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Biomedical subjects

M A Pfaller

Publications and source records attributed to M A Pfaller.

At least 433 records · Page 24Linked to original sources

Risk factors for hospital-acquired candidemia. A matched case-control study.

Nosocomial candidemia has become an important infection not only because of an apparently increasing incidence but also because of its high fatality rate. We studied 28 risk factors through a matched case-control study that included 88 pairs of patients hospitalized between July 1983 and December 1986. The strongest single risk factor found in the univariate analysis was the number of prior antibiotics administered: the exposure odds ratio (OR) was 12.50 when patients who received three to five antibiotics were compared with those who received none to two antibiotics. A multiple logistic regression analysis using a conditional likelihood method was performed to evaluate several risk factors simultaneously. The final model selected by a stepwise procedure included the following variables: number of antibiotics received prior to infection (OR, 1.73 per unit increase), isolation of Candida species from sites other than blood (OR, 10.37), prior hemodialysis (OR, 18.13), and prior use of a Hickman catheter (OR, 7.23). It remains to be shown in controlled clinical trials whether limiting the number of antibiotics or instituting prophylaxis and/or early treatment for high-risk patients will reduce the incidence of nosocomial candidemia.

Anti-Bacterial Agents↗

Disseminated Fusarium infections in patients following bone marrow transplantation.

Intensive immunosuppressive therapy and broad spectrum antibiotics predispose cancer patients to opportunistic fungal infections. Fusarium has rarely been reported as a pathogen in immunocompromised patients, but is almost uniformly fatal. Only six cases of disseminated Fusarium infection have been described in patients following bone marrow transplantation (BMT). We report here two additional cases. Fusarium infection initially presented with pyomyositis in one patient and with embolic skin lesions in another following T cell-depleted BMT. Both patients died with active Fusarium infection despite an extensive course of amphotericin B, rifampicin and granulocyte transfusions. From this experience and from a review of the literature, Fusarium infections appear to be increasing in prevalence as significant pathogens in immunocompromised hosts and are resistant to many conventional forms of therapy.

Adult↗

Removal of nosocomial pathogens from the contaminated glove. Implications for glove reuse and handwashing.

STUDY OBJECTIVE: To evaluate the effectiveness of three different types of handcleansing agents in decontaminating gloved hands that were inoculated with a series of four nosocomial pathogens. DESIGN: A controlled, experimental trial. SETTING: Tertiary care referral center. PATIENTS OR OTHER PARTICIPANTS: Five healthy volunteers participated in all portions of the study. INTERVENTIONS: A standard concentration of one of four representative nosocomial pathogens was placed on the gloved hand, spread, and allowed to dry. One of three different handcleansing agents--a nonmedicated soap, a 60% isopropyl alcohol preparation, or 4% chlorhexidine gluconate--was used to cleanse the gloves, which were cultured using a broth-bag technique. The gloves were then removed and the hands were cultured in a similar manner. MEASUREMENTS AND MAIN RESULTS: The handwashing agents reduced the median log10 counts of organisms to 2.1 to 3.9 after an inoculation of 10(7) colony forming units. The proportion of positive glove cultures for Staphylococcus aureus, 8% to 100%; Serratia marcescens, 16% to 100%; and Candida albicans, 4% to 60% varied greatly after use of the different handcleansers (P less than 0.001), and varied considerably for Pseudomonas aeruginosa, 20% to 48% (P = 0.085). After the gloves were removed, the differences among the observed proportions of hands contaminated with the test organisms varied from 5% to 50%, depending on the handcleansing agent used (P less than 0.001). CONCLUSIONS: In the era of universal precautions these data suggest that it may not be prudent to wash and reuse gloves between patients. Further, handwashing is strongly encouraged after removal of gloves.

1-Propanol↗

Hospital-acquired candidemia. The attributable mortality and excess length of stay.

Between 1977 and 1984, estimates of hospital-acquired bloodstream infections caused by Candida species increased in the United States from 0.5 to 1.5 per 10,000 admissions (National Nosocomial Infection Study data). We examined crude and attributable mortality rates and excess length of stay in 88 closely matched pairs of cases and controls with illnesses occurring between July 1983 and December 1986. The crude mortality rates for cases and controls were 57% and 19%, respectively; thus the attributable mortality rate was 38% with a 95% confidence interval of 26% to 49%. The risk ratio was 2.94 with a 95% confidence interval of 1.95 to 4.43. The median length of stay was 48 days for all cases and 40 days for all controls. An analysis of the length of stay for the 34 matched pairs that survived showed a median of 70 days for cases and 40 days for controls. Candida bloodstream infections represented 10% of all nosocomial bloodstream infections in the period studied at our University Hospital; they are associated with a significant medical and economic burden well above that expected of the underlying diseases alone.

