Anti-tumor necrosis factor-alpha therapy during murine Klebsiella pneumoniae bacteremia: increased mortality in the absence of liver injury

Klebsiella pneumoniae is a leading cause of gram-negative bacterial pneumonia, often resulting in bacteremia concurrent with the localized pulmonary infection. The beneficial role of tumor necrosis factor (TNF)-alpha during pulmonary infection has been well documented; however, consequences of TNF-alpha production during systemic bacterial infection are controversial. A murine model of K. pneumoniae was developed to address this important issue. Liver-associated TNF-alpha mRNA was induced within 30 min after intravenous bacterial inoculation and remained elevated through 6 h before returning to near-baseline at 24 h postinfection. Intravenous K. pneumoniae infection induced liver cellular injury that was completely ablated when mice were pretreated with a neutralizing anti-TNF-alpha antibody. Interestingly, this reduction in liver injury failed to translate into improved survival. Mice receiving anti-TNF-alpha continued to succumb to the infection even out to day 10 postinfection. Bacterial clearance after TNF-alpha neutralization was significantly impaired at later time points during infection. Correlating with impaired bacterial clearance was diminished production of liver-associated MIP-2, MIP-1alpha, MCP-1, and interferon-gamma. Further evidence of diminished antibacterial immune responses was noted when the activational status of splenic natural killer cells in anti-TNF-alpha-treated mice was examined 24 h postinfection. Natural killer cells displayed decreased CD69 expression. Combined, these data indicate that the beneficial effects of TNF-alpha during systemic K. pneumoniae infection outweigh the detrimental effects of TNF-alpha-mediated hepatocyte cellular injury. Anti-TNF-alpha therapy, although preventing liver injury during blood-borne bacterial infection, results in a dampened anti-bacterial host response, resulting in decreased bacterial clearance and overall survival.     

声波牙刷刷牙时间与儿童牙菌斑控制的关系

目的观察声波牙刷刷牙不同时间儿童牙菌斑控制的效果,为临床口腔卫生指导及儿童牙病预防提供理论依据。方法选择年龄4～5岁的儿童32例,在刷牙前进行菌斑染色,采用声波牙刷刷牙0．5、1．0、2．0及3．0min,分别记录菌斑牙面数及菌斑指数,计算菌斑百分率。结果应用声波牙刷刷牙2．0min,菌斑百分率（14．81％）可达基本控制范围内。刷牙0．5、1．0及2．0min时菌斑百分率及菌斑指数与刷牙前比较差异均有统计学意义（x2=91．84～730．80,F=76．692,P〈0．05）;刷牙3．0min与刷牙2．0min相比,菌斑百分率及菌斑指数差异无统计学意义（P〉O．05）。结论声波牙刷对儿童牙菌斑控制有良效;建议儿童在专业口腔卫生指导下用声波牙刷刷牙每次2．0min。     

Impact of liver cirrhosis on mortality in patients with community-acquired bacteremia

Few studies have analyzed the impact of liver cirrhosis, a clinically significant comorbid medical condition, on the mortality of patients with community-acquired bacteremia. We conducted an observational study of 839 consecutive community-acquired bacteremia patients who were hospitalized through the emergency department (ED). We compared the 30-day mortality of bacteremia patients with and without liver cirrhosis using Cox proportional hazards regression. The probability of survival at day 30 was significantly different for the cirrhotic and noncirrhotic groups (53% versus 82%, respectively; P < 0.001 by the log-rank test). Multivariate analysis indicated that liver cirrhosis was associated with an increased risk of short-term mortality (hazard ratio, 2.0; 95% confidence interval, 1.1–3.5), as well as age, higher comorbidity index, and markers obtained from clinical presentation at ED. In conclusion, in addition to the effects from other prognostic factors, liver cirrhosis has a significant impact on the mortality of patients with community-acquired bacteremia.     

