Treatment Considerations for CNS Infections Caused by Vancomycin-Resistant Enterococcus faecium: A Focused Review of Linezolid and Daptomycin

2020 ◽  
Vol 54 (12) ◽  
pp. 1243-1251 ◽  
Author(s):  
Benjamin J. Lee ◽  
Betty N. Vu ◽  
Amanda N. Seddon ◽  
Hayley A. Hodgson ◽  
Sheila K. Wang

Objective: To review the current literature describing pharmacology, pharmacokinetics/pharmacodynamics (PK/PD), efficacy, and safety of linezolid and daptomycin for the treatment of central nervous system (CNS) infections caused by vancomycin-resistant Enterococcus (VRE) faecium. Data Sources: A literature search of PubMed/MEDLINE databases was conducted (from 1950 to April 2020) utilizing the following key terms: vancomycin-resistant Enterococcus, VRE, meningitis, ventriculitis, CNS infection, daptomycin, and linezolid. Study Selection and Data Extraction: All relevant studies and case reports describing the treatment of VRE faecium from the CNS with linezolid or daptomycin were included. Data Synthesis: A total of 17 reports describing 22 cases were identified. There were 15 of 19 cases involving linezolid that reported clinical cure, of which 53.3% were monotherapy. Only 5 of 9 cases involving intravenous (IV) daptomycin resulted in cure; all 4 cases reporting daptomycin administration via the intrathecal or intraventricular route achieved clearance from the cerebrospinal fluid (CSF). Relevance to Patient Care and Clinical Practice: The preferred treatment option for VRE faecium infections involving the CNS remains unclear. Supporting evidence through observational case reports have described varying outcomes with linezolid and daptomycin. This review compares reported outcomes between the 2 agents and provides a thorough discussion on drug- and patient-specific variables to consider. Conclusions: Linezolid monotherapy appears to be safe and effective for the treatment of susceptible-VRE faecium CNS infections, with consideration of therapeutic drug monitoring in special populations and with prolonged treatment duration. Daptomycin is an effective treatment option via intrathecal or intraventricular administration when neurosurgical access is available. The role of IV daptomycin remains inconclusive.

Pathology ◽  
2001 ◽  
Vol 33 (2) ◽  
pp. 216-221
Author(s):  
Lynette L. E. Oon ◽  
Moi-Lin Ling ◽  
Yoke-Fong Chiew

2021 ◽  
Vol 41 (3) ◽  
pp. 261-272
Author(s):  
Chau Wei Ling ◽  
Kamal Sud ◽  
Connie Van ◽  
Syed Tabish Razi Zaidi ◽  
Rahul P. Patel ◽  
...  

The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.


Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 126
Author(s):  
Salvatore Princiotto ◽  
Stefania Mazzini ◽  
Loana Musso ◽  
Fabio Arena ◽  
Sabrina Dallavalle ◽  
...  

The global increase in infections by multi-drug resistant (MDR) pathogens is severely impacting our ability to successfully treat common infections. Herein, we report the antibacterial activity against S. aureus and E. faecalis (including some MDR strains) of a panel of adarotene-related synthetic retinoids. In many cases, these compounds showed, together with favorable MICs, a detectable bactericidal effect. We found that the pattern of substitution on adarotene could be modulated to obtain selectivity for antibacterial over the known anticancer activity of these compounds. NMR experiments allowed us to define the interaction between adarotene and a model of microorganism membrane. Biological assessment confirmed that the scaffold of adarotene is promising for further developments of non-toxic antimicrobials active on MDR strains.


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