Administration Of Linezolid Research Articles

A case of long-term administration of linezolid for infections caused by MRSA with careful monitoring and no adverse events

A case of long-term administration of linezolid for infections caused by MRSA with careful monitoring and no adverse events

Clinical research for saliva-based therapeutic drug monitoring of linezolid.

Linezolid is primarily used to treat of methicillin-resistant Staphylococcus aureus and multidrug-resistant tuberculosis infections. Thrombocytopenia due to linezolid usage is a concern, and therapeutic drug monitoring has been reported to be effective in its prevention. Plasma concentrations provide valuable information for treatment decisions; however, collecting plasma samples can be burdensome for both patients and healthcare providers. Therefore, there is interest in saliva as an alternative for monitoring, considering its potential to replace plasma samples. Patients hospitalized at Hokkaido University Hospital and Hokkaido Spinal Cord Injury Center between April 2022 and July 2024, who received oral or intravenous linezolid treatment, were enrolled. The concentrations of linezolid were simultaneously measured in plasma and saliva samples. We determined the concentration profiles of linezolid in the saliva and examined the correlation between saliva and plasma linezolid concentrations. Eighteen patients receiving linezolid were enrolled. The average of saliva/plasma (S/P) concentration ratios of linezolid were 1.018. A strong correlation was found between the salivary and plasma concentrations of linezolid (R= .833, P< .001). Notably, in patients receiving intravenous administration of linezolid, the correlation was even more pronounced (R= .885, P< .001). Additionally, when focusing on the S/P ratio of the trough concentrations in the morning and at night, the S/P ratios at night were much closer to 1.0. The concentrations of linezolid in plasma and saliva were similar, indicating their potential applicability in clinical settings. The monitoring of linezolid concentrations in saliva has been shown to be particularly suitable for patients receiving intravenous administration.

Therapeutic drug monitoring of linezolid in Chinese premature neonates: a population pharmacokinetic analysis and dosage optimization.

This study aimed to develop a pharmacokinetic model of linezolid in premature neonates and evaluate and optimize the administration regimen. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the blood concentration data of 54 premature neonates after intravenous administration of linezolid, and the relevant clinical data were collected. The population pharmacokinetic (PPK) model was established by nonlinear mixed effects modeling. Based on the final model parameters, the optimal administration regimen of linezolid in premature neonates with different body surface areas (BSA) was simulated and evaluated. The pharmacokinetic properties of linezolid in premature neonates are best described by a single-compartment model with primary elimination. The population typical values for apparent volume of distribution and clearance were 0.783 L and 0.154 L/h, respectively. BSA was a statistically significant covariate with clearance (CL) and volume of distribution (Vd). Monte Carlo simulations showed that the optimal administration regimen for linezolid in premature neonates was 6 mg/kg q8h for BSA 0.11 m2, 7 mg/kg q8h for BSA 0.13 m2, and 9 mg/kg q8h for BSA 0.15 m2 with minimum inhibitory concentration (MIC) ≤1 mg/L, 7 mg/kg q8h for BSA 0.11 m2, 8 mg/kg q8h for BSA 0.13 m2, and 10 mg/kg q8h for BSA 0.15 m2 with MIC = 2 mg/L. A pharmacokinetic model was developed to predict the blood concentration on linezolid in premature neonates. Based on this model, the optimal administration regimen of linezolid in premature neonates needs to be individualized according to different BSA levels.

A modified BPaL regimen for tuberculosis treatment replaces linezolid with inhaled spectinamides.