The effect of hepatic cirrhosis on the pharmacokinetics and blood pressure response to nicardipine

The present study was designed to compare the pharmacokinetic handling of a single oral dose of nicardipine in normal subjects and in patients with hepatic cirrhosis and to compare the sensitivity of the two groups to its hypotensive effect. Nicardipine plasma concentrations were substantially higher in the subjects with hepatic cirrhosis with impaired antipyrine clearance, as shown by a significantly higher average Cmax and AUC. The terminal elimination half-life in this group varied from 0.8 to 60.2 hours (median, 11.7 hours), compared with 0.6 to 4.1 hours (median, 1.4 hours) in the group of eight subjects with normal liver function. In the cirrhotic patients with impaired antipyrine clearance, the AUC of the pyridine metabolite averaged 10% of that of the parent drug, whereas in normal subjects the ratio averaged 48%. This finding suggests less conversion of nicardipine to this metabolite in subjects with impaired hepatic function. Peak blood pressure decreases were greater in the cirrhotic group, which was in keeping with the higher plasma levels in these subjects.     

The disposition of dapsone in cirrhosis.

Acetylation and N-hydroxylation of dapsone were evaluated in drug-free, non-smoking, normal subjects and subjects with cirrhosis (n = 7 for each group) after oral administration of 100 mg dapsone. Acetylation was not correlated with oral dapsone clearance or reduced in cirrhosis (0.37 +/- 0.43 versus 0.52 +/- 0.32). Fractional metabolic clearance of dapsone to its hydroxylamine was associated with dapsone oral clearance (r = 0.96, p less than 0.001, n = 14). In patients with cirrhosis, liver disease was associated with a trend to reduction in oral clearance (22%) and metabolic clearance of dapsone (48%). Protein binding was minimally reduced by cirrhosis (73% +/- 1% versus 69% +/- 3% in patients with cirrhosis (p less than 0.02). The dapsone recovery ratio was validated as a phenotypic index of the metabolic clearance of dapsone (r = 0.74, p less than 0.05). In an extended comparison of 14 patients with cirrhosis to 70 control subjects, cirrhosis was associated with reductions of 28% in dapsone recovery ratio (p less than 0.001), and 37% in acetylation ratio (p less than 0.01). Neither dapsone recovery ratio nor acetylation ratio correlated with Pugh Score, conventional liver function tests, indocyanine green clearance, or phenotypic measures of S-mephenytoin hydroxylase or debrisoquin hydroxylase activity. We conclude that cirrhosis is associated with minor changes in dapsone disposition and that dosage modification is not required. In addition, there is evidence that cirrhosis has a selective influence on activity of individual isozymes of cytochrome P450.     

Rabeprazole: pharmacokinetics in patients with stable, compensated cirrhosis.

This single-center, open-label study was undertaken to compare the tolerability and pharmacokinetic profiles of rabeprazole, a new proton-pump inhibitor (PPI), in healthy volunteers and in subjects with chronic cirrhosis. Thirteen healthy men and 10 men with stable, compensated cirrhosis documented by biopsy or liver/spleen scan received a single 20-mg rabeprazole dose. Blood samples were drawn before and up to 24 hours after drug administration for the determination of plasma rabeprazole concentrations using high-performance liquid chromatography. Adverse events, vital signs, electrocardiograms, physical findings, and clinical laboratory test results were monitored before and during treatment to determine how rabeprazole was tolerated. Chronic liver disease substantially altered the pharmacokinetic profile of rabeprazole. The maximum rabeprazole concentration (+/- SD) in subjects with cirrhosis (635+/-199 ng/mL) was approximately 50% higher than that in the healthy volunteers (401+/-246 ng/mL), and both area under the curve and elimination half-life were increased by approximately 100%. Oral clearance in subjects with cirrhosis was 38% of that in the healthy volunteers. Rabeprazole was well tolerated by both groups. Three subjects reported a total of 5 clinical adverse events that were judged as definitely or possibly related to rabeprazole treatment. Some minor changes in laboratory values were judged to be clinically insignificant. In patients with mild-to-moderate liver dysfunction, clearance of this PPI, as with other members of the class, was markedly reduced and plasma levels were increased. Although caution is always warranted in patients with severe liver disease, drug accumulation is unlikely with rabeprazole 20 mg once daily, and dose adjustment does not appear to be indicated in patients with mild-to-moderate liver dysfunction.     

