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Background: Although they are effective in outpatient settings, computerized reminders have not been proved to increase preventive care in inpatient settings., Methods: We conducted a randomized, controlled trial to determine the effects of computerized reminders on the rates at which four preventive therapies were ordered for inpatients. During an 18-month study period, a computerized system processed on-line information for all 6371 patients admitted to a general-medicine service (for a total of 10,065 hospitalizations), generating preventive care reminders as appropriate. Physicians who were in the intervention group viewed these reminders when they were using a computerized order-entry system for inpatients., Results: The reminder system identified 3416 patients (53.6 percent) as eligible for preventive measures that had not been ordered by the admitting physician. For patients with at least one indication, computerized reminders resulted in higher adjusted ordering rates for pneumococcal vaccination (35.8 percent of the patients in the intervention group vs. 0.8 percent of those in the control group, P<0.001), influenza vaccination (51.4 percent vs. 1.0 percent, P< 0.001), prophylactic heparin (32.2 percent vs. 18.9 percent, P<0.001), and prophylactic aspirin at discharge (36.4 percent vs. 27.6 percent, P<0.001)., Conclusions: A majority of hospitalized patients in this study were eligible for preventive measures, and computerized reminders significantly increased the rate of delivery of such therapies.

Relatively simple objective criteria are now available to predict which patients are at risk for bad outcomes from community-acquired pneumonia. In general, these include older patients and those with certain coexisting illnesses (especially neoplastic disease) or findings of altered mental status, hypotension, severe tachycardia, tachypnea, fever, acidemia, azotemia, hypoxemia, hyperglycemia, anemia, or hyponatremia. The major causes of severe pneumonia are S pneumoniae, H influenzae, and L pneumophila. Less common causes include mixed aerobic and anaerobic mouth flora, as well as M pneumoniae, C pneumoniae, gram-negative bacilli, and S aureus. Specific diagnosis is hampered by a lack of reliable diagnostic tests, but Gram's stain of expectorated sputum and cultures of sputum and blood may occasionally be helpful. Many empirical treatment regimens have been recommended, including those of the American Thoracic Society and the Infectious Diseases Society of America, which are reviewed here. It is hoped that better diagnostic tools will permit future targeting of microbes with narrow-spectrum therapy to diminish the risk of selection of resistant strains with empirical regimens.

We report a multicentric, open trial of intravenous followed by oral ofloxacin, 400 mg every 12 h, as therapy for 100 cases of nosocomial pneumonia and community-acquired pneumonia requiring hospitalization. The typical subject was 57 yr old, and underlying diseases, such as chronic obstructive pulmonary diseases (COPD), diabetes mellitus, and congestive heart failure, were common. For 10 subjects previous therapy had failed. There were 118 pathogens isolated in blood or sputum; S. pneumoniae was the most common (42), followed by H. influenzae (13), Klebsiella spp. (11), and S. aureus (10). Ofloxacin was administered for an average of 5.7 days intravenously followed by 6.9 days orally. Response to therapy was judged to be cure in 71 subjects, improvement in 24, and failure in 5. Among the more seriously ill subjects, ofloxacin therapy was successful for four of five immunocompromised subjects, for 12 of 12 subjects with nosocomial pneumonia, three of whom were on the ventilator, and for nine of 10 subjects with community-acquired pneumonia and bacteremia, including seven of eight cases due to S. pneumoniae. Univariate risk factor analysis revealed underlying COPD and/or tachypnea upon admission to be associated with failure of ofloxacin therapy, with bacteremia suggestive of failure. Conversely, ofloxacin was equally effective in cases in whom previous therapy failed and in cases of nosocomial pneumonia, multilobar pneumonia, and/or pneumonia due to S. pneumoniae. Results for P. aeruginosa were inconclusive. Intravenous followed by oral ofloxacin was highly effective in many difficult cases of pneumonia.

The purpose of this study was to evaluate the L-CLONE Legionella pneumophila Serogroup 1 Urine Antigen Latex Test (Access Medical Systems, Inc., Branford, Conn.) for detection of Legionella antigen in urine. A total of 481 frozen urine samples previously tested by an in-house solid-phase radioimmunoassay (RIA) was thawed and retested by using L-CLONE. Included in this sample were 140 RIA-positive samples from culture-positive or serologically confirmed cases of legionellosis and 341 RIA-negative samples from patients with non-Legionella respiratory disease or bacteriuria. The original RIA test result was accepted as the true value. L-CLONE correctly identified 76 of 140 (54%) known positive samples. False-negative results could not be attributed to a low Legionella antigen concentration or to a Legionella antigen subgroup. L-CLONE correctly identified 252 of 341 (74%) known negative samples. False-positive results were experienced in all groups of negative samples, regardless of the patients' underlying diseases. A total of 141 fresh urine samples was tested; all were Legionella antigen negative by RIA. L-CLONE provided 86% specificity. The sensitivity of the L-CLONE in testing fresh urine samples could not be evaluated because of the lack of Legionella antigen RIA-positive samples.

Objective: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis., Design: Double-blind, randomized, placebo-controlled trial., Setting: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals., Patients: Hospitalized adults with signs of gram-negative infection and a systemic septic response., Intervention: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later., Main Outcome Measures: Mortality over the 30-day study period, resolution of organ failures, and safety., Results: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified., Conclusions: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.

A patient accidentally received approximately 3 g of ofloxacin intravenously. She experienced only moderately severe central nervous system symptoms, which resolved within 9 h. The peak serum ofloxacin level was 39.3 micrograms/ml, approximately seven times the usual peak level. Ofloxacin may possess a considerable safety margin in humans.

