Biomedical subjects

M A Pfaller

Publications and source records attributed to M A Pfaller.

At least 55 records · Page 3Linked to original sources

PubMed2004

Geographic variation in the susceptibilities of invasive isolates of Candida glabrata to seven systemically active antifungal agents: a global assessment from the ARTEMIS Antifungal Surveillance Program conducted in 2001 and 2002.

We examined the susceptibilities to amphotericin B, flucytosine, fluconazole, posaconazole, ravuconazole, voriconazole, and caspofungin of 601 invasive isolates of Candida glabrata and grouped the isolates by geographic location: North America (331 isolates), Latin America (58 isolates), Europe (135 isolates), and Asia-Pacific (77 isolates). Caspofungin (MIC at which 90% of isolates tested are susceptible [MIC(90)], 0.12 microg/ml; 100% of strains are susceptible [S] at a MIC of </=1 microg/ml) and flucytosine (MIC(90), 0.12 microg/ml; 99.2% S) were the most active agents in all geographic regions. Fluconazole susceptibility was highest in the Asia-Pacific region (80.5% S, 3.9% resistant [R]) and lowest in North America (64% S, 10.3% R) and Latin America (62.1% S, 3.4% R). The extended-spectrum triazoles were most active in the Asia-Pacific region (90 to 96.1% S) and least active in North America (82.5 to 90.3% S). All 46 isolates that were resistant to fluconazole were susceptible to caspofungin (MIC(90), 0.06 microg/ml) and flucytosine (MIC(90), 0.12 microg/ml) and exhibited variable cross-resistance to posaconazole, ravuconazole, and voriconazole.

Antifungal Agents↗

PubMed2004

Comparison of results of fluconazole disk diffusion testing for Candida species with results from a central reference laboratory in the ARTEMIS global antifungal surveillance program.

The accuracy of antifungal susceptibility tests is important for accurate resistance surveillance and for the clinical management of patients with serious infections. Our main objective was to compare the results of fluconazole disk diffusion testing of Candida spp. performed by ARTEMIS participating centers with disk diffusion and MIC results obtained by the central reference laboratory. A total of 2,949 isolates of Candida spp. were tested by NCCLS disk diffusion and reference broth microdilution methods in the central reference laboratory. These results were compared to the results of disk diffusion testing performed in the 54 participating centers. All tests were performed and interpreted following NCCLS recommendations. Overall categorical agreement between participant disk diffusion test results and reference laboratory MIC results was 87.4%, with 0.2% very major errors (VME) and 3.3% major errors (ME). The categorical agreement between the disk diffusion test results obtained in the reference laboratory with the MIC test results was similar: 92.8%. Likewise, good agreement was observed between participant disk diffusion test results and reference laboratory disk diffusion test results: 90.4%, 0.4% VME, and 3.4% ME. The disk diffusion test was especially reliable in detecting those isolates of Candida spp. that were characterized as resistant by reference MIC testing. External quality assurance data obtained by surveillance programs such as the ARTEMIS Global Antifungal Surveillance Program ensure the generation of useful surveillance data and result in the continued improvement of antifungal susceptibility testing practices.

Antifungal Agents↗

PubMed2003

Pathogen frequency and resistance patterns in Brazilian hospitals: summary of results from three years of the SENTRY Antimicrobial Surveillance Program.

