The penetration of imipenem/cilastatin into ascitic fluid in patients with chronic liver disease.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
N Rolando
Publications and source records attributed to N Rolando.
Infectious sequelae after endoscopic sclerotherapy of oesophageal varices: role of antibiotic prophylaxis.
In order to determine the incidence of infection following sclerotherapy and the role of antimicrobial prophylaxis, a prospective randomized control study was performed comparing i.v. imipenem/cilastatin, with an infusion of dextrose-saline as a control group. One hundred patients with bleeding esophageal varices were included. All episodes of infection were documented during admission to the unit. Ninety-seven patients were evaluable. Post-sclerotherapy bacteremia developed in six (5.6%) of 107 sclerotherapy sessions in the control group and one (1.1%) of the 88 sclerotherapy sessions in the imipenem/cilastatin group (P < or = 0.1, NS): six of these seven post-sclerotherapy bacteremias occurred after emergency sclerotherapy. Infection within 7 days of the procedure was documented after 43 (22.1%) of the 195 sclerotherapy sessions, 18 (20.5%) in the imipenem/cilastatin group and 25 (23.4%) in the control group (P = NS). These infections were significantly more common after emergency sclerotherapy, 40 (34.8%) of 115 sessions, than after elective sclerotherapy, three (3.8%) of 80 sessions (P < or = 0.0001). A short prophylactic antibiotic regime does not reduce the risk of early bacteremia or the frequency of infection after sclerotherapy. The higher risk of infection after emergency sclerotherapy may be therefore related more to the gastrointestinal hemorrhage and its associated effects than to sclerotherapy.
Adolescent↗
Gangrene of the anterior abdominal wall after orthotopic liver transplantation: invasive cutaneous candidiasis.
Fungal infections following liver transplantation are not uncommon and may be life-threatening. Superficial candidal infections of the bronchus, oesophagus and urinary tract are the most common mode of presentation. Invasive cutaneous and subcutaneous candidiasis is, however, very rare. We report two patients with invasive cutaneous and subcutaneous candidiasis after orthotopic liver transplantation.
Abdominal Muscles↗
Prospective controlled trial of selective parenteral and enteral antimicrobial regimen in fulminant liver failure.
To compare the efficacy of a selective parenteral and enteral antimicrobial regimen in patients with fulminant liver failure, we classified 104 patients on reaching grade II encephalopathy as infected or non-infected. Patients who were infected were randomly assigned to receive IV cefuroxime (group 1) or selective parenteral and enteral antimicrobial regimen (group 2). Noninfected patients were randomly selected to receive either selective parenteral and enteral antimicrobial regimen (group 3) or no initial antimicrobials until clinically indicated (group 4). The four groups were comparable regarding age, sex, cause of disease, coma grade, international normalization ratio, presence of kidney failure and indicators of poor prognosis on admission to the study. Clinical parameters such as white cell count, temperature or changes in the chest radiograph, which were used to stratify patients into those infected or not, were not good predictors of infection because early infection rates were similar in the two groups. Three patients died within 24 hr and were excluded from the analysis. We found 42 microbiologically confirmed infections: group 1, 6 of 21; group 2, 8 of 21; group 3, 9 of 28; and group 4, 19 of 31. A reduction in infection was seen between groups 3 and 4 (p < 0.05). Patients receiving the selective parenteral and enteral antimicrobial regimen (groups 2 and 3) had fewer infections than the control group (group 4) (p < 0.005). Groups receiving early antimicrobial therapy (groups 1, 2 and 3) had a lower incidence of infection compared with group 4 (p < 0.0005). Overall, 55.5% survived, with no significant difference between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Pristinamycin for Enterococcus faecium resistant to vancomycin and gentamicin.
Explore the source record for details and available documents.
Child↗
An open, comparative trial of aztreonam with vancomycin and gentamicin with piperacillin in patients with fulminant hepatic failure.
Fifty patients admitted with fulminant hepatic failure and clinically suspected infection were allocated to receive either aztreonam and vancomycin or piperacillin and gentamicin as first line treatment. Fourteen patients died within 48 h of admission and were excluded from the analysis. Of the remaining 36 patients, 16 received aztreonam/vancomycin and 20 piperacillin/gentamicin. There were 18 episodes of infection in the aztreonam/vancomycin group and 24 in the piperacillin/gentamicin group (P = not significant). The most frequent bacterial pathogen was Staphylococcus aureus. Fungal infection developed in 13 patients (nine in the aztreonam/vancomycin group and four in the piperacillin/gentamicin group; P = not significant). Death attributed to infection occurred in 4 (25%) of 16 patients receiving aztreonam/vancomycin and 4 (20%) of 20 receiving piperacillin/gentamicin (P = not significant). Thirteen patients (three in the aztreonam/vancomycin group and ten in the piperacillin/gentamicin group) had clinical and microbiological improvement without addition or substitution of other antibiotics. No side-effects attributed to the study drugs were recorded.
