• Hepatic impairment
• Linezolid
• Machine learning
• Population pharmacokinetics
• Thrombocytopenia

• Humans
• Linezolid/pharmacokinetics
• Linezolid/administration & dosage
• Linezolid/adverse effects
• Linezolid/blood
• Machine Learning
• Female
• Male
• Models, Biological
• Middle Aged
• Aged
• Thrombocytopenia/chemically induced
• Anti-Bacterial Agents/pharmacokinetics
• Anti-Bacterial Agents/administration & dosage
• Anti-Bacterial Agents/adverse effects
• Area Under Curve
• Liver Diseases/metabolism
• Monte Carlo Method
• Adult
• Risk Factors

• No. 82173898 National Natural Science Foundation of China
• No. 2019ZYTS-01 Institutional foundation of the first affiliated hospital of Xi'an Jiaotong University

• Humans
• Chemical and Drug Induced Liver Injury/etiology
• Anti-Bacterial Agents/adverse effects
• Anti-Bacterial Agents/therapeutic use
• Antifungal Agents/adverse effects
• Antifungal Agents/therapeutic use
• Risk Factors
• Drug Labeling
• Liver/drug effects

• bacteremia
• creatinine
• creatinine clearance
• linezolid
• renal insufficiency
• risk factor
• thrombocytopenia

• ADR
• ANN
• linezolid
• logistic regression
• risk factor
• thrombocytopenia

• Linezolid
• Meta-analysis
• Risk factors
• Systematic review
• Thrombocytopenia

• Humans
• Linezolid/adverse effects
• Thrombocytopenia/chemically induced
• Thrombocytopenia/epidemiology
• Platelet Count/methods
• Renal Insufficiency
• Risk Factors
• Anemia/chemically induced
• Anti-Bacterial Agents/adverse effects

• 2022WJC233 Hangzhou Biological Medicine and Health Industry Development Support Project

• Antibiotics
• Integrated dialysis pharmacometric model
• Intensive care
• Monte-Carlo simulation
• Population pharmacokinetics
• Probability of target attainment
• Target attainment
• Volume of distribution

• 2017-20 Damp Stiftung
• Universitätsklinikum Hamburg-Eppendorf (UKE) (5411)

• Electronic medical record database
• Linezolid
• Risk factor
• Thrombocytopenia
• Tree analysis

• Linezolid
• anemia
• hematological toxicity
• therapeutic drug monitoring
• thrombocytopenia

• Hepatic impairment
• Linezolid
• Linezolid-induced thrombocytopenia
• Overexposure

• Humans
• Linezolid/adverse effects
• Anti-Bacterial Agents/adverse effects
• Thrombocytopenia/chemically induced
• Thrombocytopenia/epidemiology
• Thrombocytopenia/drug therapy
• Patients
• Risk Factors
• Retrospective Studies

• linezolid
• pharmacodynamics
• pharmacokinetics
• simulation
• thrombocytopenia

Nocardia paucivorans is an infrequently found bacterium with the potential to cause severe infection, with a predilection for the central nervous system, both in immunocompromised and immunocompetent individuals. Rapid etiological diagnosis of nocardiosis can facilitate timely and rational antimicrobial treatment. Metagenomic next-generation sequencing (mNGS) can improve the rate and reduce the turnaround time for the detection of Nocardia.

A 49-year-old man was admitted to hospital with cough and hemoptysis. Imaging revealed pulmonary consolidation as well as multiple brain lesions. Nocardia asiatica and Nocardia beijingensis were rapidly detected by mNGS of bronchoalveolar lavage fluid (BALF) while bacterial culture of BALF and pathological biopsy of lung tissue were negative. In early stages, he was treated with trimethoprim-sulfamethoxazole (TMP-SMZ) and linezolid by individual dose adjustment based on serum concentrations and the adverse effects of thrombocytopenia and leukopenia. The treatment was then replaced by TMP-SMZ and ceftriaxone or minocycline. He was treated with 8 mo of parenteral and/or oral antibiotics, and obvious clinical improvement was achieved with resolution of pulmonary and brain lesions on repeat imaging.

mNGS provided fast and precise pathogen detection of Nocardia. In disseminated nocardiosis, linezolid is an important alternative that can give a better outcome with the monitoring of linezolid serum concentrations and platelet count.

