Alkaline phosphatase (AP) is a phosphate transferase present in bacteria and eukaryotes. In previous studies, we have shown that AP is able to dephosphorylate lipopolysaccharide (LPS) at physiological pH levels. Because LPS is the causative agent of gram-negative sepsis, we hypothesize that AP might be used as a medication during early stages of LPS-induced septic shock. We have demonstrated protective effects of AP when this enzyme was administered simultaneously with LPS. However, a major question of anti-LPS therapies is whether they are also effective after systemic infiltration of whole bacteria and if they also act in later stages of the disease. To test this, we explored the protective effects of AP from human placenta (plAP) in a bacterial challenge model in Balb/c mice. AP was intravenously administered 20 min after a bacterial intraperitoneal inoculation of 2 to 5 x 10 CFU of Escherichia coli suspended in a 100-microL volume of saline. It was shown that AP attenuated the systemic host response upon E. coli. Body temperature was normalized as compared with untreated septic mice. Also, serum nitric oxide levels 24 h after the injection of bacteria were reduced almost to control levels in mice that received AP. Moreover, survival after 24 h was significantly higher in the AP-treated group compared with the nontreated control group.
The efficacy of intraperitoneal instillation of antimicrobial agents in eliminating the bacterial contaminant in patients with generalized peritonitis remains controversial. We determined the effect of intraperitoneal instillation of taurolidine or imipenem on mortality, and on the concentration of bacteria, endotoxin, and tumor necrosis factor (TNF) in rats with intraperitoneally injected bacteria. Thirty rats were inoculated intraperitoneally with two enteric bacterial strains, followed by either taurolidine, saline, or imipenem. Abdominal fluid and blood were analyzed at different time intervals. The survival rate was highest in the imipenem group (p < 0.05). The bacterial concentration in abdominal fluid in the taurolidine and imipenem group was lower than in the saline group (p < 0.005), but the concentration in the imipenem group was lowest (p < 0.005). The endotoxin concentration in abdominal fluid and plasma in the taurolidine group was lower than in the other two groups (p < 0.05). The TNF concentration in abdominal fluid and plasma in the taurolidine group was lower than in the saline group (p < 0.05), whereas the concentration in the imipenem group was higher (p < 0.005). We conclude that topically applied taurolidine in rats with intraperitoneally injected bacteria may have a weak antibacterial effect, and lowered concentrations of endotoxin and TNF. Topically applied imipenem had a profound bactericidal activity but induced endotoxin and TNF release.
In rats with faecal peritonitis, debridement, lavage with saline, and additional instillation of imipenem/cilastatin, all have cumulatively reducing effect on bacterial growth, endotoxin concentrations, abscess formation, and mortality. Instillation of taurolidine reduces only the amount of endotoxin.
Background Patients with secondary peritonitis are treated by surgery and intravenous antibiotics depending on the micro‐organisms cultured from abdominal fluid samples. However, such samples may not be representative of the origin of the intra‐abdominal infection. Therefore, this study determined (1) whether different micro‐organisms are cultured from abdominal fluid, peritoneum and blood samples, and (2) whether fluorescence in situ hybridization (FISH), with 16S ribosomal RNA‐targeted probes applied on peritoneum samples, is more efficient than standard culturing techniques. Methods In a pilot study, samples of abdominal fluid, peritoneum and blood were obtained from two groups of patients: six patients with secondary peritonitis (peritonitis group) and five patients without peritonitis (control group). Results Standard culturing techniques revealed coagulase‐negative staphylococci (CNS) and yeast in abdominal fluid samples in three of six patients; Escherichia coli, enterococci, CNS and Citrobacter in peritoneum samples in five of six patients; and no micro‐organisms in the blood samples from the peritonitis group. In the control group, CNS were cultured from the abdominal fluid samples in one of five patients, while no micro‐organisms were cultured from peritoneum samples and CNS were cultured from the blood samples in one of five patients. The FISH technique revealed a large number of various anaerobic bacteria in peritoneum samples in one of six patients in the peritonitis group. In the control group no bacteria were detected. Conclusion Micro‐organisms cultured from abdominal fluid differ from those cultured from peritoneum samples. The FISH technique confirmed these findings in only one case. However, it is a promising technique for the identification and localization of bacteria causing secondary peritonitis. © 2000 British Journal of Surgery Society Ltd
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