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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Berger, Sarah Goekeri, Cengiz Gupta, Shishir K. Vera, Julio Dietert, Kristina Behrendt, Ulrike Lienau, Jasmin Wienhold, Sandra-Maria Gruber, Achim D. Suttorp, Norbert Witzenrath, Martin Nouailles, Geraldine |
| Abstract | Background Community-acquired pneumonia (CAP) remains a major cause of death worldwide. Mechanisms underlying the detrimental outcome despite adequate antibiotic therapy and comorbidity management are still not fully understood. Methods To model timely versus delayed antibiotic therapy in patients, mice with pneumococcal pneumonia received ampicillin twice a day starting early (24 h) or late (48 h) after infection. Clinical readouts and local and systemic inflammatory mediators after early and late antibiotic intervention were examined. Results Early antibiotic intervention rescued mice, limited clinical symptoms and restored fitness, whereas delayed therapy resulted in high mortality rates. Recruitment of innate immune cells remained unaffected by antibiotic therapy. However, both early and late antibiotic intervention dampened local levels of inflammatory mediators in the alveolar spaces. Early treatment protected from barrier breakdown, and reduced levels of vascular endothelial growth factor (VEGF) and perivascular and alveolar edema formation. In contrast, at 48 h post infection, increased pulmonary leakage was apparent and not reversed by late antibiotic treatment. Concurrently, levels of VEGF remained high and no beneficial effect on edema formation was evident despite therapy. Moreover, early but not late treatment protected mice from a vast systemic inflammatory response. Conclusions Our data show that only early antibiotic therapy, administered prior to breakdown of the alveolar–capillary barrier and systemic inflammation, led to restored fitness and rescued mice from fatal streptococcal pneumonia. The findings highlight the importance of identifying CAP patients prior to lung barrier failure and systemic inflammation and of handling CAP as a medical emergency. |
| Related Links | https://ccforum.biomedcentral.com/counter/pdf/10.1186/s13054-018-2224-5.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 13648535 |
| DOI | 10.1186/s13054-018-2224-5 |
| Journal | Critical Care |
| Issue Number | 1 |
| Volume Number | 22 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2018-11-01 |
| Access Restriction | Open |
| Subject Keyword | Intensive Critical Care Medicine Emergency Medicine Streptococcus pneumoniae Blood–air barrier Bacterial pneumonia Acute lung injury Ampicillin Innate immunity |
| Content Type | Text |
| Resource Type | Article |
| Subject | Critical Care and Intensive Care Medicine |
| Journal Impact Factor | 8.8/2023 |
| 5-Year Journal Impact Factor | 10.4/2023 |
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