Linezolid-Associated Neurologic Adverse Events in Patients with Multidrug-Resistant Tuberculosis, France

Jaspard, Marie; Butel, Nathalie; Helali, Najoua El; Marigot-Outtandy, Dhiba; Peytavin, Gilles; Véziris, Nicolas; Bodaghi, Bahram; Flandre, Philippe; Petitjean, G.; Caumes, Éric; Pourcher, Valérie

doi:10.3201/eid2608.191499

Cited by 43 publications

(43 citation statements)

References 24 publications

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“…Linezolid, which has dopaminergic properties, may cause serotonin syndrome if used with a monoamine oxidase inhibitor. Its administration with an anticholinergic substances increases encephalopathy risk [27,60,103,104].…”

Section: Oxazolidinonesmentioning

confidence: 99%

Antibiotics and the Nervous System—Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?

2021

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Antibiotics as antibacterial drugs have saved many lives, but have also become a victim of their own success. Their widespread abuse reduces their anti-infective effectiveness and causes the development of bacterial resistance. Moreover, irrational antibiotic therapy contributes to gastrointestinal dysbiosis, that increases the risk of the development of many diseases, including neurological and psychiatric. One of the potential options for restoring homeostasis is the use of oral antibiotics that are poorly absorbed from the gastrointestinal tract (e.g., rifaximin alfa). Thus, antibiotic therapy may exert neurological or psychiatric adverse drug reactions which are often considered to be overlooked and undervalued issues. Drug-induced neurotoxicity is mostly observed after beta-lactams and quinolones. Penicillin may produce a wide range of neurological dysfunctions, including encephalopathy, behavioral changes, myoclonus or seizures. Their pathomechanism results from the disturbances of gamma-aminobutyric acid-GABA transmission (due to the molecular similarities between the structure of the β-lactam ring and GABA molecule) and impairment of the functioning of benzodiazepine receptors (BZD). However, on the other hand, antibiotics have also been studied for their neuroprotective properties in the treatment of neurodegenerative and neuroinflammatory processes (e.g., Alzheimer’s or Parkinson’s diseases). Antibiotics may, therefore, become promising elements of multi-targeted therapy for these entities.

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Section: Oxazolidinonesmentioning

confidence: 99%

Antibiotics and the Nervous System—Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?

2021

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“…The main drawback, however, may be concerns about patient’s safety and tolerability. Lzd has significant long-term side effects as an ultra-broad-spectrum antibiotic and about 30–40% of patients stop linezolid treatment because of AEs [ 22 ]. Therefore, in the present study, patients were selected with inclusion criteria, and only FQs was selected as the included drug among class A drugs.…”

Section: Discussionmentioning

confidence: 99%

A highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis: a multicenter prospective study in China

Sun

Zhou

et al. 2021

BMC Infect Dis

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Background To verify the efficacy and safety of an inexpensive standardized regimen for multidrug-resistant tuberculosis (MDR-TB) with low resistance to isoniazid (INH), a multicenter prospective study was conducted in eastern China. Methods Patients diagnosed as MDR-TB with low concentration INH resistance and rifampicin resistance, second-line/injectable agents sensitive were prospectively enrolled, given the regimen of Amikacin (Ak)–Fluoroquinolones (FQs)–Cycloserine (Cs)–Protionamide (Pto)–PasiniaZid (Pa)–Pyrazinamide (Z) for 6 months followed by 12 months of FQs–Cs–Pto–Pa–Z, and then followed up for treatment outcomes and adverse events (AEs). Results A total of 114 patients were enrolled into the study. The overall favorable treatment rate was 79.8% (91/114). Among 91 cases with favorable treatment, 75.4% (86/114) were cured and 4.4% (5/114) were completed treatment. Regarding to unfavorable outcomes, among 23 cases, 8.8% (10/114) had failures, 8.8% (10/114) losing follow up, 0.9% (1/114) had treatment terminated due to intolerance to drugs and 1.8% (2/114) died. Treatment favorable rate was significantly higher in newly treated MDR-TB (91.7%, 33/36) than that in retreated MDR-TB (74.4%, 58/78, p 0.03). The investigators recorded 42 AEs occurrences in 30 of 114 patients (26.3%). Clinicians rated most AEs as mild or moderate (95.24%, 40/42). Conclusions The regimen was proved to be effective, safe and inexpensive. It is suitable for specific drug resistant population, especially for newly-treated patients, which could be expected to be developed into a short-course regimen. Clinical trials registration China Clinical Trial Registry ChiCTR-OPC-16009380

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“…Lzd is also expensive in China ($600/month) and has signi cant long-term side effects as an ultra-broad-spectrum antibiotic. About 30-40% of patients stop linezolid treatment because of AEs (19). Therefore, in present study, patients were strictly selected for inclusion, and only FQs was selected as the included drug among class A drugs.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of an Inexpensive Regimen Containing Pasiniazine for Multidrug-Resistant Tuberculosis with Low-concentration resistance to Isoniazid: a prospective cohort study in a high Tuberculosis burden area

Sun¹,

Tang²,

Wang³

et al. 2021

Preprint

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BackgroundTo verify the efficacy and safety of an inexpensive regimen for specific multidrug-resistant tuberculosis (MDR-TB) based on Minimum Inhibitory Concentration (MIC) Drug sensitivity test(DST), a prospective cohort study was conducted in China.MethodsMDR-TB cases were prospectively enrolled through a clinical access programmes with strict inclusion and exclusion criteria, given the regimen and followed up, observed the treatment outcome and adverse effects (AEs) .ResultsA total of 114 patients were enrolled into the study. The overall treatment favorable rate was 79.8% (91/114), among 91 cases with favorable treatment, 86(75.4%)cured and 5 (4.4%) completed treatment. 23 cases got unfavorable outcome including 10 8.8% (10/114) failures, 8.8%(10/114) losing follow up ,0.9%(1/114) withdrawing treatment due to intolerance to drugs and 1.8%(2/114 ) died,respectively. Treatment favorable rate was significantly higher in newly treated MDR-TB (91.7%, 33/36) than that in retreated MDR-TB (74.4%, 58/78, p = 0.03). The investigators recorded 42 AEs occurrences in 30 of 114 patients༈26.3%). Clinicians rated most AEs as mild or moderate (95.24%, 40/42) and no one was caused by Pa༈0%,0/114).ConclusionsThe regimen was proved to be effective, safe and inexpensive. It is suitable for specific drug resistant population in China, especially for newly-treated patients, which could be expected to be developed into a short-course therapy.Clinical Trials Registration: China Clinical Trial Registry ChiCTR- OPC-16009380

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Linezolid-Associated Neurologic Adverse Events in Patients with Multidrug-Resistant Tuberculosis, France

Cited by 43 publications

References 24 publications

Antibiotics and the Nervous System—Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?

Antibiotics and the Nervous System—Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?

A highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis: a multicenter prospective study in China

Efficacy of an Inexpensive Regimen Containing Pasiniazine for Multidrug-Resistant Tuberculosis with Low-concentration resistance to Isoniazid: a prospective cohort study in a high Tuberculosis burden area

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