The Nix-TB clinical trial evaluated a new 6 month regimen containing three oral drugs; bedaquiline (B), pretomanid (Pa), and linezolid (L) (BPaL regimen) for the treatment of tuberculosis (TB). This regimen achieved remarkable results as almost 90% of the multidrug-resistant or extensively drug-resistant TB participants were cured but many patients also developed severe adverse events (AEs). The AEs were associated with the long-term administration of the protein synthesis inhibitor linezolid. Spectinamide 1599 is also a protein synthesis inhibitor of Mycobacterium tuberculosis with an excellent safety profile, but it lacks oral bioavailability. Here, we propose to replace L in the BPaL regimen with spectinamide (S) administered via inhalation and we demonstrate that inhaled spectinamide 1599, combined with BPa --BPaS regimen--has similar efficacy to that of the BPaL regimen while simultaneously avoiding the L-associated AEs. The BPaL and BPaS regimens were compared in the BALB/c and C3HeB/FeJ murine chronic TB efficacy models. After 4-weeks of treatment, both regimens promoted equivalent bactericidal effects in both TB murine models. However, treatment with BPaL resulted in significant weight loss and the complete blood count suggested the development of anemia. These effects were not similarly observed in mice treated with BPaS. BPaL and BPa, but not the BPaS treatment, also decreased myeloid to erythroid ratio suggesting the S in the BPaS regimen was able to recover this effect. Moreover, the BPaL also increased concentration of proinflammatory cytokines in bone marrow compared to mice receiving BPaS regimen. These combined data suggest that inhaled spectinamide 1599 combined with BPa is an effective TB regimen without L-associated AEs.

A rare occurrence of Vancomycin-induced gastrointestinal hemorrhage without thrombocytopenia: a case report and literature review

BackgroundVancomycin-induced bleeding has been reported, attributed to the mechanism of immune thrombocytopenia. A rare case of vancomycin-induced gastrointestinal hemorrhage in a young patient with no underlying disease, receiving intravenous vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infection, is presented. This occurrence occurred without thrombocytopenia. Relevant cases reported in the literature were also reviewed.Case presentationA 34-year-old male patient presented with maxillofacial multiple spaces infection accompanying left temporal abscess, bilateral lung abscesses. Culture results from both blood and secretion indicated that the infection was caused by MRSA. The patient received standard-dose vancomycin (1 g q12h intravenously guttae) for treatment. On the 5th day of therapy, he presented with bright red blood in his stool; however, vancomycin treatment was continued. By the 9th day, a decrease in hemoglobin level to 76 g/L and a platelet (PLT) count of 424 × 109/L raised concerns about gastrointestinal hemorrhage. The hemoglobin level decreased to 62 g/L on day 12. Due to the high tissue concentration of linezolid, administration of linezolid at a dose of 600 mg q12h intravenously guttae commenced on the 13th day as an alternative to vancomycin(D13-D17). Subsequently, on the 17th day, there was an improvement in hemoglobin level to 78 g/L. However, despite treatment with linezolid, the patient’s fever showed no significant improvement, prompting a switch back to vancomycin at a dosage of 1 g q12h intravenously guttae(D18-D22). On the 21st day, there was a recurrence of gastrointestinal hemorrhage, accompanied by a hemoglobin level of 42 g/L and a PLT count of 224 × 109/L. Gastroscopy revealed the presence of a gastroduodenal ulcer. The patient had no prior history of hemorrhoids, gastrointestinal ulcers, liver cirrhosis, or purpura. Prior to admission, he had not been administered non-steroidal anti-inflammatory drugs (NSAIDs) or steroids. During hospitalization, the only medications given were vancomycin, ambroxol and lidocaine. Additional tests ruled out immunological disorders as the cause of gastrointestinal ulcers, and a positive vancomycin rechallenge test indicated an association between vancomycin and bleeding. After discontinuation of vancomycin, no further bleeding occurred. This case highlights a rare occurrence of vancomycin-induced bleeding without thrombocytopenia, classified as “Certain” according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale for standardized case causality assessment.ConclusionThis case represents the first documented instance of vancomycin-induced bleeding without thrombocytopenia, as confirmed by a positive rechallenge test. This discovery will aid in the early detection of this rare adverse reaction in future cases.

