Pharmacokinetics, Safety, and Tolerability of Tedizolid Phosphate in Elderly Subjects

Flanagan, Shawn D.; Minassian, Sonia L.; Prokocimer, Philippe

doi:10.1002/cpdd.426

Cited by 9 publications

(6 citation statements)

References 19 publications

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“…Tedizolid is still not a FDA/EMA-approved antibiotic for the treatment of LRTIs, but it does bring hope to patients suffering liver and kidney organ failure, especially for LRTIs associated with linezolid-resistant Gram-positive pathogens. Although the phase 3 trial (NCT02019420) of tedizolid for HAP has not yet yielded results, tedizolid brings hope to old patients suffering renal or hepatic failure, especially with linezolid-resistant Gram-positive pathogens pneumonia (Flanagan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Pharmacotherapy of Lower Respiratory Tract Infections in Elderly—Focused on Antibiotics

et al. 2019

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Lower respiratory tract infections (LRTIs) refer to the inflammation of the trachea, bronchi, bronchioles, and lung tissue. Old people have an increased risk of developing LRTIs compared to young adults. The prevalence of LRTIs in the elderly population is not only related to underlying diseases and aging itself, but also to a variety of clinical issues, such as history of hospitalization, previous antibacterial therapy, mechanical ventilation, antibiotic resistance. These factors mentioned above have led to an increase in the prevalence and mortality of LRTIs in the elderly, and new medical strategies targeting LRTIs in this population are urgently needed. After a systematic review of the current randomized controlled trials and related studies, we recommend novel pharmacotherapies that demonstrate advantages for the management of LRTIs in people over the age of 65. We also briefly reviewed current medications for respiratory communicable diseases in the elderly. Various sources of information were used to ensure all relevant studies were included. We searched Pubmed, MEDLINE (OvidSP), EMBASE (OvidSP), and ClinicalTrials.gov. Strengths and limitations of these drugs were evaluated based on whether they have novelty of mechanism, favorable pharmacokinetic/pharmacodynamic profiles, avoidance of interactions and intolerance, simplicity of dosing, and their ability to cope with challenges which was mainly evaluated by the primary and secondary endpoints. The purpose of this review is to recommend the most promising antibiotics for treatment of LRTIs in the elderly (both in hospital and in the outpatient setting) based on the existing results of clinical studies with the novel antibiotics, and to briefly review current medications for respiratory communicable diseases in the elderly, aiming to a better management of LRTIs in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Pharmacotherapy of Lower Respiratory Tract Infections in Elderly—Focused on Antibiotics

et al. 2019

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“…It has a good penetration into skin and soft tissue [ 45 ], a very high oral bioavailability allowing equivalent dosing when switching from IV to PO therapy [ 9 , 12 , 13 ], and convenient once-daily dosing [ 8 , 9 , 12 , 13 ]. In addition, unlike some antibiotics, such as vancomycin, daptomycin or ceftaroline, tedizolid phosphate does not require dose adjustment in special populations, including the elderly, the obese and morbidly obese, and patients with renal or hepatic impairment [ 14 , 46 – 49 ]. In trials, tedizolid phosphate IV/PO once daily for 6 days demonstrated comparable efficacy to linezolid IV/PO twice daily for 10 days in patients with cellulitis, major cutaneous abscess and wound infection, and similar clinical cure rates were observed in subgroups of patients, including those with higher BMI or moderate/severe renal impairment and the elderly [ 15 – 17 ].…”

Section: Discussionmentioning

confidence: 99%

Real-Life Evidence for Tedizolid Phosphate in the Treatment of Cellulitis and Wound Infections: A Case Series

