Abstract
The accuracy of the Microbial Identification System (MIS; MIDI, Inc.) for identification of yeasts to the species level was compared by using 438 isolates grown on prepoured BBL Sabouraud dextrose agar (SDA) and prepoured Remel SDA. Correct identification was observed for 326 (74%) of the yeasts cultured on BBL SDA versus only 214 (49%) of yeasts grown on Remel SDA (P < 0.001). The commercial source of the SDA used in the MIS procedure significantly influences the system’s accuracy.
The Microbial Identification System (MIS; Microbial ID, Inc., Newark, Del.) is an automated approach to rapid identification of unknown microbial isolates. The MIS consists of a gas chromatograph with a flame ionization detector, an autosampler, an integrator, and a computer. The MIS computer searches a software library of fatty acid compositions, compares the isolate’s fatty acid profile with those of known species, and reports the most likely species name along with the extent of correlation (the similarity index [SI]) of the isolate’s profile with a species in the database (22).
The MIS has provided an accurate, rapid, and cost-effective alternative for identification of many aerobic gram-positive and gram-negative bacterial isolates (2, 12, 16). Two recent reports, however, have noted that only 70 to 71% of yeast isolates were correctly identified by the MIS to the species level (6, 13). The yeast database for the MIS was derived by the system’s manufacturer from yeasts grown on BBL 11584 Sabouraud dextrose agar (SDA), which was purchased in the dehydrated form (Becton-Dickinson Microbiology Systems, Cockeysville, Md.) and freshly prepared in house prior to use by Microbial ID (17). Most clinical laboratories, however, buy their culture media prepoured from commercial suppliers. Of the two published studies concerning yeast identification using the MIS, one used yeasts cultured on prepoured BBL SDA (13). The commercial source of SDA for the other study (6) is unknown. The present study evaluated the relative ability of the MIS to accurately identify yeasts grown on prepoured SDA plates obtained from two widely used commercial sources: BBL and Remel, Inc. (Lenexa, Kans.). The intent was to determine if significantly different levels of accuracy of MIS performance could be experienced when yeasts were cultured on SDA purchased from different commercial sources.
The majority of yeasts (375; 86%) used during the present study were freshly isolated from clinical specimens. In addition, 63 (14%) of the isolates were stock cultures of less frequently recovered yeasts (from the Laboratories for Mycology, New York State Department of Health), which had previously been recovered from clinical specimens. More than 75% of the total isolates studied had been recovered from genital, urine, and wound specimens submitted for culture. Multiple isolates of the same species from the same patients were excluded from the study. Isolates were initially subcultured to SDA (BBL) and to cornmeal agar with 0.5% Tween 80 (CMT); each subculture was incubated at 25°C.
Conventional identification.
Each of the fresh clinical isolates, as well as the stock cultures of yeasts, was preliminarily identified by determination of its microscopic morphology on CMT and by its colony morphology and pigment production on SDA. Clinical isolates were identified as Candida albicans by their typical microscopic appearances on CMT, including the production of chlamydospores (10, 11, 23). Isolates of Candida dubliniensis were identified by their ability to produce chlamydospores and their inability to grow at 45°C (19). Isolates of most of the remaining species were identified by using the Yeast Biochemical Card (YBC; bioMerieux Vitek, Hazelwood, Mo.) (7–9, 18), which was inoculated and incubated according to the manufacturer’s specifications as previously described (13). Fresh clinical isolates which could not be conclusively identified by using the combination of their microscopic morphology and the YBC were identified by using the API 20C Aux (bioMerieux Inc.) (9, 18, 20) and/or additional conventional tests as appropriate and as previously described (13). Stock cultures of clinical isolates were identified by the API 20C (bioMerieux Vitek). The identification carried out as described above was considered the correct identification.
Chromatographic analysis.
Isolated colonies of each yeast to be studied were quadrant streaked onto two commercially obtained SDA plates (BBL and Remel). The cultures were incubated aerobically at 28 ± 1°C for 24 ± 2 h, and extracts were prepared and analyzed chromatographically as specified in the MIS instructions (22) and as previously described (13). Version 3.8 of the YSTCLN database in the MIS computer was used to identify isolates. For each isolate, the computer printout either listed one or more possible species choices with an SI for each choice ranging from 0 to 1.000, or it reported “no match,” the inability of the MIS to identify the isolate. For the present study, the MIS result was considered correct if the correct species name of an isolate was listed on the MIS printout as the first choice, regardless of the SI.
