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P H Edelstein

Publications and source records attributed to P H Edelstein.

At least 55 records · Page 3Linked to original sources

In vitro activity of RP 74501-RP 74502, a novel streptogramin antimicrobial mixture, against clinical isolates of Legionella species.

Agar and broth microdilution MICs of RP 74501-RP 74502, a mixture of streptogramin antimicrobial agents that inhibited 90% of 22 Legionella strains tested, were 0.64 and 0.08 microgram/ml, respectively; respective erythromycin values were 1.0 and 0.12 microgram/ml. RP 74501-RP 74502 at 1 microgram/ml was more active than the same erythromycin concentration in a macrophage system for both L. pneumophila strains studied but at a lower concentration (0.25 microgram/ml) was much less active than erythromycin.

Animals↗

Comparison of three buffers used in the formulation of buffered charcoal yeast extract medium.

Growth of Legionella spp. on buffered charcoal yeast extract medium supplemented with alpha-ketoglutarate and formulated with 3-(n-morpholino)propanesulfonic acid (MOPS), 3-(n-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), or n-(2-acetamido)-2-aminoethanesulfonic acid (ACES) buffer was similar. With three exceptions, growth was no different in buffered yeast extract broth supplemented with alpha-ketoglutarate and formulated with MOPS or ACES buffer.

Animals↗

Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection.

OBJECTIVE: To determine if the leukocyte esterase and bacterial nitrite rapid dipstick test for urinary tract infection (UTI) is susceptible to spectrum bias (when a diagnostic test has different sensitivities or specificities in patients with different clinical manifestations of the disease for which the test is intended). DESIGN: Cross-sectional study. PATIENTS: A total of 366 consecutive adult patients in whom clinicians performed urinalysis to diagnose or exclude UTI. SETTING: An urban emergency department and walk-in clinic. MEASUREMENTS: After the patient encounter, but before dipstick test or culture was done, clinicians recorded the signs and symptoms that were the basis for suspecting UTI and for performing a urinalysis and an estimate of the probability of UTI based on the clinical evaluation. For all patients who received urinalysis, dipstick tests and culture were done in the clinical microbiology laboratory by medical technologists blinded to clinical evaluation. Sensitivity for the dipstick was calculated using a positive result in either leukocyte esterase or bacterial nitrite, or both, as the criterion for a positive dipstick, and greater than 10(5) CFU/mL for a positive culture. RESULTS: In the 107 patients with a high (greater than 50%) prior probability of UTI, who had many characteristic UTI symptoms, the sensitivity of the test was excellent (0.92; 95% CI, 0.82 to 0.98). In the 259 patients with a low (less than or equal to 50%) prior probability of UTI, the sensitivity of the test was poor (0.56; CI, 0.03 to 0.79). CONCLUSIONS: The leukocyte esterase and bacterial nitrite dipstick test for UTI is susceptible to spectrum bias, which may be responsible for differences in the test's sensitivity reported in previous studies. As a more general principle, diagnostic tests may have different sensitivities or specificities in different parts of the clinical spectrum of the disease they purport to identify or exclude, but studies evaluating such tests rarely report sensitivity and specificity in subgroups defined by clinical symptoms. When diagnostic tests are evaluated, information about symptoms in the patients recruited for study should be included, and analyses should be done within appropriate clinical subgroups so that clinicians may decide if reported sensitivities and specificities are applicable to their patients.

Adolescent↗

Molecular diagnosis of Ureaplasma urealyticum septic arthritis in a patient with hypogammaglobulinemia.

OBJECTIVE: We report a hypogammaglobulinemic patient with a destructive oligoarticular arthritis, whose synovial fluid cultures were repeatedly sterile. METHODS AND RESULTS: We identified a Ureaplasma urealyticum infection in his affected joints, using a polymerase chain reaction (PCR) assay. CONCLUSION: The PCR technique promises to be extremely valuable in the rapid and specific diagnosis of infectious arthritis.

Adult↗

In vitro activities of fleroxacin against clinical isolates of Legionella spp., its pharmacokinetics in guinea pigs, and use to treat guinea pigs with L. pneumophila pneumonia.