The association between rifamycin-SV (R-SV) related hyperbilirubinaemia and antipyrine clearance as a new test of liver function in cirrhosis

Abstract. Several clearance tests have been used to assess the residual hepatic efficiency in liver cirrhosis. However, the altered clearance values found in cirrhotic patients may reflect not only the impairment in liver function but also a derangement in the hepatic blood-flow. Therefore, this study was designed to explore the possibility that the competition between Rifamicyn-SV and bilirubin at the hepatic uptake site might be used as an index for quantitative assessment of residual hepatic efficiency in 48 patients with chronic liver disease. In this test, the interference of hepatic blood flow would be negligible. Antipiryne clearance was also evaluated in the same subjects in order to explore the cytoplasmic microsomial efficiency. Rifamicyn-SV intravenous load was followed by a sustained increase in bilirubinaemia which significantly related with the degree of liver function as assessed by the Chil-Pugh criteria. Also, antipiryne clearance was significantly altered in cirrhotic patients compared to controls. Moreover, a positive correlation was found between the Rifamicyn-SV test and Antipiryne clearance. We suggest that a combination of these tests might be of use in the quantitative assessment of liver function.     

Dynamical system analysis of Staphylococcus epidermidis bloodstream infection

Unlike many localized infections, the development and resolution of bacteremia involves physical and immunological interactions between many anatomic sites. In an effort to better understand these interactions, we developed a computational model of bacteremia as a dynamical system fashioned after multicompartmental pharmacodynamic models, incorporating bacterial proliferation and clearance in the blood, liver, spleen, and lungs, and the transport of pathogens between these sites. A system of four first-order homogeneous ODEs was developed. Blood and organ bacterial burdens were measured at various time points from 3 to 48 h postinoculation using an LD25 murine model of Staphylococcus epidermidis bacteremia. Using these empiric data, solutions to the mathematical model were recovered. A bootstrap resampling method was used to generate 95% confidence intervals around the solved parameters. The validity of the model was examined in parallel experiments using animals acutely immunocompromised with cyclophosphamide; the model captured abnormalities in bacterial partitioning previously described with this antineoplastic agent. Lastly, the approach was used to explore possible benefits to clinically observed hyperdynamic blood flow during sepsis: in simulation, normal mice, but not those treated with cyclophosphamide, enjoyed significantly more rapid bacterial clearance from the bloodstream under hyperdynamic conditions.     

肝移植围手术期血流动力学及血浆一氧化氮和内皮素含量的变化

目的探讨一氧化氮(NO)和内皮素(ET)对肝硬化患者肝移植围手术期体、肺循环的影响。方法24例终末期肝硬化患者接受改良背驮式肝移植术,术中持续监测心率(HR)、心排血量(CO)、平均动脉压(MABP)、平均肺动脉压(MPAP)、中心静脉压(CVP)、肺动脉楔压(PAWP)、心排血指数(CI)、体循环阻力指数(SVRI)和肺循环阻力指数(PVRI)。分别于麻醉后术前、无肝前10min、无肝30min、新肝30min和术毕5个时间点采集中心静脉血,用硝酸还原法和放射免疫法分别测定血浆NO和ET1水平。结果1MABP在下腔静脉和门静脉阻断及开放后短期内有一过性下降〔分别由(81±11)mmHg(1mmHg=0.133kPa)降至(79±9)mmHg,再降至(57±19)mmHg,P均<0.05〕,应用血管活性药物后,可基本维持稳定。2CVP、MPAP和PAWP在无肝期均显著降低(P均<0.05);而在新肝期显著增高并维持高于术前水平。3CI在无肝期显著降低(P<0.05),新肝10min后显著增高(P<0.05)。4SVRI和PVRI在无肝期均显著增高(P均<0.05);血管开放后新肝15min内SVRI和PVRI高于术前水平,新肝30min后SVRI显著低于术前水平。5与术前值比较:阻断后,血浆NO水平明显降低(P<0.05),新肝期和术毕均升高(P均<0.05);在无肝30min、新肝30min血浆ET1水平均升高(P均<0.05)。结论肝硬化患者肝移植围手术期血流动力学变化显著,新肝期易发生轻度肺高压。新肝期NO和ET增高,其临床意义有待进一步研究。     

