Fleroxacin uptake in ischaemic limb tissue.

Antibiotic application to patients with ischaemia of lower limbs may be indicated to avoid or treat infection of soft tissues. Fleroxacin, a fluoroquinolone, active against various Gram-negative and Gram-positive organisms may be used for this purpose. We evaluated the diffusion of fleroxacin into bone, subcutaneous fat, muscle and tendon tissues of lower limb tissue after a 400 mg i.v. dose. Concentrations in ischaemic tissues were similar to those found in non-ischaemic sites. Since the maximum antibiotic levels found were lower than the MICs of various pathogens relevant for infection, we suggest to increase the dose used for this peri-operative prophylaxis to 800 mg.

Inflammatory consequences of the translocation of bacteria and endotoxin to mesenteric lymph nodes.

BACKGROUND: Translocation of intestinal bacteria to mesenteric lymph nodes (MLNs) has been documented in humans under a variety of circumstances, yet its clinical significance remains to be established. The aim of this study was to correlate detectable translocation to MLNs of bacteria and endotoxin with local and systemic signs of inflammation. METHODS: From each of 10 patients with carcinoma of the cecal region two MLNs were harvested prior to resection. The presence of bacteria and endotoxin in the lymphatic tissue and blood was determined by culture methods and DNA preparation (PCR) and by a Limulus assay, respectively. Inflammatory mediators were determined in plasma and in MLN homogenates. RESULTS: Viable bacteria were detected in MLNs of 7 patients and in 9 of 20 lymph nodes. PCR revealed traces of bacteria in 4 patients and in 6 of their MLNs. Combining both modalities, the translocation rate was 80% and 55% for patients and MLNs, respectively. There was no detectable bacteremia. Endotoxin was found in the plasma of 7 patients and in 9 MLNs from 5 patients. There was no correlation between culture findings and endotoxin concentrations. Moreover, bacteriological data did not correspond to local or systemic inflammation. The group of MLN with detectable endotoxin differed significantly from LPS-negative nodes with respect to interleukin-6, interleukin-10, and sCD14. Systemic concentrations of endotoxin and inflammatory parameters did not correspond to levels within MLNs. CONCLUSION: Translocation to MLNs occurs in patients with cecal carcinoma. This, however, seems not to be of major clinical significance if no additional physiologic insults are encountered. Irrespective of the presence of bacteria, there are variations in inflammatory reactions between lymph nodes from one and the same patient, probably reflecting fluctuating response mechanisms to low-grade translocation.

Antibacterial activity of peritoneal exudate in patients treated with 2 g cefotiam for surgical anti-microbial prophylaxis.

The objective of this study was to investigate the presence of antibacterial activity in peritoneal exudate (PE) of patients treated with cefotiam (CFT). CFT (2 g) was administered as a 'single-shot' antimicrobial prophylaxis to 6 patients at the beginning of colorectal resection. Samples of PE were collected from each patient on days 1, 2 and 3 after surgery. CFT was detectable in the samples of day 1 for 5 of the 6 patients. The influence of PE on antibacterial activity of the antimicrobial drug was evaluated carrying out the MICs of CFT against Escherichia coli K-12, E. coli (ATCC 10798), Klebsiella pneumoniae (ATCC 1003), Proteus rettgeri (Sanelli) and Staphylococcus aureus (ATCC 29213) with and without the addition of PE. The presence of PE enhanced the antimicrobial activity of CFT against gram-negative strains, but not against S. aureus (ATCC 29213). These results suggest the presence of substances in PE that possess endogenous antibacterial activity. Thus, antimicrobial activity in PE cannot be predicted by evaluating pathogen sensitivity in vitro only.

The influence of ischemic bowel wall damage on translocation, inflammatory response, and clinical course.

BACKGROUND: While vascular patency and overall viability of the gut can be evaluated perioperatively, damage to the mucosal barrier can hardly be judged in the perioperative setting and, moreover, will probably determine the clinical course. METHODS: In 19 consecutive cases with intestinal ischemia, the clinical course was correlated to the severity of the disease (APACHE II; Septic Severity Score, SSS), the intraabdominal and systemic inflammatory response, and the translocation of bacteria and endotoxin. RESULTS: The comparison of the 10 survivors with the nonsurviving group revealed no differences as to the length of history, serum lactate levels, white blood cell counts, body temperature, markers of the inflammatory response, or quantity and macroscopic quality of the exudate. Differences were found in intraperitoneal bacteriology (prevalence 0.37, negative predictive value for lethal outcome 0.8), endotoxin concentrations in the exudate (P = 0.02) and in the plasma (P = 0.015), fibrinopeptide A levels (exudate P = 0.036; plasma P = 0.015), PGE2 plasma concentration (P = 0.0357), and APACHE II (P = 0.0034) and SSS (P = 0.0027) values. CONCLUSION: The clinical course of ischemic bowel wall necrosis seems to depend on the severity of the disease at admission and on the integrity of the mucosal barrier rather than on inflammatory response, therapeutic measures, or supportive treatment.

Intraperitoneal micro-organisms and the severity of peritonitis.

