Clinical Infectious Diseases Advance Access published March 25, 2015 1
The never ending struggle against development of drug resistance der Werf2, J.W.C. Alffenaar1,#
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A. Daskapan1, Y. Stienstra2, O.W. Akkerman3, W.C.M de Lange3, J.G.W. Kosterink1,4, T.S. van
¹University of Groningen, University Medical Center Groningen, Department of Clinical pharmacy and Pharmacology, Groningen, The Netherlands
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University of Groningen, University Medical Center Groningen, Department of Internal
Medicine – Infectious Diseases, Groningen, The Netherlands 3
University of Groningen, University Medical Center Groningen, Department of Pulmonary
an
Diseases and Tuberculosis, Groningen, The Netherlands 4
University of Groningen, Department of Pharmacy, Section Pharmacotherapy and
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Pharmaceutical Care, Groningen, The Netherlands #
Address of correspondence: University of Groningen, University Medical Center Groningen,
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Department of Clinical Pharmacy and Pharmacology, Po box 30.001, 9700 RB Groningen, The Netherlands, Email:
[email protected], Tel: +31 503614070, Fax: +31 503614087
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© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e‐mail:
[email protected].
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2 Dear Editor, We read with interest the paper by Narendran and colleagues [1]. They suggest that HIV‐
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infected patients who are receiving the thrice‐weekly antituberculosis therapy are at higher risk of acquired rifampicin resistance compared to HIV‐uninfected patients, despite the use of combination antiretroviral therapy.
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therapy, particularly in the perspective of the emergence of drug‐resistance resulting in difficult to treat MDR/XDR cases. Both in vitro and clinical data showed that low area under the
concentration‐time curve (AUC) and maximum plasma concentration of rifampicin in relation to
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minimum inhibitory concentration (MIC) were associated with the occurrence of resistance [2, 3]. Therefore it seems relevant to collect pharmacokinetic data in clinical studies.
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The pharmacokinetics of rifampicin is highly variable; and especially in case of TB/HIV co‐ infection, reduced rifampicin exposure is not uncommon [4]. It can be expected that low drug exposure, while on thrice weekly dosing, is likely to have a higher impact on clinical outcome than after daily dosing. The World Health Organisation therefore now discourages thrice weekly
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anti‐TB therapy in case of TB/HIV co‐infection.
We earlier demonstrated that therapeutic drug monitoring (TDM) in combination with drug susceptibility testing may help to optimize treatment in individual patients [5]. Since low rifampicin plasma concentrations are so strikingly common [6], we argue in favour of routine
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TDM in TB/HIV co‐infected patients. We recognize that obtaining full pharmacokinetic curves is not feasible in most routine settings, but optimal sampling strategies to estimate drug exposure in combination with dried blood spot analysis may provide a feasible alternative [7, 8]. Dried
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blood spot analysis provides sample stability and easy logistics at low costs per sample, making TDM available in low‐ and middle income countries [7].
Further, we speculate that the rifampicin resistance in the study by Narendran and colleagues could be influenced by cotrimoxazol use. Earlier data showed that co‐trimoxazole was active against TB [9] and increased efficacy of rifampicin treatment [10]. In their study, HIV‐infected
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We emphasize the necessity of studies investigating the possible effects of HIV on anti‐TB
3 patients with a CD4 count