Culture of dialysis fluids on nutrient-rich media for short periods at elevated temperatures underestimate microbial contamination.

Recommended culture methods for monitoring bacterial contamination of H2O, dialysate and bicarbonate concentrate in dialysis centers in the USA involves culturing these fluids for 48 h at 37 degrees C. A variety of media and commercial culture methods are accepted for monitoring these fluids. Over a 3-month a comparison was made between an acceptable culture method, tryptic soy agar (TSA) employing the pour plate (PP) technique at 37 degrees C for 48 h, and PP cultures on standard methods agar (SMA) and R2A agar, incubated at ambient temperature (23 degrees C) for 48, 72, 168 h. Increases in the colony counts over time occurred for all three fluids. However, counts wee greater on SMA and R2A than on TSA. The increases over the standard 48-hour TSA cultures ranged as high as 10(4) times for 23 degrees C cultures at 7 days of incubation. Endotoxin levels even in the most contaminated samples were found to be below the acceptable 5 EU/ml recommended for reprocessor water. Bacterial colonies that appeared at 48, 72 and 168 h were isolated and identified. Pseudomonas, Moraxella, Acinetobacter and CDC group VI C-2 were among some of the common bacteria isolated. This study indicates that the media utilized, the time and temperature of incubation may result in a significant underestimation of the bacterial population of water and dialysis fluids, thus potentially placing the patient at a higher risk.

Bacteriology of hemodialysis fluids: are current methodologies meaningful?

Reports of increasing endotoxic reactions in dialysis centers using high-flux dialyzers and high contamination in liquid bicarbonate concentrates have resulted in concern for the microbial contamination of dialysate. The influence of salt-supplemented media on the recovery of bacterial contaminants from the fluids used in hemodialysis has been examined. This study found a negative influence of a 2% NaCl supplementation of growth media for both purified water and dialysate. Salt-supplemented pour plate cultures of bicarbonate concentrate samples were not statistically different from nonsupplemented cultures (p = 0.2). The influence of the bicarbonate salt on recovery in the pour plates was not addressed. The different media recommended for monitoring microbial contamination of dialysis fluids were compared. As previously reported, both water and dialysate collected from a relatively large geographic area showed higher recoveries on Reasoner's R2A agar than on media recommended by the Association for Advancement of Medical Instrumentation (AAMI) standards (p < 0.0001). Standard methods agar (SMA) and trypticase soy agar (TSA) produced the next highest recovery for water and dialysate, respectively. The higher recoveries generally observed on R2A or SMA suggest that to provide better patient safety these media should be selected for monitoring bacterial contamination of water, and R2A, SMA, or TSA for dialysate. The variability in the species identified across the three fluids and variability in counts observed in the different fluids suggest that significant dialysate contamination may occur from sources other than the water and bicarbonate concentrates.

Microbial and endotoxin contamination in water and dialysate in the central United States.

The purified water supplies and randomly selected dialysates of 51 chronic and acute dialysis centers in the central United States were surveyed to assess the relative risks to dialysis patients from microbial and endotoxin contamination. A culture medium more sensitive than those generally employed in routine quality assurance assays was used for recovery of bacteria from water. With this medium, 35.3% of the water samples and 19% of the dialysate samples were out of compliance with the Association for the Advancement of Medical Instrumentation (AAMI) standards: 200 and 2,000 colony forming units (CFU)/ml, respectively. There was no correlation observed between the type of water purification system or the frequency of disinfection of the system and the bacterial and endotoxin contamination levels. There was also no correlation found between the bacterial and fungal CFU per ml and the endotoxin concentration per ml (EU/ml). It is recommended that more sensitive culturing methods be used to provide adequate bacterial monitoring of dialysate center water supplies. Dialysis centers should monitor endotoxin in dialysate on a regular schedule and immediately after any endotoxemic-like patient reactions. Yeast and fungi were observed in 10% and 64% of the water systems, respectively. Dialysate was contaminated by yeast and fungi in 30% and 70% of the centers, respectively. The concentrations of these microbes in both fluids were much lower than bacteria. However, they were observed often enough to warrant further investigation of their impact on the well-being of dialysis patients.

