Pharmacokinetics of moxifloxacin and linezolid during and after pregnancy in a patient with multidrug-resistant tuberculosis

Abstract

Worldwide, tuberculosis (TB) is among the top five causes of death for women aged 15-44 years [1]. In 2014, an estimated 480 000 of newly reported TB cases were multidrug-resistant (MDR) TB [1]. Pregnancy is a risk factor for reactivation of TB, but data about multidrug-resistant (MDR)-TB in pregnant women are lacking. There are few data about the efficacy and safety of second-line anti-TB drugs during pregnancy for both the mother and the unborn child [2]. One study from Peru showed a mortality rate of 13% in 38 patients and 13% of these 38 patients were lost to follow-up. Five of the pregnancies ended in spontaneous abortions, and one child was stillborn. Data for pregnant women did not differ from the general MDR-TB population in Peru [2]. To assure efficacy while minimising adverse events, therapeutic drug monitoring (TDM) has been proposed [3]. In TDM of anti-TB drugs, the accurately measured exposure to the drug [4] is evaluated in relation to the minimum inhibitory concentration (MIC) of the offending strain of Mycobacterium tuberculosis [5]. Low drug exposure is associated with an increased risk of treatment failure or with acquired resistance. High drug exposure might result in increased toxicity and adverse events [6]. Little is known about the effects of pregnancy in patients with MDR-TB with regards to the pharmacokinetics of second-line anti-TB drugs [2]. During pregnancy, pharmacokinetic parameters might change over time because of dynamic physiological changes in different stages of pregnancy, leading to inadequate treatment and poor outcome. In this case study, we aimed to describe the pharmacokinetics of moxifloxacin (Mfx) and linezolid (Lzd) during and after pregnancy in a patient with MDR-TB. A 25-year-old HIV-negative female from Somalia presented with a cough of several months' duration. She had arrived in the Netherlands 10 months earlier [7]. Her sister had been diagnosed with TB 12 years ago, and had been treated successfully. Physical examination revealed an enlarged lymph node in her neck. Culture from a fine-needle aspirate yielded M. tuberculosis. The chest radiograph showed no abnormalities; she was started on rifampin, isoniazid, pyrazinamide and ethambutol. Molecular susceptibility testing of the cultured isolate showed mutations in both the rpoB and katG genes. She was diagnosed with MDR-TB and transferred to our TB reference centre at 11 weeks' gestation. The first-line anti-TB drugs were discontinued and we decided to wait for further susceptibility results before starting with-second line anti-TB drugs to avoid giving inactive but potentially toxic drugs to the fetus. We considered it safe to withhold the treatment for some time as lymph node TB is paucibacillary and she was clinically stable without apparent disease activity apart from the nuchal lymph nodes. In vitro phenotypical susceptibility testing was performed, and the isolate appeared resistant to the first-line drugs rifampicin, isoniazid and ethambutol, but susceptible to all injectables, moxifloxacin, prothionamide, ...

Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline

“…Full-text review and data extraction were conducted by three reviewers. Our initial search yielded 280 publications, of which 16 met inclusion criteria for full-text review (312–327); however, 3 publications were eventually excluded because of lack of data on medications or outcomes (315, 325, 327). The remaining 13 articles were observational case reviews without any comparison groups.…”

Retrospective record review of pregnant women treated for rifampicin-resistant tuberculosis in South Africa

“…South Africa has one of the world's most serious tuberculosis (TB) epidemics, that in recent decades has been driven by the human immunodeficiency virus (HIV) epidemic [1,2]. TB is amongst the top five causes of death in women of childbearing age in the 15-�44 year group [3]. In 2018, there were an estimated 11,000 Rifampicin (RIF)-resistant TB cases in South Africa, of these an estimated 62% were multidrug-resistant TB (MDR-TB) [1].…”

Treatment of multidrug-resistant tuberculosis using therapeutic drug monitoring: first experiences with sub-300 mg linezolid dosages using in-house made capsules

“…We use a holistic approach to treat MDR-TB, focusing multidisciplinarily on optimizing treatment using pharmacokinetics (PK) and pharmacodynamics, assessing and optimizing nutritional status, providing physical therapy and social care [7]. Treatment regimens are based on the WHO guidelines, but are individualized based on drug susceptibility testing (DST) combined with TDM if the regimen consists of second-line drugs or if patients are at risk for PK variability [8]. DST is performed at Dutch National Mycobacterial Reference Laboratory (RIVM, Bilthoven, The Netherlands).…”