Non-lytic #antibiotic #treatment in community-acquired #pneumococcal #pneumonia does not attenuate inflammation: the #PRISTINE trial (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Non-lytic antibiotic treatment in community-acquired pneumococcal pneumonia does not attenuate inflammation: the PRISTINE trial

Geert H Groeneveld, Tanny J van der Reyden, Simone A Joosten, Hester J Bootsma, Christa M Cobbaert Jutte, J C de Vries, Ed J Kuijper, Jaap T van Dissel

Journal of Antimicrobial Chemotherapy, dkz207, https://doi.org/10.1093/jac/dkz207

Published: 18 May 2019

 

Abstract

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.

Topic: antibiotics – rifampin – inflammation – immune response – community acquired  pneumonia – biological markers – cell wall – lactams – plasma – pneumococcal infections – pneumonia, pneumococcal – treatment outcome – inflammatory response – community – toll-like receptor 2 – attenuation

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; S. pneumoniae; Pneumonia; Beta-lactams; Rifampin.

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gimi69

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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