Decontamination of the digestive tract and oropharynx in ICU patients.

BACKGROUND: Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) are infection-prevention measures used in the treatment of some patients in intensive care, but reported effects on patient outcome are conflicting. METHODS: We evaluated the effectiveness of SDD and SOD in a crossover study using cluster randomization in 13 intensive care units (ICUs), all in The Netherlands. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible. In each ICU, three regimens (SDD, SOD, and standard care) were applied in random order over the course of 6 months. Mortality at day 28 was the primary end point. SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin, colistin, and amphotericin B in the oropharynx and stomach. SOD consisted of oropharyngeal application only of the same antibiotics. Monthly point-prevalence studies were performed to analyze antibiotic resistance. RESULTS: A total of 5939 patients were enrolled in the study, with 1990 assigned to standard care, 1904 to SOD, and 2045 to SDD; crude mortality in the groups at day 28 was 27.5%, 26.6%, and 26.9%, respectively. In a random-effects logistic-regression model with age, sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, intubation status, and medical specialty used as covariates, odds ratios for death at day 28 in the SOD and SDD groups, as compared with the standard-care group, were 0.86 (95% confidence interval [CI], 0.74 to 0.99) and 0.83 (95% CI, 0.72 to 0.97), respectively. CONCLUSIONS: In an ICU population in which the mortality rate associated with standard care was 27.5% at day 28, the rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9 percentage points with SOD. (Controlled Clinical Trials number, ISRCTN35176830.)

Detection of late pp67-mRNA by NASBA in peripheral blood for the diagnosis of human cytomegalovirus disease in AIDS patients.

OBJECTIVE: To evaluate the value of late-pp67-mRNA nucleic acid sequence-based amplification (NASBA) in comparison to DNA-PCR, blood culture and pp65-antigenemia assay for the detection of human cytomegalovirus (HCMV) disease in HIV-infected patients. METHODS: The results of pp67-mRNA NASBA, DNA-PCR, culture and pp65-antigenemia assay were compared in 402 whole blood specimens of 98 HIV-infected patients with a low CD4 lymphocyte count who had not yet received highly active antiretroviral therapy (HAART). Thirty-seven samples were obtained from 30 patients with a diagnosis of HCMV disease and 365 samples from 68 patients without HCMV disease. RESULTS: The highest agreement of test results was observed between pp67-mRNA NASBA and quantitative pp65-antigenemia, with a threshold of nine antigen-positive cells/10(5) leukocytes (kappa-value 0.70, 95% CI=0.58-0.82). The sensitivity of pp67-mRNA NASBA for the diagnosis of HCMV disease (59.3%) was identical to that of the quantitative pp65-antigenemia assay, higher than that of the blood culture (48.2%) but lower than that of the DNA-PCR (77.8%). Pp67-mRNA NASBA (92.3%), quantitative pp65-antigenemia assay (92.3%) and blood culture (93.9%) were highly specific for the diagnosis of HCMV disease and as a result, had a higher positive predictive value (76.2, 76.2 and 76.5%, respectively) than the qualitative DNA-PCR (58.3%) and the qualitative pp65-antigenemia assay (47.6%). CONCLUSION: pp67-mRNA NASBA, an easy and rapid to perform assay, well-standardised by virtue of co-amplified internal system control RNA, provides a high specificity and positive predictive value for the diagnosis of HCMV disease in HIV-infected patients, comparable to that of the quantitative pp65-antigenemia assay and blood culture.

Value of different assays for detection of human cytomegalovirus (HCMV) in predicting the development of HCMV disease in human immunodeficiency virus-infected patients.

In the present prospective study, five blood tests for detection of human cytomegalovirus (HCMV), nucleic acid sequence-based amplification (NASBA) for detection of early (immediate-early antigen) and late (pp67) mRNA, PCR for detection of HCMV DNA (DNA PCR), culture, and pp65 antigenemia assay, and culture and DNA PCR of urine and throat swab specimens were compared for their abilities to predict the development of disease caused by HCMV (HCMV disease). Of 101 human immunodeficiency virus (HIV)-infected patients with

Quantitative pp65-antigenemia assay for the prediction of human cytomegalovirus disease in HIV-infected patients.

OBJECTIVE: To evaluate the ability of a quantified pp65-antigenemia assay to predict the development of human cytomegalovirus (HCMV) disease in patients with an advanced HIV infection. DESIGN: A prospective longitudinal study between March 1993 and December 1996. Blood samples for the pp65-antigenemia assay were drawn at 2-3 month intervals. SETTING: AIDS department of an institutional tertiary care centre. PATIENTS: A total of 101 HIV-infected patients with CD4 lymphocyte counts of 100/mm3 or less were enrolled. Ninety-seven patients were eligible for analysis. All patients gave informed consent. MAIN OUTCOME MEASURES: The development of HCMV disease. RESULTS: Of the 97 patients, 24 developed HCMV disease after a median follow-up of 10.6 months. Three months before the development of HCMV disease, an increase in the median number of pp65-antigen-positive leukocytes was observed. The highest combination of sensitivity (45%) and specificity (94%) for the development of HCMV disease within the next 3 months was found when an assay cut-off level of 48/10(5) pp65-antigen-positive leukocytes was applied, with a positive predictive value (PPV) for the development of HCMV disease of 75%. The Kaplan-Meier estimate of HCMV disease-free survival after patients reached 48/10(5) or more antigen-positive leukocytes on longitudinal follow-up was a median 3.7 months [95% confidence interval (CI), 2.5-8.5]. The hazard ratio (HR) of this threshold level for the development of HCMV disease was 9.6 (95% CI, 4.2-21.8). CONCLUSION: Longitudinal follow-up using the pp65-antigenemia assay of HIV-infected patients with a low CD4 lymphocyte count improves the identification of patients who will develop HCMV disease in the foreseeable future, and should be considered for the selection of patients who may benefit from pre-emptive HCMV treatment.

