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

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

The strengths of our study are the high percentage of pneumococcal infections included, the frequent sequential measurement of a spectrum of biomarkers in the first 48 h to assess our hypothesis and the complete biomarker profile used to evaluate specific inflammatory responses. Initially, we included only patients with a high severity score (CURB-652) as the percentage of pneumococcal infection is highest in this group and the high severity would best contrast with the possible effects. After inclusion of the eighth Non-lytic antibiotic treatment effect on inflammation in CAP JAC study patient, we extended our inclusion criteria to patients having a specific risk factor for pneumococcal pneumonia to speed up inclusions. 17 We applied extensive testing for pneumococcal infection to ensure the identification of all patients with pneumococcal pneumonia. 23 We were able to confirm a pneumococcal infection in 41% of patients. This percentage is higher than in comparable hospital and intensive care studies with community-acquired pneumonia. 11, 26, 27 In vitro studies and animal models have demonstrated differences in LTA release and inflammatory responses within hours in lytic versus non-lytic antibiotic treatment of S. pneumoniae. 12, 28, 29 Although extensive sampling is a challenge in human trials, it is essential for the testing of our hypothesis. Therefore, the large number of sequential samples that we collected is an important strength of our study. With the extensive sampling, we detected that the expression of CCL5 was significantly different between pneumococcal pneumonia versus non-pneumococcal pneumonia 24 h after the start of treatment. CCL5 is known to be upregulated in pneumococcal infection and to be an essential chemokine in pneumococcal adaptive immunity. 30 Our finding needs to be validated in a larger cohort of pneumonia patients.