Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profile

ABSTRACT Patients with Mycobacterium intracellulare pulmonary disease are more likely to experience poor treatment outcomes if they have been observed with microbiological persistence after 6 months of treatment. This study aims to identify the risk factors for microbiological persistence and descri...

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Main Authors: Xuejiao Luo, Xubin Zheng, Yong Fang, Fangyou Yu, Haiyan Cui, Qin Sun, Wei Sha
Format: Article
Language:English
Published: American Society for Microbiology 2023-10-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.00805-23
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author Xuejiao Luo
Xubin Zheng
Yong Fang
Fangyou Yu
Haiyan Cui
Qin Sun
Wei Sha
author_facet Xuejiao Luo
Xubin Zheng
Yong Fang
Fangyou Yu
Haiyan Cui
Qin Sun
Wei Sha
author_sort Xuejiao Luo
collection DOAJ
description ABSTRACT Patients with Mycobacterium intracellulare pulmonary disease are more likely to experience poor treatment outcomes if they have been observed with microbiological persistence after 6 months of treatment. This study aims to identify the risk factors for microbiological persistence and describe the changes in the minimum inhibitory concentration (MIC) during antimycobacterial treatment. This retrospective case-control study enrolled patients diagnosed with M. intracellulare pulmonary disease between April 2017 and September 2021 at Shanghai Pulmonary Hospital. Patients with positive cultures after 6 months of treatment (positive group) were matched by age and sex in a 1:1 ratio to patients with negative conversion (negative group). Totally, 46 pairs of patients were analyzed. Risk factors for microbiological persistence at month 6 were smoking, previous tuberculosis treatment, chronic lung diseases, a positive baseline acid-fast bacilli smear, and adverse drug reactions; the risk was reduced by a regimen containing ethambutol, ≥3 effective drugs, and a higher pre-treatment absolute lymphocyte count. Regarding the drug-resistance profile, the negative group had a higher proportion of susceptibility to clarithromycin (100.0% vs 84.8%, P = 0.012). Most isolates were susceptible or intermediate to amikacin in both groups (93.5% and 84.8%, respectively). Nine patients (16.4%, 9/55) had a change in the drug-resistance profile, including four who changed from clarithromycin susceptible to clarithromycin resistant, and the other three reversed. Two pairs of isolates had a change in resistance to amikacin. In conclusion, risk factors for microbiological persistence were identified, and the change in MIC values during antimycobacterial treatment indicated the need for monitoring to enable timely adjustment of the regimen. IMPORTANCE Nontuberculous mycobacteria pulmonary disease (NTM-PD) has been recognized as an important public health issue because of its increasing incidence globally, low cure rate, and high recurrence rate. NTM-PD has innate resistance to many first-line anti-tuberculous drugs, which limits the treatment options. Mycobacterium intracellulare is reportedly the most important pathogenic NTM and accounts for the highest proportion of NTM-PD in China. A previous study suggested that poor microbiological response after 6 months of treatment is predictive of treatment failure. The present study investigated the risk factors associated with persistent positive sputum cultures by treatment month 6 in patients with M. intracellulare pulmonary disease and the variation in minimum inhibitory concentration patterns in clinical settings. This information might help to identify patients at higher risk of treatment failure and enable the timely provision of necessary interventions.
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spelling doaj.art-ee59bfacf0d5484db6cf3abf36781ee82023-10-17T13:04:35ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-10-0111510.1128/spectrum.00805-23Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profileXuejiao Luo0Xubin Zheng1Yong Fang2Fangyou Yu3Haiyan Cui4Qin Sun5Wei Sha6Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University , Shanghai, ChinaDepartment of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University , Shanghai, ChinaDepartment of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University , Shanghai, ChinaDepartment of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University , Shanghai, ChinaDepartment of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University , Shanghai, ChinaDepartment of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University , Shanghai, ChinaDepartment of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University , Shanghai, ChinaABSTRACT Patients with Mycobacterium intracellulare pulmonary disease are more likely to experience poor treatment outcomes if they have been observed with microbiological persistence after 6 months of treatment. This study aims to identify the risk factors for microbiological persistence and describe the changes in the minimum inhibitory concentration (MIC) during antimycobacterial treatment. This retrospective case-control study enrolled patients diagnosed with M. intracellulare pulmonary disease between April 2017 and September 2021 at Shanghai Pulmonary Hospital. Patients with positive cultures after 6 months of treatment (positive group) were matched by age and sex in a 1:1 ratio to patients with negative conversion (negative group). Totally, 46 pairs of patients were analyzed. Risk factors for microbiological persistence at month 6 were smoking, previous tuberculosis treatment, chronic lung diseases, a positive baseline acid-fast bacilli smear, and adverse drug reactions; the risk was reduced by a regimen containing ethambutol, ≥3 effective drugs, and a higher pre-treatment absolute lymphocyte count. Regarding the drug-resistance profile, the negative group had a higher proportion of susceptibility to clarithromycin (100.0% vs 84.8%, P = 0.012). Most isolates were susceptible or intermediate to amikacin in both groups (93.5% and 84.8%, respectively). Nine patients (16.4%, 9/55) had a change in the drug-resistance profile, including four who changed from clarithromycin susceptible to clarithromycin resistant, and the other three reversed. Two pairs of isolates had a change in resistance to amikacin. In conclusion, risk factors for microbiological persistence were identified, and the change in MIC values during antimycobacterial treatment indicated the need for monitoring to enable timely adjustment of the regimen. IMPORTANCE Nontuberculous mycobacteria pulmonary disease (NTM-PD) has been recognized as an important public health issue because of its increasing incidence globally, low cure rate, and high recurrence rate. NTM-PD has innate resistance to many first-line anti-tuberculous drugs, which limits the treatment options. Mycobacterium intracellulare is reportedly the most important pathogenic NTM and accounts for the highest proportion of NTM-PD in China. A previous study suggested that poor microbiological response after 6 months of treatment is predictive of treatment failure. The present study investigated the risk factors associated with persistent positive sputum cultures by treatment month 6 in patients with M. intracellulare pulmonary disease and the variation in minimum inhibitory concentration patterns in clinical settings. This information might help to identify patients at higher risk of treatment failure and enable the timely provision of necessary interventions.https://journals.asm.org/doi/10.1128/spectrum.00805-23Mycobacterium intracellulareminimum inhibitory concentrationclinical characteristicsnontuberculous mycobacteriaculture conversionantimycobacterial treatment
spellingShingle Xuejiao Luo
Xubin Zheng
Yong Fang
Fangyou Yu
Haiyan Cui
Qin Sun
Wei Sha
Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profile
Microbiology Spectrum
Mycobacterium intracellulare
minimum inhibitory concentration
clinical characteristics
nontuberculous mycobacteria
culture conversion
antimycobacterial treatment
title Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profile
title_full Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profile
title_fullStr Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profile
title_full_unstemmed Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profile
title_short Risk factors for microbiological persistence after 6 months of treatment for Mycobacterium intracellulare and its impact on the drug-resistance profile
title_sort risk factors for microbiological persistence after 6 months of treatment for mycobacterium intracellulare and its impact on the drug resistance profile
topic Mycobacterium intracellulare
minimum inhibitory concentration
clinical characteristics
nontuberculous mycobacteria
culture conversion
antimycobacterial treatment
url https://journals.asm.org/doi/10.1128/spectrum.00805-23
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