In rats with peritonitis, Montravers et al. showed that adjunction of Enterococcus faecalis was associated with increased mortality as well as higher levels of TNFα and IL-6 in peritoneal fluid [32, 33]. Evidence regarding a specific role of some pathogens on the pattern of the sepsis response is rather small, preventing any definitive conclusion from these results. However it is well known that patients with severe sepsis or septic shock may benefit from aggressive

antimicrobial treatment in order to curb the spread of the multiple organ dysfunction syndrome caused by an ongoing peritoneal trigger. For these patients, a de-escalated approach may be the most appropriate strategy. Increasing rates of resistance and a more comprehensive understanding of the sepsis process have prompted many experts to advocate the use of broad-spectrum antimicrobial regimens in the initial

VX-680 stages of treatment for sepsis [34, 35]. Subsequent modification (de-escalation) of the initial regimen becomes possible later, when culture results are available and clinical status can be better assessed, 48–72 hours after initiation of empiric therapy. When treating abdominal sepsis, clinicians must be aware that drug pharmacokinetics may differ significantly between patients due to the variable pathophysiology of sepsis, and must also take into account the pathophysiological PDGFR inhibitor and immunological status of the patient [36]. The “dilution effect”, also called the ‘third spacing’ phenomenon, must be considered when administering hydrophilic agents such as β-lactams, aminoglycosides, and glycopeptides, which selectively distribute to the extracellular

space. Low plasma antimicrobial levels can contribute to lower than expected antimicrobial concentrations in peritoneal fluid with potentially reduced antimicrobial delivery to the target tissues. In fact, the target plasma concentration (Ct) that should be achieved with the loading dose (LD) depends solely on the volume of distribution (Vd) of the drug (LD = Ct × Vd). If the Vd is enlarged the Ct will results in a lower than expected level with the standard LD [36]. Higher than standard loading doses of β-lactams, aminoglycosides, or ATM Kinase Inhibitor glycopeptides should be administered to ensure optimal drug exposure to the infection site buy Pomalidomide in patients with severe sepsis or septic shock [36]. Lastly it should be kept in mind that the loading dose of lipophilic antibiotics (Macrolides, Fluoroquinolones, Tetracyclines, Chloramphenicol, Rifampicin, Linezolid) which are not influenced by the “diluition effect”, should not be influenced by the severe sepsis or septic shock status [36]. Once appropriate initial loading is achieved, it is mandatory to reassess the antimicrobial regimen daily, because the pathophysiological changes that may occur, may significantly affect drug disposition in the critically ill patients.