Antimicrobial-induced endotoxaemia in patients with sepsis in the field of acute pyelonephritis.
BACKGROUND
In vitro results have shown that antimicrobial agents may induce the Gram-negative bacteria to release endotoxins (LPS), which in turn, could trigger the secretion of cytokines from monocytes.


OBJECTIVE
To compare the effect of cefuroxime, netilmicin or ciprofloxacin on serum levels of LPS and tumour necrosis factor-alpha (TNFalpha).


METHODS
Seventy-four patients with acute pyelonephritis caused by Gram-negative bacteria and signs of sepsis were randomly assigned to receive one of three intravenous regimens of cefuroxime, netilmicin or ciprofloxacin. Blood samples were collected before therapy and at specified time intervals for 96 hours after the initiation of treatment for the determination of serum levels of LPS and of TNFalpha.


RESULTS
Patients treated with cefuroxime presented an early peak of LPS and of TNFalpha in serum two hours after the initiation of treatment compared to the other study groups. After that time interval, concentrations of LPS and TNFalpha were similar in all the study groups. Fever accompanied by endotoxaemia was still detected for 48 hours after the start of therapy in 36, 37.5 and 36% of patients treated with cefuroxime, netilmicin and ciprofloxacin respectively. The corresponding figures for these agents at 72 hours were 28, 12.5 and 24%, respective and 12, 4.2 and 4% at 96 hours (P value not significant).


CONCLUSIONS
With the exception of an early peak in the serum levels of LPS and TNFalpha in patients treated with cefuroxime, no significant difference could be detected amongst the study groups as far as their effect on serum levels of LPS and TNFalpha were concerned. This suggests that these three antimicrobial agents may be administered safely at the early stages of sepsis.
Giamarellos-Bourboulis
E J
EJ
4th Department of Internal Medicine, University of Athens, Medical School, Athens General Hospital "G Gennimatas," Greece. giamarel@internet.gr
Perdios
J
J
Gargalianos
P
P
Kosmidis
J
J
Giamarellou
H
H
D000208:Acute Disease; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002444:Cefuroxime / Q000009:adverse effects* / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000009:adverse effects* / Q000627:therapeutic use*; D019446:Endotoxemia / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009428:Netilmicin / Q000009:adverse effects* / Q000627:therapeutic use*; D011704:Pyelonephritis / Q000150:complications / Q000188:drug therapy*; D018805:Sepsis / Q000188:drug therapy* / Q000209:etiology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D009428:Netilmicin; D002939:Ciprofloxacin; D002444:Cefuroxime