Hypokalemia Among Patients Receiving Treatment for Multidrug-Resistant Tuberculosis

Shin, Sonya; Furin, Jennifer; Alcántara, Félix; Hyson, Anne; Joseph, Keith; Sánchez, Epifanio; Rich, Michael

doi:10.1378/chest.125.3.974

Cited by 52 publications

(45 citation statements)

References 11 publications

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“…Of note, however, electrolyte abnormalities were effectively managed in all patients with no long-term consequences. The association of capreomycin with electrolyte disturbance and renal impairment during treatment for tuberculosis (TB) is well reported (29)(30)(31). In settings in which regular rapid and reliable blood monitoring is not feasible, the nephrotoxicity of capreomycin may lead to death due to hypokalemia and renal failure (18,29).…”

Section: Discussionmentioning

confidence: 99%

“…Renal impairment was defined as mild if the creatinine concentration was 1.5 times the baseline creatinine concentration and severe it was over 3 times the baseline creatinine concentration (33). Hypokalemia was defined as any drop in the potassium level to below 3.5 mmol/liter (29). Hypomagnesemia was defined as any magnesium concentration measurement below 0.7 mmol/liter (33).…”

Section: Methodsmentioning

confidence: 99%

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Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

Arnold

Cooke

Kon

et al. 2017

Antimicrob Agents Chemother

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The prolonged use of injectable agents in a regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health Organization, despite its association with ototoxicity and nephrotoxicity. We undertook this study to look at the relative adverse effects of capreomycin and amikacin. We reviewed the case notes of 100 consecutive patients treated at four MDR-TB treatment centers in the United Kingdom. The median total duration of treatment with an injectable agent was 178 days (interquartile range [IQR], 109 to 192 days; n ϭ 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; n ϭ 12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324 to 735 days; n ϭ 8) for those with extensively drug-resistant tuberculosis (XDR-TB). Injectable use was longer for those started with capreomycin (183 days; IQR, 123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days) (P ϭ 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated with an injectable for over 6 months and 12 of 85 (14%) were treated with an injectable for over 8 months. Forty percent of all patients discontinued the injectable due to hearing loss. Fiftyfive percent of patients experienced ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.2 to 22.6; P ϭ 0.03) more likely to occur in those started on amikacin than in those treated with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of 37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number of patients experiencing a rise in the creatinine level of Ͼ1.5 times the baseline level. Hearing loss is frequent in this cohort, though its incidence is significantly lower in those starting capreomycin, which should be given greater consideration as a first-line agent.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

Arnold

Cooke

Kon

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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“…While adverse effects associated with MDR-TB therapy may be controlled effectively, some of these need special attention [14,15]. Psychiatric problems such as depression can significantly affect patient quality of life, as well as physician's approach toward MDR-TB therapy.…”

Section: Introductionmentioning

confidence: 99%

Depression and its Associated Factors with Multidrug-Resistant Tuberculosis at Baseline

Javaid¹,

Mehreen²,

Khan³

et al. 2017

J Depress Anxiety

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“…Furthermore, MDR-TB may result when TB therapy is discontinued or interrupted or when improper drug regimens, including monotherapy, are prescribed (Blumberg et al, 2003). MDR-TB treatment may require .2 years of chemotherapy with less effective and more toxic second-line drugs (Horsburgh et al, 2000;Shin et al, 2004). Furthermore, there are many patients with TB and human immunodeficiency virus (HIV)/AIDS coinfection, and an estimated 1.1 million new TB cases were reported among people with HIV/AIDS (World Health Organization, 2014).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Metabolism of Delamanid, a Novel Anti-Tuberculosis Drug, in Animals and Humans: Importance of Albumin Metabolism In Vivo

et al. 2015

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Delamanid, a new anti-tuberculosis drug, is metabolized to M1, a unique metabolite formed by cleavage of the 6-nitro-2,3-dihydroimidazo[2,1-b] oxazole moiety, in plasma albumin in vitro. The metabolic activities in dogs and humans are higher than those in rodents. In this study, we characterized the pharmacokinetics and metabolism of delamanid in animals and humans. Eight metabolites (M1-M8) produced by cleavage of the imidazooxazole moiety of delamanid were identified in the plasma after repeated oral administration by liquid chromatography-mass spectrometry analysis. Delamanid was initially catalyzed to M1 and subsequently metabolized by three separate pathways, which suggested that M1 is a crucial starting point. The major pathway in humans was hydroxylation of the oxazole moiety of M1 to form M2 and then successive oxidation to the ketone form (M3) mainly by CYP3A4. M1 had the highest exposure among the eight metabolites after repeated oral dosing in humans, which indicated that M1 was the major metabolite. The overall metabolism of delamanid was qualitatively similar across nonclinical species and humans but was quantitatively different among the species. After repeated administration, the metabolites had much higher concentrations in dogs and humans than in rodents. The in vitro metabolic activity of albumin on delamanid probably caused the species differences observed. We determined that albumin metabolism is a key component of the pharmacokinetics and metabolism of delamanid. Nonhepatic formation of M1 and multiple separate pathways for metabolism of M1 suggest that clinically significant drug-drug interactions with delamanid and M1 are limited.

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Hypokalemia Among Patients Receiving Treatment for Multidrug-Resistant Tuberculosis

Cited by 52 publications

References 11 publications

Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

Depression and its Associated Factors with Multidrug-Resistant Tuberculosis at Baseline

Pharmacokinetics and Metabolism of Delamanid, a Novel Anti-Tuberculosis Drug, in Animals and Humans: Importance of Albumin Metabolism In Vivo

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