BACKGROUND: Pathogen frequency and resistance patterns may vary significantly from country to country and also in different hospitals within a country. Thus, regional surveillance programs are essential to guide empirical therapy and infection control measures. METHODS: Rank order of occurrence and antimicrobial susceptibility of pathogenic species causing bloodstream infections (BSI), lower respiratory tract infections (LRTI), wound or skin and soft tissue infections (WSSTI), and urinary tract infections (UTI) in hospitalized patients were determined by collecting consecutive isolates over a specified period of time, as part of the SENTRY Antimicrobial Resistance Surveillance Program (SENTRY). All isolates were tested by reference broth microdilution. RESULTS AND CONCLUSIONS: A total of 3,728 bacterial strains were obtained from January, 1997, to December, 1999, from 12 Brazilian hospitals located in 4 states. The largest number of isolates were obtained from patients with BSI (2,008), followed by LRTI (822 cases), UTI (468 cases), and WSSTI (430 cases). Staphylococcus aureus was the most frequently isolated pathogen in general (22.8% - 852 isolates), followed by E. coli (13.8% - 516 cases) and Pseudomonas aeruginosa (13.3% - 496 cases). Staphylococcus aureus was also the most common species isolated from BSI (23.6%) and WSSTI (45.8%), and P. aeruginosa was the most frequent species isolated from patients with LRTI (29.4%). The main bacterial resistance problems found in this study were: imipenem resistance among P. aeruginosa (69.8% susceptibility) and Acinetobacter spp. (88.1% susceptibility); ESBL production among K. pneumoniae (48.4%) and E. coli (8.9%); resistance to third generation cephalosporins among Enterobacter spp. (68.1% susceptible to ceftazidime) and oxacillin resistance among S. aureus (34.0%) and coagulase negative staphylococci (80.1%). Only the carbapenems (88.1% to 89.3% susceptibility) showed reasonable activity against the Acinetobacter spp. isolates evaluated.

Anti-Bacterial Agents↗

PubMed2003

In vitro susceptibility testing of filamentous fungi: comparison of Etest and reference M38-A microdilution methods for determining posaconazole MICs.

The performance of the Etest for posaconazole susceptibility testing of 72 isolates of filamentous fungi was assessed in comparison with the National Committee for Clinical Laboratory Standards (NCCLS) approved standard broth microdilution method (M38-A). The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48h at 35 degrees C. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48h at 35 degrees C. The isolates included Aspergillus fumigatus, A. flavus, A. nidulans, A. niger, A. versicolor, A. oryzae, A. terreus, Cladosporium spp., Curvularia sp., Exophiala sp., Fusarium spp., Paecilomyces spp., Pithomyces sp., Penicillium spp. and Scedosporium apiospermum. Overall agreement between Etest and microdilution MICs was 84% for Aspergillus spp. and 100% for the less common opportunistic molds, with the exception of Penicillium spp. (67%). Where a discrepancy was observed between Etest and the reference method, the Etest tended to give lower values. The Etest method using RPMI agar appears to be a useful method for determining posaconazole susceptibilities of filamentous fungi.

Antifungal Agents↗

PubMed2003

Antimicrobial activity against strains of Escherichia coli and Klebsiella spp. with resistance phenotypes consistent with an extended-spectrum beta-lactamase in Europe.

Extended-spectrum beta-lactamases (ESBLs) have continued to evolve after their initial detection in Europe nearly two decades ago. The summary results from the MYSTIC Program (31 medical centers) were utilized to assess the extent of ESBL occurrence in Europe from 1997 to 2000. ESBL phenotype rates in Klebsiella spp. (32.8%) and Escherichia coli (14.4%) were generally stable, but extensive hospital-to-hospital and unit-to-unit variations were noted. The highest ESBL rates were found in eastern Europe (including Turkey) and in intensive care unit patient populations. Carbapenems remained active against the ESBL-producing strains (meropenem MIC90, 0.25-1 mg/L), while some other agents, such as aminoglycosides, fluoroquinolones, and piperacillin-tazobactam, were significantly less effective. International surveillance initiatives should be maintained to monitor future progression of this important resistance.

Anti-Bacterial Agents↗

PubMed2003

In vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp., including 157 fluconazole-resistant isolates.