When the MIS result was either a misidentification to the species level or “no match,” the microscopic morphology of the isolate was determined again and the API 20C Aux or appropriate conventional test systems were inoculated to confirm the species’ identification. In addition, a fresh extract from a new subculture of the isolate on the appropriate commercially obtained SDA, incubated at 28°C, was analyzed in the chromatograph a second time. If an isolate was misidentified the first time it was analyzed in the MIS, it was counted as a misidentification, regardless of whether it was correctly or incorrectly identified by the system when reanalyzed in the MIS. If an isolate was unidentified by the MIS when first tested and then correctly or incorrectly identified when the chromatography was repeated, it was counted as a correct or incorrect identification, respectively. The Z test for differences in proportions for independent samples was used for statistical analysis of results (24). A P value of <0.05 was selected as the minimum level determining significance.
MIS performance by commercial source of SDA.
Of 438 yeast isolates from the 22 species of yeasts that were studied, 326 (74%) versus only 214 (49%) were correctly identified by the MIS to the species level following growth on BBL and Remel SDA, respectively (Table 1) (P < 0.001). Significantly more isolates from BBL SDA were correctly identified by the MIS to the species level when C. albicans (P < 0.01), Candida glabrata (P < 0.001), Candida guilliermondii (P < 0.05), Candida tropicalis (P < 0.001) and Saccharomyces cerevisiae (P < 0.005) were chromatographically analyzed. Of the 438 yeasts studied, 68 (16%) and 100 (23%) were misidentified by the MIS when the yeasts were cultured on BBL and Remel SDA, respectively (Table 2) (P < 0.01). When cultured on Remel SDA, 14 (67%) of the 21 misidentified isolates of C. albicans were called C. tropicalis and 37 (100%) of the misidentified isolates of C. glabrata were named S. cerevisiae by the MIS. In all, 44 (10%) versus 124 (28%) of the yeasts cultured on BBL and Remel SDA, respectively, were unidentified by the MIS (P < 0.001).
TABLE 1.
Comparison of the Microbial Identification System with conventional tests for identification of yeasts grown on premade SDA plates from BBL and Remel
| Species identified with conventional tests (no. of isolates tested) | No. (%) of isolates tested with MIDI systema
|
P values for correct identifications | |||||
|---|---|---|---|---|---|---|---|
| Correctly identified to species level
|
Incorrectly identified to species level
|
Unidentified (no match)
|
|||||
| BBL SDA | Remel SDA | BBL SDA | Remel SDA | BBL SDA | Remel SDA | ||
| Candida spp. | |||||||
| C. albicans (69) | 59 (86) | 44 (64) | 9 (13) | 21 (30) | 1 (1) | 4 (6) | <0.01 |
| C. dubliniensis (5) | 3 (60) | 3 (60) | 2 (40) | 2 (40) | NS | ||
| C. famata (4) | 4 (100) | 4 (100) | NS | ||||
| C. glabrata (50) | 44 (88) | 3 (6) | 5 (10) | 37 (74) | 1 (2) | 10 (20) | <0.001 |
| C. guilliermondii (14) | 14 (100) | 9 (64) | 5 (36) | <0.05 | |||
| C. krusei (26) | 20 (77) | 20 (77) | 1 (4) | 1 (4) | 5 (19) | 5 (19) | NS |
| C. lusitaniae (13) | 9 (69) | 9 (69) | 4 (31) | 3 (23) | 1 (8) | NS | |
| C. parapsilosis (93) | 86 (92) | 79 (85) | 2 (2) | 1 (1) | 5 (5) | 13 (14) | NS |
| C. rugosa (8) | 1 (13) | 8 (100) | 7 (88) | NS | |||
| C. tropicalis (80) | 50 (63) | 13 (16) | 16 (20) | 3 (4) | 14 (18) | 64 (80) | <0.001 |
| Cryptococcus spp. | |||||||
| C. albidus (2) | 2 (100) | 1 (50) | 1 (50) | NS | |||
| C. humicolus (2) | 2 (100) | 1 (50) | 1 (50) | NS | |||
| C. neoformans (9) | 7 (78) | 5 (56) | 2 (22) | 4 (44) | NS | ||
| C. terreus (4) | 3 (75) | 3 (75) | 1 (25) | 1 (25) | NS | ||
| Geotrichum candidum (4) | 3 (75) | 4 (100) | 1 (25) | NS | |||
| Hansenula anomala (6) | 5 (83) | 5 (83) | 1 (17) | 1 (17) | NS | ||
| Kluyveromyces marxianus (13) | 8 (62) | 7 (54) | 4 (31) | 2 (15) | 1 (8) | 4 (31) | NS |
| Rhodotorula spp. | |||||||
| R. pilamanae (1) | 1 (100) | 1 (100) | NS | ||||
| R. rubra (12) | 11 (92) | 11 (92) | 1 (8) | 1 (8) | NS | ||
| Saccharomyces cerevisiae (12) | 12 (100) | 4 (33) | 8 (67) | <0.005 | |||
| Sporobolomyces salmonicolor (1) | 1 (100) | 1 (100) | NS | ||||
| Trichosporon beigelii (10) | 3 (30) | 5 (50) | 4 (40) | 4 (40) | 3 (30) | 1 (10) | NS |
| Total (438) | 326 (74) | 214 (49) | 68 (16) | 100 (23) | 44 (10) | 124 (28) | <0.001 |
MIDI, Microbial ID, Inc.