• Disseminated nocardiosis
• Metagenomic next-generation sequencing
• Linezolid
• Thrombocytopenia
• Case report

• HFpEF
• SGLT-2 inhibitor
• linezolid
• pancytopenia

• Antimicrobial agents
• Linezolid
• Platelets
• Risk factors
• Thrombocytopenia
• Vancomycin

In recent years, many studies on population pharmacokinetics of linezolid have been conducted. This comprehensive review aimed to summarize population pharmacokinetic models of linezolid, by focusing on dosage optimization to maximize the probability of attaining a certain pharmacokinetic-pharmacodynamic parameter in special populations. We searched the PubMed and EMBASE databases for population pharmacokinetic analyses of linezolid using a parametric non-linear mixed-effect approach, including both observational and prospective trials. Of the 32 studies, 26 were performed in adults, four in children, and one in both adults and children. High between-subject variability was determined in the majority of the models, which was in line with the variability of linezolid concentrations previously detected in observational studies. Some studies found that patients with renal impairment, hepatic failure, advanced age, or low body weight had higher exposure and adverse reactions rates. In contrast, lower concentrations and therapeutic failure were associated with obese patients, young patients, and patients who had undergone renal replacement techniques. In critically ill patients, the inter-individual and intra-individual variability was even greater, suggesting that this population is at an even higher risk of underexposure and overexposure. Therapeutic drug monitoring may be warranted in a large proportion of patients given that the Monte Carlo simulations demonstrated that the one-size-fits-all labeled dosing of 600 mg every 12 h could lead to toxicity or therapeutic failure for high values of the minimum inhibitory concentration of the target pathogen. Further research on covariates, including renal function, hepatic function, and drug–drug interactions related to P-glycoprotein could help to explain variability and improve linezolid dosing regimens.

• Natural Science Foundation of Zhejiang Province

• Liver transplant
• daptomycin
• enterococci
• mortality
• vancomycin-resistant

• hospital pharmacometrics
• methicillin resistant Staphylococcus aureus
• pharmacometrics
• target concentration intervention
• therapeutic drug monitoring

• anaemia
• linezolid
• predictive model
• receiver operating characteristic curve
• risk factors

• Linezolid
• clinical outcome
• dosage
• liver function test

• Drug Monitoring
• Humans
• Linezolid/adverse effects
• Linezolid/pharmacokinetics
• Models, Theoretical
• Thrombocytopenia/chemically induced
• Thrombocytopenia/drug therapy

Surgery for patients with complicated liver cancer often results in a long exposure to anesthesia with an increase in side effects. Continued long-term exposure to isoflurane may promote liver cancer progression. Small ubiquitin-like modifier (SUMO) 2 and 3, also known as SUMO2/3, conjugates to substrate proteins when cells undergo acute stress. However, whether or not SUMO2/3 is involved in isoflurane-mediated liver cancer progression is unknown. In the present study, hepatocellular carcinoma (HCC) cells were exposed to 2% isoflurane for 12 h, followed by 36 h of drug withdrawal, and the formation of SUMO2/3 conjugates and cancer behavioral characteristics were studied. The results demonstrated that the formation of SUMO2/3 conjugates was significantly increased following HCC cells being exposed to isoflurane for 0.5 h, and continued to increase for 48 h, even after the drug had been withdrawn. Furthermore, isoflurane-exposed HCC cells exhibited increased proliferation and invasion activity during the subsequent observation period. SUMO specific protease 3 (SENP3), which inhibits the binding of SUMO2/3 to its target proteins, was overexpressed and it was discovered that isoflurane-induced SUMOylation was significantly inhibited, and accordingly, the proliferation and invasion abilities of HCC cells were decreased to a certain extent. These findings indicated that SUMO2/3 is involved in the progression of HCC cells, at least in the Hep3B cell line, induced by the anesthetic isoflurane, and that inhibition of SUMO2/3 may antagonize the response. These results provided a novel target for decreasing the adverse reactions occurring in patients with HCC during anesthesia, particularly those who are exposed to isoflurane for long periods of time.