Caspofungin is an echinocandin antifungal agent with broad-spectrum activity against Candida and Aspergillus spp. The in vitro activities of caspofungin against 3,959 isolates of Candida spp. obtained from over 95 different medical centers worldwide were compared with those of fluconazole and itraconazole. The MICs of the antifungal drugs were determined by broth microdilution tests performed according to the NCCLS method using RPMI 1640 as the test medium. Caspofungin was very active against Candida spp. (MIC at which 90% of the isolates were inhibited [MIC(90)], 1 micro g/ml; 96% of MICs were < or =2 micro g/ml). Candida albicans, C. dubliniensis, C. tropicalis, and C. glabrata were the most susceptible species of Candida (MIC(90), 0.25 to 0.5 micro g/ml), and C. guilliermondii was the least susceptible (MIC(90), >8 micro g/ml). Caspofungin was very active against Candida spp., exhibiting high-level resistance to fluconazole and itraconazole (99% of MICs were < or =1 micro g/ml). These results provide further evidence for the spectrum and potency of caspofungin activity against a large and geographically diverse collection of clinically important isolates of Candida spp.

Anti-Bacterial Agents↗

PubMed2003

Characterization of heteroresistance to fluconazole among clinical isolates of Cryptococcus neoformans.

Strains of Cryptococcus neoformans expressing heteroresistance to fluconazole have been described previously. The present study was conducted to investigate the prevalence of heteroresistance among clinical isolates of C. neoformans and to characterize the heteroresistant phenotypes. A total of 107 clinical isolates of C. neoformans for which the MICs of fluconazole ranged from 0.25 to 32 microg/ml were selected. The isolates were chosen to represent a broad geographic distribution. Of the 107 C. neoformans isolates tested, 4 grew on medium containing fluconazole at concentrations that were four to eight times higher than the MICs for each strain. A fifth isolate, for which the fluconazole MIC was 32 microg/ml, grew on agar with 64 microg of fluconazole per ml. These five isolates (4.7% of the total number) were confirmed to exhibit heteroresistant compositions by population analysis. The degree and frequency of resistance varied among the isolates. Stepwise selection by exposure to fluconazole resulted in subclones of all five strains for which the fluconazole MIC was >64 microg/ml. Subclones of three strains demonstrated a homogeneous population of resistant cells on medium containing 64 microg of fluconazole/ml. The resistance was sensitive to incubation temperature, that is, heteroresistance was demonstrable only at 30 degrees C by agar-based tests, and was reversible through serial transfers on fluconazole-free medium over a period of 8 days. These results suggest that the fluconazole-heteroresistant phenotype of C. neoformans exists in a significant proportion of clinical isolates and that fluconazole resistance can be developed by selection from heteroresistant clones and induction by exposure to fluconazole.

Antifungal Agents↗

PubMed2003

In vitro activities of voriconazole, posaconazole, and four licensed systemic antifungal agents against Candida species infrequently isolated from blood.

We determined the in vitro susceptibilities of 314 strains of Candida spp., representing 13 species rarely isolated from blood, to posaconazole and voriconazole as well as four licensed systemic antifungal agents (amphotericin B, flucytosine, fluconazole, and itraconazole). The organisms included 153 isolates of C. krusei, 67 isolates of C. lusitaniae, 48 isolates of C. guilliermondii, 10 isolates of C. famata, 10 isolates of C. kefyr, 6 isolates of C. pelliculosa, 5 isolates of C. rugosa, 4 isolates of C. lipolytica, 3 isolates of C. dubliniensis, 3 isolates of C. inconspicua, 2 isolates of C. sake, and 1 isolate each of C. lambica, C. norvegensis, and C. zeylanoides. MIC determinations were made by the National Committee for Clinical Laboratory Standards reference broth microdilution method and Etest (amphotericin B). Resistance to both amphotericin B and fluconazole was observed in strains of C. krusei, C. lusitaniae, C. guilliermondii, C. inconspicua, and C. sake. Resistance to amphotericin B, but not to fluconazole, was also observed among isolates of C. kefyr and C. rugosa. Posaconazole and voriconazole were active (MIC, < or = 1 micro g/ml) against 94 to 100% of these isolates. In contrast to the more common species of Candida causing bloodstream infection, these rare species appear to be less susceptible to the currently licensed systemic antifungal agents, with the exception of voriconazole. Continued surveillance will be necessary to detect the emergence of these species as more prevalent, resistant pathogens. The new triazoles appear to offer acceptable coverage of uncommon Candida sp. bloodstream infections.

