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 ~ Introduction
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  Table of Contents  
BRIEF COMMUNICATION
Year : 2016  |  Volume : 34  |  Issue : 4  |  Page : 516-519
 

Pulmonary Mycobacterium kansasii disease in immunocompetent host: Treatment outcomes with short-course chemotherapy


1 Department of Clinical Research, National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India
2 Department of Bacteriology, National Institute for Research in Tuberculosis, Chennai, Tamil Nadu, India

Date of Submission02-Jul-2016
Date of Acceptance04-Oct-2016
Date of Web Publication8-Dec-2016

Correspondence Address:
C Padmapriyadarsini
Department of Clinical Research, National Institute for Research in Tuberculosis, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.195370

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 ~ Abstract 

Mycobacterium kansasii, most virulent of all atypical mycobacteria, causes pulmonary disease identical to the disease caused by Mycobacterium tuberculosis. Early identification of the species and prompt initiation of treatment for M. kansasii is necessary to prevent morbidity and mortality due to this disease. This case series highlights the similarity in the clinical presentation of both M. tuberculosis and M. kansasii and response to direct observation of short-course chemotherapy with rifampicin, in the management of pulmonary M. kansasii disease. Larger studies are required to evaluate the long-term effect of short-course chemotherapy, especially use of moxifloxacin, in the management of pulmonary M. kansasii disease.


Keywords: Moxifloxacin, pulmonary Mycobacterium kansasii, rifampicin, short-course chemotherapy


How to cite this article:
Padmapriyadarsini C, Nair D, Gomathi N S, Velayudham B. Pulmonary Mycobacterium kansasii disease in immunocompetent host: Treatment outcomes with short-course chemotherapy. Indian J Med Microbiol 2016;34:516-9

How to cite this URL:
Padmapriyadarsini C, Nair D, Gomathi N S, Velayudham B. Pulmonary Mycobacterium kansasii disease in immunocompetent host: Treatment outcomes with short-course chemotherapy. Indian J Med Microbiol [serial online] 2016 [cited 2017 Jan 19];34:516-9. Available from: http://www.ijmm.org/text.asp?2016/34/4/516/195370



 ~ Introduction Top


With new and improved tuberculosis (TB) diagnostic tools, pulmonary infections due to non-tuberculous mycobacterium (NTM) are being increasingly recognised worldwide. The isolation of NTM raises the question of their clinical significance especially in endemic settings like India. Although more than 150 different species of NTM have been described, pulmonary infections are most commonly due to Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus.[1]

M. kansasii has been considered the most virulent of the NTM. Pulmonary disease caused by M. kansasii is nearly identical to the disease caused by Mycobacterium tuberculosis, including chest X-ray (CXR) findings. The American Thoracic Society (ATS) recommends an 18-month regimen of daily isoniazid, rifampin and ethambutol, in the management of M. kansasii lung disease.[1] To date, no short-course or intermittent treatment regimen has been approved or endorsed by the ATS. In an in vitro susceptibility study of 148 M. kansasii strains isolated from clinical specimens, moxifloxacin followed by levofloxacin, clarithromycin and linezolid showed a good therapeutic alternative.[2] Here, we report a series of patients treated with a short-course regimen for M. kansasii pulmonary disease, with favourable response at the end of 2-year of follow-up.


 ~ Case Reports Top


Patients reported here were enrolled in a randomised controlled clinical trial that assessed the efficacy of moxifloxacin in shortening the duration of TB treatment in new sputum smear positive, non-HIV-infected patients. As per the trial protocol, based on sputum smear status and CXR findings, they were randomised to either a 3- or 4-month regimen of daily moxifloxacin [M], isoniazid [H], rifampicin [R], ethambutol [E] and pyrazinamide [Z] (3MHREZ7 or 2MHREZ7/2MHR7 or 2MHREZ7/2MHR3) or 6-month of thrice-weekly regimen (2EHRZ3/4RH3).

After starting treatment under direct observation, sputum samples were subjected to Lowenstein–Jensen solid culture for acid-fast bacilli. Following the growth of mycobacteria, species were identified using high-performance liquid chromatography technique. Patients, who grew M. tuberculosis in their sputum, were retained in the clinical trial while those showing NTM were considered as pre-treatment exclusions. However, by the time culture results were available patients had already completed more than 2 months of treatment and/or had become sputum culture negative. Further management of these patients was individualised based on the presence of symptoms or CXR deterioration. Sputum conversion was defined as three consecutive negative cultures at the end of treatment. All patients were followed for 24 months. Recurrence was defined as two consecutive positive cultures 1 month apart, after culture conversion. National Institute for Research in Tuberculosis's (NIRT's) Institutional Ethics Committee approval was obtained for the clinical trial and informed written consent was taken from all patients before enrolment to the study.

[Table 1] gives the clinical details of all the nine cases whereas [Table 2] shows their response to treatment and follow-up.
Table 1: Clinical details of cases

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Table 2: Response to treatment and 24-month follow-up

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 ~ Discussion Top


We report nine immunocompetent patients suffering from M. kansasii pulmonary disease. The clinical and radiologic findings were indistinguishable from M. tuberculosis. Most reported patients of M. kansasii infection are males with a history of heavy smoking and pre-existing pulmonary conditions such as bronchiectasis, chronic bronchitis, TB or pneumoconiosis.[3],[4],[5] Smoking may influence the cilia and macrophage function in airways while prior lung infection with TB or pneumoconiosis can provide a nidus for M. kansasii infection. M. kansasii being more pathogenic can readily establish significant infection in relatively normal lung tissue also. In our case series, all were males with 6 of them being smokers with none showing any pre-existing pulmonary conditions.