Comparison of incidence of hyponatremia between linezolid and vancomycin in neonates and infants

A previous study reported that the incidence of hyponatremia after linezolid (LZD) use was higher than that with vancomycin (VCM) use in adults. However, hyponatremia due to LZD in neonates and infants was not investigated. This study aimed to compare the incidence of hyponatremia between LZD and VCM use in neonates and infants.The retrospective study was conducted at the Aichi Medical University Hospital. All patients who were cared for in NICU or GCU and received ≥3 days of LZD or VCM were included in this study. Hyponatremia was defined as serum sodium level ≤134 mEq/L and ≥5 % decrease from baseline after administration of LZD or VCM.A total of 76 patients (LZD, N = 36; VCM, N = 37) were included. There was no significant difference in the incidence of hyponatremia between the two groups (19.4 % vs 16.2 %, p = 0.72). The proportion of patients with a minimum value of serum sodium ≤134 mEq/L during treatment was 47.3 % in the LZD group and 35.1 % in the VCM group (p = 0.29), and the decrease in serum sodium level from baseline to the minimum value was 80.5 % and 78.4 %, respectively (p = 0.85).In conclusion, there was no significant difference in the incidence of hyponatremia between the LZD and VCM groups. Therefore, it is not necessary to avoid LZD use in neonates and infants because of the risk of hyponatremia.

WITHDRAWN: A successful management of concurrent infection with cranial Nocardia gipuzkoensis and pulmonary Klebsiella pneumoniae: A case report

BackgroundSuccessful management of concurrent infection with cranial N. gipuzkoensis and pulmonary Klebsiella pneumoniae has never been described. Case presentationA 71-year-old female was given referral to our hospital due to intracal space occupying lesion for over 20 days. Initial chief complaints implied cranial and pulmonary inflammation. Subsequently, drainage of brain lesion was obtained and identified as Nocardia gipuzkoensis infection through microbial culture and metagenomic next-generation sequencing (mNGS). Sputum culture determined as Klebsiella pneumoniae infection. Combined with results of antimicrobial susceptibility tests and allergic history, the patient was improved after being treated with two-week Meropenem (2g/8h iv) combined Vancomycin (1g/12h iv), and reached neurological recovery followed with oral administration of Linezolid (0.6g/12h po) and Levofloxacin (0.5g/24h po) for over 6 weeks. ConclusionA successful administration of concurrent infections was reported. It might provide supporting evidence for shortening the intravenous administration of nocardiosis.

A Modified BPaL Regimen for Tuberculosis Treatment replaces Linezolid with Inhaled Spectinamides.

Tuberculosis (TB) is an airborne infectious disease that spreads via aerosols containing Mycobacterium tuberculosis (Mtb), the causative agent of TB. TB can be cured by administration of 3-4 drugs for 6-9 months but there are limited treatment options for patients infected with multidrug (MDR) and extensively resistant (XDR) strains of Mtb. BPaL is a new all-oral combination of drugs consisting of Bedaquiline (B), Pretomanid (Pa) and Linezolid (L). This regimen was able to cure ∼90% of MDR and XDR TB patients in clinical trials but many patients developed severe adverse events (AEs) associated to the long-term administration of linezolid. We evaluated a new regimen in which Linezolid in the BPaL regimen was replaced with inhaled spectinamide 1599. In the current study, we demonstrate that 4-weeks of treatment with inhaled spectinamide 1599 in combination with Bedaquiline and Pretomanid has equivalent efficacy to the BPaL drug combination and avoids the L-associated-AEs.

Hypertensive Crisis Associated with Serotonin Syndrome Following Linezolid Administration: Report of Two Cases

Hypertensive Crisis Associated with Serotonin Syndrome Following Linezolid Administration: Report of Two Cases

Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database.

