Pharmacokinetic and pharmacodynamics evaluation of ceftobiprole medocaril for the treatment of hospital-acquired pneumonia

Lagacé-Wiens, Philippe; Rubinstein, Ethan

doi:10.1517/17425255.2013.788150

Cited by 9 publications

(7 citation statements)

References 60 publications

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“…The anti-MRSA cephalosporin ceftobiprole has been studied and approved only for skin and skin structure infections (SSSIs), 31 yet it is frequently used offlabel in some countries for ventilator-associated pneumonia (VAP) at these recommended doses despite indications that these are unlikely to achieve pharmacodynamic targets in patients with VAP. 32 In addition, the majority of currently used b-lactams underwent clinical outcome testing in Phase 3 trials several decades ago, when MICs for many organisms were lower. Longitudinal surveillance programmes document steady decreases in the susceptibility of several Gram-negative (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa etc.)…”

Section: Reviewmentioning

confidence: 99%

Therapeutic drug monitoring of the β-lactam antibiotics: what is the evidence and which patients should we be using it for?: Figure 1.

Huttner

Harbarth

Hope

et al. 2015

J. Antimicrob. Chemother.

108

100

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Traditional antibiotic dosing was not designed for today's escalating antibiotic resistance, lack of novel antibiotics and growing complexity in patient populations. Dosing that ensures optimal antibiotic exposures should be considered essential to increase the likelihood of effective patient treatment. Given the variability in these exposures across different patients, a 'one-dose-fits-all' approach is increasingly problematic. Therapeutic drug monitoring (TDM) of the β-lactams, the most widely used antibiotic class, is underutilized in certain populations. Clinical experience with β-lactam TDM remains relatively scarce. Patients most likely to benefit from such an intervention include the critically ill, the obese, the elderly and those with cystic fibrosis. Most centres actively performing β-lactam TDM target a minimum 100% of the time during the dosing interval that the free (unbound) concentration of antibiotic exceeds the MIC of the pathogen (100% fT>MIC), which is higher than a traditional target supported by in vitro data. Ideally, isolated pathogens should undergo MIC testing along with TDM on a regular basis, allowing clinicians to address the triad of bug, drug and patient ('mug') in equal measure.

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Section: Reviewmentioning

confidence: 99%

Therapeutic drug monitoring of the β-lactam antibiotics: what is the evidence and which patients should we be using it for?: Figure 1.

Huttner

Harbarth

Hope

et al. 2015

J. Antimicrob. Chemother.

108

100

View full text Add to dashboard Cite

show abstract

“…However, at current dosing, conflicting data exist for the support of ceftobiprole use in VAP. Suggestions that ceftobiprole is unlikely to meet the desired pharmacodynamic targets when pharmacokinetic parameters are altered have been countered by Monte Carlo simulation based on phase 1 studies showing that target attainment is likely to be achieved, even in severely ill patients [121,122]. There needs to be a re-assessment of the quality of data for ceftobiprole use in SSTI, however the pneumonia data were of good quality.…”

Section: Ceftarolinementioning

confidence: 99%

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Edwards

Andini

Esposito

et al. 2014

Journal of Global Antimicrobial Resistance

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“…However, β-Lactams are the most common cause of most antibiotics-associated adverse events, including severe kidney or liver toxicity, neurotoxicity, and cytopenia ( 59 ). One study showed a 2.5% incidence of gastrointestinal events with β-Lactam and a higher incidence of diarrhea when the above combination was used ( 60 ). More importantly, the β-Lactams assessed in this study included only first and second-generation cephalosporins, and no valid direct evidence could be produced to support the efficacy of the novel cephalosporins on OM.…”

Section: Discussionmentioning

confidence: 99%

Comparing the efficacy of different antibiotic regimens on osteomyelitis: A network meta-analysis of animal studies

Shi

Wu²,

et al. 2022

Front. Med.

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BackgroundDespite the surge in the number of antibiotics used to treat preclinical osteomyelitis (OM), their efficacy remains inadequately assessed.ObjectiveTo establish network comparisons on the efficacy of antibiotic regimens on OM in animal studies.MethodsPubMed, Embase, Web of Science, and The Cochrane Library were searched from inception to March 2022 for relevant articles. Odds ratios (ORs) were generated for dichotomous variants, and the standard mean difference (SMD) was calculated for constant variables. The predominant outcomes were the effective rate of sterility, also known as sterility rates, as well as the bacterial counts at the end of the experiments and antibiotic concentrations in serum or bone. All the network meta-analyses were performed using STATA MP 16.0. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; no. CRD42022316544).ResultsA total of 28 eligible studies with 1,488 animals were included for data analysis, including 13 antibiotic regimens. Regarding the effective rate of sterility, glycopeptides (GLY), linezolid (LIN), rifampicin (RIF)+β-Lactam, and β-Lactam showed significant efficacy compared with placebo (OR ranging from 0.01 to 0.08). For radiological grade, only RIF+GLY (SMD: −5.92, 95%CI: −11.65 to −0.19) showed significant efficacy compared with placebo. As for reducing bacteria count, fosfomycin (FOS), tigecycline (TIG), GLY, LIN, RIF, RIF+β-Lactam, RIF+GLY, aminoglycosides (AMI), and clindamycin (CLI) showed significant efficacy compared with placebo (SMD ranging from −6.32 to −2.62). Moreover, the bone concentrations of GLY were higher 1 h after administration and the higher blood concentrations were higher after 1 h and 4 h compared with the other antibiotics.ConclusionMultiple antibiotic regimens showed significant efficacy in animals with OM, including increasing effective rates of sterility, reducing bacterial counts, and lowering radiological scores. Among them, RIF+GLY was the most promising treatment regimen owing to its optimal efficacy. Based on the preclinical studies included in our meta-analysis, head-to-head clinical randomized controlled trials are required to confirm these findings in humans.

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Pharmacokinetic and pharmacodynamics evaluation of ceftobiprole medocaril for the treatment of hospital-acquired pneumonia

Cited by 9 publications

References 60 publications

Therapeutic drug monitoring of the β-lactam antibiotics: what is the evidence and which patients should we be using it for?: Figure 1.

Therapeutic drug monitoring of the β-lactam antibiotics: what is the evidence and which patients should we be using it for?: Figure 1.

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Comparing the efficacy of different antibiotic regimens on osteomyelitis: A network meta-analysis of animal studies

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