Adolescent↗

Comparison of the lysis centrifugation and radiometric blood culture systems for recovery of yeast.

The performance of the Isolator (lysis centrifugation) and Bactec (radiometric) detection systems for the recovery of fungi from blood was studied prospectively by comparison of 2,188 paired cultures obtained at two geographically separated teaching hospitals. Eight-three yeast isolates were recovered from 78 (3.6%) cultures that were obtained from 43 patients. Seventy-three (88%) yeast strains were recovered using the Isolator system, and 60 (72%) were recovered in the Bactec system. The average time for recovery of yeast was 2.3 days for the Isolator system and 3.1 days for the Bactec system. Optimal recovery can be accomplished through the use of both systems.

Blood↗

Prospective evaluation of the Gen-Probe assay for detection of legionellae in respiratory specimens.

A prospective evaluation of a DNA probe assay for detection of Legionella species was performed on 427 consecutive respiratory specimens submitted over an 18-month period. The Gen-Probe assay utilizing both low (greater than or equal to 4.0) and high (greater than 7.0) ratio threshold values was compared to direct fluorescent antibody staining (DFA) as a predictor of isolation of Legionella on culture. The highest sensitivity (63%) was obtained with the lower threshold ratio, but was not significantly different from the result obtained with a threshold ratio of greater than 7.0 (50%, p = 0.722) or DFA results (44%, p = 0.479). The specificity of the DNA probe assay was improved with the high threshold (99%) compared either to the low threshold ratio (95%, p = 0.002) or DFA (97%, p = 0.055). When the DNA probe was compared to DFA and/or Legionella isolation on culture, a significantly lower specificity (97% versus 99%, p = 0.0006) and higher sensitivity (74% versus 37%, p = 0.013) was obtained with a threshold value of greater than or equal to 4.0 than greater than 7.0. Ten of 20 specimens with a DNA probe ratio between 4.0 and 7.0 were DFA positive, although only two were isolated on culture. The DFA assay and both probe threshold ratios have a high negative predictive value when compared to culture. However, only the threshold ratio of greater than 7.0 has a sufficiently high positive predictive value to be useful alone.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Probes↗

In vitro activity of FCE 22101, imipenem, and ceftazidime against over 6,000 bacterial isolates and MIC quality control limits of FCE 22101.

Six geographically separate laboratories within the USA tested 6,198 bacterial isolates against FCE 22101 (a penem), imipenem (a carbapenem) and ceftazidime (a third-generation cephalosporin). Ninety-three percent of 2,749 Enterobacteriaceae were inhibited by FCE 22101, while 95% were susceptible to ceftazidime and 99% were susceptible to imipenem. FCE 22101 had little activity against Pseudomonas spp. but was active against most gram-positive pathogens, including enterococci. FCE 22101 MICs for standard quality control strains were defined as 0.5-2.0 micrograms/ml for Escherichia coli ATCC 25922, 2-8 micrograms/ml for Enterococcus faecalis ATCC 29212 and 0.06-0.25 microgram/ml for Staphylococcus aureus ATCC 29213.

Anti-Bacterial Agents↗

Influence of in vitro susceptibility testing conditions on the anti-candidal activity of LY121019.

LY121019 is a new antifungal antimicrobic that is structurally similar to the lipopeptide agents echinocandin B and aculeacin A. Because of the importance of in vitro test conditions on the activity of other antifungal agents, we studied the effects of inoculum size, time and temperature of incubation, pH, and medium composition on the in vitro activity of LY121019 against Candida albicans, Candida tropicalis, and Candida parapsilosis. LY121019 was highly active against Candida albicans and Candida tropicalis and inactive against Candida parapsilosis. The in vitro activity of LY121019 is marked by a paradoxical dose-response with isolates of Candida albicans and Candida tropicalis and is influenced by choice of inoculum size, time and temperature of incubation, medium composition, and pH. We recommend the use of an inoculum size of less than 10(5) organisms/ml, a defined medium buffered to a pH of 7.0, and incubation at 30 degrees C for 24 hr for future in vitro studies of LY121019.

Amphotericin B↗

Multicenter in vitro evaluation of lomefloxacin (NY-198, SC-47111), including tests against nearly 7,000 bacterial isolates and preliminary recommendations for susceptibility testing.

