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Biomedical subjects

M A Pfaller

Publications and source records attributed to M A Pfaller.

At least 397 records · Page 22Linked to original sources

Detection of circulating candida enolase by immunoassay in patients with cancer and invasive candidiasis.

BACKGROUND: Invasive candidiasis is a major nosocomial infection that is difficult to diagnose. Few biochemically defined markers of invasive candidiasis are known. Initial findings suggested that the presence of candida enolase in the blood may be a novel marker for invasive candidiasis. METHODS: We tested 170 patients at high risk for invasive candidiasis for candida enolase antigenemia. All the patients had cancer and neutropenia. We detected antigen using a double-sandwich liposomal immunoassay for candida enolase in serially collected serum samples. Invasive candidiasis was proved by finding candida species in deep nonmucosal tissue, blood cultures, or both. Antigen testing was performed with the investigator blinded to tissue or culture diagnosis. RESULTS: Among 24 patients with proved invasive candidiasis, 149 serum samples were tested for enolase antigenemia; 80 were positive and 69 negative (sensitivity per sample, 54 percent). Multiple sampling improved the detection of antigenemia, which was found in 11 of 13 proved cases of deep tissue infection (85 percent) and in 7 of 11 proved cases of fungemia (64 percent). Specificity was 96 percent as measured against control groups including patients with mucosal colonization, bacteremia, and other deep mycoses. Antigenemia was detected in the absence of fungemia in 5 cases of deep tissue candidiasis, but was not detected in 6 cases of fungemia alone. CONCLUSIONS: Candida enolase antigenemia is a novel marker for invasive candidiasis. It may be a useful indicator of deep infection in patients with cancer and neutropenia and may complement the diagnostic usefulness of blood cultures.

Antigens, Fungal↗

Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment.

OBJECTIVE: To determine the safety and efficacy of mupirocin calcium ointment in the elimination of Staphylococcus aureus nasal and hand carriage in healthy persons. DESIGN: A double-blind, placebo-controlled, randomized trial. SETTING: Clinical research unit of a tertiary medical center. SUBJECTS: Health care workers with stable S. aureus nasal carriage. INTERVENTIONS: Subjects (n = 68) were randomly assigned to receive either mupirocin or placebo intranasally twice daily for 5 days. MEASUREMENTS AND MAIN RESULTS: Cultures of the hands and nares were obtained at baseline and 72 hours after therapy. The nares were also cultured 1, 2, 4, and 12 weeks after therapy. Antimicrobial susceptibility testing and restriction endonuclease analysis of plasmid DNA were used to confirm strain identity. There were no serious side effects. Mupirocin decreased the frequency of S. aureus nasal carriage at each time interval: At 3 months, 71% of subjects receiving mupirocin remained free of nasal S. aureus compared with 18% of controls. This difference (53%; 95% CI; 26% to 80%) was significant (P less than 0.0001). Additionally, analysis of plasmid patterns showed that 79% of subjects in the mupirocin group were free of the initial colonizing strain at 3 months. The proportion of hand cultures positive for S. aureus in the mupirocin group after therapy was lower than in the placebo group (2.9% compared with 57.6%). This difference (53%; 95 CI, 30% to 80%) was significant, after adjustment for the frequency of hand carriage at baseline (P less than 0.0001). CONCLUSIONS: When applied intranasally for 5 days, mupirocin calcium ointment is safe and effective in eliminating S. aureus nasal carriage in healthy persons for up to 3 months and appears to have a corresponding effect on hand carriage at 72 hours after therapy.

Administration, Intranasal↗

Antimicrobial activity of RU29246 (HR916 metabolite) compared with four other oral beta-lactams tested against more than 5000 clinical isolates.