Assessment of liver function by the aminopyrine breath test

The aminopyrine breath-test (ABT) has been proposed as a non-invasive quantitative test of liver function and reserve. To evaluate its usefulness, we compared the ABT with standard liver function tests, Child's classification of liver disease and ICG clearance, as means of assessing liver function in 30 patients with cirrhosis. The cumulative output of 14CO2 in breath during the 6 h following [14C]aminopyrine administration was significantly decreased in the cirrhotic group as compared with control subjects. The severity of liver dysfunction, as assessed by Child's classification, was associated with a progressive and statistically significant impairment of the ABT. There was a good correlation between the ABT and ICG systemic clearance (r = 0.770, P less than 0.001) and also between the ABT and ICG intrinsic clearance (r = 0.885, P less than 0.001), a measure which is independent of hepatic blood flow variations. These results further strengthen the concept that the ABT is a simple non-invasive method to assess quantitatively liver function and reserve, and could be useful in following the evolution of patients with liver disease.     

320排CT半自动法测量肝脏体积指数在肝硬化中的应用价值

目的 探讨320排CT半自动法测量肝脏体积(LV)指数在肝硬化中的应用价值。方法 使用320排螺旋CT半自动法测量肝硬化组20例和对照组20名的LV,并根据公式计算LV指数。绘制LV指数和LV测量值的ROC曲线,对肝硬化组的LV指数、LV测量值与肝功能血清学指标以及肝功能Child-Pugh评分分别进行相关分析。结果 肝硬化组的LV测量值为(997.31±293.37)cm³,LV指数为0.76±0.20;对照组的LV测量值为(1104.66±153.15)cm³,LV指数为0.88±0.11。LV测量值ROC曲线下的面积为0.68,LV指数ROC曲线下的面积为0.77。LV指数与肝功能Child-Pugh评分显著负相关(r=-0.54,P<0.05)。结论 LV指数能更好地反映肝硬化患者LV减小的程度,具有较高的敏感度和特异度,可用于辅助诊断肝硬化。     

Clinical characteristics and outcomes of pneumococcal bacteremia in adult patients with liver cirrhosis

Few studies have assessed the clinical characteristics and outcomes of invasive pneumococcal diseases in cirrhotic patients. We reviewed the medical records of adult cirrhotic patients with pneumococcal bacteremia from January 1997 to April 2006. During this time, 62 episodes of pneumococcal bacteremia occurred in 59 patients with liver cirrhosis, 45 (76.3%) of whom were classified as Child–Pugh grade C. The most common source of infection was spontaneous bacterial peritonitis (SBP) (45.8%), followed by primary bacteremia (40.7%) and pneumonia (10.1%). The 30-day mortality rate was 16.9%, with all fatalities in patients classified as Child–Pugh grade C. The median model for end-stage liver disease score of patients who died was significantly higher than that of survivors (26.5 versus 17.0, P = 0.001). Pneumococcal bacteremia in adult cirrhotic patients was more commonly associated with SBP than with pneumonia. Most cases of bacteremia and fatal outcomes occurred in patients with advanced cirrhosis.     

Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis

The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP in the femoral artery blood was significantly higher than in the group of patients with normal liver function (median 145 microg/l, 95% CI 98-195 versus 57 microg/l, 95% CI 42-92, p<0.001). A significant decrease in the concentration of PINP between the femoral artery (median 57 microg/l, 95% CI 42-92) and the hepatic vein (median 45 microg/l, 95% CI 40-70, p<0.001) was found in patients with normal liver function. In this group we also observed a significantly higher concentration of PINP in femoral artery blood (median 60 microg/l, 95% CI 45-87) as compared with that in renal vein (median 50 microg/l, 95% CI 40-65, p<0.001). In contrast, serum-PINP did not differ between arterial and hepatic or venous venous blood in patients with alcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney. It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired/reduced in patients with alcoholic cirrhosis.     