Introduction: Linezolid is an oxazolidinone antibiotic that is active against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Real-world studies on the safety of linezolid in large populations are lacking. This study aimed to determine the adverse events associated with linezolid in real-world settings by analyzing data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: We retrospectively extracted reports on adverse drug events (ADEs) from the FAERS database from the first quarter of 2004 to that of 2023. By using disproportionality analysis including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), along with the multi-item gamma Poisson shrinker (MGPS), we evaluated whether there was a significant association between linezolid and ADE. The time to onset of ADE was further analyzed in the general population and within each age, weight, reporting population, and weight subgroups. Results: A total of 11,176 reports of linezolid as the "primary suspected" drug and 263 significant adverse events of linezolid were identified, including some common adverse events such as thrombocytopenia (n = 1,139, ROR 21.98), anaemia (n = 704, ROR 7.39), and unexpected signals that were not listed on the drug label such as rhabdomyolysis (n = 90, ROR 4.33), and electrocardiogram QT prolonged (n = 73, ROR 4.07). Linezolid-induced adverse reactions involved 27 System Organ Class (SOC). Gender differences existed in ADE signals related to linezolid. The median onset time of all ADEs was 6 days, and most ADEs (n = 3,778) occurred within the first month of linezolid use but some may continue to occur even after a year of treatment (n = 46). Conclusion: This study reports the time to onset of adverse effects in detail at the levels of SOC and specific preferred term (PT). The results of our study provide valuable insights for optimizing the use of linezolid and reducing potential side effects, expected to facilitate the safe use of linezolid in clinical settings.

Differential distribution of linezolid in diseased and nondiseased bones in patients with spinal tuberculosis

BackgroundLinezolid exhibits antibacterial activity against sensitive and drug-resistant strains of Mycobacterium tuberculosis. Knowledge on the distribution of linezolid in different types of bones in patients with spinal tuberculosis (TB) is lacking, which limits the pharmacokinetic and pharmacodynamic studies of linezolid. This study aimed to evaluate the distribution of linezolid in diseased and nondiseased bones in patients with spinal TB.MethodsSpinal TB patients treated with linezolid-containing regimens and whose diseased and nondiseased bones were collected during surgery were enrolled retrospectively from January 2017 to February 2022. Blood, nondiseased bones, and diseased bones were collected simultaneously during the operation. Linezolid concentrations in the plasma, nondiseased bones, and diseased bones were subjected to high-performance liquid chromatography–tandem mass spectrometry.ResultsSeven eligible spinal TB patients, including one rifampicin-resistant case, were enrolled. Following a 600 mg oral administration of linezolid before surgery, the median concentrations of linezolid in plasma, nondiseased bone, and diseased bone of the seven patients were 8.23, 1.01, and 2.13 mg/L, respectively. The mean ratios of linezolid concentration in nondiseased bones/plasma, diseased bones/plasma and diseased bones/nondiseased bones reached 0.26, 0.49, and 2.27, respectively. The diseased bones/plasma presented a higher mean ratio of linezolid concentration than nondiseased bones/plasma, and the difference was statistically significant (t = 2.55, p = 0.025). Pearson’s correlation analysis showed the positively correlation of linezolid concentrations in diseased and nondiseased bones (r = 0.810, p = 0.027).ConclusionsLinezolid exhibits a higher concentration distribution in diseased bones than in nondiseased bones.

Serotonergic agents and linezolid: Impact of exposure to more than one agent concomitantly on risk of adverse effects