Lomefloxacin (NY-198 or SC-47111) is a difluoro-quinolone derivative having a C-methyl at the 3-position of the piperazine ring, thus minimizing its metabolic alteration in vivo. In our research, its antimicrobial activity was most similar to that of difloxacin, enoxacin, fleroxacin, and norfloxacin but usually less than that of ciprofloxacin and ofloxacin against most species. Lomefloxacin shared cross-resistance with other 4-quinolones but remained very active against ceftazidime-resistant organisms, including stably derepressed beta-lactamase producing Gram-negative bacilli. Lower pH increased the lomefloxacin MICs. MBCs were usually identical to the measured MIC, and the lomefloxacin MICs were not significantly increased by high inoculum concentrations. The Enterobacteriaceae were found to have a very low rate of spontaneous mutation to lomefloxacin resistance (10(-8)-10(-9). In vitro tests by 5-micrograms and 10-micrograms lomefloxacin disks and dilution methods were correlated, and the 10-micrograms disk was recommended for clinical trials using a less than or equal to 4 micrograms/ml susceptible breakpoint. The quality assurance guidelines for dilution tests were determined by a multilaboratory study.

4-Quinolones↗

Evaluation of laboratory methods for the classification of oxacillin-resistant and oxacillin-susceptible Staphylococcus aureus.

The purpose of this study was to examine the efficacy of the oxacillin disk diffusion test and the methicillin and oxacillin agar screen tests as predictors of oxacillin resistance as defined by the reference broth microdilution method. A total of 444 clinical isolates of Staphylococcus aureus collected from individual patients over a four-year period were tested by (1) the oxacillin disk diffusion test, with particular attention to the presence of fine growth of a resistant subpopulation within the zone of inhibition (Ox Grow interpretive criteria); (2) the agar screen method using agar plates with 4% NaCl and either 6 mg/L oxacillin or 10 mg/L methicillin; and (3) the oxacillin and methicillin broth microdilution test methods with 2% NaCl supplementation. Overall, 62 (14%) isolates were resistant and 382 (86%) isolates were susceptible to oxacillin with the use of the reference broth microdilution system. The results indicate that the disk diffusion test with the use of the Ox Grow criteria had a high sensitivity (94%) and negative predictive value (98%) but a low specificity (67%) and positive predictive value (32%) when compared with the reference broth dilution test. Similarly, the agar screen tests had a high sensitivity (95-97%) and negative predictive values (99%) but low specificity (64-74%) and positive predictive values (30-37%). These data indicate that the agar screen tests and the oxacillin disk test with the use of the Ox Grow interpretive criteria may be useful as screening tests for detecting resistance to the penicillinase-resistant penicillins but that all resistant isolates should be confirmed by the reference broth dilution method because of the large number of false-resistant screening test results.

Bacteriological Techniques↗

Implications of acquired oxacillin resistance in the management and control of Staphylococcus aureus infections.

Refinements in testing for resistance to penicillinase-resistant penicillins (PRP) in Staphylococcus aureus have resulted in confusion in classifying isolates as PRP susceptible or resistant. Specifically, a group of organisms has been identified that produce large amounts of beta-lactamase and appear borderline resistant. These organisms have been called "occult resistant" or "acquired oxacillin-resistant" S. aureus (AORSA). A retrospective study was conducted to evaluate the implication of this in vitro phenomenon in managing patients with AORSA infections. Among 134 patients with S. aureus infections, 89 were infected with oxacillin-susceptible S. aureus (OSSA), 26 with AORSA, and 19 with oxacillin-resistant S. aureus (ORSA). There were no significant differences in outcomes when OSSA and AORSA infections were treated with PRP (chi 2MH = .990; P = .32). These results do not suppor the contention that AORSA infections should be managed differently from OSSA infections. Identifying AORSA may not be helpful in guiding antimicrobial therapy or predicting the outcome of infections with AORSA.

Adult↗

Laboratory, clinical, and epidemiological aspects of coagulase-negative staphylococci.

Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, are increasingly important causes of nosocomial infection. Microbiologists and clinicians no longer can afford to disregard clinical isolates of coagulase-negative staphylococci as contaminants. Accurate species identification and antimicrobial susceptibility testing, in a clinically relevant time frame, are important aids in the diagnosis and management of serious coagulase-negative staphylococcal infections. Emphasis in the clinical laboratory should be placed on the routine identification of S. epidermidis and Staphylococcus saprophyticus, with identification of other species of coagulase-negative staphylococci as clinically indicated. The application of newer techniques, such as plasmid analysis and tests for slime production and adherence, contribute to our understanding of the epidemiology and pathogenesis of coagulase-negative staphylococci and may also be helpful in establishing the diagnosis of infection.

Coagulase↗

Comparison of the Quantum II, API Yeast Ident, and AutoMicrobic systems for identification of clinical yeast isolates.