• hepatocellular carcinoma
• invasion
• isoflurane
• proliferation
• small ubiquitin-like modifier

• haematological toxicity
• linezolid
• therapeutic drug monitoring

Bone marrow suppression has a wide variety of causes. One of the overlooked causes is linezolid, a drug that is now being extensively used in the management of not only soft tissue infections but also hospital-acquired infections. Methicillin-resistant Staphylococcus aureus (MRSA) is widely being treated with linezolid. It becomes imperative that we comprehensively understand the hematological adverse effect profile of this drug. A reversible myelosuppression is seen with its extended use, though a number of risk factors like renal impairment are usually present. A prompt diagnosis can help us to timely discontinue the drug. We report one such case of an elderly patient with septic arthritis of the knee who developed pancytopenia after 32 days of linezolid therapy. Withdrawal of the drug led to a complete recovery of the blood counts in 21 days.

• bone marrow suppression
• linezolid
• pancytopenia
• sideroblasts

• Adverse drug reaction
• antibiotic
• linezolid
• monitoring
• myelosuppression
• neutropenia
• side effect
• subcutaneous ureteral bypass
• thrombocytopenia
• urinary tract infection

• T32 OD011130 NIH HHS

• dosage optimization
• linezolid
• liver dysfunction
• pharmacokinetics
• therapeutic drug monitoring

Antimicrobial treatment in critically ill patients remains challenging. The aim of this study was to develop a population pharmacokinetic model for linezolid in critically ill patients and to evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and effluent samples were drawn after linezolid administration at defined time points, and linezolid levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3. The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated (AUC₂₄/MIC > 80 and 100% T_>MIC). A two-compartment model best described the pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose of linezolid did not cover infections caused by pathogens with MIC ≥ 2 mg/L. Continuous infusion may be an alternative, especially when renal function is preserved.

• continuous infusion
• continuous renal replacement therapies
• critically ill
• linezolid
• pharmacokinetic/pharmacodynamics
• population pharmacokinetics

• Haematotoxicity
• Linezolid
• Thrombocytopenia

• frequency
• linezolid
• renal impairment
• risk factor
• thrombocytopenia

Tedizolid 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.

Two 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.

Two 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.

Tedizolid 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.

Editorial assistance and the article processing charges were funded by Bayer AG, Berlin, Germany.

• Extended treatment duration
• MRSA
• Real-life evidence
• Severe cellulitis
• Severe surgical wound infection
• Tedizolid phosphate

• RECORD statement
• Reporting quality
• linezolid
• pharmacovigilance
• thrombocytopenia

• critical care
• drug information
• infectious disease
• medication safety
• pharmacy education

• adverse effect
• linezolid
• risk factor
• thrombocytopenia

• MRSA
• clinical trials
• linezolid
• pneumonia
• skin infections

• pediatric
• lactic acidosis
• linezolid
• vancomycin resistant enterococcus
• multidrug resistance
• mitochondria

Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug's pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic metabolites. With the exception of trovafloxacin and telithromycin (now severely restricted), hepatotoxicity crude incidence remains globally low but variable. Thus, amoxicillin/clavulanate and co-trimoxazole, as well as flucloxacillin, cause hepatotoxic reactions at rates that make them visible in general practice (cases are often isolated, may have a delayed onset, sometimes appear only after cessation of therapy and can produce an array of hepatic lesions that mirror hepatobiliary disease, making causality often difficult to establish). Conversely, hepatotoxic reactions related to macrolides, tetracyclines and fluoroquinolones (in that order, from high to low) are much rarer, and are identifiable only through large-scale studies or worldwide pharmacovigilance reporting. For antibiotics specifically used for tuberculosis, adverse effects range from asymptomatic increases in liver enzymes to acute hepatitis and fulminant hepatic failure. Yet, it is difficult to single out individual drugs, as treatment always entails associations. Patients at risk are mainly those with previous experience of hepatotoxic reaction to antibiotics, the aged or those with impaired hepatic function in the absence of close monitoring, making it important to carefully balance potential risks with expected benefits in primary care. Pharmacogenetic testing using the new genome-wide association studies approach holds promise for better understanding the mechanism(s) underlying hepatotoxicity.