Background: The off-target effects linezolid have the potential to cause serotonin syndrome when given in conjunction with serotonergic agents. Despite package insert labeling as a contraindication, several postmarketing studies have demonstrated a low incidence of serotonin syndrome with the concomitant use of linezolid and other serotonergic agents. Linezolid provides a convenient oral option for gram-positive infections. However, due to concerns for serotonin syndrome, the use of linezolid is sometimes avoided. Methods: We performed a single-center, retrospective, medical record review of all adult inpatients from September 2021 to September 2022. Patients included had 1 administration of linezolid and 1 inpatient administration of a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) within 14 days. The primary outcome was the incidence of serotonin syndrome as defined by the Hunter serotonin toxicity criteria, which were retrospectively applied to each patient based on medical-record documentation. We compared patients receiving 1 versus multiple serotonergic agents. Secondary outcomes included duration of hospitalization and adverse outcomes based on concerns for serotonin syndrome such as need for rescue, ICU admission, or change in medication. Results: Of the 50 included patients from a convenience sample, 27 (54%) were on linezolid and &gt;1 serotonergic agent. Patients had similar baseline characteristics (Table 1). The most common concomitant agent used was an SSRI. Other agents that predispose patients to serotonin syndrome included opioid analgesics and other classes of antidepressants (Fig. 1). Serotonin syndrome occurred within 48 hours in 1 patient on an SNRI and a continuous fentanyl drip. There was no need for rescue or ICU admission due to serotonin syndrome. No patients were readmitted due to serotonin syndrome, and no differences were observed in hospital lengths of stay. Conclusions: Exposure to a single serotonergic agent combined with receipt of linezolid was not associated with any cases of serotonin syndrome. Exposure to multiple serotonergic agents was not associated with a high incidence of serotonin syndrome. This small series supports previous reports demonstrating relative safety of linezolid given with serotonergic agents and encourages review of interruptive drug–drug interaction alerts for linezolid within the electronic ordering system.Disclosures: None

Linezolid induced toxic optic neuropathy in drug resistant tuberculosis-A case series

In developing countries like India, Linezolid is widely used for the treatment of Multi drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Long-term administration of Linezolid is reported to cause toxic optic neuropathy causing bilateral, progressive visual loss in patients. We report case details of three patients on anti-tubercular therapy presented to us with sudden, progressive, painless blurring of vision of both eyes the cause of which was confirmed to be toxic optic neuropathy due to linezolid. Subsequently, cessation of the drug resulted in complete visual recovery in two patients whereas one patient had minimal visual improvement due to secondary optic atrophy. Clinicians and health care workers need to be aware of sight threatening complications of Linezolid.

The Protective Effects of Pyridoxine on Linezolid-Induced Hematological Toxicity, Hepatotoxicity, and Oxidative Stress in Rats.

Linezolid is often used to treat antibacterial-resistant infections. Linezolid can cause side effects. To date, the effectiveness of the simultaneous administration of pyridoxine and linezolid is unclear. Here we investigate the protective effect of pyridoxine on linezolid-induced hematological toxicity, hepatotoxicity, and oxidative stress in rats. The 40 male pediatric Spraque-Dawley rats were separated into 4 groups: control, linezolid, pyridoxine, and linezolid-pyridoxine. A complete blood count, liver function test, and measurements of antioxidant enzyme activities for superoxide dismutase, glutathione peroxidase, catalase, and lipid peroxidation were performed in blood before treatment and 2 weeks after administration of the treatment. White blood cell and hemoglobin counts for the linezolid group decreased, and the alanine aminotransferase level in the linezolid group increased compared to their respective baseline values. Post-treatment white blood cell decreased in the linezolid and linezolid- pyridoxine groups compared to those in the control group (P < .001). Alanine aminotransferase levels increased in the linezolid and linezolid-pyridoxine groups compared to those in the control group (P < .001 and P < .05, respectively). The activity of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde levels increased in the linezolid group compared to the control group (P < .001, P < .05, P < .001, and P < .001, respectively). Linezolid plus pyridoxine treatment caused a significant decrease in malondialdehyde levels and superoxide dismutase, catalase, and glutathione peroxidase enzyme activities compared to the linezolid group (P < .001, P < .01, P < .001, and P < .01, respectively). Pyridoxine may be an effective adjuvant agent for the prevention of linezolid toxicity in rat models.

