Old antibitiotics, new solutions: old narrow spectrum betalactamine and cotrimoxazole with PK/PD optimization as a treatment for gram negative bacteria in ICU

Introduction :
The use of broad-spectrum antibiotics, including an anti-anaerobic spectrum, is associated with the emergence of multi-resistant bacteria. However, all the new molecules on the market targeting GNB are very broad-spectrum, implying a strong ecological impact. Particularly in resuscitation, the volume of antibiotic prescriptions is very high. It is necessary to limit the pressure of antibiotic selection by using molecules with a narrower spectrum and less ecological impact. We propose to use in the existing pharmacopoeia the narrow spectrum molecules whose optmisation of PK/PD parameters would allow them to be used as an alternative to Carbapenems, third and fourth generation Cephalosporins or fluroquinolones.

Methods :
Systematic review of the literature allowing in a first step to select antibiotics active against GNB with a low ecological impact. In a second step, a literature review will allow to define the modalities of use of the selected molecules for the optimization of the PK/PD parameters integrating dosage, stability data and infusion modalities.

Results and Discussion :
Cefoxitin, temocillin, Amoxicillin ac clavulanic, aztreonam, piperacillin, piperacillin tazobactam, cotrimoxazole were selected for their lower ecological impact and their possible integration in an antibiotic stewardship program in intensive care. We propose continuous infusion administration methods to optimize the PK/PD parameters of its time-dependent molecules at maximum doses. Under the conditions of use in intensive care, the stability data allow the use of electric syringes for the infusion of temocillin, aztreonam and cefoxitin, the other molecules will have to be used with a volumetric pump.

Conclusions :
An antibiotic stewardship policy in resuscitation can integrate alternatives to molecules with high ecological impact with the use of Cefoxitin, temocillin, piperacillin, aztreonam and cotrimoxazole in continuous infusion using electric syringes or volumetric pumps.