Résumé
Bien qu’en recul, la persistance d’infections graves à bactéries Gram positif résistantes, telles que le Staphylococcus aureus résistant à la méticilline (SARM) et le pneumocoque résistant à la pénicilline (PRP), incite à élargir la gamme des antibiotiques actifs à leur encontre, les glycopeptides ne devant rester l’unique recours. En effet, outre leur perte d’efficacité vis-à-vis du SARM, les entérocoques résistants à la vancomycine (ERV) sont régulièrement responsables d’épidémies hospitalières. Ainsi, la classe des Oxazolidinones s’est enrichie d’un nouveau membre, le tédizolide dont l’activité antimicrobienne couvre les Gram positif dont les SARM, les PRP et les ERV. Cette molécule pourrait être plus efficace et moins toxique que le linézolide, autorisant des durées d’administration plus longues. Elle n’est pour l’instant indiquée que pour le traitement des infections de la peau et des tissus mous (IPTM). Les céphalosporines actives sur le SARM et dites de cinquième génération (C5G) sont également d’apparition récente. En plus d’une forte bactéricidie et d’un profil de tolérance satisfaisant, ces C5G se sont montrées intéressantes pour le traitement des pneumonies communautaires (ceftaroline), des pneumonies liées aux soins (ceftobiprole) et des IPTM. Malgré un spectre intéressant couvrant les bacilles Gram négatif dont Pseudomonas aeruginosa pour ce qui concerne le ceftobiprole, des données cliniques supplémentaires sont nécessaires avant de valider leur utilisation en réanimation compte tenu des contraintes pharmacocinétiques propres aux patients les plus sévères. Des schémas d’administration adaptés pourraient être nécessaires afin d’optimiser la pharmacodynamie de ces molécules.
Abstract
Although decreasing in the past years, severe infections caused by Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant pneumococci, remain a matter of concern. Indeed, there is a need for new antibiotics given the issues raised by the use of glycopeptides. Accordingly, in addition to possible loss of efficiency against MRSA and safety concerns, vancomycin-resistant enterococci are regularly responsible for significant outbreaks among hospitalized patients. In this context, the Oxazolidinone family has grown since tedizolid, the spectrum of which includes the above-mentioned resistant pathogens, has been successfully developed. Current data suggest that tedizolid could be more efficient and less toxic than linezolid, thus allowing longer durations of treatment. Indeed, although the drug is licensed only for the treatment of acute bacterial skin and skin structure infections (ABSSSIs), several clinical trials are currently ongoing. New cephalosporins owing antibacterial activity against MRSA have also appeared recently. In addition to a strong bactericidal activity and a favourable safety profile, these drugs have proven efficient for the treatment of infections involving Gram-positive agents, that is, community-acquired pneumonia (ceftaroline), health care-associated pneumonia (ceftobiprole), as well as ABSSSIs. In spite of a broad spectrum of activity covering Gram-negative bacteria including Pseudomonas aeruginosa (ceftobiprole only), clinical data are mandatory before expanding their use to the critically ill patients with pneumonia, given pharmacokinetic issues in this setting. Administration of these drugs should actually be optimized in order to make use of their whole efficiency.
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Charles, PE., Dargent, A. & Andreu, P. Nouvelles molécules anti-infectieuses. Quelle place en médecine intensive réanimation pour le tédizolide, la ceftaroline et le ceftobiprole ?. Méd. Intensive Réa 26, 207–217 (2017). https://doi.org/10.1007/s13546-017-1271-2
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DOI: https://doi.org/10.1007/s13546-017-1271-2