Validity of Time to Sputum Culture Conversion to Predict Cure in Patients with Multidrug-Resistant Tuberculosis: A Retrospective Single-Center Study

Arshad Javaid Khyber Medical University, Peshawar, Pakistan;
Programmatic Management Unit of Drug-Resistant Tuberculosis, Lady Reading Hospital, Peshawar, Pakistan;

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Nafees Ahmad Faculty of Pharmacy and Health Sciences, University of Baluchistan,Quetta, Pakistan;

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Afsar Khan Afridi Programmatic Management Unit of Drug-Resistant Tuberculosis, Lady Reading Hospital, Peshawar, Pakistan;

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Anila Basit Department of Pulmonology, Postgraduate Medical Institute, Peshawar, Pakistan;

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Amer Hayat Khan Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia;

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Izaz Ahmad Department of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore, Pakistan;

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Muhammad Atif Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan

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DOI:
https://doi.org/10.4269/ajtmh.17-0936
Volume/Issue:
Volume 98: Issue 6
Page(s):
1629–1636
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To evaluate the predictive value of time to sputum culture conversion (SCC) in predicting cure and factors associated with time to SCC and cure in multidrug-resistant tuberculosis (MDR-TB) patients, a retrospective study was conducted at programmatic management unit of drug resistant tuberculosis (TB), Peshawar. A total of 428 pulmonary MDR-TB patients enrolled at the study site from January 1, 2012 to August 31, 2014 were followed until treatment outcome was recorded. Survival analysis using Cox proportional hazards model and multivariate binary logistic regression were, respectively, used to identify factors associated with time to SCC and cure. A P value < 0.05 was considered statistically significant. Overall, 90.9% patients achieved SCC, and 76.9% were cured. Previous use of second-line drugs (SLDs) (hazard ratio [HR] = 0.637; 95% confidence interval [CI] = 0.429–0.947), ofloxacin resistance (HR = 0.656; 95% CI = 0.522–0.825) and lung cavitation (HR = 0.744; 95% CI = 0.595–0.931) were significantly associated with time to SCC. In predicting cure, sensitivities of SCC at 2, 4, and 6 months were 64.1% (95% CI = 58.69–69.32), 93.0% (95% CI = 89.69–95.52), and 97.6% (95% CI = 95.27–98.94), respectively, whereas specificities were 67.7% (95% CI = 57.53–76.73), 51.5% (95% CI = 41.25–61.68), and 44.4% (95% CI = 34.45–54.78), respectively. Furthermore, patients’ age of 41–60 (odds ratio [OR] = 0.202; 95% CI = 0.067–0.605) and > 60 years (OR = 0.051; 95% CI = 0.011–0.224), body weight > 40 kg (OR = 2.950; 95% CI = 1.462–5.952), previous SLD use (OR = 0.277; 95% CI = 0.097–0.789), lung cavitation (OR = 0.196; 95% CI = 0.103–0.371) and ofloxacin resistance (OR = 0.386; 95% CI = 0.198–0.749) were significantly associated with cure. Association of SCC with cure was substantially stronger at 6 months (OR = 32.10; 95% CI = 14.34–71.85) than at 4 months (OR = 14.13; 95% CI = 7.92–25.21). However in predicting treatment outcomes, the combined sensitivity and specificity of SCC at 4 months was comparable to SCC at 6 months. Patients with risk factors for delayed SCC were also at high risk of unsuccessful outcomes.

Author Notes

Address correspondence to Nafees Ahmad, Faculty of Pharmacy and Health Sciences, University of Baluchistan, Quetta, Pakistan. E-mail: nafeesuob@gmail.com

Authors’ addresses: Nafees Ahmad, Faculty of Pharmacy and Health Sciences, University of Baluchistan, Quetta, Pakistan, E-mail: nafeesuob@gmail.com. Arshad Javaid, PMDT, Lady Reading Hospital, Peshawar, Pakistan, and Khyber Medical University, Peshawar, Pakistan, E-mail: arshadj34@gmail.com. Afsar Khan Afridi, PMDT, Lady Reading Hospital, Peshawar, Pakistan, E-mail: afsarafridik@yahoo.com. Anila Basit, Department of Pulmonology, Lady Reading Hospital, Peshawar, Pakistan, E-mail: anilalrh@gmail.com. Amer Hayat Khan, Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia, E-mail: dramer2006@gmail.com. Izaz Ahmad, Department of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore, Pakistan, E-mail: izazswat09@gmail.com. Muhammad Atif, Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan, E-mail: pharmacist_atif@yahoo.com.

These authors contributed equally to this work.

Copyright:
© The American Society of Tropical Medicine and Hygiene 2018
Received:
01 Dec 2017
|
Accepted:
04 Mar 2018
|
Published Online:
02 Apr 2018
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
  • 1.

    World Health Organization, 2016, Companion Handbook to the WHO Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis. (WHO/HTM/TB/2014.11). Geneva, Switzerland: WHO. Available at: http://apps.who.int/iris/bitstream/10665/130918/1/9789241548809_eng.pdf. Accessed November 22, 2017.

    • PubMed
    • Export Citation
  • 2.

