48 h after first growth in a lower-middle income setting with high rates of antibiotic resistance.

Keywords: Antibacterial agents; Bacteraemia; Matrix-assisted laser desorption-ionization mass spectrometry; Microbiological techniques; Vietnam.

Copyright © 2019. Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
Trial flow. a2 patients randomised to MALDITOF had identification by routine methods. They were analysed as per their randomisation arm (i.e. included in MALDITOF group).
Fig. 2
Fig. 2
Time from growth to optimal antimicrobial therapy (OAT).

References

    1. Petti C.A., Polage C.R., Quinn T.C., Ronald A.R., Sande M.A. Laboratory medicine in Africa: a barrier to effective health care. Clin Infect Dis. 2006;42(3):377–382.
    1. Caliendo A.M., Gilbert D.N., Ginocchio C.C., Hanson K.E., May L., Quinn T.C. Better tests, better care: improved diagnostics for infectious diseases. Clin Infect Dis Off Publ Infect Dis Soc Am. 2013;57(Suppl 3):S139–S170.
    1. Wertheim H.F., Puthavathana P., Nghiem N.M., van Doorn H.R., Nguyen T.V., Pham H.V. Laboratory capacity building in Asia for infectious disease research: experiences from the South East Asia Infectious Disease Clinical Research Network (SEAICRN) PLoS Med. 2010;7(4)
    1. Yao K., McKinney B., Murphy A., Rotz P., Wafula W., Sendagire H. Improving quality management systems of laboratories in developing countries: an innovative training approach to accelerate laboratory accreditation. Am J Clin Pathol. 2010;134(3):401–409.
    1. Kinh N.V., Wertheim H.F.L., Thwaites G.E., Khue L.N., Thai C.H., Khoa N.T. Developing an antimicrobial resistance reference laboratory and surveillance programme in Vietnam. Lancet Glob Health. 2017;5(12):e1186–e11e7.
    1. Nkengasong J.N., Nsubuga P., Nwanyanwu O., Gershy-Damet G.M., Roscigno G., Bulterys M. Laboratory systems and services are critical in global health: time to end the neglect? Am J Clin Pathol. 2010;134(3):368–373.
    1. Davies J., Abimiku A., Alobo M., Mullan Z., Nugent R., Schneidman M. Sustainable clinical laboratory capacity for health in Africa. Lancet Global Health. 2017;5(3):e248–e249.
    1. Malkin R.A. Design of health care technologies for the developing world. Ann Rev Biomed Eng. 2007;9:567–587.
    1. Dixon P., Davies P., Hollingworth W., Stoddart M., MacGowan A. A systematic review of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry compared to routine microbiological methods for the time taken to identify microbial organisms from positive blood cultures. Eur J Clin Microbiol Infect Dis. 2015;34(5):863–876.
    1. Scott J.S., Sterling S.A., To H., Seals S.R., Jones A.E. Diagnostic performance of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry in blood bacterial infections: a systematic review and meta-analysis. Infect Dis (Lond) 2016;48(7):530–536.
    1. Bizzini A., Greub G. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, a revolution in clinical microbial identification. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2010;16(11):1614–1619.
    1. Ombelet S., Ronat J.B., Walsh T., Yansouni C.P., Cox J., Vlieghe E. Clinical bacteriology in low-resource settings: today's solutions. Lancet Infect Dis. 2018;18(8):e248–e258.
    1. Huang A.M., Newton D., Kunapuli A., Gandhi T.N., Washer L.L., Isip J. Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia. Clin Infect Dis Off Publ Infect Dis Soc Am. 2013;57(9):1237–1245.
    1. Perez K.K., Olsen R.J., Musick W.L., Cernoch P.L., Davis J.R., Peterson L.E. Integrating rapid diagnostics and antimicrobial stewardship improves outcomes in patients with antibiotic-resistant Gram-negative bacteremia. J Infect. 2014;69(3):216–225.
