Higher Incidence Of Bacterial Infections Research Articles

Combined liver-kidney transplantation in patients with cirrhosis and chronic kidney disease

The outcome of patients with cirrhosis and chronic kidney disease treated with combined liver-kidney transplantation (CLKT) is not well known because most series of patients treated with CLKT include not only patients with cirrhosis but also patients with inherited diseases without cirrhosis. To evaluate to what extent the combined kidney transplantation impairs posttransplantation outcome compared to liver transplantation (LT) alone, the outcome of patients with cirrhosis and chronic kidney disease treated with CLKT (n = 20) was compared to that of a group of patients with cirrhosis without chronic kidney disease treated with LT alone matched by age, sex, year of transplantation and severity of cirrhosis (n = 60). The primary end point of the study was survival, and secondary end points were outcome of renal function and complications within 6 months of transplantation. Patients with CLKT had a higher incidence of bacterial infections and transfusion requirements compared to LT patients. The incidence of acute renal failure during the first 6 months was similar, yet the severity of renal failure was greater in patients with CLKT. Hospital and intensive care unit (ICU) stays were longer in the CLKT group. One- and three-year survival probabilities in patients treated with CLKT were 80 and 75% compared to 97 and 88%, respectively, in patients treated with LT. In conclusion, CLKT for patients with cirrhosis and chronic kidney disease is associated with a relatively high frequency of postoperative complications that moderately impairs short-term survival. However, 3-year survival of patients with cirrhosis treated with CLKT is excellent.

Analysis of antibiotics treatment in 86 cases of liver transplant recipients

To analyze the characteristic of bacterial infections, and the relationship between antibiotics treatment and bacterial infections after liver transplantation, and to prevent antibiotic-resistant bacterial infections. 86 liver transplant recipients were retrospected. Different indexes including limited daily dose, the frequency of medication, drug use index were used to evaluate the rationality of the use of antibiotics, three-dimensional test was used to explore extended-spectrum beta-lactamase and AmpC enzyme of Gram-negative bacteria. The major pathogens of infection after liver transplantation were Enterococcus faecalis, Enterobacter cloacae, fungi and E. coli. Pre-operative antibiotic utilization rate was 83.7%, it was mainly a single use of antibiotics; After- operative antibiotic usage was 100.0%, it was mainly joint use of two or three antibiotics; The top 3 antibiotics used were cephalosporins, the combined enzyme inhibitors and penicillin. Antibiotics with drug utilization index (DUI) more than 1.1 included ampicillin and Lalin proxy. 43.3% and 31.8% of Gram -Negative bacteria produced ESBLs and AmpC, respectively, while 21.3% Gram -Negative bacteria produced two enzymes. There is high incidence of bacterial infections after liver transplantation. The use of antibiotics is high dose, high-frequency and reasonable; High resistance of bacterial infections was prone to develop and the prevention of the high resistance of bacterial infections is very important.

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

The precise effects of CD34+ cell dose on the outcome of allogeneic transplantation for aplastic anaemia (AA) are not known. Previous studies have used the total mononuclear cell count to quantify stem cell dose. We evaluated the effects of CD34+ cell dose on the clinical and haematological end points of transplantation. The transplant variables and outcome parameters on 46 patients with acquired AA were assessed by comparing low vs high CD34+ cell doses. Infusion of less than 2 x 10(6)/kg of CD34+ cells was associated with an increased incidence of graft failures (P=0.03), higher incidence of bacterial infections (P=0.006) and a delay in the engraftment of neutrophils (P=0.046). The latter was found to be an effect of stem cell source (non-PBSC) rather than the CD34+ count. Other parameters, such as plt engraftment (P=0.63), red cell (P=0.94) and plt (P=0.31) transfusion independence, chimerism, acute and chronic GVHD (P=1.0) and OS (P=0.57), were not significantly influenced by the CD34+ cell dose. These findings are different to the published studies on the relevance of CD34+ cell dose in allogeneic transplantation for haematological cancers.

