Linezolid for endocarditis: a case series of 14 patients

Tascini, Carlo; Bongiorni, Maria Grazia; Doria, Roberta; Polidori, Marina; Iapoce, Riccardo; Fondelli, Serena; Tagliaferri, Enrico; Soldati, Ezio; Paolo, Antonello Di; Leonildi, Alessandro; Menichetti, Francesco

doi:10.1093/jac/dkq506

Cited by 24 publications

(23 citation statements)

References 5 publications

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“…Therefore, it is possible to hypothesize that increasing the linezolid dosage would increase the success rate of linezolid treatment. Some authors have suggested a continuous infusion of 1,200 mg/daily after a 300-mg loading dose, demonstrating an improvement of pharmacodynamic indices (8), good diffusion to epithelial lining fluid (22), and good clinical outcome in a small series of cases (23).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

Morata

Cuesta

Rojas

et al. 2013

Antimicrob Agents Chemother

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Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC 24 /MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (C min ) and to determine factors associated with a C min < 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with a C min determination at the steady state and within the first 10 days of treatment were retrospectively reviewed. Concentrations were measured using high-pressure liquid chromatography. Univariate and multivariate analysis were performed to identify risk factors of low C min . A total of 29.5% of patients had a C min < 2 mg/liter. The percentage was significantly higher in patients with an estimated glomerular filtration (eGF) > 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of C min < 2 mg/liter were an eGF > 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P ‫؍‬ 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P ‫؍‬ 0.006). A linezolid C min of <2 mg/liter was found in 29.5% of cases, and the risk was significantly higher among those with an eGF > 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy.L inezolid belongs to a family of antimicrobials (oxazolidinones) that inhibit bacterial protein synthesis by preventing the fusion of 30S and 50S ribosomal subunits (1). During the last 10 years, linezolid has been widely used with good clinical results for the treatment of skin and soft tissue infections or nosocomial and health care-related pneumonia (2, 3). Linezolid has time-dependent activity, and the best predictors of its efficacy are the percentage of time that plasma concentrations exceed the MIC and the area under the concentrationtime curve over 24 h in the steady state divided by the MIC (AUC 24 /MIC ratio) (4). In a retrospective study of linezolid in a compassionate use program, a higher success rate was observed when concentrations remained above the MIC for the entire dosing interval and when AUC 24 /MIC values were 80 to 120 (5). Some recent data suggest that the linezolid trough plasma concentration (C min ), in some patients, is below the MIC 90 of linezolid for staphylococci (6).The aim of our study was to analyze the linezolid trough plasma concentration in a consecutive series of patients with an acute infection and to determine how often trough concentrations were Ͻ2 mg/liter (MIC 90 of linezolid for Staphylococcus aureus) and other clinically relevant thresholds (0.5, 1, and 4 mg/liter). MATERIALS AND METHODSThe linezolid trough plasma concent...

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Section: Discussionmentioning

confidence: 99%

Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

Morata

Cuesta

Rojas

et al. 2013

Antimicrob Agents Chemother

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“…Linezolid is also indicated for the treatment of necrotizing pneumonia due to MSSA and MRSA strains secreting the Panton–Valentine leukocidin (PVL) virulence factor given its ability to block toxin production [ 29 ] and has been extensively studied for SSTIs, outperforming vancomycin in terms of clinical cures [ 30 – 35 ]. Linezolid has successfully been used off label for the treatment of secondary MRSA bacteremia [ 36 , 37 ], endocarditis [ 38 , 39 ], and central nervous system infections [ 40 – 42 ]. The greater efficacy of linezolid over vancomycin observed in some of the above noted clinical studies may be due to the upward drifting MICs of MSSA ansd MRSA to vancomycin as well as the presence of heteroresistance to vancomycin, although not all studies are consistent in demonstrating greater mortality with the presence of heteroresistance [ 43 – 50 ].…”

Section: Reviewmentioning

confidence: 99%

Treatment of gram - positive infections in critically ill patients

Guillamet

Kollef

2014

BMC Infect Dis

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Gram-positive bacteria to include methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), and enterococci, to include vancomycin-resistant enterococci (VRE), display a remarkable array of resistance and virulence factors, which have contributed to their prominent role in infections of the critically ill. Over the last three decades infections with these pathogens has increased as has their overall resistance to available antimicrobial agents. This has led to the development of a number of new antibiotics for the treatment of Gram-positive bacteria. At present, it is important that clinicians recognize the changing resistance patterns and epidemiology of Gram-positive bacteria as these factors may impact patient outcomes. The increasing range of these pathogens, such as the emergence of community-associated MRSA clones, emphasizes that all specialties of physicians treating infections should have a good understanding of the infections caused by Gram-positive bacteria in their area of practice. When initiating empiric antibiotics, it is of vital importance that this therapy be timely and appropriate, as delays in treatment are associated with adverse outcomes. Although vancomycin has traditionally been considered a first-line therapy for serious MRSA infections, multiple concerns with this agent have opened the door for alternative agents demonstrating efficacy in this role. Similarly, the expansion of VRE as a pathogen in the ICU setting has required the development of agents targeting this important pathogen.

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“…Most PK-PD analyses were small, containing 59 patients on average (range 2 to 404). 24,25 Only 15 analyses (15%) studied more than 100 patients. Only two of the included studies made any comparison between the patients included in the study and patients excluded.…”

Section: Population Characteristics Site Of Infection and Infecting mentioning

confidence: 99%

Methodological features of clinical pharmacokinetic–pharmacodynamic studies of antibacterials and antifungals: a systematic review

McAleenan

Ambrose

Bhavnani

et al. 2020

Journal of Antimicrobial Chemotherapy

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Background Pharmacokinetic (PK)–pharmacodynamic (PD) indices relate measures of drug exposure to antibacterial effect. Clinical PK–PD studies aim to correlate PK–PD indices with outcomes in patients. Optimization of dosing based on pre-clinical studies means that PK–PD relationships are difficult to establish; therefore studies need to be designed and reported carefully to validate pre-clinical findings. Objectives To describe the methodological features of clinical antibacterial and antifungal PK–PD studies that reported the relationship between PK–PD indices and clinical or microbiological responses. Methods Studies published between 1980 and 2015 were identified through systematic searches. Methodological features of eligible studies were extracted. Results We identified 85 publications containing 97 PK–PD analyses. Most studies were small, with fewer than 100 patients. Around a quarter were performed on patients with infections due to a single specific pathogen. In approximately one-third of studies, patients received concurrent antibiotics/antifungals and in some other studies patients received other treatments that may confound the PK–PD–outcome relationship. Most studies measured antimicrobial concentrations in blood/serum and only four measured free concentrations. Most performed some form of regression, time-to-event analysis or used the Hill/Emax equation to examine the association between PK–PD index and outcome. Target values of PK–PD indices that predict outcomes were investigated in 52% of studies. Target identification was most commonly done using recursive partitioning or logistic regression. Conclusions Given the variability in conduct and reporting, we suggest that an agreed set of standards for the conduct and reporting of studies should be developed.

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Linezolid for endocarditis: a case series of 14 patients

Cited by 24 publications

References 5 publications

Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

Treatment of gram - positive infections in critically ill patients

Methodological features of clinical pharmacokinetic–pharmacodynamic studies of antibacterials and antifungals: a systematic review

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