S2k-Leitlinie der PEG zur kalkulierten parenteralen Initialtherapie bakterieller Erkrankungen bei Erwachsenen

Brinkmann, Alexander; Röhr, Anka C.; Frey, Otto; Krüger, Wolfgang; Brenner, Thorsten; Richter, Daniel C.; Bodmann, Klaus-Friedrich; Kresken, Michael; Grabein, B.

doi:10.1007/s00101-018-0512-8

Cited by 19 publications

(18 citation statements)

References 51 publications

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“…Recommendations of current guidelines [1][2][3]5] and the survival benefit of linezolid therapy compared to vancomycin in soft tissue infections [43] will lead to the more frequent use of linezolid, especially in intensive care medicine. We have confirmed the numerous plasma-based scientific results to date showing that the current dose of linezolid is sufficient in non-obese patients for a low MIC of 0.5 or 1 mg/L.…”

Section: Discussionmentioning

confidence: 99%

“…Linezolid is used for the treatment of complicated skin and soft tissue infections with methicillin-resistant Staphylococcus aureus [1][2][3] and for toxic shock syndrome [4], and has become an important treatment option in empirical antimicrobial therapy in intensive care medicine, e.g., recommended in German guidelines for septic shock with a risk of methicillin-resistant Staphylococcus aureus (MRSA) infection [5]. In addition, linezolid is a frequently used antibiotic for the treatment of vancomycin-resistant Enterococcus (VRE), which is increasingly triggering serious infections in critically ill patients.…”

Section: Introductionmentioning

confidence: 99%

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Linezolid Concentrations in Plasma and Subcutaneous Tissue are Reduced in Obese Patients, Resulting in a Higher Risk of Underdosing in Critically Ill Patients: A Controlled Clinical Pharmacokinetic Study

Simon

Busse

Petroff

et al. 2020

JCM

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Background: Linezolid is used for the treatment of soft tissue infections in critically ill patients. However, data for characterizing the pharmacokinetics (PK) and assessing whether effective concentrations are reached at the target site are lacking. We hypothesized that current dosing regimens do not lead to effective concentrations in the plasma and interstitial fluid (ISF) of subcutaneous tissue in obese patients. Methods: As a controlled clinical model, critically ill obese and non-obese patients undergoing intra-abdominal surgery received 600 mg linezolid as a single infusion. Concentrations in the plasma and microdialysate from the ISF of subcutaneous tissue were determined up to 8 h after dosing. Pharmacokinetic analysis was performed by non-compartmental methods. As a therapeutic target, we used f AUC/MIC > 80. Results: Fifteen obese (BMI: 48.7 ± 11.2 kg/m 2 ) and 15 non-obese (23.9 ± 2.1 kg/m 2 ) patients were analyzed. AUC 0-8 in ISF decreased by −1.69 mg*h/L (95% CI: −2.59 to −0.79, p < 0.001) for every 10 kg increase in weight. PK in obese patients were characterized by lower maximal plasma concentrations (median 3.8 vs. 8.3 mg/L, p < 0.001) and a higher volume of distribution (41.0 vs. 30.8 L, p < 0.001), and the therapeutic target was not reached for MIC ≥ 1 mg/L in ISF and ≥ 2 mg/L in plasma. Conclusions: Increasing the weight led to a decrease of linezolid concentrations in the plasma and subcutaneous tissue. The current dosing regimen does not seem to produce sufficient concentrations to kill bacteria with MIC ≥ 2 mg/L, especially as empirical antimicrobial therapy in critically ill obese patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Linezolid Concentrations in Plasma and Subcutaneous Tissue are Reduced in Obese Patients, Resulting in a Higher Risk of Underdosing in Critically Ill Patients: A Controlled Clinical Pharmacokinetic Study

Simon

Busse

Petroff

et al. 2020

JCM

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“…Wenn eine Phlegmone klinisch nicht ausgeschlossen werden kann, soll bei Nichtansprechen der Penicillintherapie nach 2-3 Tagen auf ein Staphylokokken-wirksames Medikament umgestellt werden. Im Gesicht können S. aureus und Haemophilus Infektionen hervorrufen, die klinisch nicht von einem Erysipel zu unterscheiden sind [19]. Daher sollte hier primär eine Therapie eingesetzt werden, die beide Erreger miterfasst (▶ Tab.…”