Antiviral therapy increases the risk of bacterial infections in HCV-infected cirrhotic patients awaiting liver transplantation: A retrospective study

Recurrence of hepatitis C after liver transplantation (LT) is universal and may cause premature graft loss. We evaluated the efficacy and safety of antiviral therapy in HCV-infected patients with decompensated cirrhosis awaiting LT. Fifty-one patients underwent treatment with peginterferon-alfa-2a and ribavirin. A control group of 51 untreated individuals awaiting LT were matched by age, Child-Pugh and MELD scores and time on the waiting list. Case and control patients were comparable for all relevant variables. Fifteen treated patients (29%) had undetectable HCV-RNA at the time of transplantation and 10 (20%) achieved SVR. Early virological response and non-1 genotype were the strongest predictors of viral clearance. There was a higher incidence of bacterial infections in treated patients vs controls, particularly in Child-Pugh B-C individuals (17 vs 3 episodes) (log-rank=0.0016). Importantly, the incidence of spontaneous bacterial peritonitis (SBP) in patients who were not receiving norfloxacin prophylaxis (n=83) was significantly higher in the treated group than in controls (log-rank=0.01). Our data demonstrate that antiviral treatment prevents hepatitis C recurrence in 20% of HCV-infected patients. However, treatment should be recommended with caution in individuals with poor liver function who do not receive norfloxacin prophylaxis for SBP, since it increases the risk of bacterial infections.

A Prospective Study on Incidence of Bacterial Infections in Portuguese Dialysis Units

Background: Viral infection has been the main epidemiologic concern in the hemodialysis unit; however, bacterial infection is responsible for more than 30% of all causes of morbidity and mortality in our patients, vascular access infection being the culprit in 73% of all bacteremias. Methods: A prospective multicenter cohort study of bacterial infections incidence, conducted from January to July 2004 in five hemodialysis units, to record and track bacterial infections, using a validated database from CDC’s Dialysis Surveillance Network Program. Results: 4,501 patient-months (P-M) were surveilled, being dialyzed through a native fistula (AVF) in 60.6%, a graft (PTFE) in 31.3%, a tunneled catheter (TC) in 7.6%, and a transient catheter (C) in 0.5%. As target events, we registered 166 hospitalizations – 3.7/100 P-M (2.2/100 P-M in patients with AVF, 4 in PTFE, 9.9 in TC, and 19 in C), and 182 intravenous antibiotic courses. Of these 182 antibiotic treatments, 47.8% included vancomycin, only 30% had blood cultures drawn pretreatment, and only 36% were positive. We recorded 98 infections at the vascular access site 2.18/100 P-M (0.95 in AVF, 1.6 in PTFE, 12.6 in TC, and 42.85 in C) and 2.13 infections/100 P-M at other sites. The isolated microorganisms were Staphylococcus epidermidis in 40.1%, Staphylococcus aureus in 30.1%, Pseudomonas in 13.3%, and Escherichia coli in 3.3%. Although we found a diversity of practice patterns, the number of target events (8.4/100 P-M) and the bacterial infections incidence (4.31/100 P-M) were remarkably homogeneous in the five centers. Conclusion: (1) High incidence of bacterial infections, causing major morbidity; (2) infectious risk is vascular access type-dependent, with dramatic rise in catheters; (3) underutilization of blood cultures to orient diagnosis and therapy, and (4) high rates of vancomycin prescription.

Phenotypical characterization of changes in thymus and spleen associated with lymphoid depletion in free-ranging harbor porpoises ( Phocoena phocoena)