Linezolid As An Add On Treatment In The Intensive Phase Of Tubercular Meningitis. A Randomized Controlled Pilot Trial. (S25.004)

<h3>Objective:</h3> To study whether administration of linezolid given for 4 weeks along with four drug standard weight-based Anti-Tubercular (ATT) regimen in intensive phase of tubercular meningitis (TBM) will help reduce mortality and morbidity. <h3>Background:</h3> Most agents used in the treatment of TBM have limited CNS penetration thereby limiting its efficacy. CSF penetration of linezolid is about 80–100 % and has been repurposed as a class C, core MDR-TB drug. <h3>Design/Methods:</h3> The study was a prospective, single center, randomized, open label with blinded outcome assessment pilot trial carried out in patients with TBM. Patients fulfilling the eligibility criteria were randomized using computer generated numbers and permuted randomization block design in a 1:1 ratio into two treatment groups either to receive standard ATT alone or add on oral 600 mg BD linezolid daily for 4 weeks along with standard ATT[rifampicin (10 mg/kg), isoniazid (5mg/kg), pyrazinamide (15–30 mg/kg, ethambutol (15 mg/kg) or streptomycin (0.75–1gm/day)]. Primary outcome was safety and mortality at the end of one and three months measured by intention to treat analysis. <h3>Results:</h3> A total of 29 patients (15 in intervention and 14 in the control arm) were recruited and 27 completed three months of follow up. There was no significant difference between two groups in mortality at one and three months with Odds ratio (95% CI) of 2[0.161 to 24.87] and p=1 at one month and 0.385[0.058 to 2.538] with p=value 0.39 at three months respectively. No major safety concerns were observed with the use of Linezolid. Favorable shift of mRS(modified Rankin Scale) at three months was observed in the Linezolid arm only (intra group p= 0.031with effect size (95% CI )1.667[0.353 to 7.875]. <h3>Conclusions:</h3> Linezolid was not effective in improving the mortality in TBM patients. Study with a larger sample size is desirable to demonstrate the benefits of Linezolid in TBM. <b>Disclosure:</b> Dr. Sahib has nothing to disclose. Dr. Bhatia has nothing to disclose. M.V. Padma Srivastava has nothing to disclose. Mamta Singh Bhushan has nothing to disclose. Vishnu VY has nothing to disclose. Roopa Rajan has received research support from DBT. Roopa Rajan has received research support from DST-SERB. The institution of Roopa Rajan has received research support from Michael J Fox Foundaton. The institution of Anu Gupta has received research support from ICMR. Dr. Srivastava has nothing to disclose.

Implementation of an antimicrobial stewardship program in the Vascular Surgery ward of a university tertiary care hospital in Pavia, Northern Italy

PurposeThe commitment of multidisciplinary teams in antimicrobial stewardship programs (ASPs) is often inadequately considered, especially in surgical wards. We wanted to evaluate clinical, microbiological, and pharmacological outcomes before and after the implementation of an ASP in the Vascular Surgery ward of Fondazione IRCCS Policlinico San Matteo, a tertiary care hospital in Pavia, Italy.MethodsThis was a quasi-experimental quality-improvement study. The antimicrobial stewardship activity was conducted twice a week for 12 months and consisted of both prospective audit and feedback of all the ongoing antimicrobial prescriptions by the infectious diseases’ consultants and educational meetings for the healthcare workers of the Vascular Surgery ward. For comparison between the study periods, Student t test (Mann–Whitney test for skewed distributions) was used for quantitative variables (ANOVA or Kruskall-Wallis for > 2 groups respectively), and Pearson’s chi-squared test (Fisher exact test where appropriate) for categorical variables. 2-tailed tests were used. P-value significance cut-off was 0.05.ResultsDuring the 12-month intervention period, among a total number of 698 patients, 186 prescriptions were revised, mostly leading to de-escalating an ongoing antimicrobial therapy (39, 20.97%). A statistically significant reduction in isolates of carbapenem-resistant Pseudomonas aeruginosa (p-value 0.003) and the absence of Clostridioides difficile infections were reported. No statistically significant changes were observed in terms of length of stay and all-cause in-hospital mortality. A significant decrease in the administration of carbapenems (p-value 0.01), daptomycin (p-value < 0.01) and linezolid (p-value 0.43) was registered. A significant reduction in antimicrobial costs was also observed.ConclusionsThe implementation of a 12-month ASP brought significant clinical and economic results, highlighting the benefits of a multidisciplinary teamwork.