Endotoxin and bacterial contamination of dialysis center water and dialysate; a cross sectional survey.

The bacterial and endotoxin levels of purified water and effluent dialysate were examined in a cross section of dialysis centers in the central United States. All samples were collected within a four-hour drive of the University of Louisville and were collected, processed and analyzed by our personnel, to eliminate variability in sample handling. A medium capable of higher bacteria recovery from aqueous environments than those ordinarily employed in clinical assays was used. Endotoxins were determined by a quantitative colorimetric assay. By the more sensitive bacterial assay 53% of the centers had bacterial counts above the AAMI standard of 200 colony-forming units per ml (CFU/ml) for water and 35% of the centers had bacterial counts above the 2000 CFU/ml standard for dialysate in at least one sampling period. The samples showed 35% and 19% of water and dialysate above the standards, respectively. While there are no standards for endotoxin concentrations in water used to prepare dialysate, 2% of the centers had endotoxin levels in their water above five endotoxin units per ml (5 EU/ml = 1 ng/ml in our assay kit), the limit set by the AAMI standards for reprocessor water. Both bacterial and endotoxin levels tended to be elevated in dialysate, with the highest levels of endotoxin in dialysates posing an obvious potential risk when high-flux dialyzers are used.

Dialysate contamination and back filtration may limit the use of high-flux dialysis membranes.

Endotoxins, or fragments thereof, can reach the blood stream of dialysis patients, transported by diffusion and connection across the intact high-flux membrane. This transfer depends upon the phenomenon of back filtration. Back filtration generally occurs under conventional high-flux dialysis conditions with membranes having an ultrafiltration coefficient in blood (UF-C) above 20 ml/hr/m2/mmHg. The clinical consequences of back filtration vary from center to center depending primarily on the quality of dialysate. We therefore surveyed the bacterial and endotoxin levels of purified water and effluent dialysate in a cross section of dialysis centers in the central United States. Using a high recovery medium, we found that 53% of the centers had bacterial counts above the Association for the Advancement of Medical Instruments standard in water (20% cfu/ml) and 35% above the standard in dialysate (2,100 cfu/ml). Endotoxin concentrations higher than 5.0 EU/ml in both water and dialysate were found in 4% and 11.8% of the centers, respectively. Since high-flux membranes are believed to be of benefit for long-term dialysis patients, manufacturers will have to offer dialysate preparation systems with additional safety features. The proper membrane design will be a key to the success of such systems.

Bacterial contamination of hemodialysis center water and dialysate: are current assays adequate?

Many dialysis centers depend on clinical laboratories or a commercially available dip culture to determine the contamination levels in water and dialysate. To determine whether these standard clinical culture procedures adequately quantitate bacterial contamination in hemodialysis center water and dialysate, test results of two routine clinical media was compared, trypticase soy agar (TSA) and plate count agar (PCA), with those of nutrient-poor R2A medium. Dialysate samples demonstrated significant differences in media, the temperature of incubation, and plating techniques (pour plate versus spread plates). Purified water for dialysis demonstrated significant differences only for media; however, temperature was an important variable. Selective growth on R2A agar of some water- and dialysate-contaminating species was studied by velvet disk and loop transfer of colonies. A strong selectivity for water-borne bacteria was demonstrated by R2A agar; the bacteria that did not grow on TSA and PCA have been identified.

Forecasting coronary heart disease incidence, mortality, and cost: the Coronary Heart Disease Policy Model.