Harbor porpoises from the North and Baltic Seas exhibit a higher incidence of bacterial infections compared to whales from less polluted arctic waters. Furthermore, thymic atrophy and splenic depletion, associated with elevated concentrations of environmental contaminants, such as polychlorinated biphenyls (PCB) and polybrominated diphenyl ether (PBDE) body burdens, have been found in wildlife harbor porpoises. Thus, there is currently a debate about the potential adverse effect of xenobiotics on the immune system and therefore on the health status of this and other marine mammal species. The aim of the present study was to characterize phenotypical changes in lymphoid organs of harbor porpoises and their possible association with increased disease susceptibility due to an impaired immune response in this marine mammal species. Therefore, 29 by-caught and stranded harbor porpoises were necropsied and the health status was evaluated based upon the severity of main pathological findings. In addition, the distribution of CD2-, CD3ɛ-, and CD45R-positive cells as well as B lymphocytes, MHC class II-expressing and antigen-presenting cells was determined in the thymus and spleen using immunohistochemistry. Thymic atrophy and splenic depletion were associated with an impaired health status in investigated whales. Phenotypical changes in atrophic thymuses were characterized by a depletion of immature cortical thymocytes and medullary B cells. Furthermore, findings in depleted spleens were consistent with a loss of peripheral T lymphocytes in the periarteriolar lymphoid sheath (PALS). Based upon the results, an altered thymopoiesis and impaired cellular immune function cannot be excluded in whales with evidence of lymphoid depletion.

Increased blood interleukin-10 mRNA levels in diseased free-ranging harbor porpoises ( Phocoena phocoena)

Harbor porpoises from the North and Baltic Seas exhibit a higher incidence of bacterial infections compared to whales from less polluted arctic waters. Toxicological analysis revealed an association between elevated body burdens of environmental contaminants, such as polychlorinated biphenyls (PCB) and polybrominated diphenyl ether (PBDE) and lymphoid depletion in thymus and spleen of these whales. However, it remains undetermined if changes in the immune system are primarily contaminant-induced or a sequel of infectious diseases and emaciation. The aim of the present study was to investigate changes of blood cytokine mRNA levels in healthy and diseased harbor porpoises. Therefore, 29 by-caught and stranded whales were necropsied and the health status was evaluated based upon main pathological findings. Furthermore, the degree of thymic atrophy and splenic depletion was histologically graded using a semi-quantitative scoring system. Gene expression of interleukin (IL)-2, IL-4, IL-6, IL-10, transforming growth factor-β and tumor necrosis factor-α in the blood was measured by real time reverse transcription-polymerase chain reaction. Thymic atrophy and splenic depletion were correlated with an impairment of the animals’ health status. Additionally, a marked up-regulation of IL-10 was predominately found in severely diseased whales with evidence of chronic bacterial infections. Furthermore, increased IL-10 levels were associated with splenic depletion. Other investigated cytokines were not significantly associated with the health status or lymphoid depletion, respectively. The present study indicated that lymphoid depletion represents a sequel of chronic infectious diseases in a portion of investigated harbor porpoises. Regarding this, expression of anti-inflammatory cytokines, such as IL-10 might represent a consequence of continuous stimulation of the immune system and induction of immunomodulatory mechanisms in this cetacean species.

Induction of polymorphonuclear leukocyte response by human cytomegalovirus

Neutrophils are important in the defense against bacterial infections, by ingesting and killing invading microorganisms. Because of the higher incidence of bacterial infections in patients with active human cytomegalovirus (HCMV) infections, we hypothesized that HCMV-infected neutrophils were inefficient in eliminating the bacteria. Therefore, we mock infected or infected neutrophils with HCMV by contact with HCMV-infected human pulmonary artery endothelial cells. We found that HCMV infection without N-formyl-methionyl-leucyl-phenylalanine (fMLP) stimulation increased the surface expression of CD11b to the same extent as fMLP stimulation of mock infected cells. Also, HCMV-infected neutrophils became more efficient in phagocytosing serum opsonized yeast particles than mock infected cells. Furthermore, we observed an increase in intracellular free calcium and chemiluminescence in HCMV-infected cells, in response to fMLP compared to fMLP-treated mock cells. We also found that apoptosis was significantly inhibited in HCMV-infected neutrophils. In conclusion, our results suggest that neutrophils become more effective in performing their effector functions when infected with HCMV. Thus, the higher incidence of bacterial infections in HCMV patients might not be due directly to a dysfunction in the neutrophils. Instead, the fact that apoptosis is inhibited may cause over-reactive neutrophils to remain in the tissues, where they will start leaking their contents, damaging the tissues and contributing to inflammatory processes.

