Pharmacological management of sepsis in adults with a focus on the current gold standard treatments and promising adjunctive strategies: evidence from the last five years

ABSTRACT

Introduction: The last five years, there have been considerable changes in our perception on the pathogenesis of sepsis. This review aims to summarize the current progress of the last five years in the management and research fields of sepsis in a holistic approach. To achieve this, accumulated evidence over the last five years coming from randomized clinical trials (RCTs) and observational studies in adults for the management of sepsis is provided.

Areas covered: In this review, the authors discuss available strategies in sepsis, divided into standard-of-care and adjunctive therapies. Standard-of-care approaches comprise antimicrobials, fluids, vasoactive agents, steroids. Antimicrobials remain the mainstay of treatment. However, key-point of management is early recognition of the patient that guides early start of antimicrobials. Patients with suspected infection and any two of: an altered mental state, more than 22 breaths per minute and systolic blood pressure below 100 mmHg should receive early intervention with broad-spectrum antimicrobials and fluids.

Expert opinion: Low dose hydrocortisone replacement and fludrocortisone seem promising for the patient at septic shock. Adjunctive macrolide treatment of severe CAP is also associated with survival benefit. Future studies will help to provide additional insight into the field.

KEYWORDS:

• Sepsis
• antimicrobials
• cytokines
• immunosuppression
• inflammation
• macrolides

Article highlights

• Current gold standard of sepsis management is early recognition of the patient followed by the administration of broad-spectrum antimicrobials.

• The three elements of the qSOFA score are a screening tool for recognition of high risk for death.

• A recent study suggests that low dose hydrocortisone with fludrocortisone replacement decreases mortality from septic shock.

• Immunointervention strategies with anticytokine drugs, antioxidants, statins, stimulatory cytokines, and IgGAM have conflicting results.

• Adjunctive macrolide treatment is associated with survival benefit in severe CAP.

This box summarizes key points contained in the article.

Declaration of interest

EJ Giamarellos-Bourboulis has received honoraria for talks and consultancy, which was paid to the University of Athens, from AbbVie USA, Abbott CH, Biotest Germany, Brahms GmbH, InflaRx GmbH, the Medicines Company, Merck Sharp and Dohme Greece and XBiotech Inc. He has also received independent educational grants from AbbVie, Abbott, Astellas, AxisShield, bioMerieux Inc, InflaRx GmbH, the Medicines Company and XBiotech Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

EJ Giamarellos-Bourboulis has received funding from the Framework 7 Program ‘HemoSpec’ and from the Horizon 2020 Marie Curie Project ‘European Sepsis Academy’.