TABLE 2.
Misidentifications of yeast species by the Microbial Identification System based on commercial source of SDA medium
| Species identified with conventional tests | No. of misidenti-fications | No. (%) of isolates misidentified as the following species:
|
|||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
C. albicans
|
C. guilliermondii
|
C. krusei
|
C. lusitaniae
|
C. parapsilosis
|
C. tropicalis
|
C. neoformans
|
G. candidum
|
K. marxianus
|
R. rubra
|
S. cerevisiae
|
T. beigelii
|
||||||||||||||
| BBL | Remel | BBL | Remel | BBL | Remel | BBL | Remel | BBL | Remel | BBL | Remel | BBL | Remel | BBL | Remel | BBL | Remel | BBL | Remel | BBL | Remel | BBL | Remel | ||
| Candida spp. | |||||||||||||||||||||||||
| C. albicans | 30 | 3 (10) | 3 (10) | 3 (10) | 4 (13) | 3 (10) | 14 (47) | ||||||||||||||||||
| C. dubliniensis | 6 | 3 (50) | 3 (50) | ||||||||||||||||||||||
| C. famata | 8 | 1 (13) | 1 (13) | 3 (38) | 3 (38) | ||||||||||||||||||||
| C. glabrata | 42 | 5 (12) | 37 (88) | ||||||||||||||||||||||
| C. guilliermondii | 5 | 2 (40) | 3 (60) | ||||||||||||||||||||||
| C. krusei | 2 | 1 (50) | 1 (50) | ||||||||||||||||||||||
| C. lusitaniae | 7 | 3 (43) | 1 (14) | 1 (14) | 2 (29) | ||||||||||||||||||||
| C. parapsilosis | 3 | 2 (67) | 1 (33) | ||||||||||||||||||||||
| C. rugosa | 1 | 1 (100) | |||||||||||||||||||||||
| C. tropicalis | 19 | 3 (16) | 1 (5) | 9 (47) | 4 (21) | 2 (11) | |||||||||||||||||||
| Cryptococcus spp. | |||||||||||||||||||||||||
| C. albidus | 3 | 1 (33) | 1 (33) | 1 (33) | |||||||||||||||||||||
| C. humicolus | 3 | 2 (67) | 1 (33) | ||||||||||||||||||||||
| C. neoformans | 6 | 1 (17) | 1 (17) | 1 (17) | 3 (50) | ||||||||||||||||||||
| C. terreus | 6 | 1 (17) | 1 (17) | 1 (17) | 1 (17) | 1 (17) | 1 (17) | ||||||||||||||||||
| Hansenula anomala | 10 | 1 (10) | 1 (10) | 3 (30) | 4 (40) | 1 (10) | |||||||||||||||||||
| Kluyveromyces marxianus | 6 | 1 (17) | 1 (17) | 2 (33) | 1 (17) | 1 (33) | |||||||||||||||||||
| Rhodotorula pilimanae | 2 | 1 (50) | 1 (50) | ||||||||||||||||||||||
| Sporobolomyces salmonicolor | 1 | 1 (100) | |||||||||||||||||||||||
| Trichosporon beigelii | 8 | 2 (25) | 2 (25) | 2 (25) | 2 (25) | ||||||||||||||||||||
| Total | 168 | 8 (5) | 7 (4) | 14 (8) | 3 (2) | 1 (1) | 1 (1) | 10 (6) | 10 (6) | 9 (5) | 11 (7) | 6 (4) | 18 (11) | 4 (2) | 4 (2) | 3 (2) | 2 (1) | 1 (1) | 2 (1) | 4 (2) | 1 (1) | 5 (3) | 37 (22) | 3 (2) | 4 (2) |
Only 24 isolates (5 Candida dubliniensis, 4 Candida famata, 2 Crytococcus albidus, 2 Cryptococcus humicolus, 4 Cryptococcus terreus, 6 Hansenula anomala, and 1 Rhodotorula pilamanae) for which the MIS software library had no data were studied. Of these isolates, 20 (83%) and 18 (75%) were misidentified by the MIS when cultures were grown on BBL and Remel SDA, respectively (a difference that was not significant [NS]), and the remaining isolates were unidentified by the system. Of the 438 yeast isolates studied, 138 (32%) cultured on BBL SDA and 246 (56%) grown on Remel SDA had to be chromatographically analyzed a second time (P < 0.001) because the initial results were either unidentified (“no match”) or incorrect. For these reanalyzed isolates, results from only 26 (19%) of the 138 BBL cultures and 22 (9%) of the 246 Remel cultures changed from “no match” when first tested to correct. Another 20 (14%) of the yeasts retested from BBL SDA and 17 (7%) of those retested from Remel SDA changed from incorrect when first analyzed chromatographically to correct. All remaining yeasts that had to be chromatographically analyzed a second time gave results that were either incorrect or “no match.”