Snm1-Deficient Mice Exhibit Accelerated Tumorigenesis and Susceptibility to Infection

The eukaryotic SNM1 gene family has been implicated in a number of cellular pathways, including repair of DNA interstrand cross-links, involvement in VDJ recombination, repair of DNA double-strand breaks, and participation in cell cycle checkpoint pathways. In particular, mammalian SNM1 has been shown to be required in a mitotic checkpoint that causes arrest of cells in prophase prior to chromosome condensation in response to spindle poisons. Here, we report on the phenotype of a knockout of Snm1 in the mouse. Snm1-/- mice are viable and fertile but exhibit a complex phenotype. Both homozygous and heterozygous mice show a decline in survival compared to wild-type littermates. In homozygous mutant males, this reduction in survival is principally due to bacterial infections in the preputial and mandibular glands and to a lesser extent to tumorigenesis, while in homozygous and heterozygous females, it is due almost solely to tumorigenesis. The high incidence of bacterial infections in the homozygous mutant males suggests an immune dysfunction; however, examinations of T- and B-cell development and immunoglobulin class switching did not reveal a defect in these pathways. Crossing of Snm1 mutant mice with a Trp53 null mutant resulted in an increase in mortality and a restriction of the tumor type to lymphomas, particularly those of the thymus. Taken together, these findings demonstrate that Snm1 is a tumor suppressor in mice that in addition has a role in immunity.

Investigations of the Potential Influence of Environmental Contaminants on the Thymus and Spleen of Harbor Porpoises (Phocoena phocoena)

Harbor porpoises from the German North and Baltic Seas exhibit a higher incidence of bacterial infections compared to whales from less polluted arctic waters. The potential adverse effect of environmental contaminants such as polychlorinated biphenyls (PCBs) and heavy metals on the immune system and the health status of marine mammals is still discussed controversially. The aim of the present study was to investigate the possible influence of PCB, polybrominated diphenyl ether (PBDE), toxaphene, (p,p'-dichlorodiphenyl)trichlorethane (DDT), and (p,p'-dichlorodiphenyl)dichlorethene (DDE) on the immune system of harbor porpoises. Lymphoid organs are influenced by a variety of factors, and therefore special emphasis was given to separating the confounding effect of age, health status, nutritional state, geographical location, and sex from the effect of contaminant levels upon thymus and spleen. Contaminant analysis and detailed pathological examinations were conducted on 61 by-caught and stranded whales from the North and Baltic Seas and Icelandic and Norwegian waters. Stranded harbor porpoises were more severely diseased than by-caught animals. Thymic atrophy and splenic depletion were significantly correlated to increased PCB and PBDE levels. However, lymphoid depletion was also associated with emaciation and an impaired health status. The present report supports the hypothesis of a contaminant-induced immunosuppression, possibly contributing to disease susceptibility in harbor porpoises. However, further studies are needed to determine if lymphoid depletion is primarily contaminant-induced or secondary to disease and emaciation in this cetacean species.

Association between combined properdin and mannose-binding lectin deficiency and infection with Neisseria meningitidis

Background Individuals genetically deficient of properdin are more susceptible to meningococcal disease. Likewise low concentration or decreased biological activity of mannose-binding lectin (MBL) is associated with higher incidence of bacterial infections during childhood. In this study we report our findings in a Danish family with a remarkably high incidence of meningococcal meningitis—in total four cases, one of them fatal. Methods Properdin and MBL were quantified by ELISA and the properdin gene was screened for sequence variations using denaturing high-performance liquid chromatography (DHPLC) and subsequent sequencing of abnormal patterns. The MBL gene was genotyped for the three known variant alleles ( B, C and D) as well as three promoter polymorphisms (−221 Y/ X, −550 H/ L and +4 P/ Q). Results Two out of six males with undetectable properdin activity had meningitis. They had also low MBL serum levels or carried an MBL variant allele, whereas high MBL concentrations were measured in three out of four properdin deficient males—without meningitis. A splice site mutation in exon 10 (c.1487-2A > G) was found in the properdin gene and co segregated with biochemically measured properdin deficiency. Conclusion Our results indicate that a combined deficiency of both properdin and MBL increases the risk of infection with Neisseria meningitidis and stress the importance of epistatic genetic interactions in disease susceptibility.

