Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis

Court, Richard; Centner, Chad M.; Chirehwa, Maxwell; Wiesner, Lubbe; Denti, Paolo; Vries, Nihal de; Harding, Joseph W.; Gumbo, Tawanda; Maartens, Gary; McIlleron, Helen

doi:10.1016/j.ijid.2021.03.001

Cited by 28 publications

(26 citation statements)

References 27 publications

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“…Peripheral neuropathy is commonly associated with long-term use of LZD and less frequently with INH, CS and FQs. 72 , 77 These possible and serious AEs require patient and care provider awareness, as well as monthly peripheral neuropathy and vision assessment. Peripheral neuropathy in young children can be difficult to diagnose and signs may include refusal to bear weight or complaints of pain or irritability.…”

Section: Standardmentioning

confidence: 99%

Clinical standards for the dosing and management of TB drugs

Alffenaar

Stocker

Forsman

et al. 2022

int j tuberc lung dis

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BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on ‘best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

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Section: Standardmentioning

confidence: 99%

Clinical standards for the dosing and management of TB drugs

Alffenaar

Stocker

Forsman

et al. 2022

int j tuberc lung dis

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“…In fact, it would have been interesting to see if the pathogenic effects attributed to D-cycloserine in a mouse model of Gaucher disease ( 98 ) could have been offset by pyridoxine coadministration. It is worth noting that administration of high doses of pyridoxine, with or without D-cycloserine administration, can lead to peripheral neuropathy ( 100 ), indicating that a carefully selected dose of pyridoxine is necessary.…”

Section: D-cycloserine–safety Considerationsmentioning

confidence: 99%

Substrate Reduction Therapy for Krabbe Disease: Exploring the Repurposing of the Antibiotic D-Cycloserine

Levine

Tsau

2022

Front. Pediatr.

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Krabbe disease is a lysosomal storage disease that is caused by a deficiency in galactosylceramidase. Infantile onset disease is the most common presentation, which includes progressive neurological deterioration with corresponding demyelination, development of globoid cells, astrocyte gliosis, etc. Hemopoietic stem cell transplantation (HSCT) is a disease modifying therapy, but this intervention is insufficient with many patients still experiencing developmental delays and progressive deterioration. Preclinical studies have used animal models, e.g., twitcher mice, to test different experimental therapies resulting in developments that have led to progressive improvements in the therapeutic impact. Some recent advances have been in the areas of gene therapy and substrate reduction therapy (SRT), as well as using these in combination with HSCT. Unfortunately, new experimental approaches have encountered obstacles which have impeded the translation of novel therapies to human patients. In an effort to identify a safe adjunct therapy, D-cycloserine was tested in preliminary studies in twitcher mice. When administered as a standalone therapy, D-cycloserine was shown to lengthen the lifespan of twitcher mice in a small but significant manner. D-Cycloserine is an FDA approved antibiotic used for drug resistant tuberculosis. It also acts as a partial agonist of the NMDA receptor, which has led to numerous human studies for a range of neuropsychiatric and neurological conditions. In addition, D-cycloserine may inhibit serine palmitoyltransferase (SPT), which catalyzes the rate-limiting step in sphingolipid production. The enantiomer, L-cycloserine, is a much more potent inhibitor of SPT than D-cycloserine. Previously, L-cycloserine was found to act as an effective SRT agent in twitcher mice as both a standalone therapy and as part of combination therapies. L-Cycloserine is not approved for human use, and its potent inhibitory properties may limit its ability to maintain a level of partial inactivation of SPT that is also safe. In theory, D-cycloserine would encompass a much broader dosage range to achieve a safe degree of partial inhibition of SPT, which increases the likelihood it could advance to human studies in patients with Krabbe disease. Furthermore, additional properties of D-cycloserine raise the possibility of other therapeutic mechanisms that could be exploited for the treatment of this disease.

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“…Cycloserine was discontinued and replaced in all studies. Indeed, several authors have reported the relative psychiatric toxicity of cycloserine [27][28].…”

Section: Serious Adverse Effectsmentioning

confidence: 99%

Risk Management Assessments of Anti-tuberculosis Adverse Drug Reaction: A Systematic Review

et al. 2021

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To improve adherence to treatment, quality of life of patients on anti-tuberculosis drugs, and prevent antibiotic resistance, we conducted this systematic review to support risk minimization actions. Methods: Medline, Scopus, and Web of Science were searched with a focus on adverse drug reactions. Two independent reviewers assessed the methodological quality of the included studies using criteria defined by the Newcastle Ottawa Scale. Results: Seven studies were included, and four risk management strategies were identified (psychological intervention, drug dose reduction with or without prescription of adjunctive drugs, drug switching, permanent or temporary drug discontinuation). The strategies adopted were dependent on the nature and severity of the adverse events. All drugs responsible for serious adverse effects were changed or discontinued. Conclusions: The results highlight the relatively low frequency of adverse events leading to permanent discontinuation of 1st-line anti-tuberculosis drugs, but also emphasize the high incidence of adverse events leading to permanent discontinuation of cycloserine.

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Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis

Cited by 28 publications

References 27 publications

Clinical standards for the dosing and management of TB drugs

Clinical standards for the dosing and management of TB drugs

Substrate Reduction Therapy for Krabbe Disease: Exploring the Repurposing of the Antibiotic D-Cycloserine

Risk Management Assessments of Anti-tuberculosis Adverse Drug Reaction: A Systematic Review

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