The activities of fleroxacin against 22 clinical Legionella isolates were determined by agar and broth microdilution susceptibility testing. The fleroxacin MIC required to inhibit 90% of strains tested on buffered charcoal yeast extract agar medium supplemented with 0.1% alpha-ketoglutarate was 0.64 micrograms/ml and was 0.04 microgram/ml when testing was done with buffered yeast extract broth supplemented with 0.1% alpha-ketoglutarate. Fleroxacin (0.25 microgram/ml) reduced the bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 1 log10 CFU/ml, but regrowth occurred over a 3-day period; fleroxacin was significantly more active than erythromycin in this assay. Single-dose (10 mg/kg of body weight given intraperitoneally) pharmacokinetic studies performed in guinea pigs with L. pneumophila pneumonia revealed peak levels in plasma and lungs to be 3.3 micrograms/ml and 3.5 micrograms/g, respectively, at 0.5 h and 0.8 microgram/ml and 0.8 microgram/g, respectively, at 1 h. The half-life of the terminal phase of elimination from plasma and lung was approximately 2 h. All 17 infected guinea pigs treated with fleroxacin (10 mg/kg/day) for 2 days survived for 14 days post-antimicrobial therapy, as did all 16 guinea pigs treated with the same dose of fleroxacin for 5 days. Only 1 of 16 animals treated with saline survived. The animals treated with fleroxacin for 2 days lost more weight and had higher temperatures than those treated with the antibiotic for 5 days. Fleroxacin is effective against L. pneumophila in vitro and in a guinea pig model of Legionnaires' disease. Fleroxacin should be evaluated as a treatment for human Legionnaires' disease.

Animals↗

In vitro activity of Ro 23-9424 against clinical isolates of Legionella species.

Agar and broth microdilution MICs of Ro 23-9424 that inhibited 90% of 22 Legionella clinical isolates tested were 0.64 and 0.08 micrograms/ml, respectively; respective erythromycin values were 1.0 and 0.12 micrograms/ml. Ro 23-9424 (1 microgram/ml) was slightly more active than the same erythromycin concentration in a macrophage system, for both Legionella pneumophila strains studied.

Animals↗

In vitro activity of azithromycin against clinical isolates of Legionella species.

The activities of azithromycin, erythromycin, and ciprofloxacin against 21 Legionella isolates were measured by an agar dilution method and in macrophages. The MICs for 90% of strains tested were 2.0, 1.0, and 0.5 micrograms/ml for azithromycin, erythromycin, and ciprofloxacin, respectively. Azithromycin and ciprofloxacin were both bactericidal in the macrophage system, but erythromycin was bacteriostatic.

Animals↗

Rifampin resistance of Legionella pneumophila is not increased during therapy for experimental Legionnaires disease: study of rifampin resistance using a guinea pig model of Legionnaires disease.

Isolates of Legionella pneumophila serogroup 1, obtained from guinea pigs with experimentally induced Legionnaires disease, were tested for rifampin resistance. Thirteen isolates were from animals treated with rifampin alone, four isolates were from animals treated with saline, and three isolates each were from animals treated with erythromycin or erythromycin plus rifampin; all of these isolates were derived from the same parent strain, F889. Most of the isolates were obtained from rifampin-treated animals that survived infection but had persistence of bacteria in their lungs at necropsy. No differences in rifampin agar dilution MICs were detected for the 23 isolates and parent strain that were tested. None of the 13 isolates from animals treated with rifampin alone had a high number of resistant organisms detected by using a rifampin gradient plate assay. Thirteen isolates plus the parent strain were tested by using a quantitative method of determining resistance frequency. Considerable heterogeneity among isolates was observed, but there was no evidence of increased resistance for any treatment group. The range of rifampin resistance frequencies was 10(-7) to 10(-8). No evidence for rifampin-induced resistance of L. pneumophila was found in this study.

Animals↗

Comparison of different agars used in the formulation of buffered charcoal yeast extract medium.

The effect of agar type used for buffered charcoal yeast extract medium supplemented with 0.1% alpha-ketoglutarate was tested based on the growth and size of Legionella pneumophila. Oxoid Agar no. 1, Difco Bacto and Bitek agars, and BBL Granulated, Grade A, and Select agars were tested. For colony size the agars were ranked in the following order: Oxoid agar no. 1 much greater than Bacto greater than Bitek approximately Granulated approximately Grade A greater than Select. Colony yield per plate was similar for all agars except for Grade A, which gave significantly fewer colonies after 3 days, but not 4 days, of incubation. Agar type significantly influences L. pneumophila growth on buffered charcoal yeast extract medium supplemented with 0.1% alpha-ketoglutarate.

Agar↗

Inappropriate testing for diarrheal diseases in the hospital.

