Impact of cefuroxime administration on endotoxin (LPS) and tumour necrosis factor-alpha (TNFalpha) blood levels in patients suffering from acute pyelonephritis: a preliminary report.

It has been suggested that treatment of systemic infections caused by Gram-negative bacteria with beta-lactam agents might add to the inflammatory process by resulting in the release of endotoxins (LPS) upon death of the Gram-negative bacteria. To evaluate that hypothesis, 25 patients with acute pyelonephritis of Gram-negative aetiology were given intravenous cefuroxime 1.5 g tid. Blood samples were collected at various time intervals for blood culture and for the determination of LPS, tumour necrosis factor-alpha (TNFalpha) and cefuroxime levels. LPS remained elevated at levels equal to those before the administration of cefuroxime over the first 24 h of therapy. A positive correlation was detected between LPS and drug levels 6 h after the initiation of therapy. Fever persisted in 50, 37.5 and 16.7% of patients 48, 72 and 96 h after the start of treatment, respectively, followed by a rise of LPS at levels above the baseline. Blood cultures taken at the same time were sterile. A wide range of TNFalpha levels were found at similar times of sampling, indicating that LPS triggers considerable TNFalpha production in the serum of some patients but not in others. It is concluded that antibiotic-induced endotoxaemia is a phenomenon that might be observed in patients receiving cefuroxime and that might be responsible for the persistence of fever despite negative blood cultures.