More than 25 production lots of SDA from each manufacturer were used during the present study. No significant differences were observed in MIS performance with yeasts cultured on different production lots of SDA from either manufacturer. While the pH (5.6) was the same from each commercial source, the ingredients were similar but not identical (Table 3) (1, 21). When different species calls were made by the MIS for the same isolate grown on the two commercial sources of SDA, the different sources of metabolic substrates used in the two culture media resulted in qualitative or quantitative differences in the isolate’s fatty acid profile and in an MIS misidentification.
TABLE 3.
Ingredients of commercially available SDAa
Since the conclusion of the present study, the authors have compared MIS identification of 91 yeast isolates (14 species) from both freshly prepared BBL 11584 SDA and prepoured BBL SDA (13a). Of these isolates, the MIS correctly identified 72 (79%) from prepoured SDA versus 65 (71%) from freshly prepared SDA (NS). MIS results obtained with the prepoured medium appear to be at least as accurate as those obtained with the fresh product.
The results of the present study indicate that accurate MIS identification of yeasts to the species level is dependent, at least in part, on the commercial source of prepoured SDA medium that may be used to culture the organisms just prior to chromatographic analysis. The percentage of yeasts correctly identified with BBL SDA in the present study (74%) was similar to both our previous findings with BBL SDA (70% [13]) and the findings of another study (71% [6]) using SDA from an unspecified source, but it was significantly greater than that obtained when yeasts were cultured during the present study on SDA obtained from Remel (49%).
The percentage of yeasts correctly identified in this or other studies will also be influenced, in part, by the number and variety of each species included in the study. For example, the MIS correctly identified (from BBL SDA) more than 90% of the isolates of C. guilliermondii, Candida parapsilosis, Rhodotorula rubra, and S. cerevisiae (Table 1). In addition, while the MIS correctly identified 88% of the isolates of C. glabrata which had been cultured on BBL SDA, only 6% of the isolates of that species were correctly identified when cultured on Remel SDA. A similarly low level of correct species identification (33%) was observed for S. cerevisiae isolates cultured on Remel SDA (while the remaining 67% were unidentified), compared to the accuracy (100%) for isolates of that species grown on BBL SDA. Therefore, if a larger number of isolates of yeast species such as C. glabrata and S. cerevisiae had been included in the study, the overall percentage of yeasts accurately identified by the MIS, at least when cultured on Remel SDA, would have been reduced.
In the present study, yeast isolates were frequently misidentified as other species that have traditionally been either more susceptible or more resistant to antifungal therapy. Misidentification of yeast species may lead to the selection of inappropriate therapy by physicians, both because many yeast species respond differently to amphotericin B and the azole agents (3–5, 11, 14, 15, 23, 25) and because the majority of clinical laboratories in the United States usually report yeast species identifications without accompanying antifungal drug susceptibility results. In the present study, for example, of the isolates of C. albicans (which is usually susceptible to amphotericin B and the azoles) studied, 3 (4%) were misidentified by the MIS as C. guilliermondii (which may be resistant to amphotericin B and fluconazole [11, 15, 23]) when cultured on either BBL or Remel SDA and 14 (20%) were misidentified as C. tropicalis (which may be resistant to both amphotericin B and the newer azoles [11, 15, 23]) when grown on Remel SDA prior to chromatographic analysis (Table 2).
As previously suggested (13, 23), the database for the potentially useful MIS yeast identification system needs to be improved. The database should be derived from yeasts cultured on commercially available, prepoured SDA because that, not medium prepared in house, is what is used most commonly and most practically in clinical laboratories.
Acknowledgments
Statistical analysis of the results was performed by Sally Cavanaugh, York Hospital Department of Research.
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