Legionella pneumophila postoperative pneumonia may be an important cause of morbidity and mortality in selected surgical patients. This report presents five postoperative neurosurgical patients in whom the diagnosis of Legionnaires' disease was made. Their clinical course and treatment are presented. Clinical manifestations, methods of diagnosis, and treatment of L. pneumophila pneumonia are discussed. It is pointed out that neurosurgical patients who have received high doses of corticosteroids and who develop nosocomial postoperative pneumonias should be suspected of having Legionnaires' disease.

Alpha- or beta-acetylglucosamine are major antigen determinants of ribitol teichoic acids of the cell walls of coagulase-positive staphylococci. Teichoic acid antibodies have been detected by quantitative immunoprecipitation methods, agar-gel diffusion, counterimmunoelectrophoresis, crossed immunoelectrophoresis, radioimmunoassay and enzyme-linked immunosorbent assay. Almost all adults have detectable antibodies if a sufficiently sensitive method is used. Elevated concentrations of teichoic acid antibodies result from a recent staphylococcal disease such as endocarditis, bacteremia with metastatic foci of abscesses in which drainage and/or antibiotic therapy is delayed, but increases in teichoic acid antibodies are infrequent in transient staphylococcal bacteremia such as from infected intravascular cannulae or abscesses in patients who are treated early. Detection of high concentrations of teichoic acid antibodies may allow a specific bacteriological diagnosis earlier than cultures, when cultures are negative as in partially treated endocarditis, and when cultures are difficult to obtain or evaluate such as deep seated abscesses, drainage from osteomyelitis or pneumonias. In addition, elevated concentrations of teichoic acid antibodies in patients with staphylococcal bacteremia are strong presumptive evidence for endocarditis, metastatic foci, or abscesses.

An enzyme linked immunosorbent assay was developed to detect urinary antigen excreted by patients with Legionnaires' disease. Of 47 patients tested, antigen was detected in 39. Antigen was not detected in any of 178 urine specimens from patients with other pulmonary, bacteremic, or urinary tract infections after performance of a quick and simple confirmatory test. The assay required more time to perform than a previously described radioimmunoassay but was of equivalent sensitivity and specificity and did not require expensive equipment of contact with radioactive reagents. We conclude that enzyme linked immunosorbent assay is a rapid, sensitive, and specific means for rapidly diagnosing Legionnaires' disease which can be performed in clinical laboratories unwilling or unable to use radioisotopes.

We describe a simple and rapid method to dissociate antigen-antibody complexes to allow antigen detection by radioimmunoassay. Immunoglobulins and immune complexes were precipitated from serum in 50%-saturated ammonium sulfate. The precipitate was dissolved in distilled water and heated at 90 degrees C for 15 min to free the antigen and denature the antibody irreversibly. With this treatment, the sensitivity for detecting staphylococcal antigen added to human serum improved greater than or equal to 16-fold and was similar to the sensitivity in buffer. After intravenous injection of antigen into a rabbit with high levels of staphylococcal antibodies, antigen was detected only after thermodissociation. Also, in 4 of 26 patients with Staphylococcus aureus bacteremia, circulating antigen was detected after thermodissociation. Thermodissociation of immune complexes is a simple, rapid method and should be useful for detecting other heat-stable antigens.

Staphylococcal bacteremia occurs frequently in patients undergoing long-term hemodialysis (dialysis patients). Although such bacteremia is frequently uncomplicated, it may be associated with endocarditis, metastatic infection or suppuration at the access site requiring excision of the access device for control of the infection (complicated bacteremia). To distinguish patients with uncomplicated bacteremia from those with complications, we measured staphylococcal teichoic acid antibodies by agar-gel diffusion and immunoglobulin G (IgG) antibodies by radioimmunoassay in 18 patients with staphylococcal bacteremia undergoing long-term hemodialysis. Although teichoic acid antibodies were not detected in five patients with uncomplicated bacteremia, they were observed in only three of 13 patients with complicated bacteremia. IgG staphylococcal antibodies were present in 10 of 13 patients with complicated bacteremia compared to none of five patients with uncomplicated bacteremia compared to none of five patients with uncomplicated bacteremia (p less than 0.05). Thus, radioimmunoassay was spuerior to agar-gel diffusion in identifying dialysis patients with complicated bacteremia. In patients with increased concentrations of IgG staphylococcal antibodies by radioimmunoassay, the diagnosis of endocarditis, metastatic infection and suppuration at the access site should be considered. Prolonged antibiotic therapy and/or operative removal of the access device may be necessary.

Of 495 patients reported in a large urban histoplasmosis outbreak, we studied 276 whose serologic tests were done in a single laboratory. Serologic test results were positive in 96% of these patients (compared with less than 5% of controls from an endemic area), cultures were positive in 22%, and special stains in 19%. The immunodiffusion test results were negative in 13% of patients who had positive findings by complement fixation, and 1% had positive results only by immunodiffusion. The complement fixation test was almost twice as sensitive as the immunodiffusion test in patients with subclinical infection. The serologic response differed significantly among the clinical syndromes with higher titers in cavitary and lower titers in disseminated disease. Factors associated with titers of 1:64 or greater to both antigens were black race and immunocompetence. High mycelial titers were also associated with more intense exposure, and high yeast titers were associated with age less than 36 years. No prognostic significance could be proved for fourfold titer rises or falls or persistence of precipitins.

