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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 142-143

Recurrent tuberculosis due to subtherapeutic levels of antitubercular treatment


1 Department of Thoracic Medicine, Madras Medical College, Chennai, Tamil Nadu, India
2 Department of Institute of Thoracic Medicine, Madras Medical College, Chennai, Tamil Nadu, India

Date of Submission06-Mar-2021
Date of Decision11-Mar-2021
Date of Acceptance12-Mar-2021
Date of Web Publication28-Apr-2021

Correspondence Address:
A Kirubanandam
Department of Thoracic Medicine, Madras medical College, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/japt.japt_6_21

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  Abstract 


Most patients with tuberculosis respond well to treatment. Even in patients with good compliance to DOTS and sensitive to first-line drugs, treatment failure or relapse still occurs, the phenomenon of cryptic adherence needs careful evaluation. We present a case of frequent recurrence due to possible subtherapeutic levels of isoniazid (INH) and rifampicin. A 32-year-old male with no other comorbidities came with complaints of cough with expectoration with constitutional symptoms. He was treated for the primary complex at the age of 12 years and declared as cured. In 2006, he was diagnosed as right axillary TB lymphadenitis which was confirmed by histopathological examination and treated with Anti tubercular treatment (ATT) for 9 months. After 2 years (2008), he had developed left axillary lymphadenitis for which he was treated again with Anti tubercular treatment empirically. In 2016, he was diagnosed as smear-negative pulmonary tuberculosis (PTB) whose chest X-ray suggestive of PTB. Hence, he was treated with Anti tubercular treatment for 6 months, declared as cured. Now (2018), he was diagnosed as sputum-positive PTB with INH and rifampicin sensitive. Hence, we did a pharmacokinetics study, which revealed subtherapeutic levels of rifampicin and isoniazid. The patient responded well after increasing the dosage of drugs. Slow responders and patients with complications warrant the need of therapeutic drug monitoring (TDM). Drug concentrations which may be help resolve the problem of slow response to Anti Tuberculosis Therapy. TDM however is not routinely indicated in each case.

Keywords: Pharmacokinetics study, recurrent tuberculosis, therapeutic drug monitoring


How to cite this article:
Kirubanandam A, Arunshankar V, Mahilmaran A. Recurrent tuberculosis due to subtherapeutic levels of antitubercular treatment. J Assoc Pulmonologist Tamilnadu 2020;3:142-3

How to cite this URL:
Kirubanandam A, Arunshankar V, Mahilmaran A. Recurrent tuberculosis due to subtherapeutic levels of antitubercular treatment. J Assoc Pulmonologist Tamilnadu [serial online] 2020 [cited 2021 Sep 20];3:142-3. Available from: http://www.japt.com/text.asp?2020/3/3/142/314970




  Introduction Top


Most patients with tuberculosis respond well to treatment. Even in patients with good compliance to DOTS and sensitive to first-line drugs, treatment failure or relapse still occurs, the phenomenon of cryptic adherence needs careful evaluation.[1],[2] We present a case of frequent recurrence due to possible subtherapeutic levels of isoniazid (INH) and rifampicin.


  Case Report Top


A 32-year-old male with no comorbidities came with complaints of cough with expectoration with constitutional symptoms. He was treated for the primary complex at the age of 12 years and completed the treatment. In 2006, he was diagnosed as right axillary TB lymphadenitis which was confirmed by histopathological examination and treated with antitubercular treatment (ATT) for 9 months. After 2 years (2008), he had developed left axillary TB lymphadenitis for which he was treated again with Anti tubercular treatment Anti tubercular treatment empirically. In 2016, he was diagnosed as sputum smear-negative pulmonary tuberculosis (PTB) whose chest X-ray [Figure 1] suggestive of PTB. Hence, he was treated with Anti tubercular treatment for 6 months and completed the treatment. Now (2018), he was diagnosed as sputum smear-positive PTB. Sputum for CBNAAT showed Rifampicin sensitive and LPA was found to be Isoniazid and Rifampicin sensitive. The patient was started on CAT 2 Anti tubercular treatment (4 pills/day) with injection streptomycin 1 g/day. Since the pharmacokinetics study [Table 1] showed inadequate concentration of INH and rifampicin, we increased the dosage of rifampicin and INH 100 mg/day each with the above dosage. Repeat pharmacokinetics study [Table 2] showed level Anti tubercular treatment in normal therapeutic range [Table 3] with the patient improving symptomatically.
Figure 1: Chest X-ray