A computer simulation model was developed to project the future mortality, morbidity, and cost of coronary heart disease (CHD) in the United States population. The model contains a demographic-epidemiologic (DE) submodel, which stimulates the distribution of coronary risk factors and the conditional incidence of CHD in a demographically evolving population; a "bridge" submodel, which determines the outcome of the initial CHD event; and a disease history (DH) submodel, which simulates subsequent events in persons with a previous CHD event. The user of the model may simulate the effects of interventions, either preventive (i.e., risk factor modification) or therapeutic, upon mortality, morbidity, and cost for up to a 30-year period. If there were no future changes in risk factors or the efficacy of therapies after 1980, baseline projections indicate that the aging of the population, and especially the maturation of the post-World War II baby-boom generation, would increase CHD prevalence and annual incidence, mortality, and costs by about 40-50 per cent by the year 2010. Unprecedented reductions in risk factors would be required to offset these demographic effects on the absolute incidence of CHD. The specific forecasts could be inaccurate, however, as a consequence of erroneous assumptions or misestimated baseline data, and the model awaits validation based on actual future data.

Case-mix, severity systems provide DRG alternatives.

Since their adoption, diagnosis related groups (DRGs) have been criticized for relying too much on the principal discharge diagnosis, for not taking the secondary diagnoses into account, and for ignoring the severity of a patient's illness or illnesses. Four case-mix and severity systems, Disease Staging, Patient Management Categories, MedisGroups, and Computerized Severity of Illness, offer alternatives to DRGs by either classifying patients into diagnostic categories or producing overall case severity scores. While most hospitals are likely to continue using DRGs or whatever successor is prescribed by regulation, some may find it useful to look seriously at these alternatives as a means of measuring the consumption of healthcare resources.

Cholesterol reduction and life expectancy. A model incorporating multiple risk factors.

In deciding whether to undertake a dietary program to reduce serum cholesterol levels, a person must consider how much benefit to expect. We developed a model that assumes cholesterol reduction is effective and safe in reducing the risk for death from ischemic heart disease. In the model, we considered asymptomatic adults with total serum cholesterol levels between 180 and 300 mg/dL. We defined risk status on the basis of blood pressure, smoking habit, and high-density-lipoprotein cholesterol level. For persons aged 20 to 60 years who are at low risk, we calculate a gain in life expectancy of 3 days to 3 months from a lifelong program of cholesterol reduction. For persons who are at high risk, the calculated gain ranges from 18 days to 12 months. Knowledge of the magnitude of the calculated benefits in increased life expectancy afforded by cholesterol reduction can assist persons in making decisions about dietary change.

The prediction of streptococcal pharyngitis in adults.

The usefulness of clinical and laboratory findings for prediction of the presence of Group A streptococci on throat culture and of an increase in antistreptococcal antibodies was investigated in 693 adult patients. Several findings were shown to increase the likelihood of streptococcal isolation, alone and in combination: tonsillar exudate, tonsillar enlargement, tender anterior cervical adenopathy, myalgias, and a positive throat culture in the preceding year. Compared with a frequency of 9.7% in all patients, the probabilities of a positive culture were quite different (ranging from 2 to 53%) in subgroups of patients with different combinations of these clinical findings. The results of a leukocyte count and measurement of C-reactive protein added little additional predictive information. While clinical findings can never predict perfectly the results of a throat culture, they nevertheless can provide useful information--particularly in tending to "rule out" streptococcal infection--in adult patients with pharyngitis.

Yield of routine annual laboratory screening in the institutionalized elderly.

We examined the yield of a battery of 19 screening laboratory tests performed routinely in 70 functionally intact patients, averaging 82.6 years of age and residing at a chronic care facility. The 70 patients underwent 3,903 screening tests (70 admission batteries and 156 batteries at annual intervals). Twenty per cent of the admission test results and 17 per cent of all subsequent annual test results were "abnormal". "New abnormal" results (previously unknown to the responsible physicians) occurred primarily in five of the 19 screening tests; they were found in 13 per cent of all admission screening tests and in 6 per cent of all annual tests. However, many of the "new abnormalities" were only minimally outside the normal range, and only 26 (0.7 per cent) led to further diagnostic evaluation. Of these 26, only four (0.1 per cent of all tests ordered) led to changes in patient management, none of which benefited the patient in an important way.

Topical v systemic agent treatment for papulopustular acne. A cost-effectiveness analysis.