Detection of a Histoplasma capsulatum polysaccharide antigen (HPA) has proved a useful approach to diagnosis of histoplasmosis. Two sandwich enzyme-linked immunosorbent assays (ELISAs) using alkaline phosphatase (AP)-or horseradish peroxidase (HRP)-conjugated antibodies were compared with solid-phase radioimmunoassay (RIA) for detection of HPA. The AP-ELISA and HRP-ELISA were each positive in 17 (89.5%) of 19 urine specimens from patients with disseminated histoplasmosis, while the RIA was positive in 18 (94.7%) of 19. Specimens from patients with nondisseminated histoplasmosis were positive by AP-ELISA in 8 of 32, by HRP-ELISA in 4 of 25, and by RIA in 12 of 25. Of control specimens from patients with other fungal infections, the AP-ELISA was negative in 22 (91.7%) of 24, the HRP-ELISA in 23 (95.8%) of 24, and the RIA in 23 (95.8%) of 24. Reproducibilities AP-ELISA and HRP-ELISA were 95.1% and 95.1%, respectively. Thus, AP-ELISA and HRP-ELISA appear less sensitive than RIA and may be falsely negative in specimens containing low levels of HPA.

We previously reported that 80% of patients with serogroup 1 Legionella pneumophila pneumonia excrete detectable quantities of specific antigens in their urine. The purpose of this study was to determine whether specific antigens can be detected in urine from patients with serogroup 4 L. pneumophila pneumonia. Antisera were prepared in 15 rabbits and used to set up 25 solid-phase radioimmunoassays. The best of these assays detected specific antigens in urine from 4 of 5 patients with culture-proven serogroup 4 infections and from 1 of 2 patients with culture-proven serogroup 10 infections. None of 100 control specimens was positive in the assays. The antigens from serogroup 4 and 10 infections behaved differently in the assays, suggesting that they are not identical molecules. This study demonstrates that it is possible to detect specific antigens in the urine of patients with serogroup 4 L. pneumophila pneumonia. This may be a useful method for diagnosing these infections rapidly.

This article reviews the complexity of the microbiological environment of odontogenic infections. With an understanding of the organisms involved, the appropriate antibiotic can be chosen. A review of current antibiotic choices and the rationale for their selection is also presented.

Immunologic attempts to detect mycoplasma antigens in fluids of infected patients have been rare and largely unsuccessful. Nucleic acid hybridization procedures appear promising on the basis of successes in detecting mycoplasmal contamination of tissue culture cells; results of attempts to apply these techniques to human infections have not been reported. Antigens can be detected in the urine of about 80% of patients with serogroup 1 Legionella pneumophila pneumonia and of some patients with serogroup 4 Legionella pneumophila and Legionella dumoffii pneumonia. The specificity of these assays is greater than 99%. In a test population in which the prevalence of Legionella pneumophila was 4%, the posterior probabilities of positive and negative results of tests for antigen were 86.5% and 99.3%, respectively. Antigen is detectable within the first 3 days of illness approximately as often as at later periods, and antigen may remain detectable for a few days to 1 yr after successful therapy. Antigen is detectable in serum, but the concentrations are considerably lower than in urine. Combining urinary antigen detection with direct fluorescent antibody examination of secretions increases the rapid diagnostic yield by 10%-20%. Monoclonal antibody studies demonstrate that subgroup specificities are present among the serogroup 1 urinary antigens. Radiometric and enzyme immunoassays detect antigen in equal proportions of patients. Latex agglutination results are positive in about 80% of those cases positive by the other methods.

We developed a latex agglutination test to detect antigen(s) of serogroup 1 Legionella pneumophila in urine and evaluated its ability to diagnose legionnaires' disease. Antigen was detected in 46, or 70%, of 66 patients with serogroup 1 legionnaires' disease but in none of 51 patients with various bacteremic infections nor 60 with urinary tract infections. One of 50 patients with other pulmonary infections was antigen-positive, an immunosuppressed patient with Pneumocystis carinii infection. Seven other patients infected with P. carinii were negative. When compared with radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) using serial dilutions of a single antigen-containing urine, latex agglutination was 16-fold less sensitive. However, 82% of RIA- or ELISA-positive specimens were positive by latex agglutination. Latex agglutination is simpler and more rapid than ELISA or RIA, and it should prove valuable in situations where ELISA or RIA are unavailable or unaffordable.

An enzyme-linked immunosorbent assay was developed to detect urinary antigen excreted by patients with Legionnaires' disease. Of 47 patients tested, antigen was detected in 39. Of these 39 specimens, 35 gave clearly positive results by visual analysis; four others required spectrophotometric verification of positive results. Antigen was not detected in any of 178 urine specimens from patients with other pulmonary, bacteremic or urinary tract infections after a quick and simple confirmatory test. The assay required more time to perform than a previously described radioimmunoassay but was of equivalent sensitivity and specificity and did not require expensive equipment or contract with radioactive reagents. We conclude that enzyme-linked immunosorbent assay is a rapid, sensitive and specific means for rapidly diagnosing legionnaires' disease that can be performed in clinical laboratories unwilling or unable to use radioisotopes.

The purpose of this 3-year study was to determine whether or not an antibiotic control program, designed by the P & T Committee, would affect the cost of antibiotics to this 473-bed general medical-surgical teaching hospital. Physician consultants from different clinical departments discussed each use of targeted antibiotics with prescribing physicians. Compared with the preprogram year, cost savings of $46,869 during the first program year, and $73,212 during the second program year were achieved. Many factors were taken into account before arriving at these figures, including cost analysis of both targeted and nontargeted antibiotics, impact of price changes, administration costs, and changes in hospital census. The authors conclude that in the absence of cost inflation, antibiotic costs would have risen considerably due to price escalation, but in the face of antibiotic controls, a modest cost savings over the 2 years analyzed was actually realized.

