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Introduction: Antimicrobial dose optimization for the treatment of sepsis remains challenging because of dynamic pharmacokinetic alterations and physiological/pathological responses of the host. Subtherapeutic plasma levels of antimicrobials are commonly observed in patients with sepsis, which potentially leads to both treatment failure and emergence of antimicrobial resistance. The knowledge of antimicrobial pharmacokinetics and pharmacodynamics is helpful in order to tailor antimicrobial dosing strategies.Areas covered: This narrative review summarizes pharmacokinetic alterations of antimicrobial agents and provides useful information on antimicrobial dose optimization. Literature was searched using PubMed database, focusing on pharmacokinetics and pharmacodynamics of antibacterial and antifungal agents in sepsis.Expert opinion: In patients with sepsis, increased volume of distribution and variable changes in renal clearance are the two major factors for antimicrobial pharmacokinetic alterations. Traditional 'one-dose-fits-all' dosing strategy is not suitable for patients with sepsis and hence individualized antimicrobial dosing adjustment is preferable. In general, the initial dose of hydrophilic antimicrobials such as s-lactams, aminoglycosides, and vancomycin should be given at a high dose regardless of renal function. Improved methods of drug administration (e.g. extended/continuous infusion of β-lactams) help to increase the chance of pharmacodynamic target attainment. The use of therapeutic drug monitoring should be considered where available.

Background Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. Method This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH Results We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. Conclusions Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Objectives: Septic shock is often complicated by severe metabolic acidosis, for which renal replacement therapy may be considered. However, little is known about the use of intermittent hemodialysis to manage this condition. The aim of this study was to compare physiologic and biochemical variables and vasopressor requirements before and after intermittent hemodialysis among patients who received intermittent hemodialysis to manage metabolic acidosis during resuscitation of septic shock. Design: This retrospective, cross-sectional study was conducted between April 2014 and September 2015. Settings: The ICU of a non-university-affiliated teaching hospital. Patients: Patients who were admitted to the ICU with septic shock and underwent intermittent hemodialysis to manage metabolic acidosis within 48 hours after the diagnosis of septic shock. Measurements and Main Results: The main outcomes were mean arterial pressure, minute ventilator volume, norepinephrine requirement, bicarbonate and pH before and after intermittent hemodialysis. Of 1,190 patients screened, 34 were included, and 33 accomplished a planned session of intermittent hemodialysis. After intermittent hemodialysis, an increased mean arterial pressure (+9.0 mm Hg; 95% CI, 6–13; p < 0.001), decreased minute ventilatory volume (–2.0 L/min; 95% CI, –3.3 to 0.8; p = 0.002), decreased norepinephrine requirement (–0.07 µg/kg/min; 95% CI, –0.12 to –0.02; p = 0.009), increased bicarbonate level (+7.2 mmol/L; 95% CI, 6.1–8.3; p < 0.001), and increased pH (+0.17; 95% CI, 0.13–0.21; p < 0.001) were observed in comparison to those before intermittent hemodialysis. Conclusions: In conclusion, intermittent hemodialysis appeared to be feasible and to stabilize hemodynamic and respiratory conditions in patients with septic shock complicated by metabolic acidosis during resuscitation.