Bacterial infections in patients requiring admission for an acute exacerbation of COPD; a 1-year prospective study

Study objective: To investigate the frequency of respiratory bacterial infections in hospitalized patients, admitted with an acute exacerbation of chronic obstructive pulmonary disease (COPD), to identify the responsible pathogens by sputum culture and to assess patient characteristics in relation to sputum culture results. Methods: We prospectively evaluated clinical data and sputum culture results of 171 patients, admitted to the pulmonology department of the University Hospital Maastricht with an acute exacerbation of COPD from 1st January 1999 until 31st December 1999. Results: Eighty-five patients (50%) had positive sputum cultures, indicating the presence of bacterial infection. Pathogens most frequently isolated were: Haemophilus influenzae (45%), Streptococcus pneumoniae (27%), and Pseudomonas aeruginosa (15%). Patients with more severely compromised lung function had a higher incidence of bacterial infections (P=0.026). There were no significant differences in age, lung function parameters, blood gas results and length of hospital stay between patients with and without bacterial infection. There were no correlations between the type of bacteria isolated and clinical characteristics. Conclusion: Incidence of bacterial infection during acute exacerbations of COPD is about 50%. Patients with and without bacterial infection are not different in clinical characteristics or in outcome parameters. Patients with lower FEV1 have a higher incidence of bacterial infections, but there is no difference in the type of bacterial infection. In the future, the pathogenic role of bacterial infection in exacerbations of COPD should be further investigated, especially the role of bacterial infection in relation to local and systemic inflammation.

Current aspects of antibiotic prophylaxis for upper gastrointestinal bleeding in cirrhosis patients.

Bacterial infection is a common complication in cirrhotic patients. The portal hypertension as well as the immune depression observed in these patients can explain this high incidence of bacterial infection. Because of the high probability of cirrhotic patients to develop infections, antibiotic prophylaxis is warranted in some conditions, such as upper gastrointestinal bleeding or after spontaneous bacterial peritonitis. Nevertheless, antibiotic prophylaxis is not widely recommended for cirrhotic patients.

Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome.

Cirrhotic patients show increased susceptibility to bacterial infections. It is not known whether tuftsin deficiency, which is associated with an increased incidence of infections in many disease states, is present in cirrhosis. Our aims were to determine whether tuftsin activity is deficient in cirrhosis and if so, whether this deficiency is related to splenic function, contributes to altered neutrophil granulocyte function, or influences the occurrence of bacterial infections and patient survival. Tuftsin activity and splenic function were assessed in 31 patients with liver cirrhosis and 31 healthy subjects. The phagocytic activity of neutrophil granulocytes from 23 patients was tested in vitro with addition of both autologous and pooled sera from healthy subjects. In 10 patients and eight controls it was also tested with addition of synthetic tuftsin. Patients were followed up until death or liver transplantation. Patients had reduced tuftsin activity (median 8% (range 3-24.5)) compared with controls (17% (11.5-37)) (p<0.001) and a higher pitted red cell count (p<0.001). Tuftsin activity was correlated with pitted cell count (p=0.02) and the Child-Pugh score (p=0.002). Nineteen of 23 patients showed deficient phagocytic activity of neutrophil granulocytes, which was correlated with tuftsin activity (p<0.001), improved in all cases but one with addition of serum from healthy subjects, and normalised with addition of synthetic tuftsin. Reduced tuftsin activity did not influence patient survival but was associated with a higher incidence of bacterial infections (p=0.029). Tuftsin activity was reduced in cirrhosis, and contributed to impaired phagocytic activity of neutrophil granulocytes. Such an abnormality appears to be related to impaired splenic function and severity of cirrhosis, and probably favours the occurrence of bacterial infections.

Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure.