Adolescent↗
Activation of the classical complement pathway in spontaneous bacterial peritonitis.
To investigate the possibility that low complement concentrations in the plasma and ascites of patients with severe liver disease could be secondary to complement consumption, complement activation was studied in 32 patients with severe liver disease, 11 of whom had spontaneous bacterial peritonitis (SBP). In patients with SBP, plasma C3 and C4 were significantly lower than in uninfected patients (mean values 0.74 v 1.13 g/l, p less than 0.01 and 0.20 v 0.28 g/l, p less than 0.05 respectively). Plasma complement activation via the classical pathway, as shown by C4d/C4, was significantly increased in patients with SBP compared with uninfected patients (37.3 v 22.2, p less than 0.01) as was C3d/C3 (14.0 v 8.11, p less than 0.01), but there was no significant difference in Ba/B between SBP and uninfected patients. Ascitic C3 concentrations were higher in patients without SBP than in infected patients (0.37 v 0.08 g/l, p less than 0.05), as were factor B values (0.11 v 0.03 g/l, p less than 0.05). There was no significant difference in ascitic C4 concentrations in patients with SBP compared with uninfected patients (0.03 v 0.07 g/l). Although consumption of C3, as shown by C3d/C3 in ascites, was increased in infected patients compared with uninfected patients (79.1 v 36.1, p less than 0.05), there was no difference in ascitic complement activation between the groups for either the classical or alternative pathways. In SBP, decreased plasma C3 and C4 are primarily caused by increased activation of the classical pathway and not impaired hepatic synthesis. Activation and consumption of C3 is one factor causing the low ascitic C3 concentrations observed in SBP.
Adult↗
Increased elastase-alpha 1-antitrypsin complex in fulminant hepatic failure: relationship to bacterial infection and activation of coagulation.
To study the effect of infection, a frequent complication of fulminant hepatic failure (FHF), on the release of elastase from polymorphonuclear leucocytes and its inhibition in circulation we have measured the concentrations of alpha 1-antitrypsin, which binds and inhibits elastase in the circulation, and of elastase-alpha 1-antitrypsin complex, in 30 patients with FHF. Elastase-alpha 1-antitrypsin complex was significantly increased in FHF as compared to controls (303 +/- 51 micrograms/l compared to 37 +/- 5 micrograms/l; n = 10; P less than 0.001) demonstrating activation of leucocytes in FHF. Infection caused greater release of leucocyte elastase, complex levels were significantly greater in patients who were infected when compared to those who were not (463 +/- 84 micrograms/l; n = 13 compared to 180 +/- 46 micrograms/l; n = 17; P less than 0.01). Also patients who survived had significantly lower complex levels than those who did not (212 +/- 49 micrograms/l; n = 18 compared to 440 +/- 94 micrograms/l; n = 12; P less than 0.02). alpha 1-Antitrypsin activity was not significantly different from control subjects (0.99 +/- 0.06 U/ml compared to 0.97 +/- 0.05 U/ml). However alpha 1-antitrypsin activity was significantly higher in patients who survived (1.17 +/- 0.05 U/ml; n = 18) compared to those who did not (0.71 +/- 0.03 U/ml; n = 12; P less than 0.001) and patients who died had significantly lower levels than control subjects (P less than 0.01) indicating the importance of maintenance of normal inhibitor levels in patients with FHF. The leucocyte activation and release of elastase in FHF was linked to activation of the coagulation system; elastase--alpha 1-antitrypsin complex levels correlated significantly with thrombin-antithrombin III complex levels (r = 0.68; P less than 0.001) and inversely with fibrinogen (r = -0.71; P less than 0.001).
Acetaminophen↗
Resistance of Enterococcus faecium to vancomycin and gentamicin.
Explore the source record for details and available documents.
Drug Resistance, Microbial↗
Fungal infection: a common, unrecognised complication of acute liver failure.