During two histoplasmosis outbreaks in Indianapolis 45 patients presented with pericarditis. The pericarditis occurred as a late complication in individual patients and during the outbreak. Risk factors for this complication included young age, immunocompetence, and male sex in persons between 20 and 39 years old. Intrathoracic adenopathy was present in 66% of cases. Since cultures were uniformly negative, including pericardial fluid or tissue from nine patients, serologic studies provided the basis for diagnosis. Although the course was usually benign, nine patients presented with tamponade and another with constrictive pericarditis. Prompt response to antiinflammatory medications and failure to identify H. capsulatum in the pericardial fluid or tissue support a noninfectious, inflammatory mechanism for this complication. Of 20 patients reexamined 1 year later, none had evidence of constriction but three had pericardial thickening by echocardiography. Histoplasmosis should be considered in patients with pericarditis from endemic areas, particularly when associated with intrathoracic adenopathy.

We have evaluated the clinical usefulness of a commercially available teichoic acid antibody assay (ENDO-STAPH). Teichoic acid antibody titers up to a 1:2 serum dilution were observed in 20% of normal subjects, thus, titers of 1:4 or more were considered positive. Of patients with Staphylococcus aureus infections, 16 of 23 with endocarditis, 12 of 20 with complicated bacteremia, three of 17 with uncomplicated bacteremia, and ten of 20 with nonbacteremic infections had positive titers. Only four of 70 controls had positive titers. Results agreed with those using our standard assay in 130 of 151 specimens. Results were reproducibly positive or negative in 17 of 18 specimens that were retested. Results were also reproducible in ten specimens retested using a different lot of standardized antigen. The ENDO-STAPH assay should broaden the clinical applications of assays for TAA.

A solid-phase radioimmunoassay designed to detect serotype 6 Pseudomonas aeruginosa antigens was evaluated for its ability to rapidly diagnose urinary tract infections. Twelve P. aeruginosa serotypes were easily differentiated in the assay from eight other gram-negative bacterial species. During log-phase growth, the assay detected antigens in culture when approximately 10(6) or more serotype 6 P. aeruginosa organisms were present. Both cell-associated and solubilized antigens were detected. The assay detected antigens in 13 of 17 urine specimens which grew greater than 10(5) P. aeruginosa, 3 of 38 which grew other gram-negative rods, and none of 83 with no growth. Two of the three positive specimens from the other gram-negative rod group probably also contained P. aeruginosa. No preincubation of the urine specimens was required, and results were available within 2.5 h. The assay represents an improvement over other procedures for rapidly diagnosing urinary tract infections in that it allows diagnosis by species and should be adaptable to semiautomation.

Because the reported frequency of teichoic acid precipitins in controls and various patient groups has varied considerably among laboratories, we studied the effect of using various concentrations of staphylococcal extracts in agar-gel diffusion tests for teichoic acid antibodies. Of 25 normal sera, only 1 was positive against an undiluted extract, but 4 were positive against a 16-fold-diluted extract. Of nine sera from patients with staphylococcal bacteremia, two were positive at a higher titer against the diluted extract. A false-positive serum against the undiluted extract had a twofold titer increase against the diluted extract. Because human immune serum globulin is generally used as a positive teichoic acid antibody control, the variability of five different lots was studied. Three lots ahd teichoic acid antibody titers of 1:4, whereas one each had titers of 1:2 and 1:8. Based on this study, we feel that staphylococcal extracts should not be diluted. If immune serum globulins are used to determine the adequacy of ultrasonic extracts, newly acquired globulin lots should be standarized against an ultrasonic extract of proven sensitivity and specificity.

Purpose: Disseminated histoplasmosis is a serious and often rapidly progressive, opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), supporting the importance of rapid diagnostic tests. We investigated Histoplasma capsulatum polysaccharide antigen (HPA) detection, a promising new method for rapid diagnosis of histoplasmosis., Patients and Methods: Sixty-one cases of disseminated histoplasmosis in patients with AIDS form the basis of this report. Control cases were patients with AIDS who had other opportunistic infections and whose cultures were negative for H. capsulatum. A slightly modified radioimmunoassay procedure was used to measure the levels of HPA in urine and blood specimens., Results: High levels of HPA were detected in the urine of 59 of 61 (96.7%) and the blood of 37 of 47 (78.7%) patients with AIDS complicated by disseminated histoplasmosis. Treatment with amphotericin B reduced levels of HPA in the urine in 19 of 21 (90.5%) and the serum of all 10 patients tested. HPA levels increased in the urine in all eight and in the serum in all five patients with culture-proven relapse., Conclusion: In conclusion, HPA detection offers a rapid method for diagnosing disseminated histoplasmosis. Additional experience is required to establish the role of this test in monitoring the effects of treatment and in identifying relapse in patients with AIDS.

Of patients with staphylococcal infections, high levels of IgM antibodies of staphylococci measured by radioimmunoassay were present in 13 of 17 patients with endocarditis, nine of 23 with complicated bacteremia, one of 20 with uncomplicated bacteremia, and two of 21 with nonbacteremic infections. Of control subjects, high levels of IgM antibodies were present in seven of 26 individuals with gram-positive infections, two of 16 with gram-negative infections, two of 20 with rheumatoid arthritis, and two of 50 uninfected persons. Concomitant elevation of IgG and IgM antibody levels occurred in 20 of 40 patients with endocarditis or complicated bacteremia compared with two of 41 patients with other types of staphylococcal infections and three of 112 control subjects. IgM antibodies only were present early in the infection in six of 13 patients with staphylococcal endocarditis or complicated bacteremia. IgG or IgM antibody levels remained elevated at least four weeks after initiation of treatment.