    Holtz TH, Sternberg M, Kammerer S, Kammerer S, Laserson KF, Riekstina V, Zarovska E, Skripconoka V, Wells CD, Leimane V, 2006. Time to sputum culture conversion in multidrug-resistant tuberculosis: predictors and relationship to treatment outcome. Ann Intern Med 144: 650–659.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Fortún J, Martín-Dávila P, Molina A, Navas E, Hermida JM, Cobo J, Gómez-Mampaso E, Moreno S, 2007. Sputum conversion among patients with pulmonary tuberculosis: are there implications for removal of respiratory isolation? J Antimicrob Chemother 59: 794–798.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Kurbatova EV et al. 2015. Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies. Lancet Respir Med 3: 201–209.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Joseph P, Desai VBR, Mohan NS, Fredrick JS, Ramachandran R, Raman B, Wares F, Ramachandran R, Thomas A, 2011. Outcome of standardized treatment for patients with MDR-TB from Tamil Nadu, India. Indian J Med Res 133: 529–534.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Lu P, Liu Q, Martinez L, Yang H, Lu W, Ding X, Zhu L, 2017. Time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis: a prospective cohort study from urban China. Eur Respir J 49: 1601558.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Ige O, Akindele Y, Oladokun R, Adebiyi O, 2014. Sputum culture conversion among the first cohorts of MDR-TB patients managed in Nigeria at a tertiary care hospital. Eur Respir J 44: 2625.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Rodriguez M et al. 2013. Successful management of multidrug-resistant tuberculosis under programme conditions in the Dominican Republic. Int J Tuberc Lung Dis 17: 520–525.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Wells CD, Gupta R, Hittel N, Geiter LJ, 2015. Long-term mortality assessment of multidrug-resistant tuberculosis patients treated with delamanid. Eur Respir J 45: 1498–1501.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    World Health Organization, 2016. Global Tuberculosis Report 2016. Geneva, Switzerland: WHO. Available at: http://www.who.int/tb/publications/global_report/en/. Accessed November 23, 2017.

    • PubMed
    • Export Citation
  • 11.

    Tahseen S, Qadeer E, Khanzada FM, Rizvi AH, Dean A, Van Deun A, Zignol M, 2016. Use of Xpert (R) MTB/RIF assay in the first national anti-tuberculosis drug resistance survey in Pakistan. Int J Tuberc Lung Dis 20: 448–455.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Basit A et al. 2014. Predictors of two months culture conversion in multidrug-resistant tuberculosis: findings from a retrospective cohort study. PLoS One 9: e93206.

  • 13.

    Qazi F, Khan U, Khowaja S, Javaid M, Ahmed A, Salahuddin N, Hussain H, Becerra MC, Golub JE, Khan AJ, 2011. Predictors of delayed culture conversion in patients treated for multidrug-resistant tuberculosis in Pakistan. Int J Tuberc Lung Dis 15: 1556–1560.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Javaid A, Ahmad N, Khan AH, Shaheen Z, 2017. Applicability of the World Health Organization recommended new shorter regimen in a multidrug-resistant tuberculosis high burden country. Eur Respir J 3: 1601967.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Ahmad N, Javaid A, Basit A, Afridi A, Khan M, Ahmad I, Sulaiman SA, Khan AH, 2015. Management and treatment outcomes of MDR-TB: results from a setting with high rates of drug resistance. Int J Tuberc Lung Dis 19: 1109–1114.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Falzon D et al. 2012. Resistance to fluoroquinolones and second-line injectable drugs: impact on MDR-TB outcomes. Eur Respir J 42: 156–168.

  • 17.

    Johnston JC, Shahidi NC, Sadatsafavi M, Fitzgerald JM, 2009. Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis. PLoS One 4: e6914.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Kurbatova EV et al. 2012. Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects. Tuberculosis (Edinb) 92: 397–403.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Migliori G et al. 2008. Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases. Eur Respir J 31: 1155–1159.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Javaid A, Shaheen Z, Shafqat M, Khan AH, Ahmad N, 2017. Risk factors for high death and loss-to-follow-up rates among patients with multidrug-resistant tuberculosis at a programmatic management unit. Am J Infect Control 45: 190–193.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Hovhannesyan A, Breeze E, 2012. Time to sputum conversion in multidrug-resistant tuberculosis patients in Armenia: retrospective cohort study. Global J Med Pub Health 1: 24–28.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Yew WW, Chan CK, Chau CH, Tam CM, Leung CC, Wong PC, Lee J, 2000. Outcomes of patients with multidrug-resistant pulmonary tuberculosis treated with ofloxacin/levofloxacin-containing regimens. Chest 117: 744–751.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Su W, Feng J, Chiu Y, Huang S, Lee Y, 2011. Role of 2-month sputum smears in predicting culture conversion in pulmonary tuberculosis. Eur Respir J 37: 376–383.

  • 24.

    Gammino V et al. 2011. Bacteriologic monitoring of multidrug-resistant tuberculosis patients in five DOTS-Plus pilot projects. Int J Tuberc Lung Dis 15: 1315–1322.

  • 25.

    Tierney DB et al. 2014. Time to culture conversion and regimen composition in multidrug-resistant tuberculosis treatment. PLoS One 9: e108035.

  • 26.

    Leimane V, Riekstina V, Holtz TH, Zarovska E, Skripconoka V, Thorpe LE, Laserson KF, Wells CD, 2005. Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study. Lancet 365: 318–326.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Byrd RP, Mehta JB, Roy TM, 2002. Malnutrition and pulmonary tuberculosis. Clin Infect Dis 35: 634–635.

  • 28.

    Tahaoğlu K, Törün T, Sevim T, Ataç G, Kir A, Karasulu L, Ozmen I, Kapakli N, 2001. The treatment of multidrug-resistant tuberculosis in Turkey. N Engl J Med 345: 170–174.

  • 29.

    Ahmad N, Javaid A, Sulaiman SAS, Basit A, Afridi AK, Jaber AAS, Khan AH, 2016. Effects of multidrug resistant tuberculosis treatment on patients’ health related quality of life: results from a follow up study. PLoS One 11: e0159560.

    • PubMed
    • Search Google Scholar
    • Export Citation
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