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Letter to the Editor

Membrane Filtration Is Suitable for Reliable Elimination of Mycobacterium tuberculosis from Saliva for Therapeutic Drug Monitoring

Simone H. J. van den Elsen, Tridia van der Laan, Onno W. Akkerman, Adri G. M. van der Zanden, Jan-Willem C. Alffenaar, Dick van Soolingen
Geoffrey A. Land, Editor
Simone H. J. van den Elsen
aUniversity of Groningen, University Medical Centre Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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Tridia van der Laan
bNational Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
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Onno W. Akkerman
cUniversity of Groningen, University Medical Centre Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands
dUniversity of Groningen, University Medical Centre Groningen, Tuberculosis Centre Beatrixoord, Haren, The Netherlands
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Adri G. M. van der Zanden
eLaboratory for Medical Microbiology and Public Health, Hengelo, The Netherlands
fSt. Laurentius Hospital, Department of Medical Microbiology, Roermond, The Netherlands
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Jan-Willem C. Alffenaar
aUniversity of Groningen, University Medical Centre Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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Dick van Soolingen
bNational Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
gRadboud University Nijmegen Medical Centre, Departments of Pulmonary Diseases and Medical Microbiology, Nijmegen, The Netherlands
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Geoffrey A. Land
Carter BloodCare & Baylor University Medical Center
Roles: Editor
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DOI: 10.1128/JCM.01248-17
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LETTER

Tuberculosis (TB) remains an infectious disease of worldwide concern. Therapeutic drug monitoring (TDM) of blood could be helpful in optimizing TB treatment, as anti-TB drug exposure shows interpatient variability (1). TDM in saliva instead of blood is currently being studied as a more practical alternative, since saliva sampling is noninvasive and more acceptable to patients (2, 3). Along with the growing interest in the pharmacokinetics of anti-TB drugs, TDM is increasingly used in daily routine practice. However, the saliva of infectious TB patients contains Mycobacterium tuberculosis and TDM sample analysis usually does not take place in a biosafety level 3 laboratory. A quantitative study found a mean bacterial load of 7 × 104 (range, 1 × 102 to 6 × 105) CFU/ml in the saliva of infectious TB patients (4). Laboratory-acquired TB infections should be prevented by applying biosafety measures when working with M. tuberculosis-containing saliva samples (5). Therefore, saliva samples from TB patients require sterilization prior to laboratory processing (e.g., centrifugation). Unfortunately, heat sterilization is not possible because of the thermal instability of drugs. The objective of this experiment was to test whether membrane filtration is able to reliably decontaminate a solution containing M. tuberculosis.

Five M. tuberculosis strains (Table 1) were incubated in Mycobacteria Growth Indicator Tubes (MGITs; Becton, Dickinson and Company, United States) after the addition of 0.8 ml of oleic acid, albumin, dextrose, and catalase as a growth supplement. For each strain, 2.0 ml of culture fluid containing at least 105 to 106 CFU/ml was filtered in duplicate with a polyvinylidene fluoride membrane filter with a pore size of 0.22 μm and a diameter of 33 mm (Millex-GV; Merck Millipore, Ireland). The filtrate was inoculated into a new MGIT with culture fluid. For each strain, 0.5 ml of culture fluid containing at least 105 to 106 CFU/ml was also inoculated into a new MGIT as a positive control. All tubes were incubated at 36.5°C for 55 days in the Bactec MGIT 960 system (Becton, Dickinson and Company, United States). No mycobacterial growth was observed in the MGITs inoculated with filtrate, while all of the control tubes were positive within 2 weeks (Table 1).

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TABLE 1

Growth of five strains of M. tuberculosis in positive-control samples and filtratesa

This is the first description of membrane filtration of M. tuberculosis-containing fluids for sterilization in the process of TDM. No mycobacterial growth was measured in any of the filtrates. The membrane filter therefore successfully filtered all of the bacteria of multiple M. tuberculosis strains from culture fluids. We found no difference among the five strains in the number of growth units in the filtrates. It is not possible to test all of the M. tuberculosis isolates received at a mycobacterial laboratory, but according to this experiment, variation in the feasibility of membrane filtration between different strains is not likely. Membrane filtration of solutions with a larger bacterial load than that tested here requires further investigation, as sterilization cannot be ensured by only this experiment. However, the bacterial load in saliva from TB patients is usually not as large as that tested in this experiment (4). Because of the satisfying results obtained with culture fluids with large bacterial loads, we conclude that membrane filtration is suitable for the decontamination of salivary TDM samples from infectious TB patients.

ACKNOWLEDGMENT

This study received no funding.

We have no conflict of interest to report.

  • Copyright © 2017 American Society for Microbiology.

All Rights Reserved .

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Membrane Filtration Is Suitable for Reliable Elimination of Mycobacterium tuberculosis from Saliva for Therapeutic Drug Monitoring
Simone H. J. van den Elsen, Tridia van der Laan, Onno W. Akkerman, Adri G. M. van der Zanden, Jan-Willem C. Alffenaar, Dick van Soolingen
Journal of Clinical Microbiology Oct 2017, 55 (11) 3292-3293; DOI: 10.1128/JCM.01248-17

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Membrane Filtration Is Suitable for Reliable Elimination of Mycobacterium tuberculosis from Saliva for Therapeutic Drug Monitoring
Simone H. J. van den Elsen, Tridia van der Laan, Onno W. Akkerman, Adri G. M. van der Zanden, Jan-Willem C. Alffenaar, Dick van Soolingen
Journal of Clinical Microbiology Oct 2017, 55 (11) 3292-3293; DOI: 10.1128/JCM.01248-17
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KEYWORDS

Mycobacterium tuberculosis
biosafety
membrane filtration
saliva
therapeutic drug monitoring
Drug Monitoring
Filtration
Mycobacterium tuberculosis
saliva

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