To aid in the rapid diagnosis of staphylococcal infection, a solid-phase radioimmunoassay for Staphylococcus aureus antigen was developed and evaluated in rabbits with staphylococcal endocarditis. Test specimens containing antigen were added to polystyrene tubes coated with antibody to S. aureus. Antigens immobilized on the tube were detected by adding radiolabeled antibody to S. aureus. Sensitivity for antigen was 0.312 microgram/ml in buffer and 1.25 microgram/ml in 50% rabbit serum. Cross-reactions were not observed with antigens extracted from streptococci; however, antigen extracted from Staphylococcus epidermidis (which contained ribitol-teichoic acid) could also be detected at low concentrations. Antigen was detected in each of 12 rabbits with S. aureus endocarditis but not in control rabbits. This assay is sensitive, specific, reproducible, and capable of detecting antigens in the serum of rabbits with endocarditis.

Treatment of nasal carriers of coagulase-positive staphylococci with a wide variety of topical systemic antibiotics suppressed these organisms only during treatment. Treatment of methicillin-sensitive or methicillin-resistant staphylococci with oral rifampin plus cloxacillin, vancomycin, fusidic acid, or trimethoprim-sulfamethoxazole eradicated the colonizing Staphylococcus aureus in approximately 80 percent of studies. An alternative approach is replacement of virulent S.aureus with the 502 A S. aureus strain. The latter approach has aborted epidemics of staphylococcal diseases in newborn nurseries and has prevented recurrent furunculosis.

Eighty healthy men with nasal carriage of coagulase-positive staphylococci were given cloxacillin, rifampin, cloxacillin plus rifampin, or no drug. Treatment with rifampin alone or with rifampin plus cloxacillin eradicated the original strain from 80% of the men for 12 weeks after treatment; 15%-20% of the 80 subjects acquired a strain of a different phage type. Treatment with cloxacillin alone did not significantly alter the rate of carriage. Only one of 40 men receiving rifampin (either alone or with cloxacillin) acquired rifampin-resistant, coagulase-positive staphylococci; seven of the 40 acquired rifampin-resistant, coagulase-negative staphylococci. Rifampin-resistant organisms did not persist in repeat nasal cultures five months after treatment. Of the 40 subjects given rifampin alone or rifampin plus cloxacillin, 60% had repeat nasal cultures done one year later. Only 50% were found to be carriers of coagulase-positive staphylococci. In another study, coagulase-positive staphylococci were eradicated from 70% of 20 carriers undergoing renal dialysis who received rifampin plus cloxacillin.

A Gram-negative bacillus that defies identification was isolated from blood cultures of 17 patients with fever. Fifteen patients were male adults, and 14 patients had underlying diseases, including previous splenectomy in five, which impair host defenses against infection. Illnesses occurred in the summer and autumn in 14 cases and had been recently preceded by dog bites in 10 cases. Clincal syndromes included cellulitis in seven cases, primary bacteremia without localization in four, purulent meningitis in four, and endocarditis in three. Three patients died. The organism grows slowly on blood or chocolate agar in 10% CO, is oxidase- and catalase-positive, and is negative for nitrate reduction, indole production, and urease. It produces acid from glucose, lactose, and maltose. These features distinguish it from all previously described and classified bacteria. Furthermore, the epidemiologic features of the patients suggest that this organism is an opportunistic invader and may have an animal reservoir in nature.

A radioimmunoassay was previously developed for detection of Histoplasma capsulatum antigen in the blood and urine of patients with disseminated histoplasmosis. In this investigation, cerebrospinal fluid (CSF) specimens from 14 episodes of Histoplasma meningitis occurring in 12 patients were tested by radioimmunoassay. Histoplasma capsulatum antigen was detected in the CSF of five patients. Cerebrospinal fluid cultures were positive for H capsulatum in three of these five patients. Antibodies to H capsulatum were found in nine of the 13 CSF specimens tested. The radioimmunoassay for Histoplasma antigen was also positive in the CSF in one of 11 patients with coccidioidal meningitis but not in 17 patients with cryptococcal meningitis. It was concluded that Histoplasma antigen is present in the CSF of some patients with histoplasmosis and chronic meningitis, but cross-reactions may occur in patients with coccidioidal meningitis.

The diagnosis of Histoplasma capsulatum infection by serologic testing for the presence of antibodies is limited by a high rate of false positive and false negative results and by the requirement that the patient have a normal immune response. We have developed a radioimmunoassay for the detection of H. capsulatum antigen in urine and serum specimens. Antigenuria was noted in 20 of 22 episodes of disseminated histoplasmosis that occurred in 16 patients, in 6 of 32 patients with self-limited infection, in 2 of 32 patients with cavitary histoplasmosis, and in 4 of 8 patients with a sarcoid-like illness caused by H. capsulatum. The detection of antigen in urine was reproducible in 38 of 41 (93 percent) retests of specimens. H. capsulatum antigen was also detected in the serum during 11 of the 22 episodes of disseminated histoplasmosis, in none of the 12 episodes of other types of histoplasmosis in patients with antigenuria, in 1 of the 33 patients with histoplasmosis who lacked the urinary antigen, and in none of the 50 controls. Antigenemia and antigenuria decreased after initiation of antifungal therapy and recurred in patients who had a relapse. We conclude that this radioimmunoassay for H. capsulatum antigen represents a useful new method for the rapid diagnosis of disseminated histoplasmosis.