Prevention of Yersinia enterocolitica growth in red-blood-cell concentrates.

In response to concern about Yersinia enterocolitica contamination of blood products, we have studied the effects on Y enterocolitica growth of holding whole blood at 22 degrees C for 20 h and then removing leucocytes. Thirty pools of three bags of blood were inoculated with Y enterocolitica (2 x 10(1)-3 x 10(4) colony-forming units/ml). One bag in each pool was processed to red-blood-cell concentrate after 6 h at 4 degrees C (RBC); the other two were held at 22 degrees C for 20 h before processing to buffy-coat-depleted RBC (BCd-RBC). One of these bags was then depleted of leucocytes by filtration (Ld-RBC). All bags were stored at 4 degrees C for 5 weeks. RBC bags showed Y enterocolitica growth after the shortest storage times, followed by BCd-RBC then Ld-RBC (p less than 0.03-0.001). We recommend that whole blood should be held at 22 degrees C to make use of inherent bactericidal activity; leucocytes should then be removed.

[Epidemiological surveillance of antibiotic resistance in a general hospital for the assessment of 'blind' antibiotics policy]. / Epidemiologische surveillance van antibioticumresistentie in een algemeen ziekenhuis ter beoordeling van 'blind' antibioticumbeleid.

A study was made of the epidemiology of gentamicin-resistant Gram-negative rods in a large general hospital over the last 12 years, and of the consequences of the presence of these bacteria for antibiotics policies, especially the use of gentamicin. Resistant bacteria were endemic at a low level: of the clinical isolates, 670 from 488 patients contained resistant bacteria, 2% of all Gram-negative rod isolates. Sporadically there were minor epidemics. Especially seriously ill, elderly patients became infected. Every year multiresistant bacteria contributed to a number of deaths. The choice of gentamicin as a drug of first, blind, choice in life-threatening infections remained justified. Continuous monitoring of Gram-negative rods is an important instrument for a preventive policy.

Endotoxins in portal blood.

Endotoxemia may complicate diseases of the bowel and liver, and is associated with the occurrence of renal failure, coagulation disorders and death. The bowel contains a large quantity of endotoxins. According to the classical hypothesis, endotoxins continuously transmigrate through the bowel mucosa, thereby entering the portal circulation. However, previous studies on portal endotoxemia were contradictory. We studied the presence of endotoxins in the portal vein in 21 consecutive patients with no diseases of the liver or the bowel, using a sensitive chromogenic endotoxin assay. In only two patients was low level portal endotoxemia detected after cross-clamping of the aorta, and subsequent reperfusion. We conclude that the normal bowel mucosa is an efficient barrier for endotoxins. Therefore, intestinal endotoxemia complicating liver disease is likely to result from enhanced permeability of the bowel mucosa.

Endotoxaemia: an early predictor of septicaemia in febrile patients.

In 473 consecutive febrile patients a sensitive and rapid chromogenic limulus assay was used to assess the value of endotoxaemia versus bacteraemia for predicting development of the syndrome of septicaemia. In each patient three blood specimens for culture and endotoxin testing were obtained at the onset of fever. Blood pressure, urinary output, and the occurrence of thrombocytopenia and metabolic acidosis were recorded prospectively during three days of follow-up. Septicaemia developed in 19 patients (4%). The sensitivity, specificity, and likelihood ratio for a positive result with the endotoxin assay were 79%, 96%, and 20, respectively. The corresponding indices for bacteraemia were 89%, 78%, and only 4. The results suggest that endotoxaemia is a clinically valid indicator for impending gram-negative septicaemia (positive predictive value 48%) and that the absence of endotoxaemia virtually rules out the risk that septicaemia will ensue (negative predictive value 99%).

Comparison of reliability of tests to distinguish upper from lower urinary tract infection.

The results of scintiphotography with gallium-67 (67Ga), renography with technetium-99m diethylene triamine penta-acetic acid, immunofluorescence of antibody coated bacteria, and determination of renal beta 2 microglobulin excretion were compared in 19 patients with upper and 15 patients with lower urinary tract infection. All patients with acute pyelonephritis showed an appreciable unilateral or bilateral uptake of 67Ga and an increased excretion of beta 2 microglobulin, whereas immunofluorescence of antibody coated bacteria yielded positive results in only 10. In patients with lower urinary tract infections excretion of beta 2 microglobulin and uptake of 67Ga were always normal, whereas immunofluorescence of antibody coated bacteria was positive in three cases. Scintiphotography with 67Ga and determination of renal beta 2 microglobulin excretion are currently the most reliable non-invasive methods of detecting acute pyelonephritis.

Transformation and T antigen induction by linearized BK virus DNA.

Linearized unit length DNA obtained after cleavage of the supercoiled DNA of the human papovavirus BKV by PstI (.031) induced transformation and T antigen less efficiently than DNA cleaved by EcoRI (0.0), BamHI (0.98), KpnI (0.90) or HhaI (0.73). BKV DNA cleaved by XbaI (0.27 and 0.95) did not induce T antigen.

Isolation of a variant of BK virus with altered restriction endonuclease pattern.

A papovavirus was isolated from the urine of a 24 year old female who underwent bone marrow transplantation after a relapse of acute myeloid leukemia. The virus (JL) resembles BK virus in its antigenic and growth properties, but has a different restriction endonuclease pattern after digestion with the restriction endonucleases Eco R1 and R Hind II + III.