Defects in superoxide and hydrogen peroxide production may be implicated in the high incidence of bacterial infections in patients with acute liver failure (ALF). In the present study, oxygen radical production in patients with ALF due to paracetamol overdose was compared with that of healthy volunteers. Neutrophils from 14 ALF patients were stimulated via the complement receptors using zymosan opsonized with ALF or control serum. Superoxide and hydrogen peroxide production by ALF neutrophils stimulated with zymosan opsonized with ALF serum was significantly reduced compared with the control subjects (P < 0.01). This defect persisted when zymosan opsonized by control serum was used (P < 0.05). Superoxide and hydrogen peroxide production in neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) from a further 18 ALF patients was unaffected compared with control neutrophils. Serum C3 complement levels were significantly reduced in ALF patients compared with control subjects (P < 0.0005). These results demonstrate a neutrophil defect in ALF due to paracetamol overdose, that is complement dependent but independent of serum complement, possibly connected to the complement receptor.

Infectious complications during neutropenia subsequent to peripheral blood stem cell transplantation.

Type, severity and incidence of infection during the neutropenic period after peripheral blood stem cell transplantation (PBSCT) for treatment of malignant disease were studied in 66 patients treated at a single institution. Data of 34 female and 32 male patients with a median age of 43 years suffering from leukemia (12), lymphoma (35), multiple myeloma (six) or solid tumors (13) were retrospectively analyzed. All patients had received at least 2.5 x 10(6) CD34-positive cells for stem cell rescue after high-dose chemotherapy. Ninety-four percent of the patients experienced at least one febrile episode during their post-transplant course. The patients recovered quickly and defervesced after a median of 4 days. The incidence of bacteremia was 39% and gram-positive cocci were the predominant pathogens. In contrast, severe organ infections were rare. Only 5% of the patients suffered from lung infiltrates. No invasive fungal infections were observed. No transplant-related deaths occurred in the 66 patients studied. We conclude that the severe, but shortlasting neutropenia after peripheral blood stem cell transplantation is associated with a high incidence of bacterial infection. The severity of the majority of these infections is moderate. With appropriate anti-infective therapies these infections can be managed and life-threatening infectious complications, in particular fungal infections, are rare. Empirical anti-infective regimens specifically designed for this clinical situation should be explored.

Immunotoxicity of PCBs (Aroclors) in relation to Great Lakes.

Polychlorinated biphenyls (PCBs) are among the most widespread environmental pollutants and a prominent contaminant of the Great Lakes basin. Due to their resistance to biodegradation and lipophilic properties, PCBs bioaccumulate in fish tissues and in fish-eating humans. PCBs are also known to cross the placenta and to be excreted into the mother's milk, thus predisposing the infant to potentially adverse health effects. For example, a higher incidence of bacterial infections was reported for breast-fed infants born to mothers who consumed large amounts of Great Lakes fish compared to the incidence in control infants whose mothers ingested low amounts of fish. While data regarding the PCB-induced immunotoxic effects in humans are scarce, data derived from the use of experimental animals, including nonhuman primates, indicate that the immune system is a potential target for the immunotoxic effects of PCBs. Such studies have used the commercially available PCB mixtures alone. However, PCBs have the potential of partially antagonizing the effects of other structurally related compounds including the highly toxic dioxins, which are also present in small amounts in the Great Lakes. Thus, to fully evaluate the magnitude of the immunotoxic risk PCBs pose to humans, consideration should be given to investigations in which the interactive effects of PCBs are combined with other contaminants present in the Great Lakes.