The activity of RU29246, the active metabolite of the oral cephalosporin ester HR916, was compared in a multicenter study with that of the four oral beta-lactam antibiotics cephalexin, cefaclor, cefixime and amoxicillin/clavulanate (amoxicillin/CA). RU29246 was generally 2- to 8-fold more active than the other oral cephalosporins and comparable to amoxicillin/CA against staphylococci, and was the most active cephalosporin against group B streptococci. All four cephalosporins were ineffective against enterococci. RU29246 was the only cephalosporin consistently active against Acinetobacter, but all beta-lactam antibiotics had poor activity against Pseudomonas spp. and Xanthomonas maltophilia. RU29246 was comparable to cefixime and more active than the other cephalosporins against members of the family Enterobacteriaceae. However, all of the antibiotics had poor activity against Enterobacter cloacae and Serratia marcescens. Quality control reference ranges for the quality control organisms Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 are proposed for the broth dilution method based on data derived from this multicenter study.

Amoxicillin↗

Feasible and desirable future targets for reducing the costs of hospital infections.

The authors propose that there are, in general, five methods to reduce the costs of hospital infection: reduce the incidence, reduce the morbidity causing prolonged illness, reduce hospital stay, reduce the costs of currently effective preventive and control measures, and stop all ineffective measures. The feasible and desirable components of these methods are described.

Communicable Disease Control↗

Handwashing: efficacy versus acceptance. A brief essay.

The efficacy of handwashing for preventing transmission of infections in the hospital is well accepted. Nevertheless, compliance by health care workers is estimated at approximately 40%. Based on observations of effective behavioural changes in other areas of public health, the authors suggest that hospital epidemiologists consider testing the use of both social pressures and marketing techniques to influence current handwashing practices in hospitals.

Consumer Behavior↗

Use of antimicrobial susceptibility testing for epidemiology and the selection of oral, parenteral and topical regimens for control of CAPD-associated Staphylococcus aureus infection.

Staphylococcus aureus is an important cause of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Using standard broth microdilution and disk diffusion methodology, we evaluated the in vitro activity of selected antimicrobial agents against S. aureus strains isolated from CAPD patients to assess candidate regimens for 1) topical agent control of colonization, 2) oral chemotherapy of CAPD infectious complications, and 3) parenteral treatment of serious CAPD-associated staphylococcal infections. A total of 34 isolates (31 patients) of S. aureus were available for testing, including 29 isolates (29 patients) from pericatheter skin, four isolates (four patients) from the nares, and one isolate from an episode of peritonitis. Six of the isolates were oxacillin-resistant (ORSA). The antimicrobial agents tested by broth microdilution included 17 different quinolones, 10 cephalosporins, six glycopeptides, two aminoglycosides, and imipenem. A total of eight potential topical agents, including the antistaphylococcal agent mupirocin, were tested by disk diffusion. All of the quinolones, with the exception of nalidixic acid (MIC90 greater than 16 micrograms/ml), had excellent activity against both ORSA and oxacillin-susceptible S. aureus (OSSA) with the most active agent being WIN57273 (MIC90 less than or equal to 0.015 microgram/ml). Imipenem and the cephalosporins, with the exception of cefixime, ceftazidime, and E-1040, possessed good activity against OSSA. None of the beta-lactam agents tested were active against ORSA. Likewise, the aminoglycosides, amikacin and gentamicin, exhibited good activity against OSSA strains but no activity against ORSA strains. All glycopeptides tested demonstrated excellent activity against ORSA strains. Of the topical antimicrobial agents tested only bacitracin, mupirocin, and nitrofurantoin were active against all OSSA and ORSA strains tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Diagnostic applications of DNA probes.

This review has described several of the most common molecular biologic techniques that are, or will be, employed in the diagnostic laboratory. The potential advantages of these DNA probe assays in the diagnosis of infectious diseases include: rapid detection and identification of infectious agents; the ability to screen selected specimens using batteries of probes; and the detection of nonviable or difficult-to-culture organisms. The potential disadvantages of DNA probe assays include: the use of isotopic detection methods for optimum sensitivity; limited diagnostic sensitivity of current assays; slow turna-round time for some assay formats; expense of current reagents; limited availability of many probes; lack of technical expertise in most diagnostic laboratories; and the requirement for antimicrobial susceptibility testing (requires culture). Given the above advantages and disadvantages, there are several key issues that must be considered before adopting DNA probe technology in the diagnostic laboratory; the cost of performing routine culture and identification versus the cost of screening with probes--both the number and type of specimens and the time savings that may be realized by eliminating routine cultures; the prevalence of the infectious agent--even the best DNA probe assay may not be useful or practical in a low-prevalence situation; the need for additional equipment and space; and the interpretation of false-positive and false-negative results--additional research is needed in this area. However, laboratories must consider these issues when using a test other than the current gold standard (i.e., culture). DNA probe technology is with us and expanding rapidly. The intelligent application of this new technology will require communication between laboratorians and clinicians and careful consideration of the many advantages and disadvantages discussed above.