Shlyapnikov

Jáuregui

Khachatryan³

et al. 2018

Infect Dis Ther

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IntroductionTedizolid phosphate 200 mg, once daily for 6 days, has recently been approved for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) in several countries; however, clinical experience in real-life settings is currently limited. Here, we report on the use of tedizolid with an extended treatment duration for complex and severe ABSSSIs in real-world clinical settings.MethodsTwo patients with cellulitis and two patients with surgical site infection (SSI), aged 26–60 years, were treated with tedizolid phosphate 200 mg, intravenous/oral (IV/PO) or IV only, once daily at four different institutions.ResultsTwo morbidly obese patients had non-necrotizing, non-purulent severe cellulitis, which were complicated by sepsis or systemic inflammatory response syndrome plus myositis. One female patient failed on first-line empiric therapy with IV cefalotin, clindamycin and imipenem (3–4 days), and was switched to IV/PO tedizolid (7 + 5 days). One male patient received IV clindamycin plus IV/PO tedizolid (5 + 5 days), but clindamycin was discontinued on Day 3 due to an adverse event. For both patients, clinical signs and symptoms improved within 72 h, and laboratory results were normalized by Days 7 and 8, respectively. Two other patients (one obese, diabetic female with chronic hepatitis and chronic obstructive pulmonary disease) had complicated SSIs occurring 10 days after hernia repair with mesh or 3 months after spinal fusion surgery with metal implant. First patient with previous methicillin-resistant Staphylococcus aureus (MRSA) bacteremia received a 7-day tedizolid IV course empirically. The second patient with culture-confirmed MRSA infection received a 14-day IV course. Both patients responded within 72 h, and local and systemic signs normalized by end of treatment. There were no reports of thrombocytopenia.ConclusionTedizolid phosphate 200 mg for 7–14 days was a favored treatment option for patients with severe/complex ABSSSIs, and was effective following previous treatment failure or in late-onset infections.FundingEditorial assistance and the article processing charges were funded by Bayer AG, Berlin, Germany.

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“…Similarly, no disparity in PK profiles was noted in morbidly obese patients compared to the nonobese subjects [23]. There were no significant Table 1 Pharmacokinetic parameters of tedizolid at a therapeutic dosage (200 mg/day) AUC 0-∞ AUC from zero to infinity, AUC 0-24 AUC from 0 to 24 hours, C max maximum concentration, IV intravenous, SD standard deviation from the mean, V d volume of distribution a AUC = area under the concentration-time curve Data from [4,5,15,18,20,21,25,28]…”

Section: Obese Populationmentioning

confidence: 99%

“… AUC 0–∞ AUC from zero to infinity, AUC 0–24 AUC from 0 to 24 hours, C max maximum concentration, IV intravenous, SD standard deviation from the mean, V d volume of distribution a AUC = area under the concentration–time curve Data from [ 4 , 5 , 15 , 18 , 20 , 21 , 25 , 28 ] …”

Section: Pharmacokineticsmentioning

confidence: 99%

“…The small sample size ( n = 6) of the study indicates that further research might be needed to position TDZ for clinical use in children. Tedizolid displayed similar PK characteristics (200-mg single dose) in elderly subjects when compared to the adult population (AUC 0–72 of 34.7 vs 29.9 mg∙h/L) and hence no dose adjustment seems necessary in this patient collective [ 20 ].…”

Section: Pharmacokineticsmentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Tedizolid

2022

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Tedizolid is an oxazolidinone antibiotic with high potency against Gram-positive bacteria and currently prescribed in bacterial skin and skin-structure infections. The aim of the review was to summarize and critically review the key pharmacokinetic and pharmacodynamic aspects of tedizolid. Tedizolid displays linear pharmacokinetics with good tissue penetration. In in vitro susceptibility studies, tedizolid exhibits activity against the majority of Gram-positive bacteria (minimal inhibitory concentration [MIC] of ≤ 0.5 mg/L), is four-fold more potent than linezolid, and has the potential to treat pathogens being less susceptible to linezolid. Area under the unbound concentration-time curve (fAUC) related to MIC (fAUC/MIC) was best correlated with efficacy. In neutropenic mice, fAUC/MIC of ~ 50 and ~ 20 induced bacteriostasis in thigh and pulmonary infection models, respectively, at 24 h. The presence of granulocytes augmented its antibacterial effect. Hence, tedizolid is currently not recommended for immunocompromised patients. Clinical investigations with daily doses of 200 mg for 6 days showed non-inferiority to twice-daily dosing of linezolid 600 mg for 10 days in patients with acute bacterial skin and skin-structure infections. In addition to its use in skin and skin-structure infections, the high pulmonary penetration makes it an attractive option for respiratory infections including Mycobacterium tuberculosis. Resistance against tedizolid is rare yet effective antimicrobial surveillance and defining pharmacokinetic/pharmacodynamic targets for resistance suppression are needed to guide dosing strategies to suppress resistance development.

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Pharmacokinetics, Safety, and Tolerability of Tedizolid Phosphate in Elderly Subjects

Cited by 9 publications

References 19 publications

Pharmacotherapy of Lower Respiratory Tract Infections in Elderly—Focused on Antibiotics

Pharmacotherapy of Lower Respiratory Tract Infections in Elderly—Focused on Antibiotics

Real-Life Evidence for Tedizolid Phosphate in the Treatment of Cellulitis and Wound Infections: A Case Series

Pharmacokinetics and Pharmacodynamics of Tedizolid

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