Antifungal Agents↗

PubMed2003

Evaluation of Etest method for determining voriconazole and amphotericin B MICs for 162 clinical isolates of Cryptococcus neoformans.

The performance of the Etest for voriconazole and amphotericin B susceptibility testing of 162 isolates of Cryptococcus neoformans was assessed against the National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 72 h at 35 degrees C. MICs were determined by Etest for all 162 isolates with RPMI 1640 agar containing 2% glucose (RPG agar) and were read after incubation for 72 h at 35 degrees C. The Etest results for both voriconazole and amphotericin B correlated well with reference MICs. Agreement was 94% for voriconazole and 99% for amphotericin B. When discrepancy was noted between the results obtained by Etest and broth microdilution for voriconazole, the Etest generally provided a higher MIC. The Etest method using RPG agar appears to be a useful method for determining the susceptibility of C. neoformans to voriconazole and amphotericin B.

Amphotericin B↗

PubMed2003

Exophiala oligosperma causing olecranon bursitis.

A 62-year-old male with a history of Wegener's granulomatosis and immunosuppressive therapy presented with chronic olecranon bursitis. A black velvety mould with brown septate hyphae and tapered annellides was isolated from a left elbow bursa aspirate and was identified as an Exophiala species. Internal transcribed sequence rRNA sequencing showed the isolate to be identical to Exophiala oligosperma. The patient was successfully treated with aspiration and intrabursal amphotericin B.

Bursa, Synovial↗

PubMed2003

Evaluation of Etest method for determining fluconazole and voriconazole MICs for 279 clinical isolates of Candida species infrequently isolated from blood.

The performance of Etest in fluconazole and voriconazole testing of 279 isolates of uncommon Candida spp. was assessed in comparison with the National Committee for Clinical Laboratory Standards (NCCLS)-approved standard broth microdilution (BMD) method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 h at 35 degrees C. The isolates include Candida krusei, C. lusitaniae, C. guilliermondii, C. kefyr, C. rugosa, C. lipolytica, C. pelliculosa, C. dubliniensis, C. famata, C. zeylanoides, C. inconspicua, and C. norvegensis. Overall agreement between Etest and BMD MICs was 96% for fluconazole and 95% for voriconazole. Where a discrepancy was observed between Etest and the reference method, the Etest tended to give lower values with both fluconazole and voriconazole. The Etest method using RPMI agar appears to be a useful method for determining fluconazole and voriconazole susceptibilities of uncommon species of Candida.

Antifungal Agents↗

PubMed2003

In vitro susceptibility testing of Aspergillus spp.: comparison of Etest and reference microdilution methods for determining voriconazole and itraconazole MICs.

The performance of the Etest for voriconazole and for itraconazole susceptibility testing of 376 isolates of Aspergillus spp. was assessed in comparison with the National Committee for Clinical Laboratory Standards (NCCLS) proposed standard microdilution broth method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 h at 35 degrees C. The isolates included A. fumigatus, A. flavus, A. niger, A. terreus, A. versicolor, A. glaucus, A. nidulans, A. ustus, and A. sydowii. Overall agreement percentages between the Etest and microdilution MICs were 97.6% for voriconazole and 95.8% for itraconazole. Where a discrepancy was observed between Etest and the reference method, the Etest tended to give lower values with voriconazole and higher values with itraconazole. The Etest method using RPMI agar appears to be a useful method for determining the voriconazole and itraconazole susceptibilities of Aspergillus spp.

