Linezolid Toxicity and Mitochondrial Susceptibility: A Novel Neurological Complication in a Lebanese Patient

Hassan, Ossama K. Abou; Karnib, Mohamad; El-Khoury, Riyad; Nemer, Georges; Ahdab-Barmada, Mamdouha; Bou‐Khalil, Pierre

doi:10.3389/fphar.2016.00325

Cited by 21 publications

(12 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Substantial reduction of the cost occurred with the release of generic versions of linezolid at the end of 2015. Rare but serious neurological complications (optic and peripheral sensory neuropathies) have been reported with prolonged linezolid use and are more prevalent in subjects with preexisting neurological conditions, alcoholics, diabetics, or recipients of chemotherapeutic agents as was the case in our subject [ 12 – 15 ]. Duration but not the indication for linezolid use is the major determinant of neurological side effects, and studies have shown that optic neuropathies resolve after linezolid cessation, while peripheral neuropathies do not [ 12 ].…”

Section: Discussionmentioning

confidence: 77%

“…Other important side effects include myelosuppression (especially thrombocytopenia and rarely aplastic anemia) and type B lactic acidosis. [ 15 ]. These side effects appear to be mediated by direct mitochondrial protein synthesis inhibition by linezolid, and they disappear gradually after linezolid withdrawal [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…[ 15 ]. These side effects appear to be mediated by direct mitochondrial protein synthesis inhibition by linezolid, and they disappear gradually after linezolid withdrawal [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Nocardia spp. Pneumonia in a Solid Organ Recipient: Role of Linezolid

Mwandia

Polenakovik

2018

Case Reports in Infectious Diseases

View full text Add to dashboard Cite

We describe a rare infection with Nocardia spp. (N. pseudobrasiliensis species identification based on high-performance liquid chromatography analysis) in a 68-year-old renal transplant recipient. He presented with pneumonia complicated by hypoxic respiratory failure. He was allergic to sulphonamides. He was initially successfully treated with linezolid. However, he suffered severe sensory neuropathy after 4 months of therapy, necessitating linezolid cessation and completion of treatment with azithromycin. He had clinical and radiological resolution of his pneumonia and was disease free at subsequent follow-up 4 years later. This case highlights the need for alternative therapies for nocardiosis for patients that cannot be treated with sulphonamides due to allergies or/and infection with multidrug-resistant pathogens. It also illustrates the treatment limiting side effects of long-term therapy with linezolid.

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nocardia spp. Pneumonia in a Solid Organ Recipient: Role of Linezolid

Mwandia

Polenakovik

2018

Case Reports in Infectious Diseases

View full text Add to dashboard Cite

show abstract

“…Its half-life is approximately double, which allows for once-daily dosing. Finally, it seems safer as, although TD is a more potent inhibitor of mitochondrial protein synthesis than linezolid, the risks of adverse effects related to mitochondrial dysfunction (i.e., lactic acidosis, myelosuppression, and neuropathy) were found to be inferior to those for linezolid in studies carried out in animal models [ 79 , 80 ]. TD is approved for the treatment of aSSTIs by the FDA [ 81 ] and EMA [ 82 ].…”

Section: Oral and Parenteral Antibioticsmentioning

confidence: 99%

New Antibiotics for the Treatment of Acute Bacterial Skin and Soft Tissue Infections in Pediatrics

et al. 2020

View full text Add to dashboard Cite

Acute bacterial skin and soft tissue infections (aSSTIs) are a large group of diseases that can involve exclusively the skin or also the underlying subcutaneous tissues, fascia, or muscles. Despite differences in the localization and severity, all these diseases are due mainly to Gram-positive bacteria, especially Staphylococcus aureus and Streptococcus pyogenes. aSSTI incidence increased considerably in the early years of this century due to the emergence and diffusion of community-acquired methicillin-resistant S. aureus (CA-MRSA). Despite the availability of antibiotics effective against CA-MRSA, problems of resistance to these drugs and risks of significant adverse events have emerged. In this paper, the present knowledge on the potential role new antibiotics for the treatment of pediatric aSSTIs is discussed. The most recent molecules that have been licensed for the treatment of aSSTIs include ozenoxacin (OZ), ceftaroline fosamil (CF), dalbavancin (DA), oritavancin (OR), tedizolid (TD), delafloxacin (DL), and omadacycline (OM). However, only OZ and CF have been licensed for use in children with aSSTIs, although the superiority of these antibiotics to those routinely used for the treatment of aSSTIs should be further demonstrated. Waiting for additional studies, OZ and CF should be prescribed for aSSTI treatment in the presence of the potential failure of old molecules.

show abstract

“…One of the drugs suffering from poor water solubility and associated with an increased risk of mitochondrial toxicity is linezolid (LIN, Fig. 1), a wide-range antibiotics used mainly to treat infections caused by resistant strains of Gram-positive bacteria (Moellering, 2003;Abou Hassan et al, 2016). To date, crystal structures of two polymorphic forms of LIN are known, orthorhombic form II (Maccaroni et al, 2008), which is a commercially available form, and triclinic form III (Rao & Reddy, 2005;Tanaka & Hirayama, 2008), which is also mistakenly referred to in the literature as form IV (Wielgus et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Structural variety of heterosynthons in linezolid cocrystals with modified thermal properties

Khalaji

Wróblewska

Wielgus

et al. 2020

Acta Crystallogr B Struct Sci Cryst Eng Mater

View full text Add to dashboard Cite

In a search for new crystalline forms of linezolid with modified thermal properties five cocrystals of this wide range antibiotic with aromatic acids were obtained via mechanochemical grinding and analyzed with single crystal X-ray diffraction, solid-state NMR spectroscopy, powder X-ray diffraction and DSC measurements. The coformers used in this study were benzoic acid, p-hydroxybenzoic acid, protocatechuic acid, γ-resorcylic acid and gallic acid. In each of the cocrystals distinct structural features have been found, including a variable amount of water and different heterosynthons, indicating that there is more than one type of intermolecular interaction preferred by the linezolid molecule. Basing on the frequency of the observed supramolecular synthons, the proposed hierarchy of the hydrogen-bond acceptor sites of linezolid (LIN) is C=Oamide > C=Ooxazolidone > C—O—Cmorpholine > C—N—Cmorpholine > C—O—Coxazolidone. In addition, aromatic–aromatic interactions were found to be important in the stabilization of the analyzed structures. The obtained cocrystals show modified thermal properties, with four of them having melting points lower than the temperature of the phase transition from linezolid form II to linezolid form III. Such a change in this physicochemical property allows for the future application of melting-based techniques of introducing linezolid into drug delivery systems. In addition a change in water solubility of linezolid upon cocrystalization was evaluated, but only in the case of the cocrystal with protocatechuic acid was there a significant (43%) improvement in solubility in comparison with linezolid.

show abstract

Linezolid Toxicity and Mitochondrial Susceptibility: A Novel Neurological Complication in a Lebanese Patient

Cited by 21 publications

References 22 publications

Nocardia spp. Pneumonia in a Solid Organ Recipient: Role of Linezolid

Nocardia spp. Pneumonia in a Solid Organ Recipient: Role of Linezolid

New Antibiotics for the Treatment of Acute Bacterial Skin and Soft Tissue Infections in Pediatrics

Structural variety of heterosynthons in linezolid cocrystals with modified thermal properties

Contact Info

Product

Resources

About