An outbreak of histoplasmosis estimated to involve more than 100,000 residents in Indianapolis, Indiana, occurred between September 1978 and August 1979. In the 435 cases evaluated, 52% of the patients were between 15 and 34 years old, and 63% were black. Fifteen patients died, and 46 progressive disseminated infection. Twenty-four patients had pericarditis, and 26 had rheumatologic syndromes. Unusual manifestations that occurred in 18 patients included esophageal and vocal cord ulcers, parotitis, adrenal insufficiency, uveitis, fibrosing mediastinitis, interstitial nephritis, intestinal lymphangiectasia, and epididymitis. The highest attack rate was in the central part of the city, which is a densely populated, disproportionately black section. The source of the outbreak has not been proved by positive culture results; two sites, however, were suspected on an epidemiologic basis.

The purposes of this study were to determine whether antigen is excreted by patients with Legionnaires disease early enough after the onset of symptoms to be useful for making therapeutic decisions and whether antigen excretion ends when successful treatment is concluded. Specific antigen was detected in the urine of 14 (88%) of 16 patients with Legionnaires disease during days 1 to 3 of symptoms, 33 (80%) of 41 patients during days 4 to 7, 25 (89%) of 28 patients during days 8 to 14, and 11 of 11 patients after day 14, by solid-phase immunoassays for serogroup 1 Legionella pneumophila antigen. Antigen excretion persisted for 42 days or longer after the onset of treatment in at least 15 patients. The longest documented duration of excretion was 326 days. We conclude that antigen can be detected approximately as often early after symptoms begin as later, allowing meaningful therapeutic decisions to be made, but that prolonged antigen excretion may negate the diagnostic value of urinary antigen detection for relapsing or recurrent L. pneumophila pneumonia.

It has been difficult to obtain pure Pneumocystis carinii antigen either from cultures or from infected lungs for use in producing a specific antibody against P. carinii. This report describes an approach toward producing a monoclonal antibody that bypasses the antigen purification steps. P. carinii infection was developed in Sprague-Dawley rats by the method of immunosuppression with cortisone. The infected lungs were homogenized, and the homogenate was used to immunize Sprague-Dawley rats. Rat spleen cells were then fused with SP2/0 mouse myeloma cells. Hybridoma clones were screened for antibody production against P. carinii by immunoperoxidase staining techniques and by enzyme-linked immunosorbent assay, using as antigens homogenates of normal rat lung, homogenates of P. carinii-infected rat lung, and harvests of P. carinii grown with WI-38 cells. Out of six hybridoma clones obtained that produced antibodies against P. carinii, one was able to produce ascitic fluid. This monoclonal antibody reacted with two P. carinii antigens with masses of about 35,000 and 65,000 daltons in P. carinii-infected lungs and three proteins with masses of about 35,000, 65,000, and 110,000 daltons in P. carinii that was harvested from a WI-38 cell culture.

Serogroup 1 Legionella pneumophila was isolated from the pericardial fluid of a nonimmunosuppressed patient with pulmonary infiltrates, cardiac tamponade, and histologic evidence of pericarditis. This is the first reported case in which the association of L. pneumophila infection and pericarditis has been proved by growth of the organism from pericardial fluid. Physicians caring for patients with pericarditis of unknown cause should consider L. pneumophila in their differential diagnosis because special diagnostic efforts and relatively specific therapy are required for its optimal management.

Medical and surgical house physicians at three teaching hospitals with different antibiotic control programs (ACPs) were surveyed to determine their attitudes about and preferences for these programs. Questionnaires were mailed to resident physicians who had trained at all three hospitals. One hospital had no antibiotic prescribing policy (open prescribing), one employed an infectious-disease physician consultant who discussed antibiotic orders for certain reserved drugs with prescribing physicians but did not otherwise restrict access to the drugs (educational ACP), and the third hospital required approval of an infectious-disease physician for dispensing of reserved drugs by the pharmacy department (restrictive ACP). The survey response was 77% after one follow-up mailing to nonrespondents. Regardless of hospital type, physicians preferred the educational ACP to either open prescribing or the restrictive ACP. Based on personal experiences, significantly fewer physicians encountered patient-care problems with the educational ACP than with either open antibiotic prescribing or the restrictive ACP. Significantly more physicians perceived that the educational ACP was more beneficial for patient antibiotic therapy and will be more beneficial for future antibiotic prescribing than the restrictive ACP. Most respondents believed that ACPs save hospitals money, that ACPs can be implemented without compromising either patient care or physician performance, and that they would encounter similar ACPs in the future. Educational ACPs should be considered at teaching hospitals with interested infectious-disease consultants.

Ninety-one patients with community-acquired lower respiratory infections were treated orally in a comparative 10-day trial of ofloxacin versus amoxicillin or erythromycin. Approximately one-half of the patients had no major underlying disease and the other half had some form of chronic lung disease. Pneumonia was present in 31 percent of the patients and the remainder had purulent bronchitis. Bacterial pathogens were recovered from 60 percent of the patients, with Haemophilus influenzae (33 isolates) and Streptococcus pneumoniae (16 isolates) being the most common. Ofloxacin was found to be a safe, well-tolerated therapeutic agent, which was as effective clinically as amoxicillin or erythromycin and with an advantage of less frequent administration. Ofloxacin was more effective than amoxicillin (90 percent versus 75 percent; p = 0.05) in elimination of pathogenic bacteria from lower airway cultures. Caution should be exercised in the use of ofloxacin, at least in short-term treatment regimens, with anaerobic pulmonary infections; additional information is needed for S. pneumoniae given the relatively high minimal inhibitory concentrations for this species.

