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. 2022 Mar 12;22(1):246.
doi: 10.1186/s12879-022-07250-4.

Time-to-positivity of Mycobacterium avium complex in broth culture associates with culture conversion

Christina M Mingora  1 , Bryan A Garcia  2 , Kevin C Mange  3 , Dayton W Yuen  3 , Monika Ciesielska  3 , Jakko van Ingen  4 , Patrick A Flume  1 , Susan E Dorman  5   6
Affiliations

Time-to-positivity of Mycobacterium avium complex in broth culture associates with culture conversion

Christina M Mingora et al. BMC Infect Dis. .

Abstract

Background: Mycobacterial time to positivity (TTP) in liquid culture media has predictive value for longer term outcomes in pulmonary tuberculosis, but has not been thoroughly studied in nontuberculous mycobacterial pulmonary disease. This study sought to evaluate for association between TTP and sputum culture conversion to negative in pulmonary disease caused by Mycobacterium avium complex (MAC).

Methods: Data from the CONVERT trial (NCT02344004) that evaluated efficacy of guideline-based-therapy with or without amikacin liposome inhalation suspension in adults with refractory MAC-PD (Mycobacterium avium complex pulmonary disease) were analyzed. We evaluated TTP measures for sputum obtained prior to study treatment initiation and at monthly visits, assessing reproducibility of measures as well as association of TTP with culture conversion on treatment.

Results: Data from 71 participants with at least one screening visit TTP value were analyzed. For participants who provided more than one sputum sample at a given visit, there was moderate between-sample reliability, with median intraclass correlation coefficient 0.62 (IQR 0.50, 0.70). Median TTP at screening was longer in those participants who subsequently achieved vs. did not achieve culture conversion (10.5 [IQR 9.4] days vs. 4.2 [IQR 2.8] days, p = 0.0002). Individuals with culture conversion by study treatment month 6 were more likely to have a screening TTP > 5 days compared to those who did not achieve culture conversion (OR 15.4, 95% CI 1.9, 716.7, p = 0.0037) and had increasing TTPs over time.

Conclusions: TTP prior to and on treatment is associated with microbiological treatment response in patients with MAC-PD.

Keywords: Biomarker; Mycobacterium avium complex; Non-tuberculous mycobacteria.

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Conflict of interest statement

CMM has received grant funding from the National Institutes of Health. This relationship is outside of the submitted work.

BAG has received grant funding from the CHEST foundation, through grant sponsored by Insmed. He hahs also collected personal fees from Insmed, Synspira, and CMEducation Resources, LLC. These relationships are outside of the submitted work.

KCM, DWY, MC is an employee of Insmed Incorporated. This is relationship is outside of the submitted work.

JvI received reimbursement of laboratory activities with the context of the clinical trail that yielded the data for this manuscript and was member of advisory board.

PAF has received grant funding and personal fees from Insmed Pharmaceuticals. These relationships are outside of the submitted work.

SED has received grant funding from the Centers for Disease Control and Prevention as well as the National Institutes of Health. These relationships are outside of the submitted work. SED also reports that Insmed Incorporated has supported the data analysis for this manuscript.

Figures

Fig. 1
Fig. 1
Reproducibility between screening and baseline time to positivity of Mycobacterium avium complex in liquid culture. Bland–Altman scatter diagrams of the differences between baseline visit time to positivity (TTP) and screening visit TTP plotted against the median of the two measures for the shortest TTP values (a) and the longest TTP values (b). The solid line shows the median and the short horizontal dashed lines represent the 95% confidence intervals of the median. Long horizontal dashed lines represent the 95% limits of agreement, defined as the median difference plus and minus 1.96 times the standard deviation of the differences
Fig. 2
Fig. 2
Distribution of shortest time to positivity measured at screening, by converter status. Distribution of screening time to positivity (TTP) by culture conversion status. Red bars represent participants who subsequently achieved culture conversion to negative by month 6 of study participation, and blue bars represent participants who did not achieve culture conversion. TTP values are rounded up to the next whole day; for participants with more than one screening TTP value, the shortest TTP value was used
Fig. 3
Fig. 3
Time to positivity over time, by converter status. Regression analysis of shortest time to positivity (TTP) over time for converters (red) vs. non-converters (blue). SCR screening, BSL baseline
See this image and copyright information in PMC

References

    1. Jones MM, Winthrop KL, Nelson SD, Duvall SL, Patterson OV, Nechodom KE, Findley KE, Radonovich LJ, Jr, Samore MH, Fennelly KP. Epidemiology of nontuberculous mycobacterial infections in the U.S. Veterans Health Administration. PLoS ONE. 2018;13:e0197976. doi: 10.1371/journal.pone.0197976. - DOI - PMC - PubMed
    1. Hoefsloot W, van Ingen J, Andrejak C, Angeby K, Bauriaud R, Bemer P, Beylis N, Boeree MJ, Cacho J, Chihota V, Chimara E, Churchyard G, Cias R, Daza R, Daley CL, Dekhuijzen PN, Domingo D, Drobniewski F, Esteban J, Fauville-Dufaux M, Folkvardsen DB, Gibbons N, Gomez-Mampaso E, Gonzalez R, Hoffmann H, Hsueh PR, Indra A, Jagielski T, Jamieson F, Jankovic M, Jong E, Keane J, Koh WJ, Lange B, Leao S, Macedo R, Mannsaker T, Marras TK, Maugein J, Milburn HJ, Mlinko T, Morcillo N, Morimoto K, Papaventsis D, Palenque E, Paez-Pena M, Piersimoni C, Polanova M, Rastogi N, Richter E, Ruiz-Serrano MJ, Silva A, da Silva MP, Simsek H, van Soolingen D, Szabo N, Thomson R, Tortola Fernandez T, Tortoli E, Totten SE, Tyrrell G, Vasankari T, Villar M, Walkiewicz R, Winthrop KL, Wagner D, Nontuberculous Mycobacteria Network European Trials Group The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study. Eur Respir J. 2013;42:1604–1613. doi: 10.1183/09031936.00149212. - DOI - PubMed
    1. Furuuchi K, Morimoto K, Yoshiyama T, Tanaka Y, Fujiwara K, Okumura M, Izumi K, Shiraishi Y, Mitarai S, Ogata H, Kurashima A, Yoshimori K, Ohta K, Goto H, Sasaki Y. Interrelational changes in the epidemiology and clinical features of nontuberculous mycobacterial pulmonary disease and tuberculosis in a referral hospital in Japan. Respir Med. 2019;152:74–80. doi: 10.1016/j.rmed.2019.05.001. - DOI - PubMed
    1. Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ, Andrejak C, Bottger EC, Brozek J, Griffith DE, Guglielmetti L, Huitt GA, Knight SL, Leitman P, Marras TK, Olivier KN, Santin M, Stout JE, Tortoli E, van Ingen J, Wagner D, Winthrop KL. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline: executive summary. Clin Infect Dis. 2020;71:e1–e36. doi: 10.1093/cid/ciaa241. - DOI - PMC - PubMed
    1. Kwak N, Park J, Kim E, Lee CH, Han SK, Yim JJ. Treatment outcomes of Mycobacterium avium complex lung disease: a systematic review and meta-analysis. Clin Infect Dis. 2017;65:1077–1084. doi: 10.1093/cid/cix517. - DOI - PubMed

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