Blotting, Southern↗

Multicenter evaluation of the in vitro activities of three new quinolones, sparfloxacin, CI-960, and PD 131,628, compared with the activity of ciprofloxacin against 5,252 clinical bacterial isolates.

The in vitro activities of three new quinolones (sparfloxacin, CI-960, and PD 131,628) were compared with that of ciprofloxacin against 5,252 routine clinical aerobic and facultatively anaerobic bacterial isolates. Overall, CI-960 was the most active drug in vitro (MIC for 90% of the strains tested, 0.13 micrograms/ml); ciprofloxacin and sparfloxacin were the least active (MIC for 90% of the strains tested, 1.0 micrograms/ml). All three new quinolones, but particularly CI-960 and PD 131,628, exhibited significantly greater activity than ciprofloxacin against enterococci and staphylococci.

Anti-Infective Agents↗

In vitro comparison of GR69153, a novel catechol-substituted cephalosporin, with ceftazidime and ceftriaxone against 5,203 recent clinical isolates.

The activity of GR69153, a novel catechol-substituted cephalosporin, was compared with those of ceftazidime and ceftriaxone in a multicenter study against 5,203 fresh clinical isolates of gram-negative and gram-positive bacteria. GR69153 was generally very active at concentrations equivalent to or two- to fourfold lower than those of ceftazidime and ceftriaxone against gram-negative bacilli other than Citrobacter freundii, Enterobacter cloacae, and Xanthomonas maltophilia. Against Pseudomonas aeruginosa, MICs of GR69153 and ceftazidime for 50% of isolates tested (MIC50s) were, respectively, 1 and 2 micrograms/ml; the corresponding MIC90s were 4 and 16 micrograms/ml. Although MIC50s of GR69153 for staphylococci were two- to eightfold lower than those of ceftazidime or ceftriaxone, MIC90s against staphylococci and enterococci were greater than or equal to 16 micrograms/ml for all three compounds. Quality control MIC ranges for reference strains are proposed for the broth microdilution method on the basis of the GR69153 data derived from this multicenter study.

Bacteria↗

Interpretive criteria and quality control guidelines for Neisseria gonorrhoeae susceptibility test standardization for cefotetan.

Cefotetan was tested in a multilaboratory study to standardize susceptibility testing criteria and quality control guidelines for Neisseria gonorrhoeae. Cefotetan was most active against penicillinase-producing and penicillin-susceptible strains (MIC for 50% of strains tested, 0.5 micrograms/ml) and was least active against the chromosomally resistant isolates (MIC for 50% of strains tested, 2 micrograms/ml). The recommended 30-micrograms disk cefotetan interpretive criteria were as follows: susceptible at greater than or equal to 26 mm (less than or equal to 2 micrograms/ml), intermediate at 20 to 25 mm (4 micrograms/ml), and resistant at less than or equal to 19 mm (greater than or equal to 8 micrograms/ml). Quality control guidelines for agar dilution and disk diffusion tests were established by using numerous GC agar lots, three cefotetan 30-micrograms disk lots, two quality control organisms, and a volume of tests consistent with National Committee for Clinical Laboratory Standards M23-T guidelines.

Cefotetan↗

Restriction fragment analysis of a Candida tropicalis outbreak of sternal wound infections.