To assess the degree to which routine stool cultures, ova and parasite examinations, and Clostridium difficile toxin assays may be inappropriately ordered on hospitalized patients, we conducted a retrospective study to determine the relative yield of these tests on specimens collected from outpatients and inpatients as a function of time after admission. During a 3-year period, only 1 of 191 positive stool cultures and none of the 90 ova and parasite examinations with positive results were from the group of patients who had stool specimens submitted after 3 days of hospitalization. Analysis of laboratory work load for a 1-year period showed that specimens from this patient group contributed nearly 50% of the more than 3000 specimens received each year. In contrast, approximately 25% (range, 17% to 33%) of samples, regardless of admission status, were positive for C difficile toxin. Eliminating routine stool cultures and ova and parasite examinations on hospitalized patients would significantly reduce hospital and patient costs without altering patient care. Nationwide, such a policy might achieve a cost savings of +20 to +30 million per year.

Adult↗

Use of DNA probes for the diagnosis of infections caused by Mycoplasma pneumoniae and legionellae--a review.

Specific DNA probes have been made for both M. pneumoniae and Legionella species. Dot blot methods have been used in research laboratories to test culture isolates of both organisms, and also to test animal tissues with a L. pneumophila-specific probe. Commercial kits are also available for direct specimen testing for these two organisms. The commercial kits are made by a single manufacturer, Gen-Probe, Inc. (San Diego, CA), and use a novel in-solution rapid hybridization assay, using 125I-labeled cDNA to rRNAs of the organisms. The Gen-Probe M. pneumoniae probe appears to be 80% to 100% sensitive, and 97% to 100% specific, based on analysis of two clinical studies using positive culture as the diagnostic criterion. The Gen-Probe legionella probe appears to be 33% to 71% sensitive (mean 57%), and 98.9% to 99.7% specific (mean 99.7%), based on analysis of four prospective clinical studies, using positive culture as the definition of disease, with a total sample size of 3,243 patients, 49 of which were culture-positive. Both Gen-Probe direct tests appear to be clinically useful, although the poor performance of the legionella test in one major university laboratory, and the expense of performing these tests, mandate that thorough evaluations be carried out in each laboratory anticipating using the test. Culture must always be performed for legionella whether or not the DNA probe test is used. It is likely that the use of the M. pneumoniae kit would greatly speed diagnosis, but whether this would alter medical practice or result in lower morbidity and health care costs is unknown.

Costs and Cost Analysis↗

In vitro activity of sparfloxacin (CI-978; AT-4140) for clinical Legionella isolates, pharmacokinetics in guinea pigs, and use to treat guinea pigs with L. pneumophila pneumonia.

The activities of sparfloxacin, ciprofloxacin, and erythromycin for 21 clinical Legionella isolates were determined by agar and broth dilution susceptibility testing and by growth inhibition assays in guinea pig alveolar macrophages (sparfloxacin and ciprofloxacin). All three antimicrobial agents had roughly equivalent activities when buffered charcoal yeast extract agar medium supplemented with 0.1% alpha-ketoglutarate was used as the test medium; the MICs for 90% of strains were 1.0 micrograms/ml for erythromycin and sparfloxacin and 0.5 microgram/ml for ciprofloxacin. Buffered charcoal yeast extract medium supplemented with 0.1% alpha-ketoglutarate inhibited the activities of all the antimicrobial agents tested, as judged by the susceptibility of a control Staphylococcus aureus strain. Broth macrodilution MICs for two L. pneumophila strains in buffered yeast extract supplemented with 0.1% alpha-ketoglutarate were less than or equal to 0.03 microgram/ml for sparfloxacin, 0.06 microgram/ml for ciprofloxacin, and 0.25 microgram/ml for erythromycin; only erythromycin was inhibited by this medium. Ciprofloxacin and sparfloxacin (both 0.25 microgram/ml) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 2 log10 CFU/ml, but regrowth occurred over a 3-day period. Sparfloxacin, but not ciprofloxacin (both 1 microgram/ml), caused a 3- to 4-day postantibiotic effect. Pharmacokinetic and therapy studies of sparfloxacin were performed in guinea pigs with L. pneumophila pneumonia. For the pharmacokinetic study, sparfloxacin was given (10 mg/kg of body weight) to infected guinea pigs by the intraperitoneal route; peak levels in serum and lung were 2.6 micrograms/ml and 1.6 micrograms/g, respectively, at 1 h, with a terminal-phase half-life of elimination from serum of 5 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

WIN 57273 is bactericidal for Legionella pneumophila grown in alveolar macrophages.