A Retrospective Study to Compare the Incidence of Hyponatremia after Administration between Linezolid and Tedizolid.

Linezolid (LZD) and Tedizolid (TZD) are oxazolidinone antibiotic for meticillin-resistant Staphylococcus aureus (MRSA). Severe hyponatremia after LZD administration have been reported. Severe hyponatremia cause seizures, unconsciousness, and even death. Therefore, we conducted a study to assess the change of serum sodium level after LZD and TZD therapy. We enrolled 67 patients treated with LZD and 28 treated with TZD. We monitored the serum sodium level from the administration to 14 days after administration of oxazolidinone drug. Hyponatremia was defined a sodiuln level ≤134 mmol/L after the initiation of oxazolidinone drug. The frequency of hyponatremia in the LZD group was significantly higher than that in the TZD group (39.7% vs. 11.1%, p < 0.05). The rate of patients administered by injection was significantly higher than in the LZD group than in the TZD group (52.9% vs. 14.8%, p < 0.01). Multiple logistic regression analyses identified the albumin level before the oxazolidinone drug therapy as the independent variables associated with the development of hyponatremia. We revealed that TZD is safer than LZD in terms of hyponatremia. Therefore, cases that LZD is administered by injection should be used more carefully with hyponatremia in patients with low albumin level.

Linezolid pharmacokinetics: a systematic review for the best clinical practice

To summarize the pharmacokinetics of linezolid to optimize the dosing regimen in special populations. A literature search was performed in three largest medical databases, including Embase, Scopus, and PubMed. The main applied keywords were linezolid and pharmacokinetics. Of 3663 retrieved publications in the English language, 35 original research articles, clinical studies, and case reports about linezolid pharmacokinetics in different populations such as pregnant women, pediatrics, elderly subjects, obese people, individuals with organ dysfunction, and critically ill patients were included. RESULTSAND CONCLUSION: Dose adjustment is not currently recommended for linezolid in patients with mild to moderate renal or hepatic impairment, older adults, and pregnant women. Although dose adjustment is not recommended in patients with severe renal or hepatic impairment, it should be considered that these patients are more vulnerable to linezolid adverse effects and drug interactions. In pediatrics, reducing the linezolid dosing interval to 8h is suggested. Despite the lack of sufficient information in obese individuals, dosing based on body weight or use of higher dose seems to be justifiable to prevent sub-therapeutic concentrations. Although dose adjustment of linezolid is not recommended in critically ill patients, administration of linezolid as continuous intravenous infusion is suggested in this population. Blood level monitoring should be considered in populations that are vulnerable to linezolid underexposure (such as critically ill patients with augmented renal clearance, pediatrics, overweight, and obese patients) or overexposure (such as elderly, patients with hepatic and renal impairment). To assess the efficacy and safety of linezolid, the area under the concentration-time curve over 24h to minimum inhibitory concentration (AUC0-24h/MIC) equal to 80-120, percentage of time above the MIC ≥ 85%, and serum trough concentration between 2 and 7mg/L are suggested.

