Serum linezolid concentrations are reduced in critically ill patients with pulmonary infections: A prospective observational study

Zöller, Michael; Paal, Michael; Greimel, Antonia; Kallee, Simon; Vogeser, Michael; Irlbeck, Michael; Schroeder, Ines; Liebchen, Uwe; Scharf, Christina

doi:10.1016/j.jcrc.2022.154100

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…Significant differences were observed in the lung penetration rate of linezolid (e.g., patient 1 with a very low penetration rate). No specific cause can be named for this, although large inter-individual differences in the linezolid blood concentration are already known and the reasons for this are at least partially transferable to the lungs [ 9 , 12 ]. This again demonstrates the need for TDM of linezolid not only in the blood but also at the site of infection to identify patients like patient 1 with low penetration rates and to enable the target range to be achieved in these patients as well [ 3 , 21 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the concentration in the blood does not automatically indicate the concentration at the site of infection, which is hypothesized to be more relevant for a successful therapy [ 10 ]. It has been shown that patients with acute respiratory distress syndrome or pneumonia have significantly lower linezolid blood concentrations than patients with non-pulmonary infections [ 11 , 12 ]. Moreover, linezolid has been described to have a high penetration rate into the lung tissue [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial

Rebholz,

Liebchen,

Paal

et al. 2024

ICMx

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Background Therapeutic drug monitoring (TDM) of anti-infectives such as linezolid is routinely performed in blood of intensive care unit (ICU) patients to optimize target attainment. However, the concentration at the site of infection is considered more important for a successful therapy. Until now, bronchoalveolar lavage (BAL) is the gold standard to measure intrapulmonary concentrations of anti-infective agents. However, it is an invasive method and unsuitable for regular TDM. The aim of this proof-of-concept study was to investigate whether it is possible to reliably determine the intrapulmonary concentration of linezolid from endotracheal aspiration (ENTA). Methods Intubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients. Results Linezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L. Conclusions Linezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection “lung”. Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial

Rebholz,

Liebchen,

Paal

et al. 2024

ICMx

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“…These characteristics render linezolid a better e cacy in pneumonia, skin and soft tissue infection, and other infections. Because of high blood concentration of linezolid in pneumonic tissues, it is recommended as the rst-line drug in the pharmacotherapy of pneumonia (Hashemian, et al 2018;He and Wunderink 2020;Zoller, et al 2022). Regarding skin and soft tissue infection, linezolid is moderately lipophilic, can penetrate the skin and soft tissues, and has toxin-suppressive properties (Blackman, et al 2021;John 2020).…”

Section: Discussionmentioning

confidence: 99%

Comparative effectiveness and safety of five antibiotics in treating MRSA infections: A network meta-analysis

Zhang

Hong

et al. 2023

Preprint

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A considerable number of researches compared the effectiveness and safety different antibiotics for a disease caused by MRSA. However, comprehensive evaluated antibiotic therapeutic different diseases caused by MRSA is lacking. The network meta-analysis (NMA) comprehensively compared the effectiveness and safety of linezolid, teicoplanin, daptomycin, and tigecycline with vancomycin in treating methicillin-resistant Staphylococcus aureus (MRSA)-caused diseases. PubMed, Embase, Web of Science, Cochrane Library, CNKI, and Wan-fang databases were searched for studies until Sep 28, 2021. All eligible randomized controlled trials of five antibiotics were included in the NMA, and their effectiveness and safety were compared in various MRSA-attributed diseases. The dichotomous variables adopted for the odds ratio (OR) and the surface under the cumulative ranking (SUCRA) to evaluate the incidence rate. The study was performed using Rev Man 5.4 and STATA 16.0 software. SUCRA analysis revealed the superiority of linezolid to other antibiotics in total effectiveness rate (98.9%), microbial killing rate (99.6%), and total nephrotoxicity (17.8%). Regarding safety, the total adverse reaction rate of vancomycin was inferior to teicoplanin (OR 0.49, 95% CI 0.30–0.80). Vancomycin total hepatotoxicity was inferior to linezolid (OR 0.36, 95% CI 0.18–0.73) and tigecycline (OR 0.15, 95% CI 0.03–0.66), and it was also inferior to linezolid (OR 0.33, 95% CI 0.24–0.47) and teicoplanin (OR 0.35, 95% CI 0.18–0.69) in total nephrotoxicity. Linezolid had a higher risk of thrombocytopenia than teicoplanin (OR 4.24, 95% CI 1.26–14.24) and vancomycin (OR 2.14, 95% CI 1.17–3.90). Moreover, linezolid exhibited higher effectiveness in pneumonia compared to vancomycin (OR 2.06, 95% CI 1.58–2.69) and teicoplanin (OR 1.67, 95% CI 1.06–2.62). For skin and soft-tissue infections, linezolid showed superior effectiveness to vancomycin (OR 1.62, 95% CI 1.20–2.18). Regarding the microbial killing rate, vancomycin was inferior to linezolid in pneumonia (OR 0.38, 95% CI 0.29–0.49), skin soft-tissue infection (OR 0.41, 95% CI 0.21–0.79), and other infections (OR 0.40, 95% CI 0.20–0.83). And teicoplanin was inferior to linezolid in treating pneumonia (OR 0.51, 95% CI 0.33–0.81) and other infections (OR 0.39, 95% CI 0.18–0.86). The present research suggest that linezolid may be a better option for treating MRSA-caused diseases. However, caution is warranted owing to linezolid-associated thrombocytopenia.