    1. Vlek A.L., Bonten M.J., Boel C.H. Direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry improves appropriateness of antibiotic treatment of bacteremia. PloS One. 2012;7(3):e32589.
    1. Lin W.H., Hwang J.C., Tseng C.C., Chang Y.T., Wu A.B., Yan J.J. MALDI-TOF MS accelerates pathogen identification and may confer benefit in the outcome of peritoneal dialysis-related peritonitis. J Clin Microbiol. 2016;54(5):1381–1383.
    1. Wenzler E., Goff D.A., Mangino J.E., Reed E.E., Wehr A., Bauer K.A. Impact of rapid identification of Acinetobacter Baumannii via matrix-assisted laser desorption ionization time-of-flight mass spectrometry combined with antimicrobial stewardship in patients with pneumonia and/or bacteremia. Diagn Microbiol Infect Dis. 2016;84(1):63–68.
    1. Perez K.K., Olsen R.J., Musick W.L., Cernoch P.L., Davis J.R., Land G.A. Integrating rapid pathogen identification and antimicrobial stewardship significantly decreases hospital costs. Arch Pathol Lab Med. 2013;137(9):1247–1254.
    1. Cosgrove S.E., Li D.X., Tamma P.D., Avdic E., Hadhazy E., Wakefield T. Use of PNA FISH for blood cultures growing Gram-positive cocci in chains without a concomitant antibiotic stewardship intervention does not improve time to appropriate antibiotic therapy. Diagn Microbiol Infect Dis. 2016;86(1):86–92.
    1. Huong V.T., Ha N., Huy N.T., Horby P., Nghia H.D., Thiem V.D. Epidemiology, clinical manifestations, and outcomes of Streptococcus suis infection in humans. Emerg Infect Dis. 2014;20(7):1105–1114.
    1. Lo C.I., Fall B., Sambe-Ba B., Diawara S., Gueye M.W., Mediannikov O. MALDI-TOF mass spectrometry: a powerful tool for clinical microbiology at hopital principal de Dakar, Senegal (West Africa) PloS One. 2015;10(12)
    1. Osthoff M., Gurtler N., Bassetti S., Balestra G., Marsch S., Pargger H. Impact of MALDI-TOF-MS-based identification directly from positive blood cultures on patient management: a controlled clinical trial. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2017;23(2):78–85.
    1. Lockwood A.M., Perez K.K., Musick W.L., Ikwuagwu J.O., Attia E., Fasoranti O.O. Integrating rapid diagnostics and antimicrobial stewardship in two community hospitals improved process measures and antibiotic adjustment time. Infect Control Hosp Epidemiol. 2016;37(4):425–432.
    1. Rivard K.R., Athans V., Lam S.W., Gordon S.M., Procop G.W., Richter S.S. Impact of antimicrobial stewardship and rapid microarray testing on patients with Gram-negative bacteremia. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2017;36(10):1879–1887.
    1. Madaras-Kelly K., Jones M., Remington R., Hill N., Huttner B., Samore M. Development of an antibiotic spectrum score based on veterans affairs culture and susceptibility data for the purpose of measuring antibiotic de-escalation: a modified Delphi approach. Infect Control Hosp Epidemiol. 2014;35(9):1103–1113.
    1. Berkley J., Mwarumba S., Bramham K., Lowe B., Marsh K. Bacteraemia complicating severe malaria in children. Trans R Soc Trop Med Hyg. 1999;93(3):283–286.
    1. La Scola B., Raoult D. Direct identification of bacteria in positive blood culture bottles by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry. PloS One. 2009;4(11):e8041.
    1. Lange C., Schubert S., Jung J., Kostrzewa M., Sparbier K. Quantitative matrix-assisted laser desorption ionization-time of flight mass spectrometry for rapid resistance detection. J Clin Microbiol. 2014;52(12):4155–4162.

Source: PubMed

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