Radioimmunoassays for IgM and IgG histoplasmal antibodies were developed and proved to be specific for their respective immunoglobulin classes, sensitive, and reproducible. Elevated IgM antibodies were detected in 59.8% of patients with histoplasmosis and 7.9% of control subjects. Elevated IgG antibodies occurred in 80.4% of patients with histoplasmosis but in only 12.9% of control subjects. Radioimmunoassay was nearly twice as sensitive as complement fixation for identifying patients with mild, presumably asymptomatic, infection. Of 13 patients with serologic follow-up at least 1 yr later, elevated IgM antibodies cleared, whereas IgG antibodies persisted in 7. In an epidemiologic investigation of a recurrent histoplasmosis outbreak, only the radioimmunoassay was able to prove the hypothesis that construction for a swimming complex was the source of exposure. These assays promise to be useful for clinical and epidemiologic investigations.

A solid-phase radioimmunoassay was developed to detect antigens of Legionella pneumophila serogroup 4. The assay detected antigen in urine from four of seven patients with pneumonia caused by L. pneumophila serogroup 4, two of two patients with L. pneumophila Leiden 1 strain (proposed new serogroup), and 26 of 55 patients with L. pneumophila serogroup 1 (proven by culture or direct fluorescent-antibody assay). The antigen of two patients with serogroup 4, one with Leiden 1 strain, and 49 with serogroup 1 infections could be detected in a previously described assay for antigens of L. pneumophila serogroup 1. Serogroup specificity of the assays could be demonstrated if serial dilutions of urine were tested. None of 347 urine specimens used as controls were positive in the radioimmunoassay. We conclude that antigens are excreted in the urine of at least some patients with Legionnaires' disease caused by serogroup 4 and Leiden 1 strain. The urinary antigens in patients with serogroup 4 and Leiden 1 strain infections, although different from those in patients with serogroup 1 infections, serologically contain cross-reactive components.

Fulminant falciparum malaria with greater than 500,000/mm3 parasites in the peripheral blood portends a poor prognosis. We recently managed a patient who had greater than 1.2 million/mm3 parasitized erythrocytes in her peripheral blood, following initially inadequate antimalarial therapy, with exchange transfusion in addition to conventional chemotherapy. This patient recovered from her disease despite severe cerebral involvement and acute failure. We feel that exchange transfusion was a useful adjunct and should be considered in patients with life threatening falciparum malaria when conventional measures fail to control the disease.

The purpose of this study was to determine whether measurement of immunoglobulin M (IgM) antibodies against Legionella pneumophila serogroup 1 can aid in the diagnosis of Legionnaires disease. On the basis of measurements of antibody levels in 1,942 control sera, we used an IgM titer of 1:256, observed in 2.3% of the controls, as presumptive evidence of Legionnaires disease. Measurement of IgM titers permitted us to presumptively or definitively diagnose Legionnaires disease in 13 of 34 patients earlier than we would have if only IgG titers had been measured. Of the 13 patients, 5 were diagnosed serologically only by IgM antibody determination. IgM titers were presumptively diagnostic in week 1 of clinical symptoms in 4 of the 13 patients. We conclude that conjugates used for antilegionella indirect fluorescent-antibody tests should be capable of detecting IgM antibodies so that the value of serological results in diagnosing and managing Legionnaires disease will be maximized.

The rough mutant of Salmonella minnesota (Re 595) contains several broad reacting antigens including a core LPS common to many aerobic gram-negative bacteria without sugars that confer serotype specificity to most gram-negative bacteria. Therefore, antibodies against this organism can be evoked by a large number of gram-negative bacteria. Using radioimmunoassay methods, sera from 59 patients with bacteremia due to enterobacteriaceae had higher concentrations of IgG antibodies against the rough mutant of Salmonella minnesota (Re 595) than control subjects. There was a significant correlation between concentrations of antibodies against Salmonella minnesota and concentrations of antibodies against a single strain of E coli. Sera from patients with bacteremia due to E coli or Klebsiella were tested against one strain of E coli and one strain of Klebsiella. The concentrations of antibodies against the homologous antigen were not higher than the concentrations of antibodies against the heterologous antigen. Sera from patients infected with S aureus or Pseudomonas aeruginosa did not have high concentrations of antibodies against S minnesota. Antibodies against common antigen(s) in Salmonella minnesota (Re 595) are useful in diagnosis of enterobacterial infections.

In January 1981, informal surveillance of acute histoplasmosis in Indianapolis, Indiana, revealed a marked increase in disease activity for the last quarter of 1980. Fifty-one patients with onset of acute histoplasmosis during this period were identified through review of hospital admissions, emergency room visits, and serologic records at Indianapolis hospitals and the Indiana State Board of Health. In a retrospective case-control study, the authors found a significant association between developing acute histoplasmosis during this period and working or attending classes in a 2 sq mi (5.2 sq km) area encompassing the Indiana University-Purdue University campus (p = 0.015, Fisher's exact test). A review of construction activities on or near the campus during the epidemic period suggested that the probable source of infection was excavation activity for a large new indoor swimming complex (natatorium). Skin tests and serosurveys of students on campus by a newly developed radioimmunoassay for histoplasmal immunoglobulin M antibodies supported the association of infection with exposure to this site (p less than 0.05).

