Antibiotic-mediated release of tumour necrosis factor alpha and norharman in patients with hospital-acquired pneumonia and septic encephalopathy

Abstract

Objective: To investigate antibiotic-mediated release of tumour necrosis factor (TNF)-alpha and norharman in patients with hospital-acquired pneumonia with and without additional septic encephalopathy.

Design: Prospective observational study with a retrospective post hoc analysis.

Setting: Surgical intensive care unit (ICU) at a university hospital.

Patients: Thirty-seven patients were consecutively included (9 patients with hospital-acquired pneumonia, 11 patients with hospital-acquired pneumonia and septic encephalopathy, 17 control patients) in the study. Pneumonia was defined according to the criteria of the American Thoracic Society.

Interventions: Patients received cephalosporins for antibiotic treatment of hospital-acquired pneumonia. Blood samples were taken before, immediately after and 4 h after application of cephalosporins.

Measurements and results: Of the pneumonia patients, 55% developed septic encephalopathy. ICU stay, complications and mortality were significantly increased. An increased release of TNF-alpha was immediately seen in all pneumonia patients after antibiotics compared to controls, whereas the level did not differ between patients with and without septic encephalopathy. Norharman was significantly increased in pneumonia patients 4 h after antibiotic treatment, in tendency more enhanced in the pneumonia patients without encephalopathy.

Conclusions: Patients with hospital-acquired pneumonia and septic encephalopathy had a significantly longer ICU stay with higher mortality rate compared to patients with hospital-acquired pneumonia alone. Antibiotic-mediated TNF-alpha release may induce the kynurenine pathway. TNF-alpha activates indolamine-2,3-dioxygenase with neurotoxic quinolinic acid as the end product. Norharman seems to counteract this mechanism and seems to play a role in neuroprotection. The worse outcome of patients with encephalopathy expresses the need to investigate protective factors and mechanisms.