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Non-lytic antibiotic treatment in community-acquired pneumococcal pneumonia does not attenuate inflammation: the
Geert H Groeneveld1, Tanny J van der Reyden2, Simone A Joosten2
1Department of Internal Medicine and Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Background:
The inflammatory response in pneumococcal infection is primarily driven by immunoreactive bacterial cell wall components [lipoteichoic acid (LTA)]. An acute release of these components occurs when pneumococcal infection is treated with β-lactam antibiotics.
Objectives:
We hypothesized that non-lytic rifampicin compared with lytic β-lactam antibiotic treatment would attenuate the inflammatory response in patients with pneumococcal pneumonia.
Methods:
In the PRISTINE (Pneumonia treated with RIfampicin aTtenuates INflammation) trial, a randomized, therapeutic controlled, exploratory study in patients with community-acquired pneumococcal pneumonia, we looked at LTA release and inflammatory and clinical response during treatment with both rifampicin and β-lactam compared with treatment with β-lactam antibiotics only. The trial is registered in the Dutch trial registry, number NTR3751 (European Clinical Trials Database number 2012-003067-22).
Results:
Forty-one patients with community-acquired pneumonia were included; 17 of them had pneumococcal pneumonia. LTA release, LTA-mediated inflammatory responses, clinical outcomes, inflammatory biomarkers and transcription profiles were not different between treatment groups.
Conclusions:
The PRISTINE study demonstrated the feasibility of adding rifampicin to β-lactam antibiotics in the treatment of community-acquired pneumococcal pneumonia, but, despite solid in vitro and experimental animal research evidence, failed to demonstrate a difference in plasma LTA concentrations and subsequent inflammatory and clinical responses. Most likely, an inhibitory effect of human plasma contributes to the low immune response in these patients. In addition, LTA plasma concentration could be too low to mount a response via Toll-like receptor 2 in vitro, but may nonetheless have an effect in vivo.
Insights
Rifampicin did not reduce inflammation in pneumococcal pneumonia compared to standard antibiotics. The PRISTINE trial showed adding rifampicin was feasible but did not alter lipoteichoic acid (LTA) release or clinical outcomes.
Area of Science:
- Infectious Diseases
- Immunology
- Pharmacology
Background:
- Pneumococcal pneumonia inflammation is driven by lipoteichoic acid (LTA) from bacterial cell walls.
- β-lactam antibiotics cause acute LTA release during pneumococcal infection treatment.
Purpose of the Study:
- To investigate if non-lytic rifampicin attenuates inflammatory response compared to lytic β-lactam antibiotics in pneumococcal pneumonia.
- To compare LTA release, inflammatory markers, and clinical outcomes between rifampicin plus β-lactam and β-lactam alone.
Main Methods:
- The PRISTINE trial was a randomized, controlled study in community-acquired pneumococcal pneumonia patients.
- Assessed LTA release, inflammatory responses, biomarkers, and clinical outcomes in two treatment groups.
Main Results:
- No significant differences were observed in LTA release, inflammatory responses, or clinical outcomes between groups.
- Forty-one patients were included; 17 had confirmed pneumococcal pneumonia.
Conclusions:
- Adding rifampicin to β-lactam antibiotics for pneumococcal pneumonia is feasible but did not reduce LTA or inflammation.
- Potential factors include inhibitory effects of human plasma and low LTA concentrations in vivo.
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