Commercially available (ENDO-STAPH) assay for teichoic acid antibodies. Evaluation in patients with serious Staphylococcus aureus infections and in controls.

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.

Significance of Histoplasma antigen in the cerebrospinal fluid of patients with meningitis.

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.

Piperacillin and gentamicin v carbenicillin and gentamicin for treatment of serious gram-negative infections.

Piperacillin sodium, a new penicillin with remarkable in vitro activity against Pseudomonas aeruginosa and other Gram-negative bacilli, and gentamicin sulfate were compared with carbenicillin disodium and gentamicin in a prospective, randomized, double-blind comparison for treating serious Gram-negative infections. Of the 32 patients whose courses were "evaluable" for efficacy, 12 of 14 who received piperacillin and gentamicin and 13 of 18 who received carbenicillin and gentamicin had favorable outcomes. Of the 99 patients whose courses were evaluable for toxicity, nine of 51 recipients of piperacillin and gentamicin and 15 of 48 recipients of carbenicillin and gentamicin suffered clinical reactions possibly, probably, or definitely related to the penicillin. No statistically significant differences were found in the two groups in the frequencies of biochemical abnormalities, including hypokalemia, that occurred in 19 or 44 recipients of piperacillin and gentamicin and 16 of 45 recipients of carbenicillin and gentamicin. Thus, this study did not prove differences in efficacy of toxicity for piperacillin and gentamicin plus carbenicillin and gentamicin for serious Gram-negative infections.

Cavitary histoplasmosis occurring during two large urban outbreaks. Analysis of clinical, epidemiologic, roentgenographic, and laboratory features.

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.

Pericarditis as a manifestation of histoplasmosis during two large urban outbreaks.

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.

Legionella pneumophila pericarditis proved by culture of pericardial fluid.

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.

Prevention of infections of skin and skin structures.

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.

Serologic diagnosis of access device-related staphylococcal bacteremia.

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.

Histoplasma capsulatum polysaccharide antigen detection in diagnosis and management of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.

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.

Ofloxacin in community-acquired lower respiratory infections. A comparison with amoxicillin or erythromycin.

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.

Rapid diagnosis of Legionnaires' disease by urinary antigen detection. Comparison of ELISA and radioimmunoassay.

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.

Antigen detection for the rapid diagnosis of mycoplasma and Legionella pneumonia.

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.

Development and evaluation of diagnostic radiometric assays for serogroup 4 L. pneumophila urinary antigens.

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.

Legionnaire's disease in postoperative neurosurgical patients.

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.

Rapid diagnosis of Legionnaires' disease.

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.

The use of exchange transfusions: a potentially useful adjunct in the treatment of fulminant falciparum malaria.

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.

Radioimmunoassay for detection of IgG antibodies against enterobacterial antigens.

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.

Severe pneumonia. When and why to hospitalize.

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.

Recent advances in the diagnosis of serogroup 1 L. pneumophila pneumonia by detection of urinary antigen.

ELISA and radioimmunoassay were analyzed for their ability to detect antigen in urine from patients with serogroup 1 Legionnaires' disease. The sensitivity of the two assays is approximately 80 percent, and the specificity is estimated to be 99 percent or better. Assay predictive values, determined on 1,239 specimens, were 76 percent for positive, and 99 percent for negative results. Antigen was detected nearly as often during the first three days of symptoms as later. Antigen excretion lasted from four to 327 days. A latex agglutination test detected antigen in 82 percent of patients positive by the other immunoassays.

Evaluation of the L-CLONE Legionella pneumophila Serogroup 1 Urine Antigen Latex Test.

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.