The true incidence and clinical relevance of fungal infection was ascertained in a prospective study of 50 consecutive patients with acute liver failure. Fungal infection was present in 16 (32%) patients (15 candida, one aspergillus) and in seven was considered the major cause of death. All six untreated died, while five of ten patients treated with anti-fungal therapy survived. The diagnosis was made on positive cultures from at least one significant site or on histological evidence of tissue invasion. All 16 had concomitant bacterial infection and shared features suggestive of a clinical syndrome: deterioration in coma grade after initial improvement; pyrexia unresponsive to antibiotics; established renal failure; and a markedly elevated white cell count. Fungal infection is a common, serious complication of acute liver failure and therapy is indicated for those with positive cultures. A prophylactic trial would be justified in those surviving 5 days, especially, with established renal failure.
Acute Disease↗
Prospective study of bacterial infection in acute liver failure: an analysis of fifty patients.
Fifty consecutive patients admitted with acute liver failure, minimal grade II encephalopathy, were studied prospectively to determine the incidence, timing and cause of bacterial infection, the relationship to clinical criteria for infection; and the influence of early microbiological diagnosis on clinical outcome. There were 53 proven bacterial infections in 40 patients, whereas in 5 of the remaining 10 patients infection was suspected on clinical grounds in the absence of significant cultures. Seven patients (14%) had more than one bacterial infection, and four patients had simultaneous infections caused by different organisms at each site. Fourteen infections (26.4%) were associated with bacteremia, and in six of these no source was found. Twenty-five infections (47.1%) arose from the respiratory tract, 12 (22.6%) from the urinary tract and 2 (3.7%) from central venous cannulas. Thirty-seven (69.8%) of the 53 infections were due to gram-positive bacteria; Staphylococcus aureus accounted for 19 (35.8%) of all the infections. Thirty patients died (60%), 28 of whom had bacterial infection at some time; in 24 of these the infection was diagnosed less than 24 hr before death. All nine deaths that occurred more than 7 days after admission were directly attributable to microbial infection. Clinical features such as elevated temperature and elevated peripheral white blood cell count were poor indicators of bacterial infection because these were absent in 30.2% of cases. These data show that there is a high incidence of bacterial infection early in the course of acute liver failure and suggest that prophylactic antimicrobial therapy, although unproven, might be justified.
Acute Disease↗
Tumour necrosis factor production in fulminant hepatic failure: relation to aetiology and superimposed microbial infection.
Tumour necrosis factor-alpha (TNF-alpha), a cytokine derived from macrophages, is considered to be an important endogenous mediator of endotoxic shock. Patients with fulminant hepatic failure are particularly susceptible to infection and the development of multi-organ failure and similarities to endotoxic shock suggest a possible pathogenetic role for TNF in fulminant hepatic failure. In vitro TNF production was therefore investigated serially in 21 consecutive patients with fulminant hepatic failure and in 21 healthy controls. Spontaneous and lipopolysaccharide-stimulated TNF production were elevated in viral-induced fulminant hepatic failure, compared with healthy controls (P less than 0.05 and P less than 0.01, respectively). By contrast, patients with paracetamol-induced fulminant hepatic failure had normal spontaneous and lipopolysaccharide-stimulated TNF production, while those who died had significantly reduced spontaneous TNF production compared with survivors (P less than 0.02); this difference was present throughout admission. In this group elevations in TNF production above baseline were associated with Gram-positive bacterial or fungal infection but not Gram-negative bacterial infection. There was no correlation between any of the clinical complications of fulminant microbial stimuli in fulminant hepatic failure, but do not support a direct role for TNF in the evolution of the clinical complications of fulminant hepatic failure.
Acetaminophen↗
Differential effect of ARA-AMP on serum DNA polymerase activity and serum HBV-DNA in chronic hepatitis B virus infection. A possible reason for lack of efficacy.
An uncontrolled pilot study of adenine arabinoside monophosphate intramuscularly (ARA-AMP) for 5 days at 10 mg/kg/day and 23 days at 5 mg/kg/day in divided doses, was conducted in 15 consecutive patients known to be HBeAg-positive for a minimum of 12 months. Two patients were lost to follow-up (1 having developed an hepatoma). Of the remaining 13, 11 remained HBeAg-positive at 1 year. During treatment, the median serum DNA polymerase (DNAp) activity fell from 592 cpm to 203 cpm/200 microliters. Of 12 patients initially positive for DNA polymerase, complete inhibition during treatment occurred in 6 and was permanent in 2, who developed anti-HBe. In the remaining 4 and in 6 further patients in whom inhibition was substantial but incomplete, DNAp activity rose to pretreatment levels within 1 month of completing treatment. All these patients remained DNAp + HBeAg-positive at one year. Serum HBV-DNA was measured in 7 patients, 6 who were initially DNAp-positive and 4 of whom had complete inhibition of DNAp during treatment. All 7 remained positive for HBV-DNA during treatment. Although side-effects were common there were no significant changes in biochemical or haematological parameters during or subsequent to therapy. Over the subsequent 48 months 2 more patients have developed an hepatoma and a further 5 have lost HBeAg; the 4 patients who remain alive and HBeAg-positive all had chronic persistent hepatitis initially.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A controlled trial of acyclovir in stable chronic HBsAg, HBeAg-positive carriers.