The in vitro antimicrobial activity of WIN 57273, a new quinolone antimicrobial agent, was determined for 21 Legionella strains, using broth macrodilution and agar dilution testing methods; ciprofloxacin and erythromycin were tested as well. Three different buffered yeast extract media were used for the agar dilution studies, two of which were made with starch rather than charcoal. Broth macrodilution susceptibility testing was performed with buffered yeast extract broth and two Legionella pneumophila strains. Antimicrobial inhibition of L. pneumophila growth in guinea pig alveolar macrophages was also studied, using a method able to detect bacterial killing. The MICs for 90% of the 21 strains of Legionella spp. grown on buffered charcoal yeast extract medium were 0.125 microgram/ml for WIN 57273, 0.25 microgram/ml for ciprofloxacin, and 1.0 micrograms/ml for erythromycin. These MICs were falsely high, because of inhibition of drug activity by the medium used. Use of less drug-antagonistic, starch-containing media did not support good growth of the test strains. The broth macrodilution MICs for two strains of L. pneumophila serogroup 1 were less than or equal to 0.03 microgram/ml for WIN 57273 and ciprofloxacin and 0.125 microgram/ml for erythromycin. WIN 57273, ciprofloxacin, and erythromycin all inhibited growth of L. pneumophila in guinea pig alveolar macrophages at concentrations of 1 microgram/ml, but only WIN 57273 prevented regrowth or killed L. pneumophila after removal of extracellular antimicrobial agent.

4-Quinolones↗

Evaluation of the Merifluor-Legionella immunofluorescent reagent for identifying and detecting 21 Legionella species.

We evaluated a 33-valent polyclonal indirect immunofluorescent-reagent kit (Merifluor-Legionella; Meridian Diagnostics Inc., Cincinnati, Ohio) made for the detection of Legionella species by testing bacterial isolates, seeded sputum, and negative sputum samples. Use of the reagent according to the directions of the manufacturer gave false-negative staining of homologous culture isolates due to a prozone phenomenon; this was solved by diluting test strain suspensions. After this change in testing protocol was made, the reagent gave bright fluorescent staining with 31 of the 33 Legionella strains with which it supposedly reacts. Strongly reacting Legionella strains included the type strains of L. pneumophila serogroups 1 to 10, L. longbeachae serogroups 1 and 2, and serogroup 1 of L. anisa, L. bozemanii, L. cherrii, L. dumoffii, L. gormanii, L. hackeliae, L. jamestowniensis, L. jordanis, L. maceachernii, L. micadedi, L. oakridgensis, L. rubrilucens, L. sainthelensi, L. spiritensis, L. steigerwaltii, and L. wadsworthii. Type strains of L. erythra and L. feeleii fluoresced only dimly with the reagent. Of 10 non-Legionella bacteria known to cross-stain with other polyvalent antisera, 5 also cross-reacted with the Merifluor reagent; these included 3 Bacteroides fragilis and 2 Pseudomonas fluorescens strains. The lower limit of detection of L. pneumophila serogroup 1 in seeded sputum was about 5 x 10(4) to 5 x 10(5) cells per ml. None of 21 randomly collected sputum specimens tested contained fluorescing legionellalike organisms, but 6 specimens did contain brightly fluorescing bacteria atypical in morphology for Legionella species. The Merifluor-Legionella kit appears to perform as well as other polyclonal immunofluorescent reagents used for detection of Legionella species. Because of the cross-reactions observed, which are common to all polyclonal reagents, utilization of this reagent for either bacterial identification or detection must be performed in combination with culture.

Cross Reactions↗

Nosocomial Legionnaires' disease: a global perspective.

Nosocomial Legionnaires' disease is a worldwide problem. The lack of prospective surveys using sensitive diagnostic means, such as culture, has resulted in ignorance about the exact magnitude of the problem except at a handful of individual hospitals. Contaminated hospital hot water systems, cooling towers, and non-sterile tap water used for respiratory therapy may all cause disease. Culture diagnosis is the preferred method of case ascertainment, and provides bacterial isolates which can be used to implicate specific environmental sites using molecular epidemiologic techniques. Environmental culture surveys, done in the absence of known disease, are probably not indicated, but there remains concern that wards housing very high risk patients should be legionella-free. Use of monoclonal antibody typing of environmental isolates of L. pneumophila serogroup 1 may be useful in this regard, as it can possibly detect strains most likely to cause disease. Control of nosocomial disease requires centralized management and consultation by expert engineers, epidemiologists, and microbiologists.

Bacteriological Techniques↗