Precision medicine for the treatment of severe pneumonia in intensive care

SUMMARY

Despite advances in its management, community-acquired pneumonia (CAP) remains the most important cause of sepsis-related mortality and the reason for many ICU admissions. Severity assessment is the cornerstone of CAP patient management and the attempts to ensure the best site of care and therapy. Survival depends on a combination of host factors (genetic, age, comorbidities, defenses), pathogens (virulence, serotypes) and drugs. To reduce CAP mortality, early adequate antibiotic therapy is fundamental. The use of combination therapy with a macrolide seems to improve the clinical outcome in the subset of patients with high inflammation due to immunomodulation. Guidelines on antibiotic therapy have been associated with beneficial effects, and studies of newer adjunctive drugs have produced promising results. This paper discusses the current state of knowledge regarding of precision medicine and the treatment of severe CAP patients.

KEYWORDS:

• Precision medicine
• personalized medicine
• bacterial load
• antibiotic therapy
• adjunctive therapy
• pneumonia, sepsis

Financial & competing interests disclosure

The authors were supported by CIBERES (PCI Pneumonia) in the manuscript preparation. J. Rello reported honoraria from Advisory Boards from LASCCO, Kenta Biotech and Intercells and Grants from AGAUR SGR Intercell and Valneva. A. Perez reported honoraria from LASCCO, The Medicines Company, Debiopharm, INSMED, Aridis Pharmaceuticals, Kenta Biotech, ImmunNovative Developments and is Expert of the European Commission for the FP7- HEALTH-2010, Horizon 2020, and EUREKA projects and expert of the Innovation Fund Denmark. 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

Key issues

• Combination therapy with a macrolide should be considered in patients with vasopressors or extreme hypoxemia.

• Adherence to guidelines is the variable with the greatest effect on outcomes.

• Young patients with severe hypoxemia are associated with high bacterial burden and are at high risk of death, in spite of prognostic scores indicating low severity.

• Future studies should identify patients in the emergency department at risk of requiring mechanical ventilation and likely to benefit from steroid or other adjunctive therapies.

• No single biomarker can determine risk stratification at the bedside; future approaches should include altered targets for interventions.

• Specific GWAS has been associated with poor outcomes and may help to identify subjects who have a high risk of poor prognosis and are candidates for more innovative therapies; the GWAS was the first study to support pharmacogenomics in pneumonia.

• Targeted monoclonal antibiotic trials represent the most promising approach for improving outcome in virulent organisms.

• Immunophenotyping and immunomodulatory strategies in severe infection are the most promising approach from the host’s perspective.

• Theranostics is an approach that combines diagnosis and therapy; it requires a redefinition of sepsis to develop personalized sepsis treatments.