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Table 1: Pharmacokinetics study

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Table 2: Repeat pharmacokinetics study

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Table 3: Normal therapeutic range

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  Discussion Top


Patients with uncomplicated PTB usually respond to standard treatment, although some may require extended duration of treatment. Patients who are slower to respond may be at a greater risk for poor outcomes.[1],[2] Such candidates are ideal for therapeutic drug monitoring (TDM). Few physicians prefer to check serum drug concentrations early during treatment and hoping to head off prolonged treatment duration and the potential development of drug resistance.[3] TDM allows to identify and control one of the potential causes of slow clinical response.[3],[4],[5] It is never a substitute for sound clinical judgment nor is it a substitute for DOT.[6],[7] It is a useful tool in a variety of clinical situations including patients at high risk of treatment failure or patients with delayed response. TDM allows one to achieve the desired serum concentrations, increases the chances of successful clinical and bacteriological outcomes.[8],[9] It also can resolve complicated drug-to-drug interactions before the patient experiences failure, relapse, or toxicity.[10]


  Conclusion Top


Slow responders and patients with complications warrant the need of TDM. Drug concentrations which may be help resolve the problem of slow response to Anti Tuberculosis Therapy. TDM, however, is not routinely indicated in each case.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

The authors would like to thank the NIRT, Chennai.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Alsultan A, Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis: An update. Drugs 2014;74:839-54.  Back to cited text no. 1
    
2.
Pasipanodya JG, McIlleron H, Burger A, Wash PA, Smith P, Gumbo T. Serum drug concentrations predictive of pulmonary tuberculosis outcomes. J Infect Dis 2013;208:1464-73.  Back to cited text no. 2
    
3.
Srivastava S, Pasipanodya JG, Meek C, Leff R, Gumbo T. Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability. J Infect Dis 2011;204:1951-9.  Back to cited text no. 3
    
4.
Pasipanodya JG, Srivastava S, Gumbo T. Meta-analysis of clinical studies supports the pharmacokinetic variability hypothesis for acquired drug resistance and failure of antituberculosis therapy. Clin Infect Dis 2012;55:169-77.  Back to cited text no. 4
    
5.
Tappero JW, Bradford WZ, Agerton TB, Hopewell P, Reingold AL, Lockman S, et al. Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana. Clin Infect Dis 2005;41:461-9.  Back to cited text no. 5
    
6.
Tostmann A, Mtabho CM, Semvua HH, van den Boogaard J, Kibiki GS, Boeree MJ, et al. Pharmacokinetics of first-line tuberculosis drugs in Tanzanian patients. Antimicrob Agents Chemother 2013;57:3208-13.  Back to cited text no. 6
    
7.
Heysell SK, Moore JL, Keller SJ, Houpt ER. Therapeutic drug monitoring for slow response to tuberculosis treatment in a state control program, Virginia, U S A. Emerg Infect Dis 2010;16:1546-53.  Back to cited text no. 7
    
8.
Prahl JB, Johansen IS, Cohen AS, Frimodt-Moller N, Andersen AB. Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs: A prospective observational study. J Antimicrob Chemother 2014;69:2841-7.  Back to cited text no. 8
    
9.
Sturkenboom MG, Akkerman OW, Bolhuis MS, de Lange WC, van der Werf TS, Alffenaar JW. Adequate design of pharmacokinetic-pharmacodynamic studies will help optimize tuberculosis treatment for the future. Antimicrob Agents Chemother 2015;59:2474.  Back to cited text no. 9
    
10.
Holland DP, Hamilton CD, Weintrob AC, Engemann JJ, Fortenberry ER, Peloquin CA, et al. Therapeutic drug monitoring of antimycobacterial drugs in patients with both tuberculosis and advanced human immunodeficiency virus infection. Pharmacotherapy 2009;29:503-10.  Back to cited text no. 10
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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