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“…These include obesity, augmented renal clearance (ARC), critical illness, and/or the presence of concomitant medications, such as rifampicin. 26–29 Cojutti et al performed population linezolid PK/PD analyses in overweight and obese adult patients and found that patients with estimated creatinine clearance ≥130 mL/min (ARC) and/or comedication with P-glycoprotein modulators, such as rifampicin, may require higher than conventional linezolid doses guided by TDM. 30…”

Section: Linezolid Underexposure: Missing From the Pimentioning

confidence: 99%

“…These include obesity, augmented renal clearance (ARC), critical illness, and/or the presence of concomitant medications, such as rifampicin. [26][27][28][29] Cojutti et al performed population linezolid PK/PD analyses in overweight and obese adult patients and found that patients with estimated creatinine clearance $130 mL/min (ARC) and/or comedication with P-glycoprotein modulators, such as rifampicin, may require higher than conventional linezolid doses guided by TDM. 30 Zoller et al conducted a prospective observational study of 37 critically ill patients and demonstrated that .40% of the patients had linezolid concentrations outside the target range (AUC24 ,200 mgh/L and C min ,2 mg/L), whereas Taubert et al performed extensive TDM in 55 critically ill patients receiving linezolid and reported that only 36% were within the target range (12 hours [AUC12]/MIC ratio of .50; MIC = 2 mg/L).…”

Section: Dosage Adjustmentmentioning

confidence: 99%

Why Product Information Should not be Set in Stone: Lessons from a Decade of Linezolid Therapeutic Drug Monitoring: An Opinion Paper

Marriott

Cattaneo

2023

Therapeutic Drug Monitoring

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WHAT IS 'PRODUCT INFORMATION'?The "product information" (PI) for a medicine contains the documents providing officially approved information for health care professionals and patients. The regulatory agencies for drugs (eg, the European Medicines Agency, the Food and Drug Administration, Therapeutic Goods of Australia) provide guidance and templates to give marketing authorization applicants practical advice on how to develop the PI for human medicines. A summary of the product characteristics, labelling, and package leaflets is included.The information in a PI document is written by the pharmaceutical company responsible for the medicine and approved by regulatory agencies. It provides objective information regarding the quality, safety, and effectiveness of the medicine, as demonstrated in the data provided by the pharmaceutical company. This information is intended to assist physicians, pharmacists, and other health care professionals in prescribing and dispensing medicines. In addition, health professionals in their consultations with patients can use this information so that patients are better informed about their medicines.A list of information that should be contained in the PI is highlighted in the box below. CAN A PHARMACEUTICAL COMPANY ALTER THE PI AFTER A MEDICINE IS MARKETED?As discussed above, the information in a PI document is written by the pharmaceutical company responsible for the medicine, based on the results of phase I-III registration trials. However, it is widely recognized that pharmacological and clinical data (efficacy/safety) may change when a drug is administered in real-world clinical practice. This is in large part because most complex patients, such as the elderly, patients with comorbidities receiving polypharmacy, patients with impairment of the excretory organs, or those undergoing renal replacement therapy are usually excluded from phase I-III clinical trials. In real life, these patients generally have access to the medicine in question, generating novel pharmacokinetic/pharmacodynamic (PK/PD) data when appropriate research is undertaken with the potential to reverse the key concepts provided in the PI. In addition, regulatory agencies require phase I studies aimed at characterizing the pharmacokinetics and safety of a new drug, which is conducted in healthy volunteers and typically after a single-dose administration. This is poorly representative of real-life scenarios in clinical practice and is an additional limitation to the applicability of the PI to all patients receiving a drug.In general, researchers who are independent of the pharmaceutical company that marketed the drug generate most of the data pertaining to a drug in real-life settings. It is presently unclear who should undertake periodic revisions of the PI, taking into consideration new evidence reported in the literature. If new data are generated during patent coverage, the pharmaceutical company responsible for the marketing of the medicine is expected to submit amended versions of the PI to regulatory agenci...

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Serum linezolid concentrations are reduced in critically ill patients with pulmonary infections: A prospective observational study

Cited by 6 publications

References 37 publications

Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial

Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial

Comparative effectiveness and safety of five antibiotics in treating MRSA infections: A network meta-analysis

Why Product Information Should not be Set in Stone: Lessons from a Decade of Linezolid Therapeutic Drug Monitoring: An Opinion Paper

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