Antifungal Agents↗

PubMed2003

Activities of fluconazole and voriconazole against 1,586 recent clinical isolates of Candida species determined by Broth microdilution, disk diffusion, and Etest methods: report from the ARTEMIS Global Antifungal Susceptibility Program, 2001.

The ARTEMIS Global Antifungal Susceptibility Program (ARTEMIS Program) was initiated in 2001 to provide focused surveillance of the activities of fluconazole and voriconazole against Candida spp. isolated from blood and other normally sterile sites. A total of 1,586 episodes of infection were detected at 61 international study sites. Overall, 57.7% of the infections were due to Candida albicans, followed by C. glabrata (14.8%), C. parapsilosis (12.5%), C. tropicalis (9.4%), C. krusei (2.7%), and C. lusitaniae (1.5%). Isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to fluconazole (for 99% of the isolates the MICs were <or=8 microg/ml). Likewise, 99 to 100% of these species were inhibited by <or=1 microg of voriconazole per ml. Voriconazole was also active against C. glabrata (93% of the isolates were susceptible [MICs <or= 1 microg/ml]) and C. krusei (100% of the isolates were susceptible). The agar-based Etest and disk diffusion methods performed well for the testing of both fluconazole and voriconazole compared to the broth microdilution MIC reference method. These observations establish the continued importance of C. albicans as a pathogen and the sustained activity of fluconazole and the broad spectrum of activity of voriconazole and will serve as the first-year benchmark for the ARTEMIS Program. Continued surveillance and refinement of broth- and agar-based test methods will help to identify susceptibility trends and improve the laboratory capability for antifungal susceptibility testing.

Antifungal Agents↗

PubMed2003

Evaluation of the Etest and disk diffusion methods for determining susceptibilities of 235 bloodstream isolates of Candida glabrata to fluconazole and voriconazole.

The performances of the Etest and the disk diffusion methods for testing of the susceptibilities of 235 Candida glabrata isolates to fluconazole and voriconazole were compared with that of the National Committee for Clinical Laboratory Standards (NCCLS) approved standard broth microdilution (BMD) method. The NCCLS method used RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C. Etest MICs were determined with RPMI 1640 agar containing 2% glucose (RPG agar) and with Mueller-Hinton agar containing 2% glucose and 0.5 microg of methylene blue per ml (MBE agar) and were read after incubation for 48 h at 35 degrees C. Disk diffusion testing was performed with MBE agar, 25-microg fluconazole disks, and 1- microg voriconazole disks and by incubation at 35 degrees C for 24 h. Overall agreements between the Etest and the BMD MICs obtained with RPG and MBE agars were 91 and 96%, respectively, for fluconazole and 93 and 95%, respectively, for voriconazole. Categorical agreements between the agar-based methods and BMD were 52.3 to 64.7% with fluconazole and 94.8 to 97.4% with voriconazole. The vast majority of the discrepancies by the disk diffusion and Etest methods with fluconazole were minor errors. The agar-based methods performed well in identifying isolates with resistance to fluconazole and decreased susceptibility to voriconazole.

Agar↗

PubMed2003

Variation in susceptibility of bloodstream isolates of Candida glabrata to fluconazole according to patient age and geographic location.

We examined the susceptibilities to fluconazole of 559 bloodstream infection isolates of Candida glabrata and grouped the isolates by patient age and geographic location within the United States. Susceptibility of C. glabrata to fluconazole was lowest in the Pacific (44%) and East South Central (47%) regions and was highest in the West South Central region (82%) (regions are as designated by the U.S. Bureau of the Census). Isolates from pediatric patients were virtually all susceptible to fluconazole, whereas the highest frequency of resistance was observed in isolates from patients 16 to 64 years of age.

Adolescent↗

PubMed2003

Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi.