Histological remission is recognised to follow loss of viral replication in chronic hepatitis B virus infection. The aim of antiviral therapies has been to accelerate seroconversion from HBeAg to anti-HBe, but so far none has been shown to be of significant advantage in adequate, controlled trials and toxicity has been common. A randomised controlled trial of acyclovir, 45 mg/kg/day by continuous intravenous infusion for 28 days versus no therapy has been completed in 30 patients positive for HBsAg and HBeAg for a minimum of 6 months. Patients were stratified for sex, histology and homosexual activity. Twenty-eight days therapy was associated with only a modest reduction in serum markers of viral replication. At 12-months DNAp was lost in 5/15 treated and 2/11 of the untreated group, while of the latter, 2 patients initially negative became positive. Seroconversion from HBeAg to anti-HBe had occurred in 4 of 15 treated and 1 of 15 untreated patients (95% confidence limits 12% and 51%) and was associated with histological improvement. Acyclovir had only a weak effect on viral replication and did not significantly accelerate the rate of seroconversion to anti-HBe.
Acyclovir↗
A controlled trial of 6 months thrice weekly lymphoblastoid interferon versus no therapy in chronic hepatitis B virus infection. A preliminary analysis of the first 32 patients.
A controlled trial of lymphoblastoid interferon versus no therapy in patients positive for HBsAg, HBeAg and DNA polymerase activity with separate randomisation for sexual preference and histology is underway. Thirty two patients have been followed for a minimum period of 6 months of whom 15 have been randomised to receive interferon thrice weekly for 6 months after a 5-day induction phase. Five treated patients developed an hepatitis-like illness during the 3rd month of therapy concurrent with an abrupt and complete loss of DNA polymerase activity from serum. In 3 this was permanent and anti-HBe subsequently developed; 2 of these have also lost HBsAg. In the other 2 patients inhibition of viral replication was transient. In 5 further treated patients DNA polymerase activity was completely inhibited throughout treatment only to return as soon as interferon was withdrawn. In this group serum aminotransferase became normal during treatment. In the remaining 5 treated patients, inhibition of DNA polymerase activity was never complete and serum aminotransferases were unaffected. All the control patients remain seropositive for HBsAg, HBeAg and DNA polymerase activity. The low seroconversion rate in treated patients and the absence of seroconversion in the control group are probably a reflection of the exclusion of patients with marked elevation of serum aminotransferases. The occurrence of an hepatitis-like illness in the 3rd month of therapy in a third of the patients and the loss of HBsAg in 2 of 3 who eventually seroconverted are likely to be a consequence of therapy rather than spontaneous events.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Trials as Topic↗
Quantitation of hepatitis B virus DNA (HBV DNA) in serum using the spot hybridization technique and scintillation counting.
The simple spot hybridization technique to detect HBV DNA in serum was modified to concentrate Dane particles by pelleting. This minimised interference by serum components and allowed larger volumes of sera (up to 500 microliters) to be used in serial dilution on borderline positive samples and increased the efficiency of filtering through a "Hybri.Dot' system. Quantification of HBV DNA by 32P-scintillation Cerenkov counting based on serial standards of cloned HBV DNA processed through the "Hybri.dot' was easy to perform and the assay had good sensitivity (detection limit 2 pg, mode 6.25 pg), precision and accuracy. The pellet-simple spot quantitative assay proved more sensitive than those involving lengthier extraction procedures or direct application of serum to hybridization filters. Scintillation counting curves were linear over a wider range (0-800 pg HBV DNA) than optical densitometry measurements (0-50 pg) of autoradiographs. There was an excellent correlation with DNA polymerase activity (r = 0.948; P less than 0.001) but the assay proved more sensitive since HBV DNA (greater than 45 pg cloned equivalents) was detected in 4 out of 14 DNA polymerase negative sera and in 7 of 7 borderline (DNA polymerase cpm range 116-303) samples. This sensitive, quantitative HBV DNA assay should be of considerable value in studies on infectivity and effectiveness of antiviral therapies.
DNA, Viral↗