Wu em et al /em [26] conducted multi-center randomized controlled trials and found that adjuvant therapy with thymosin-a1 improved clinical outcomes in patients with severe sepsis. uremia (blood urea nitrogen (BUN) 20?mg/dL).[5] To date, confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater (CURB-65) and pneumonia severity index (PSI), the two primary clinical assessment tools utilized, have been widely used to evaluate the mortality risk of CAP patients in clinical practice.[6,7] Several risk factors associated with high mortality in SCAP have been identified, including anti-microbial resistance, increased age, septic shock, and acute respiratory failure.[8] It is thus greatly beneficial to distinguish high-risk patients with SCAP and formulate personalized treatment strategies. Optimal ICU management and rational application of antibiotics were reported to be two key factors determining outcomes of patients with SCAP.[1] Recently, several advances in SCAP have been made and here we summarized the updated knowledge of diagnostic and therapeutic strategies for SCAP. Microbiologic Diagnostics are Needed for Antibiotic Selection is the most common pathogen among patients with CAP. Moreover, the most frequently isolated pathogen in SCAP requiring ICU admission B-Raf inhibitor 1 dihydrochloride was ((MRSA) should be considered in empiric therapy regimens. In addition, pharmacokinetic/pharmacodynamic (PK/PD) analysis is required to optimize anti-microbial dosing regimens.[16] If necessary, concentration monitoring of antibiotics should be applied for patients with SCAP. Corticosteroids in Treatment of SCAP To date, the B-Raf inhibitor 1 dihydrochloride application of corticosteroids in SCAP treatment has remained controversial. Excessive inflammatory cascade activity has been considered an important pathophysiological response in the setting of SCAP. Corticosteroids, possessing strong anti-inflammatory effects, significantly reduce cytokine expression in such patients.[17] Several recent studies showed that corticosteroid combination therapy reduced mortality, decreased the risk of acute respiratory distress syndrome (ARDS), lengths of hospital B-Raf inhibitor 1 dihydrochloride and ICU stays, as well as the time to clinical stability in patients with SCAP.[4,18,19] It is likely that low-dose steroid (eg, methylprednisolone) administration can improve patient with SCAP outcomes, especially in individuals with strong inflammatory responses or septic shock. However, some studies reported that corticosteroid combination therapy had no effect on mortality and patients might suffer severe side effects as a result of treatment.[17] Corticosteroid treatment is not recommended for viral patients with SCAP. A meta-analyses further revealed that corticosteroid combination therapy was associated with increased mortality in influenzal patients with CAP.[12,20] Bacteriophage Therapy Bacteriophages are viral entities that can infect and lyse bacteria. With an increase in the emergence of drug-resistant bacteria, bacteriophage therapy is emerging as an alternative B-Raf inhibitor 1 dihydrochloride anti-bacterial approach to control bacterial infection in cases of antibiotic treatment failure.[21] Pre-clinical animal studies have demonstrated that bacteriophage therapy markedly alleviates infections caused by multi-drug-resistant bacteria.[22] Furthermore, several clinical trials also have reported that bacteriophage therapy possesses good prospects in the treatment of patients with SCAP and does not confer any serious adverse effects.[23] Bacteriophages target bacterial pathogens with high specificity and leave the host microbiota unaffected.[24] However, it is necessary to use a cocktail of bacteriophages against a battery of common pathogens for an individual case to improve the therapeutic effect in future clinical practice. Non-antibiotic MEKK12 Treatment Strategy Recently, several non-antibiotic therapies have been explored as adjuvant treatments for SCAP, including neutralizing antibody against bacterial toxins, immunoglobulins, thymosin, granulocyte macrophage colony-stimulating factor (GM-CSF), low molecular weight/normal heparin, mesenchymal stem cells (MSCs) and growth factors. Fran?ois alpha toxin-neutralizing mAb (AR-301) had several clinical benefits for ICU patients with severe pneumonia B-Raf inhibitor 1 dihydrochloride caused by em S. aureus /em . Thymosin-a1 is also a promising beneficial immunomodulatory drug. Wu em et al /em [26] conducted multi-center randomized controlled trials and found that adjuvant therapy with thymosin-a1 improved clinical outcomes in patients with severe sepsis. GM-CSF is a cytokine secreted by leukocytes to increase granulocyte and monocyte production. Meisel em et al /em [27] showed that GM-CSF could reverse monocyte deactivation and reduce the time required for mechanical ventilation.