Early linezolid-associated lactic acidosis in a patient with Child's class C liver cirrhosis and end stage renal disease

Linezolid, an oxazolidinone antibiotic, does not required dose adjustment in patients with Child's class A and B liver cirrhosis. The dose adjustment data for Child's class C liver cirrhosis is inadequate. We reported a case of Child's class C liver cirrhosis, in which lactic acidosis, an adverse effect related to prolonged use, occurred only after two weeks of linezolid treatment. A 63-year old male had underlying diseases, such as end-stage renal disease (ESRD) and Child's class C liver cirrhosis, and was admitted for hepatic encephalopathy management and liver transplantation evaluation. Spontaneous bacterial peritonitis and septic shock occurred during admission. Because ascites culture revealed vancomycin-resistant Enterococci (VRE), daptomycin was initially prescribed. Subsequently, VRE bacteremia occurred, and infective endocarditis was confirmed. Following treatment failure with daptomycin use, intravenous linezolid (600 mg q12h) was added for synergic effect. VRE bacteremia quickly resolved following linezolid treatment, and vasopressor use was reduced. Despite stable hemodynamics, lactic acidosis still persisted, and linezolid therapeutic drug monitoring was ordered. High linezolid trough concentration (49 mg/L) was found by therapeutic drug monitoring, and linezolid-associated lactic acidosis was highly suspected. Therefore, linezolid treatment was stopped and patient's lactic acid level returned to normal after one week. VRE bacteremia recurred after discontinuation of linezolid; therefore, linezolid was re-prescribed at the lower dose (600 mg). Linezolid trough concentration was within the therapeutic range this time (6.1 mg/L), and lactic acidosis did not occur when linezolid dose was reduced. Therefore, empirically decreased dose and therapeutic drug monitoring should be considered in patients with Child's class C liver cirrhosis and ESRD.     

Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog.

We determined human and canine plasma clearance of atrial natriuretic factor (ANF) by lung, liver, and kidney from arteriovenous differences in plasma ANF and measured organ plasma flow. Human subjects had lower plasma ANF concentrations in the pulmonary vein or the pulmonary capillary wedge position when compared with the pulmonary artery, and both sites yielded pulmonary ANF extraction ratios of 24%. Canine lung ANF extraction was 19 +/- 3% and pulmonary ANF clearance was 328 +/- 78 ml/min per m2 vs. 357 +/- 53 ml/min per m2 in man. Hepatic plasma ANF clearance was 216 +/- 26 ml/min with an extraction ratio of 30 +/- 3% in humans and 199 +/- 89 ml/min and 36 +/- 6% in the dog. Renal plasma ANF clearance in human subjects was 78 +/- 12 ml/min per kidney and correlated well with each kidney's creatinine clearance (r = 0.58, P less than 0.05). The mean renal ANF extraction ratio was 35 +/- 4% in human subjects and 42 +/- 6% in the dog. These data quantitate the specific organ ANF clearances by lung, liver, and kidney in human subjects and in dogs and provide a rationale for elevated plasma ANF levels in cirrhosis, renal failure, and diseases accompanied by reduced perfusion of these organs. These findings support the conclusion that plasma ANF concentrations are dependent upon both the stimuli for ANF secretion as well as the specific organ clearances of ANF.     

肝硬化失代偿期患者病因及分级与小肠细菌过度生长的关系研究

目的研究肝硬化失代偿期患者肝硬化病因及肝硬化分级与小肠细菌过度生长的关系。方法选取2018年1月至2019年1月洪湖市中医医院收治的178例肝硬化失代偿期患者(Child-Pugh分级B级98例,C级80例)作为观察组,120例肝纤维化患者作为肝纤维化组,另选择同期50例体检健康者作为对照组。将观察组分为小肠细菌过度生长阳性组与阴性组。采用乳果糖氢呼气试验(LHBT)检测被研究者小肠细菌过度生长情况,分析肝硬化失代偿期患者肝硬化病因及肝硬化分级与小肠细菌过度生长的关系。结果观察组小肠细菌过度生长阳性率及LHBT集值均高于肝纤维化组,差异有统计学意义(P<0.05);肝纤维化组小肠细菌过度生长阳性率及LHBT集值均高于对照组,差异有统计学意义(P<0.05)。Child-Pugh分级C级肝硬化患者小肠细菌过度生长阳性率及LHBT集值均高于B级患者,差异有统计学意义(P<0.05)。K-M生存曲线结果显示,小肠细菌过度生长阳性组患者3年生存率为40.5%,小肠细菌过度生长阴性组患者3年生存率为79.8%,两组生存情况差异有统计意义(χ2=3.146,P=0.016)。受试者工作特征曲线分析结果显示,LHBT集值超过101 ppm时,其诊断肝硬化失代偿期的价值最高,曲线下面积为0.76(95%CI=0.704~0.826),诊断灵敏度、特异度分别为89.9%和65.8%。结论肝硬化失代偿期患者小肠细菌过度生长发生率高,且随着肝功能分级的升高,小肠细菌过度生长发生风险升高。小肠细菌过度生长可能促进肝硬化失代偿期病情发展。     