Similar to TB, M. kansasii lung disease presents with productive cough, heamoptysis, fever and loss of appetite.[1],[2] Unilateral disease, right-sided involvement, cavity and lesser parenchymal infiltrate than M. tuberculosis are the most commonly reported CXR pattern.[4],[6] Most of our patients were young, had symptoms of productive cough and fever with three having an episode of haemoptysis. All our patients had parenchymal infiltrates, with six of them having bilateral lesions and thin walled cavity in the upper lobe, mimicking TB disease.

Treatment against pulmonary TB should be instituted without delay when TB is suspected, even before the complete workup is available. Hence, all our 9 patients were started on anti-tuberculosis treatment (ATT), as per the trial protocol, before the results of sputum cultures revealed M. kansasii. However, as the treatment of M. kansasii consists of the same drugs as for M. tuberculosis, namely rifampicin, isoniazid and ethambutol, the patient got the benefit of ATT and started responding. Of our nine patients, five patients on short-duration ATT (three patients, cases 1, 2 and 3, received thrice-weekly regimen for 6-month [2EHRZ3/4RH3] and two patients, cases 4 and 5, received 4 months of moxifloxacin along with other drugs [2EHRZM7/2HRM]) improved with satisfactory clinical, bacteriological and radiological clearance of the disease and were declared cured. Two patients on 4-month intermittent moxifloxacin regimen relapsed but got cured with retreatment of 12-month duration with multidrug regimen. One patient died early in the course of disease, due to extensive disease.

Currently, ATS and the Infectious Diseases Society of America recommend maintaining chemotherapy with a multidrug regimen, for 18 months or at least for 12 months after achieving sputum culture negativity for pulmonary NTM disease.[1] Another study concluded that a 12-month, fixed-course treatment with HRE (supplemented with streptomycin during first 2–3 months), is better in younger patients without debilitating conditions while longer periods of treatment, guided by periodic sputum cultures, is advisable for the rest to avoid relapse.[7] The British Thoracic Society recommends a 9-month course of rifampicin and ethambutol as treatment for M. kansasii lung disease in immunocompetent patients.[8] Like clarithromycin, moxifloxacin has also been shown to have activity against clinical isolates of M. kansasii and could be used as an alternative drug as well as short-course or intermittent therapy of M. kansasii lung disease.[9],[10] Whether relapses can be prevented with longer duration of treatment is not known. Cases considered as relapses may actually be exogenous re-infections. In fact, M. kansasii is a ubiquitous pathogen to which people may be repeatedly exposed and become infected more than once. It may, therefore, not be possible to avoid new episodes of active disease completely even with treatments of longer duration. However, in our present series, none of the seven patients alive relapsed till 24-month of post-treatment follow-up, which supports the idea that a shorter duration of treatment can be effective in the management of pulmonary M. kansasii disease.

Acknowledgement

We acknowledge the help and advice offered by the Staff and Senior Doctors of the Departments of Bacteriology and Clinical Research, NIRT, Chennai, in the management of patients and preparation of this manuscript.

Financial support and sponsorship

ICMR (intramural).

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367-416.  Back to cited text no. 1
    
2.
Alcaide F, Calatayud L, Santín M, Martín R. Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levofloxacin, moxifloxacin, and four conventional antimycobacterial drugs against Mycobacterium kansasii. Antimicrob Agents Chemother 2004;48:4562-5.  Back to cited text no. 2
    
3.
Davies BS, Roberts CH, Kaul S, Klein JL, Milburn HJ. Non-tuberculous slow-growing mycobacterial pulmonary infections in non-HIV-infected patients in South London. Scand J Infect Dis 2012;44:815-9.  Back to cited text no. 3
    
4.
Matveychuk A, Fuks L, Priess R, Hahim I, Shitrit D. Clinical and radiological features of Mycobacterium kansasii and other NTM infections. Respir Med 2012;106:1472-7.  Back to cited text no. 4
    
5.
Solling AL, Gelfer E, Heimer D. Immunocompetent patients with pulmonary Mycobacterium kansasii infection: A case series and review of the literature. Clin Pulm Med 2003;10:131-5.  Back to cited text no. 5
    
6.
Inoue E, Senoo M, Nagayama N, Masuda K, Matsui H, Tamura A, et al. A comparison of chest radiographs between patients with pulmonary Mycobacterium kansasii infection and those with Mycobacterium tuberculosis infection in the initial stage of disease. Kekkaku 2013;88:619-23.  Back to cited text no. 6
    
7.
Santin M, Dorca J, Alcaide F, Gonzalez L, Casas S, Lopez M, et al. Long-term relapses after 12-month treatment for Mycobacterium kansasii lung disease. Eur Respir J 2009;33:148-52.  Back to cited text no. 7
    
8.
Management of opportunist mycobacterial infections: Joint Tuberculosis Committee Guidelines 1999. Subcommittee of the Joint Tuberculosis Committee of the British Thoracic Society. Thorax 2000;55:210-8.  Back to cited text no. 8
    
9.
Guna R, Muñoz C, Domínguez V, García-García A, Gálvez J, de Julián-Ortiz JV, et al. In vitro activity of linezolid, clarithromycin and moxifloxacin against clinical isolates of Mycobacterium kansasii. J Antimicrob Chemother 2005;55:950-3.  Back to cited text no. 9
    
10.
Srivastava S, Pasipanodya J, Sherman CM, Meek C, Leff R, Gumbo T. Rapid drug tolerance and dramatic sterilizing effect of moxifloxacin monotherapy in a novel hollow-fiber model of intracellular Mycobacterium kansasii disease. Antimicrob Agents Chemother 2015;59:2273-9.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2]



 

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2004 - Indian Journal of Medical Microbiology
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