Linezolid-related adverse effects in the treatment of rifampicin resistant tuberculosis: a retrospective study

Linezolid (LZD) is an effective drug in treating multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. This study aimed to evaluate the safety of LZD in the treatment of patients with rifampicin resistant tuberculosis. This was a multicenter retrospective study. A total of 184 patients of the rifampicin resistant tuberculosis patients treated with LZD from Jan 2018 to Apr 2020 in three hospitals were involved, and their clinical symptoms were recorded and analyzed. Meanwhile, the types and incidence of adverse effects associated with LZD were evaluated. It showed that peripheral neuritis (51, 27.7%) and hemochromatosis (42, 22.8%) were the most common adverse effects observed among these patients. The median time of symptoms after LZD treatment was 45.5 and 120.0 days, respectively. Furthermore, female patients had a significantly higher risk for leukopenia (P = 0.002) and hemochromatosis (P = 0.033) when compared with male patients. History of underlying disease was the risk factor for thrombocytopenia (P = 0.022). Patients with long duration of medication (RR = 1.004, 95%CI: 1.002–1.006, P < 0.001) and daily dosage ≥600mg (RR = 3.059, 95%CI: 1.238–7.558, P = 0.015) were at higher risk of hemochromatosis. Age was the risk factor for rash (P = 0.008) and nausea and vomiting (P = 0.018). In addition, LZD administration time was the risk factor for optic neuritis (P < 0.001) and peripheral neuritis (P < 0.001). LZD can cause adverse symptoms in patients with rifampicin resistant tuberculosis. Gender, history of underlying disease, LZD use time, LZD dosage, and age are the risk factors in the LZD treatment of these patients. During medication, bone marrow suppression and neuropathy should be closely monitored. This study could potentially provide useful information for the clinical practice.

Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid-associated thrombocytopenia.

Linezolid (LZD) may cause thrombocytopenia, which can result in discontinuation of treatment. In this study, the blood LZD trough concentration was estimated based on population pharmacokinetic (PK) parameters derived from two previously published models in the Japanese population to determine the rate of achieving the target trough value when the risk of thrombocytopenia is low and to clarify its relationship with the onset of thrombocytopenia. This study included adult patients hospitalized at Shimane University Hospital, who received LZD treatment for at least 4 days from January 2010 to December 2017. Patients whose platelet count fell below 70% before LZD administration were categorized as the thrombocytopenic group. Patient PK parameters were calculated based on the population PK models described by Matsumoto et al. and Sasaki et al., and these parameters were designated A and B, respectively. Based on these parameters, the rate of achieving an LZD trough concentration of less than 8μg/ml, which is the safety target achievement rate, was calculated using a random simulation for each patient. We further analysed the association between the incidence of thrombocytopenia and patient factors, including safety target achievement rate, through univariate, multivariate, and receiver operating characteristic (ROC) analyses. Patients (n=77) aged 72 ± 11 years and weighing 56.7 ± 10.9kg, with a creatinine clearance (CLcr ) of 60.5 ± 47.2ml/min and a cirrhosis prevalence of 9.1%, were analysed. All patients received LZD at a dose of 600 mg twice daily for a total of 10.9 ± 8.9 days. Univariate analyses revealed significant differences (p < 0.05) in the duration of LZD therapy, serum creatinine, creatinine clearance, LZD clearance, and the safety target achievement rate for parameters A and B between the thrombocytopenic and non-thrombocytopenic groups. A multivariate analysis of these factors stratified with the cutoff values obtained by ROC analysis revealed that the duration of LZD therapy and the safety target achievement rates for parameters A and B were significant factors (odds ratios for duration of LZD therapy: 7.436 [95% confidence interval (CI): 1.918-28.831] and 4.712 [95% CI: 1.567-14.163]; odds ratio for safety target achievement rate: 0.060 [95% CI: 0.016-0.232] and 0.167 [95% CI: 0.056-0.498] for parameters A and B, respectively). When the safety target achievement rates for patients treated with LZD were compared between the thrombocytopenic and non-thrombocytopenic groups, the safety target achievement rate was higher in the non-thrombocytopenic group in both the patients treated with LZD for less than 10 days and those for 10 days or more. Therefore, the safety target achievement rate estimated by the PK/PD simulation may represent to be an important index for risk assessment of LZD-induced thrombocytopenia. The risk of LZD-induced thrombocytopenia, which increased with the duration of LZD therapy, may be predicted using the safety target achievement rate obtained by the blood concentration simulation.