Clinico-statistical evaluation of the simultaneous clearance of sulfobromophthalein and galactose in chronic liver diseases

Sulfobromophthalein dye test and galactose tolerance test were performed, using both substances simultaneous i.v. injection, in 48 subjects with chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis (with and without ascites). As control group 10 normal subjects were tested. Sulfobromophthalein excretion constant ( K1BSF ) drawn from the first part of the retention curve, and the galactose excretion constant (K Gal) were considered. The following conclusions were obtained: a) K1 BSF and K Gal are well-correlated; b) K1 BSF appears more sensitive for a whole evaluation of liver involvement, in absence of evident jaundice (total serum bilirubin less than 6 mg/100 ml); c) K Gal is less reliable in presence of ascites because of the artificial increase in galactose plasmatic clearance provoked by the substance passage to the effusion fluid; d) the statistical analysis using discrimining function methods makes possible a better distinction among the various kinds of liver diseases; e) the same type of statistical analysis shows a difference between cirrhotics with ascites responding to medical therapy in comparison to treatment- resistent ascites. This fact may account for a different level of hepatic functional activity.     

Failure of hypoxic pulmonary vasoconstriction in patients with liver cirrhosis

The combination of arterial hypoxemia and low pulmonary vascular resistance in patients with liver cirrhosis is unexplained. Pulmonary microcirculatory dilation, but not gross arterio-venous shunts, has been the usual postmortem finding in patients with liver cirrhosis. When 10 patients with alcoholic liver cirrhosis breathed 10% oxygen in nitrogen, they failed to increase their pulmonary vascular resistance. However, four patients with functional murmurs, three patients with hyperkinetic heart syndrome, six patients with normal pulmonary artery pressures and intracardiac left to right shunts, and five patients with renal failure and anemia all increased their pulmonary vascular resistances when they breathed 10% oxygen in nitrogen. These findings suggested that in liver cirrhosis the normal regulating mechanism (hypoxic vasoconstriction) of the pulmonary circulation may be impaired, resulting in failure of the lung to match perfusion with ventilation.     

Sulfobromophthalein kinetics in normal subjects and patients with alcoholic cirrhosis (author's transl)

The AA. studied sulfobromophthalein kinetics in normal subjects and patients with alcoholic cirrhosis by compartmental analysis and by mathematical resolution of disappearance plasmatic curve of BSF. The comparison between the two methods gave some interesting clues for understanding BSF metabolism in alcoholic cirrhosis. From obtained data it seems that BSF clearance in these patients, besides on hepatic uptake, like normal subjects, largerly depends on intact secretory function of the liver.     

Effects of N-acetylcysteine on bacterial clearance

Abstract. The aim of this study was to investigate whether the oxygen radical scavenger N -acetylcysteine ( N -AC) impairs bacterial clearance, thus predisposing the host to increased risk of disease. Blood clearance of Escherichia coli and organ colonization were investigated in anaesthetized rabbits after pretreatment with N -AC (250 mg kg^-1 body weight, n = 16) and in sham-operated animals ( n = 12). To enable quantification of the clearance process, defined numbers of exogenous E. coli [1.3 times 108 colony-forming units (CFUs)] were injected intravenously. Parameters monitored were kinetics of bacterial elimination from the blood, and polymorphonuclear leucocyte (PMN) oxidative burst activity. Samples of liver, kidney, spleen and lung were collected for bacterial counts. Compared with controls, pretreatment with N -AC resulted in delayed bacterial elimination from blood and higher organ colonization with increased numbers of E. coli in liver, lung and kidney ( P < 0.05). N -AC treatment was associated with a suppressed PMN oxidative burst activity. Impaired bacterial clearance and enhanced organ colonization in N -AC-treated animals correlated with reduced oxidative burst activity, suggesting impaired granulocyte-dependent bacterial killing due to N -AC application.