Totally implanted catheters to reduce catheter-related infections in patients receiving interleukin-2: a 2-year experience

A high incidence of bacterial infections has been previously reported during interleukin-2 (IL-2) treatment, mainly due to catheter-related infections. Antibiotic prophylaxis has been successfully used to decrease such infections. The goal of this study was to evaluate an alternative way to reduce catheter-related infections in IL-2-treated patients by the use of totally implanted catheters. A total of 74 patients with metastatic renal cell carcinoma, referred to our institution to receive IL-2 from March 1989 to July 1991, were included in this prospective study. IL-2 was given on a 2-days-a-week schedule (24 x 10(6) IU m-2 day-1) either alone (41 patients) or in association with interferon gamma (33 patients). All these patients were prospectively evaluated for fever, bacteremia and line-site infection. Seven patients (9.5%) had one (2 patients) or more (5 patients) positive blood cultures with Staphylococcus aureus. Antibiotics were used only in 5 patients, and the catheter had to be removed in only 2 of these patients. In the other patients, no further infection developed despite the lack of antibiotics. Moreover, 9 patients had positive blood cultures with Staphylococcus epidermidis (1.9% of total number of blood cultures). In conclusion, a totally implanted catheter appears to reduce the incidence of infections in IL-2-treated patients, at least on a 2-days-a-week schedule.

Macrophage function in cirrhosis and the risk of bacterial infection.

Background. Bacterial infection is a frequent and often fatal complication in patients with cirrhosis. Macro-phages play an important part in the host defense against infection because their Fcγ receptors recognize antibody-coated bacteria. Methods. We prospectively studied macrophage Fcγ-receptor function in vivo and in vitro in 49 patients with alcoholic cirrhosis, 10 alcoholics without cirrhosis, and 20 normal volunteers. Results. The clearance of IgG-sensitized autologous red cells was decreased in 37 of the 49 patients with cirrhosis but in none of the subjects without cirrhosis. In the 49 patients clearance was inhibited by a mean (±SE) of 47 ± 3 percent at 1 hour and 53 ± 3 percent at 1 1/2 hours, as compared with the clearance in the normal controls (P &lt; 0.001). The impairment of macrophage Fcγ-receptor-dependent clearance correlated with the degree of liver insufficiency but not with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The clearance of unsensitized and heat-altered autologous erythrocytes was normal. In vitro recognition of IgG-sensitized red cells by monocytes from the patients was not significantly decreased. During a two-year follow-up period, 11 patients had severe bacterial infections, and in 4 they were fatal. The mean clearance of IgG-sensitized red cells in these 11 patients (half-time, 126.2 ± 22 hours) was significantly impaired, as compared with that in the 38 patients without severe infection (half-time, 32.2 ± 18 hours, P &lt; 0.001). Conclusions. The function of macrophage Fcγ receptors is impaired in patients with alcoholic cirrhosis, and this impairment probably contributes to the high incidence of bacterial infections among such patients. (N Engl J Med 1994;331:1122-1128.)

Impaired Function of Macrophage Fcγ Receptors and Bacterial Infection in Alcoholic Cirrhosis

Bacterial infection is a frequent and often fatal complication in patients with cirrhosis. Macrophages play an important part in the host defense against infection because their Fc gamma receptors recognize antibody-coated bacteria. We prospectively studied macrophage Fc gamma-receptor function in vivo and in vitro in 49 patients with alcoholic cirrhosis, 10 alcoholics without cirrhosis, and 20 normal volunteers. The clearance of IgG-sensitized autologous red cells was decreased in 37 of the 49 patients with cirrhosis but in none of the subjects without cirrhosis. In the 49 patients clearance was inhibited by a mean (+/- SE) of 47 +/- 3 percent at 1 hour and 53 +/- 3 percent at 1 1/2 hours, as compared with the clearance in the normal controls (P < 0.001). The impairment of macrophage Fc gamma-receptor-dependent clearance correlated with the degree of liver insufficiency but not with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The clearance of unsensitized and heat-altered autologous erythrocytes was normal. In vitro recognition of IgG-sensitized red cells by monocytes from the patients was not significantly decreased. During a two-year follow-up period, 11 patients had severe bacterial infections, and in 4 they were fatal. The mean clearance of IgG-sensitized red cells in these 11 patients (half-time, 126.2 +/- 22 hours) was significantly impaired, as compared with that in the 38 patients without severe infection (half-time, 32.2 +/- 18 hours, P < 0.001). The function of macrophage Fc gamma receptors is impaired in patients with alcoholic cirrhosis, and this impairment probably contributes to the high incidence of bacterial infections among such patients.