We used cost-effectiveness analysis to compare the costs, risks, and benefits of two strategies for clearing papulopustular acne; topical therapy alone as initial therapy or a combination of systemic antibiotics and topical agents used at the first visit. Patients treated with combination therapy had fewer weeks of morbidity from acne, and lower dollar costs but have a greater risk of side effects. If the topical therapy alone was chosen to reduce the risk of side effects in a population of patients there would be an additional $764 in costs and 238 weeks of morbidity from acne to avert a single additional instance of side effects. Initial treatment of papulopustular acne with combined oral antibiotics and topical agents thus seems to be cost-effective. After clearing is achieved, maintenance therapy with topical agents should be considered.

Serologic evidence of chlamydial and mycoplasmal pharyngitis in adults.

In a study of 763 adult patients we found serologic evidence of infection (a fourfold increase in antibodies) with Chlamydia trachomatis in 20.5 percent of the patients and with Mycoplasma pneumoniae in 10.6 percent, but with group A streptococcus (by culture) in only 9.1 percent. Pharyngitis, the most common problem for which patients seek medical care in the United States, may be caused by nonviral, potentially treatable organisms more often than had been suspected.

LAMP. A data management and analysis system for patient registries and clinical studies.

A computer system for the management and analysis of clinical data is described. The system is implemented in the ANSI standard MUMPS language and runs on popular minicomputers. The system is designed to allow clinical investigators or research assistants to define a data base, enter and edit data, produce patient-specific reports, and perform a variety of analyses on user-specified groups of subjects. Programmer intervention is not required at any stage of the management or analysis process, and on-line documentation provides a friendly environment for inexperienced users.

Heterophil antibody in adults with sore throat: frequency and clinical presentation.

We studied the prevalence and the clinical and laboratory findings of infectious mononucleosis in ambulatory adult patients with the presenting symptom of sore throat. Extensive clinical data, heterophil antibody test, and differential leukocyte count were obtained prospectively for 709 patients, aged 16 to 73 years, seen in four primary care settings. Heterophil tests were positive in 15 of 709 patients (2%); four of the 15 had greater than 10% atypical lymphocytes. No heterophil-negative patient had greater than 10% atypical lymphocytes. Heterophil-positive patients had mild disease; none was older than 40 years. Of 70 symptoms and signs evaluated, four were found significantly more often (p less than 0.005 for each) in the heterophil-positive patients: palatine petechiae, posterior auricular adenopathy, marked axillary adenopathy, and inguinal adenopathy. If any of these four easily shown physical findings was present, the likelihood of the patient having heterophil antibody was considerably increased; if absent, the probability of infectious mononucleosis was so low that not ordering a heterophil test or differential leukocyte count would have been efficient and safe.

Diagnosis and treatment of dyspepsia. A cost-effectiveness analysis.

Dyspepsia is a common problem in ambulatory care. While many authorities recommend ordering upper gastrointestinal x-ray series (UGI) before therapy, there is evidence that clinicians frequently treat dyspepsia without diagnostic procedures. Decision analysis was performed to select optimal management based on probabilities and outcome values from the published literature. The choices evaluated were Symptomatic Therapy (low dose antacids or anticholinergics), Ulcer Therapy (high dose antacids or cimetidine), or UGI followed by further tests or therapy. Our model indicates that mortality is minimized if UGI is performed prior to selection of therapy, and if endoscopy is performed when the x ray shows gastric ulcer. Weeks of pain are minimized if Ulcer Therapy is begun immediately, but direct health care costs are minimized by beginning with Symptomatic Therapy. The marginal cost per additional life saved by performing a UGI rather than beginning with Ulcer Therapy was +1.6 million to +2.3 million, depending on whether endoscopy followed the finding of gastric ulcer. Mortality advantages of the strategies beginning with UGI were sensitive to assumptions regarding the incidence of gastric cancer and the benefits of early diagnosis. With slight reductions in these base case values, the Ulcer Therapy strategy appeared to minimize all outcomes except dollar cost.