OBJECTIVE: To find out if there was any correlation between the type or number of pathogenic bacteria in peritoneal exudate, the values of various prognostic scores, the inflammatory response, and the outcome, in patients with peritonitis. DESIGN: Prospective open study. SETTING: University hospital, Germany. SUBJECTS: 51 Consecutive patients with secondary peritonitis. INTERVENTIONS: Laparotomy within 12 hours of admission or within 8 hours of diagnosis in 9 patients with postoperative peritonitis. MAIN OUTCOME MEASURES: Correlation between the severity of the disease (APACHE II score, Septic Severity Score, Mannheim Peritonitis Index, Peritonitis Index Altona II, and outcome), the intraperitoneal and the systemic inflammatory response, intraperitoneal and systemic endotoxin concentrations, and type and number of micro-organisms grown from peritoneal fluid. RESULTS: Intra-abdominal microbiological findings did not correlate with severity of illness judged by the scoring systems, the later incidence of infective complications, or the final outcome. The presence of intra-abdominal microbes was associated with signs of a systemic inflammatory response (median activation index 3 (range 1-3) compared with 2 (range 1-3)), the length of history (median 52 hours (range 3-72) compared with 16 hours (range 3-56), and local and systemic concentrations of endotoxin (peritoneal exudate: median 4800 EU/ml (range 0.06-136674) compared with 220 EU/ml (range 0.00-1800); plasma: median 0.05 EU/ml (range 0.00-1.32) compared with 0.04 EU/ml (range 0.00-0.13)). The sensitivity of the organisms to the antibiotics given (cefuroxime and metronidazole) did not influence the incidence of later infective complications or the outcome. CONCLUSIONS: These results do not suggest micro-organisms invading the peritoneal cavity and respective antibiotic treatment to be major determinants of the clinical course of peritonitis.

Effect of human bowel wall distension on translocation of indigenous bacteria and endotoxins.

The effect of colonic distension on the translocation of indigenous bacteria and endotoxins was prospectively assessed in 50 consecutive patients undergoing colonoscopy. Semiquantitative bacteriologic cultures, chromogenic LAL testing for endotoxemia, and serial determinations of inflammatory markers were used. At the end of the endoscopic procedure, true bacteremia was found in only two patients with obstructing colorectal cancer. There was no evidence of systemic endotoxemia either being induced or increased during the observation period. The endotoxin detoxifying plasma capacity was elevated in patients with preexisting inflammation and did not change within this period. Levels of TNF-alpha, interleukin-6 (IL-6), and elastase (E alpha 1PI) did not differ from baseline values. C3 alpha levels increased in 20% of the patients, whereas fibrinopeptide A values rose by up to 10(2) during colonoscopy. However, since neither endotoxin, TNF alpha, nor IL-6 levels were found to be elevated in this study, the excessive activation of the coagulation system must be related to the distension of bowel wall vessels rather than to an effect of endotoxins escaping from the lumen.

The role of intestinal endotoxin in experimental peritonitis.

Escape of endotoxin from the intraintestinal site was investigated in experimental models of intestinal ischemia and during intraabdominal infection in rats. Following the instillation of Salmonella abortus equi endotoxin (S-form) into the proximal large bowel, we recorded the presence of the lipopolysaccharide molecule in the bowel wall, the intestinal lymph nodes, the peritoneal cavity, and in the liver sinusoids by immunohistochemical methods. At 3, 6, 12, 24, and 48 hr after the operative procedure, peritoneal fluid, blood, and tissue samples were taken. Survival rates were similar between the two test-groups (occlusion of the superior mesenteric artery [SMA] and cecal ligation and puncture [CLP]) and were not influenced by the amount of the injected endotoxin. There was no detectable morbidity in the sham-operated control animals with endotoxin doses up to 20 mg. Endotoxin could only be detected at 24 and 48 hr in the SMA group in the liver as well as in the peritoneal sediment and in intestinal lymph nodes. CLP and control samples remained negative throughout the observation period. Bacteria were found intraperitoneally within 12 to 24 hr in the SMA group and within 3 to 12 hr in the CLP group.

[Endothelial cell proliferation in vitro induced by sera of patients with progressive systemic sclerosis and systemic lupus erythematosus]. / Endothelzellproliferation in vitro durch Seren von Patienten mit progressiver Systemsklerose (PSS) und systemischem Lupus erythematodes (SLE).

Endothelial cells from human umbilical cord veins proliferate in vitro up to 35-fold over control values when incubated for prolonged periods of time (up to 144 hrs) in the presence of sera from patients with SLE or PSS. The proliferation inducing capacity of patients' sera was high during remission and low during relapses. Similarly, induction of endothelial cell proliferation increased significantly following plasma separation; however, this effect did only last for a few hours. The in vitro stimulation of endothelial cells observed may be correlated to histological findings of hyperplasia and neoproliferation of vascular intima cells in SLE and PSS.

Proliferative response of human endothelial cultures to various types and treatments of human sera, to culture treatments and to various oxygen concentrations.

Endothelial cells from the human umbilical vein were exposed to different human sera, differently treated serum, to various oxygen concentrations, and various culture treatments. Endothelial proliferation was determined by measuring the uptake of [3H]-thymidine by means of autoradiography and presented as thymidine labeling index (TI) values. TI values differed according to different serum concentrations, serum types, serum preparations (WBS-PDS) and serum pretreatments. Low oxygen concentrations in the incubator atmosphere induced an early DNA synthesis response without an increase in cell number. The addition of the protease inhibitors aprotinin and soybean trypsin inhibitor to the culture medium resulted in a dose dependent TI decrease, whereas PMSF showed no influence.