- あるいは、乳酸値 > 2mmoL/L
- 十分な輸液負荷 : 晶質液（リンゲル液）> アルブミン。
- 血管収縮薬 : ノルアド、バソプレッシン、ステロイド
- 血糖 : 140-180
sepsis 3 は、必読
Intravenous antibiotic therapy should be initiated within the first six hours or earlier (eg, within one hour), after obtaining appropriate cultures, since early initiation of antibiotic therapy is associated with lower mortality. The choice of antibiotics can be complex and should consider the patient's history (eg, recent antibiotics received), comorbidities, clinical context (eg, community- or hospital-acquired), Gram stain data, and local resistance patterns.
Poor outcomes are associated with inadequate or inappropriate antimicrobial therapy (ie, treatment with antibiotics to which the pathogen was later shown to be resistant in vitro). They are also associated with delays in initiating antimicrobial therapy, even short delays (eg, an hour).
●A prospective cohort study of 2124 patients demonstrated that inappropriate antibiotic selection was surprisingly common (32 percent) . Mortality was markedly increased in these patients compared to those who had received appropriate antibiotics (34 versus 18 percent).
●A retrospective analysis of 2731 patients with septic shock demonstrated that the time to initiation of appropriate antimicrobial therapy was the strongest predictor of mortality.
When the potential pathogen or infection source is not immediately obvious, we favor broad-spectrum antibiotic coverage directed against both gram-positive and gram-negative bacteria (eg, Staphlococcus aureus, Klebsiella pneumoniae, Streptocuccus pneumoniae). Few guidelines exist for the initial selection of empiric antibiotics in severe sepsis or septic shock.
Staphylococcus aureus is associated with significant morbidity if not treated early in the course of infection. There is growing recognition that methicillin-resistant S. aureus (MRSA) is a cause of sepsis not only in hospitalized patients, but also in community dwelling individuals without recent hospitalization. For these reasons, we recommend that severely ill patients presenting with sepsis of unclear etiology be treated with intravenous vancomycin (adjusted for renal function) until the possibility of MRSA sepsis has been excluded. Potential alternative agents to vancomycin (eg, daptomycin for non-pulmonary MRSA, linezolid, ceftaroline) should be considered for patients with refractory or virulent MRSA, or a contraindication to vancomycin. These agents are discussed separately.
In our practice, if Pseudomonas is an unlikely pathogen, we favor combining vancomycin with one of the following:
●Cephalosporin, 3rd generation (eg, ceftriaxone or cefotaxime) or 4th generation (cefepime), or
●Beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillin-clavulanate), or
●Carbapenem (eg, imipenem or meropenem)
Alternatively, if Pseudomonas is a possible pathogen, we favor combining vancomycin with two of the following:
●Antipseudomonal cephalosporin (eg, ceftazidime, cefepime), or
●Antipseudomonal carbapenem (eg, imipenem, meropenem), or
●Antipseudomonal beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillin-clavulanate), or
●Fluoroquinolone with good anti-pseudomonal activity (eg, ciprofloxacin), or
●Aminoglycoside (eg, gentamicin, amikacin), or
●Monobactam (eg, aztreonam)
Selection of two agents from the same class, for example, two beta-lactams, should be avoided. We emphasize the importance of considering local susceptibility patterns when choosing an empiric antibiotic regimen.
After culture results and antimicrobial susceptibility data return, we recommend that therapy be pathogen- and susceptibility-directed, even if there has been clinical improvement while on the initial antimicrobial regimen. Gram-negative pathogens have historically been covered with two agents from different antibiotic classes. However, several clinical trials and two meta-analyses have failed to demonstrate superior overall efficacy of combination therapy compared to monotherapy with a third generation cephalosporin or a carbapenem. Furthermore, one meta-analysis found double coverage that included an aminoglycoside was associated with an increased incidence of adverse events (nephrotoxicity)． For this reason, in patients with gram negative pathogens, we recommend use of a single agent with proven efficacy and the least possible toxicity, except in patients who are either neutropenic or whose sepsis is due to a known or suspected Pseudomonas infection.
Regardless of the antibiotic regimen selected, patients should be observed closely for toxicity, evidence of response, and the development of nosocomial superinfection. There are no published randomized controlled trials testing safety of de-escalation of antibiotic therapy in adult patients with sepsis or septic shock. The duration of therapy is typically 7 to 10 days, although longer courses may be appropriate in patients who have a slow clinical response, an undrainable focus of infection, or immunologic deficiencies. In patients who are neutropenic, antibiotic treatment should continue until the neutropenia has resolved or the planned antibiotic course is complete, whichever is longer. In non-neutropenic patients in whom infection is thoroughly excluded, antibiotics should be discontinued to minimize colonization or infection with drug-resistant microorganisms and superinfection with other pathogens.
Invasive fungal infections occasionally complicate the course of critical illness in non-neutropenic patients, especially when the following risk factors are present: surgery, parenteral nutrition, prolonged antimicrobial treatment, septic shock or multisite colonization with Candida spp. However, studies do not support the routine use of empiric antifungals in this population. Several empirical anti-fungal treatments have been studied:
●In a meta-analysis of 22 studies (most often comparing fluconazole to placebo, but also using ketoconazole, anidulafungin, caspofungin, micafungin, and amphotericin B), untargeted empiric antifungal therapy possibly reduced fungal colonization and the risk of invasive fungal infection but did not reduce all-cause mortality.
●In a study of critically-ill patients ventilated at least five days, empiric antifungal treatment (mostly fluconazole) was not associated with a decreased risk of mortality or occurrence of invasive candidiasis．
●In a multicenter randomized trial (EMPIRICUS) of 260 non-neutropenic critically-ill patients with candida colonization (at multiple sites), multiple organ failure, and ICU-acquired sepsis, empiric treatment for 14 days with micafungin did not result in improved infection-free survival at 28 days but did decrease the rate of new fungal infection.
Thus, the routine administration of empirical antifungal therapy is not generally warranted in non-neutropenic critically-ill patients.