An apparent single-source outbreak of Candida tropicalis sternal wound infections in eight patients was investigated by utilizing DNA restriction fragment analysis (RFA) with HindIII and BstNI. All eight outbreak isolates appeared to be identical and were easily differentiated from control isolates by DNA RFA. Compared with an arbitrarily selected reference outbreak isolate, greater than or equal to 95% of the bands in the restriction digests identified by a computerized image analysis system from each of the outbreak isolates were identical versus 13 to 53% of the bands in any of the nine control isolates. Outbreak strains were significantly more likely to match the reference outbreak isolate than were controls (P less than 0.0001). The RFA was greatly facilitated by the use of computerized image analysis and confirmed the epidemiologic link between a scrub nurse and the infected patients.

Candida↗

Comparison of the autoSCAN-W/A rapid bacterial identification system and the Vitek AutoMicrobic system for identification of gram-negative bacilli.

The autoSCAN-W/A (W/A; Baxter MicroScan, West Sacramento, Calif.) with the new fluorometric Rapid Neg Combo 1 (RNC) panel is a fully automated fluorometric system for identification of both enteric and nonenteric gram-negative bacilli within 2 h. We compared the W/A with the Vitek AutoMicrobic System (Vitek AMS; Vitek Systems, Inc., Hazelwood, Mo.) for identification of 383 clinical isolates of gram-negative bacilli. The API 20E (Analytab Products, Plainview, N.Y.) and conventional biochemical testing were used as the reference systems. The W/A correctly identified 336 isolates (87.7%) to the species level and classified an additional 29 isolates (7.6%) as correct with low probability (overall identification = 95.3%); the Vitek AMS correctly identified 355 isolates (92.7%) to the species level and classified an additional 8 isolates (2.1%) as correct with low probability (overall identification = 94.8%). A common set of 134 isolates of gram-negative bacilli was tested in both participating laboratories as a means of assessing interlaboratory agreement with both the W/A and the Vitek AMS. The overall agreements between the two laboratories were 86% with the W/A and 92% with the Vitek AMS. The W/A performed comparably to the Vitek AMS for identification of most gram-negative bacilli, actually exceeding the Vitek AMS for identification of nonenteric bacilli. Rapid time to identification and a high level of automation make the W/A an attractive system for clinical microbiology laboratories.

Bacteriological Techniques↗

Candida zeylanoides: another opportunistic yeast.

A patient with a long history of scleroderma and gastrointestinal malabsorption requiring total parenteral nutrition was admitted with Candida zeylanoides fungemia. The yeast responded to therapy, but on two subsequent admissions for episodes of fever the blood cultures yielded the same yeast. The identity of the Candida species was established biochemically by both the API (Analytab) and Vitek system approaches. C. zeylanoides ATCC 20356 and ATCC 7351 served as controls for these analyses and for antifungal susceptibility studies and restriction endonuclease analyses of chromosomal DNA. These investigations indicated that representative isolates of the yeasts from the three episodes were identical and differed in several respects from the ATCC strains, which did not share many of the characteristics bands with the DNA restriction fragment analysis. C. zeylanoides variants capable of tolerating 35 degrees C can complicate the recovery of patients, especially individuals compromised by their underlying disease.

Amphotericin B↗

Nosocomial pneumonia in adult patients undergoing bone marrow transplantation: a 9-year study.

Two hundred seventy-five consecutive patients treated with bone marrow transplantation (BMT) during a 9-year interval were analyzed for the incidence and etiology of nosocomial pneumonia. Cases included adults who acquired pneumonia during the first hospitalization period within 100 days of the transplant. Fifty-five (20%) of the 275 patients developed nosocomial pneumonia, and the crude mortality during the hospitalization period was 74.5%. An etiology was established in 67.3% (37 of 55) of episodes. Thirty-six percent (20 of 55) of the cases were caused by Aspergillus species, either as the sole agent (15 patients) or in association with others. The crude mortality for patients with Aspergillus pneumonia was 95%. Elimination of 90% of Aspergillus cases in our unit would have the effect of reducing the overall attack rate of nosocomial pneumonia to 13.4% and the associated crude mortality to 43.4%.

Adult↗