Urine from nine patients with serogroup 1 Legionnaires' disease, 100 with infected or contaminated urine, 50 with bacteremic infections, 26 with infectious or infiltrative pulmonary diseases, and 65 with miscellaneous infectious or noninfectious illnesses, was examined by radioimmunoassay for the presence of Legionella pneumophila antigen(s). Urine of all nine Legionnaires' disease patients was clearly differentiated from that of the 241 control subjects by the assay. The antigen was detected from 2 to at least 10 days after the initiation of erythromycin therapy. A probable false-positive results occurred in a patient with necrotizing nosocomial pneumonia who died before definitive serologic evaluation for Legionnaires' disease could be completed. The antigen was stable at 100 degrees C for 30 minutes and was not degraded by trypsin. Its elution behavior suggested that its molecular weight is approximately 10 000. The radioimmunoassay appears to be a useful method for rapidly diagnosing serogroup 1 Legionnaires' disease.

Clinical features of 99 patients with staphylococcal infection were reviewed, and sera were tested by solid-phase radioimmunoassay and gel diffusion for staphylococcal antibodies to ascertain whether these variables predict the extent of infection and the need for prolonged therapy. Clinical features, including the presence of a primary site of infection or a continuous pattern of bacteremia, were not sufficient for differentiating endocarditis or complicated bacteremia from uncomplicated bacteremia. Patients with uncomplicated bacteremia were cured by 3 weeks of antibiotic therapy. Positive serologic tests for staphylococcal antibody helped distinguish patients with endocarditis or complicated bacteremia from patients with uncomplicated bacteremia. Radioimmunoassay was more sensitive than gel diffusion for identifying patients with complicated bacteremia. Our results indicate that patients with a positive antibody result 14 days after the onset of infection should be considered to have endocarditis or complicated bacteremia, but a negative antibody result would support short-term antibiotic therapy.

We assessed the ability of a solid-phase radioimmunoassay, modified to allow antigen detection in serum, to detect circulating antigens in granulocytopenic rabbits with Pseudomonas aeruginosa bacteremia. In vitro experiments with Pseudomonas lipopolysaccharide indicated that treatment of serum-lipopolysaccharide mixtures with heat, chloroform, or heparin improved the sensitivity for detecting lipopolysaccharide 8- to 16-fold. Chloroform treatment permitted antigen detection in serum or plasma of bacteremic rabbits in which antigen could be detected poorly or not at all in untreated specimens. However, chloroform-treated specimens occasionally caused dissolution of plastic tubes, resulting in nonspecific binding of 125I-labeled anti-Pseudomonas immunoglobulin G. Heating sera at 56 degree C for 30 min improved antigen detection both in both in lipopolysaccharide-serum mixtures and in bacteremic rabbits. Antigen was detected in the heated serum or plasma of 20% of 20 culture-positive granulocytopenic rabbits, none of 15 culture-negative granulocytopenic rabbits, and none of 38 normal rabbits. Antigen was detected in none of 15 rabbits with 2 to 300 colony-forming units of P. aeruginosa per ml of blood and in 4 of 5 rabbits with > 10(3) colony-forming units per ml. We conclude that circulating antigens are present in the blood of rabbits with high-level P. aeruginosa bacteremia and that these antigens can be detected by solid-phase radioimmunoassay. Further improvements in assay sensitivity will be required to detect antigens, if present, in animals with lower levels of P. aeruginosa bacteremia.

We have compared risk factors for cavitary histoplasmosis in 62 patients with that manifestation of the infection and in 679 patients with other forms of histoplasmosis, and we have evaluated the clinical and laboratory findings in 45 patients with cavitary histoplasmosis who were cared for at the Indiana University Medical Center hospitals during two large histoplasmosis outbreaks. Chronic obstructive lung disease and old age were the strongest risk factors for cavitary histoplasmosis but male sex, white race and immunosuppression were also important in certain patient groups. Fever, sweats, weight loss, productive cough, anemia, lymphopenia, and alkaline phosphatase elevation were common findings. The patients were occasionally incorrectly treated for presumed class 3 tuberculosis. Cultures were positive in 58% of patients, with sputum samples providing the highest yield (61%). Histoplasmal serologic tests provided useful clues to the diagnosis, positive in over 90% of cases. About one-third of patients recovered spontaneously while another 35% improved following treatment. About 4% developed chronic untreated cavitary histoplasmosis characterized by clinical and roentgenographic exacerbations and remissions. Of the deaths in four patients with untreated disease, one was caused by disseminated histoplasmosis while three died of other causes. Ketoconazole appeared effective in three of seven patients while its effect in three additional patients was uncertain. Toxicity precluded completion of ketoconazole therapy in one patient. Only amphotericin B has been proven to be effective therapy for cavitary histoplasmosis.

We tested urine specimens from 222 patients with serogroup 1 Legionella pneumophila pneumonia in two enzyme-linked immunosorbent assays (ELISAs) which used different monoclonal antibodies (A and B) as detector antibodies. Of 171 specimens which contained enough antigen to be detected in the ELISAs, 169 reacted in only one of the two assays. A total of 25 patients whose infections were acquired in any of three Indianapolis hospitals excreted antigen reactive with monoclonal antibody B, but 18 patients who were treated for infections acquired elsewhere reacted with monoclonal antibody A. The urinary antigen ELISA reactivity patterns correlated with the reactivity patterns of L. pneumophila isolates when a separate panel of seven monoclonal antibodies was used. The isolate patterns, in turn, correlated well with environmental isolate patterns from two of the hospitals with nosocomial cases. We conclude that at least two different epitopes exist on the antigen molecules in urine from patients with serogroup 1 L. pneumophila pneumonia and that the subtyping of urinary antigens can be useful epidemiologically.