We examined the in vitro activity of caspofungin, posaconazole, voriconazole, ravuconazole, itraconazole, and amphotericin B against 448 recent clinical mold isolates. The endpoint for reading caspofungin was the minimum effective concentration (MEC). Among the triazoles, posaconazole was most active, inhibiting 95% of isolates at 95% of Aspergillus spp. at <or=1 microg/ml compared to 83% for itraconazole and 91% for amphotericin B. Amphotericin B inhibited only 38% of Aspergillus terreus isolates at <or=1 microg/ml, whereas the three new triazoles and caspofungin inhibited all A. terreus at <or=0.5 microg/ml. The new triazoles and caspofungin have excellent in vitro activity against a very large collection of recent clinical isolates of Aspergillus spp., and some in vitro activity against selected other filamentous fungi.

Amphotericin B↗

PubMed2002

Emerging elevated mupirocin resistance rates among staphylococcal isolates in the SENTRY Antimicrobial Surveillance Program (2000): correlations of results from disk diffusion, Etest and reference dilution methods.

Staphylococci cause one-third of all serious invasive infections in the SENTRY Antimicrobial Surveillance Program including bacteremias and lower respiratory tract infections. Staphylococci are also commensals of the skin and nasal passages; therefore, topical agents active against these organisms are valuable in preventing infections or transfer of the organisms between patients and/or health care workers. Mupirocin is a potent topical anti-staphylococcal compound, but its effectiveness has been compromised by emerging resistance. In early 2000, the SENTRY Program detected 302 mupirocin-resistant isolates (131 Staphylococcus aureus, and 171 coagulase-negative staphylococci [CoNS]) from the United States (19/25 medical centers), Canada (4/5), Latin America (3/9) and Europe (7/18). One hundred sixty-eight mupirocin-resistant and 59 susceptible isolates were tested further by reference MIC, Etest (AB BIODISK, Solna, Sweden) and disk diffusion (5-microg) methods. Mupirocin resistance rates for blood stream infections varied by geographic area: for S. aureus from 1.9 to 5.6%, and for CoNS from 12.8 to 39.9%. Using elevated mupirocin MIC results, two resistant populations were noted: low-level resistance at 8-128 microg/mL and high-level resistance at > or = 1024 microg/mL. Acceptable correlation was observed between Etest and disk diffusion results (r = 0.84) without serious intermethod interpretive errors. High-level resistant isolates had heavy growth with no visible zone around the disk; low-level resistant isolates produced hazy zones of inhibition, and susceptible strains had clear zones of inhibition at > or = 17 mm. As mupirocin resistance can be plasmid-mediated, the prudent and appropriate use of this topical agent is important to minimize the ongoing development of resistance. Local surveillance for emerging mupirocin resistance appears warranted particularly in the United States and Canada, pragmatically using a disk diffusion test screening. Where more precise data are needed, the Etest is a very accurate method for distinguishing mupirocin low-level from high-level resistance patterns.

Anti-Bacterial Agents↗

PubMed2002

Antifungal susceptibility of South African oral yeast isolates from HIV/AIDS patients and healthy individuals.

The in vitro antifungal susceptibility profile of 589 oral yeast isolates from HIV/AIDS patients and healthy South Africans was determined against amphotericin B, nystatin, 5-fluorocytosine (5-FC), clotrimazole, miconazole, ketoconazole, itraconazole and fluconazole. The broth microdilution method of the National Committee on Clinical Laboratory Standards was used and MIC(50) and MIC(90) determined. A 100% susceptibility to fluconazole was observed among the 466 isolates of Candida albicans. Among C. krusei, the second most common isolate, only 2.6% of isolates were susceptible to fluconazole and itraconazole. Despite the lack of previous exposure to antifungal agents, very little difference was observed in the antifungal profile between the South African isolates and isolates from the United States (U.S.), Canada and South America. South Africa has a particularly high incidence of HIV-infection and oral candidiasis is the most common oral complication in these patients. This study provides important baseline data as the isolates were collected prior to fluconazole being made freely available to HIV/AIDS patients attending government health clinics.

AIDS-Related Opportunistic Infections↗