Section: Erysipelunclassified

Antibiotikatherapie im klinischen Alltag

Hennigs¹,

Jochum²

2020

Dtsch Med Wochenschr

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Infectious diseases are a frequent reason for medical consultations both in the inpatient and outpatient setting. Inadequate management is associated with increased costs, morbidity and mortality. In times of rising antibiotic resistance rational therapy and antimicrobial stewardship are of utmost importance. While it is crucial to avoid excessively broad antimicrobial coverage and unnecessary therapies, serious conditions must be treated effectively. The article highlights common infections and gives recommendations for empiric and targeted antibiotic treatment. Discussed are pulmonary, abdominal, urinary tract, skin and soft tissue infections, as well as sepsis and staphylococcal bloodstream infections. The recommendations consider national and international guidelines, recent publications and current antimicrobial resistance in Germany.

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“…Levofloxacin, a broad-spectrum fluoroquinolone, encompassing both Gram-negative and Gram-positive organisms including anaerobic bacteria [17], represents such a clinically well-characterised drug, which in addition showed no binding to microdialysis tubing or probes in vitro [18]. It is used for the treatment of various infections, such as community-acquired pneumonia (CAP) [19][20][21], skin and soft tissue infections, urinary tract infections, and acute exacerbation of chronic bronchitis and sinusitis [22]. Levofloxacin is a moderately lipophilic drug and hence exerts its antibiotic activity in bacteria typically residing in the ISF.…”

Section: Introductionmentioning

confidence: 99%

Which Analysis Approach Is Adequate to Leverage Clinical Microdialysis Data? A Quantitative Comparison to Investigate Exposure and Response Exemplified by Levofloxacin

Busse

Schaeftlein²,

Solms

et al. 2021

Pharm Res

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Purpose Systematic comparison of analysis methods of clinical microdialysis data for impact on target-site drug exposure and response. Methods 39 individuals received a 500 mg levofloxacin short-term infusion followed by 24-h dense sampling in plasma and microdialysate collection in interstitial space fluid (ISF). ISF concentrations were leveraged using non-compartmental (NCA) and compartmental analysis (CA) via (ii) relative recovery correction at midpoint of the collection interval (midpoint-NCA, midpoint-CA) and (ii) dialysate-based integrals of time (integral-CA). Exposure and adequacy of community-acquired pneumonia (CAP) therapy via pharmacokinetic/pharmacodynamic target-attainment (PTA) analysis were compared between approaches. Results Individual AUCISF estimates strongly varied for midpoint-NCA and midpoint-CA (≥52.3%CV) versus integral-CA (≤32.9%CV) owing to separation of variability in PK parameters (midpoint-CA = 46.5%–143%CVPK, integral-CA = 26.4%–72.6%CVPK) from recovery-related variability only in integral-CA (41.0%–50.3%CVrecovery). This also led to increased variability of AUCplasma for midpoint-CA (56.0%CV) versus midpoint-NCA and integral-CA (≤33.0%CV), and inaccuracy of predictive model performance of midpoint-CA in plasma (visual predictive check). PTA analysis translated into 33% of evaluated patient cases being at risk of incorrectly rejecting recommended dosing regimens at CAP-related epidemiological cut-off values. Conclusions Integral-CA proved most appropriate to characterise clinical pharmacokinetics- and microdialysis-related variability. Employing this knowledge will improve the understanding of drug target-site PK for therapeutic decision-making.

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S2k-Leitlinie der PEG zur kalkulierten parenteralen Initialtherapie bakterieller Erkrankungen bei Erwachsenen

Cited by 19 publications

References 51 publications

Linezolid Concentrations in Plasma and Subcutaneous Tissue are Reduced in Obese Patients, Resulting in a Higher Risk of Underdosing in Critically Ill Patients: A Controlled Clinical Pharmacokinetic Study

Linezolid Concentrations in Plasma and Subcutaneous Tissue are Reduced in Obese Patients, Resulting in a Higher Risk of Underdosing in Critically Ill Patients: A Controlled Clinical Pharmacokinetic Study

Antibiotikatherapie im klinischen Alltag

Which Analysis Approach Is Adequate to Leverage Clinical Microdialysis Data? A Quantitative Comparison to Investigate Exposure and Response Exemplified by Levofloxacin

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