The Quantum II Yeast Identification System (Abbott Laboratories) is a microprocessor-based spectrophotometric system for identification of clinical yeast isolates within 24 h. We compared the Quantum II system with the API Yeast Ident (Analytab Products) and the AutoMicrobic System Yeast Biochemical Card (AMS-YBC; Vitek Systems, Inc.) for the identification of 221 clinical yeast isolates, including 120 common clinical isolates (Candida albicans, C. tropicalis, C. parapsilosis, Torulopsis glabrata, and Cryptococcus neoformans) and 101 relatively uncommon clinical isolates. The API 20C (Analytab) was used as the reference system. The Quantum II and AMS-YBC systems correctly identified 181 (82%) and 184 (83%) isolates, respectively, whereas the Yeast Ident system correctly identified 132 (60%) isolates. Of the 120 common clinical isolates, 113 (94%) were correctly identified by Quantum II, 103 (86%) were correctly identified by AMS-YBC, and 83 (69%) were correctly identified by Yeast Ident. Of the 101 uncommon clinical isolates tested, 68 (67%) were correctly identified by Quantum II, 81 (80%) were correctly identified by AMS-YBC, and 49 (49%) were correctly identified by Yeast Ident. The overall accuracy of the Quantum II, AMS-YBC, and API Yeast Ident was not sufficient to recommend any of these systems for routine use in the clinical microbiology laboratory without substantial expansion of the respective data bases.

Diagnostic Errors↗

Multicenter evaluation of four methods of yeast inoculum preparation.

We initiated a comparative study of four methods of yeast inoculum preparation: a spectrophotometric method, the Wickerham card method, a hemacytometer method, and the Prompt inoculation system. The variability in inoculum size obtained when each method was applied to two strains each of Candida albicans, Candida tropicalis, Candida parapsilosis, Torulopsis glabrata, Cryptococcus neoformans, and Saccharomyces cerevisiae was analyzed in a single laboratory. Each method was performed in triplicate on the same day and on three separate days to provide estimates of within-day and between-day variations. Inoculum size was determined by viable colony counts. The greatest range of inoculum sizes was seen with the Wickerham card method. Viable counts ranged from 1.1 X 10(6) to 24.2 X 10(6) CFU/ml among the 12 yeast isolates. The greatest variation was observed with the Prompt system. Within-day coefficients of variation averaged 19% (range, 4 to 45%), and between-day coefficients of variation averaged 22% (range, 3 to 51%). Variation between laboratories was evaluated by comparing inoculum values obtained by each method in three different laboratories for two strains of C. albicans. The spectrophotometric method was the least variable and the Wickerham card and hemacytometer methods were the most variable methods between laboratories. The spectrophotometric method is recommended as the method of choice for preparation of a standardized inoculum suspension for susceptibility testing of yeasts.

Candida↗

Polyamine depletion and growth inhibition in Candida albicans and Candida tropicalis by alpha-difluoromethylornithine and cyclohexylamine.

The ability of two known inhibitors of polyamine synthesis, alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and cyclohexylamine, an inhibitor of spermidine synthase, to inhibit the in vitro growth and polyamine synthesis of clinical isolates of Candida tropicalis and Candida albicans was examined. Treatment of C. tropicalis and C. albicans with either DFMO or cyclohexylamine resulted in depletion of cellular polyamines and inhibition of growth. The growth inhibition produced by each of these compounds was completely reversed by exogenous polyamines. Depletion of polyamines by low concentrations of DFMO significantly enhanced the growth inhibitory activity of cyclohexylamine versus C. albicans. DFMO inhibited ODC activity in both C. albicans and C. tropicalis. These findings document the ability of cyclohexylamine and DFMO to inhibit polyamine synthesis and growth in clinically important species of Candida.

Candida↗

Growth inhibition of pathogenic yeast isolates by alpha-difluoromethylornithine: an inhibition of ornithine decarboxylase.

A large body of evidence exists suggesting that polyamines can play essential roles in cellular growth and differentiation. We examined the ability of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, the major rate-limiting enzyme in polyamine biosynthesis, to inhibit the growth of Candida albicans, C. tropicalis, and C. parapsilosis. Substantial growth-inhibition was observed for all three species at DFMO concentrations ranging from 1 to 100 mM. C. tropicalis was significantly more susceptible to DFMO than C. albicans or C. parapsilosis. Depletion of cellular polyamine pools was seen in all 3 species following exposure to DFMO and polyamine depletion enhanced the susceptibility of the organisms to DFMO. The action of DFMO was specifically antagonized by exogenous polyamines. These data suggest that polyamines are important in the growth of Candida spp. and that inhibitors of polyamine biosynthesis may be useful as antifungal agents.

Candida↗