Journal of Clinical Microbiology, July 1999, p. 2148-2152, Vol. 37, No. 7
0095-1137/99/$04.00+0
Proficiency of Clinical Laboratories in Spain in
Detecting Vancomycin-Resistant Enterococcus spp.
Juan
Alonso-Echanove,1
Belen
Robles,2
William R.
Jarvis,1,* and
The
Spanish VRE Study Group
Hospital Infections Program, Centers for
Disease Control and Prevention, Atlanta, Georgia
30333,1 and Consejeria de Servicios
Sociales, Oviedo, Principado de Asturias, 33005, Spain2
Received 23 December 1998/Returned for modification 1 February
1999/Accepted 25 March 1999
 |
ABSTRACT |
Studies in a variety of U.S. clinical laboratories have
demonstrated difficulty in detecting intermediate and low-level
vancomycin-resistant enterococci (VRE). The misclassification of "at
least intermediate resistant isolates" as vancomycin susceptible may
have both clinical implications and a negative impact on measures to
control the spread of VRE. No published study has assessed the ability
of clinical laboratories in Europe to detect VRE. So, the apparent low
prevalence of VRE in European hospitals may be, in part, secondary to
the inability of these laboratories to detect all VRE. In an effort to
assess European laboratories' proficiency in detecting VRE, we
identified 22 laboratories in Spain and asked them to test four VRE
strains and one susceptible enterococcal strain from the Centers for
Disease Control and Prevention collection. Each organism was tested by
the routine antimicrobial susceptibility testing method used by each
laboratory. Overall, VRE were correctly identified in 61 of 88 (69.1%)
instances. The accuracy of VRE detection varied with the level of
resistance and the antimicrobial susceptibility method. The
high-level-resistant strain (Enterococcus faecium; MIC, 512 µg/ml) was accurately detected in 20 of 22 (91.3%) instances,
whereas the intermediate-resistant isolate (Enterococcus gallinarum; MIC, 8 µg/ml) was accurately detected in only 11 of 22 (50%) instances. Classification errors occurred in 27 of 88 (30.9%) instances. Misclassification as vancomycin susceptible was the
most common error (16 of 27 [59.3%] instances). Our study shows that
the participating Spanish laboratories had an overall acceptable
proficiency in detecting VRE but that a substantial proportion of
VRE isolates with low or intermediate levels of resistance were
not detected. We recommend that studies be conducted to validate
laboratory proficiency testing as an important step in the prevention
and control of the spread of antimicrobial resistance.
| |
INTRODUCTION |
Enterococci are major nosocomial
pathogens and have been isolated from 9% of nosocomial bloodstream,
12% of surgical site, and 16% of urinary tract infections reported by
U.S. hospitals participating in the hospital-wide component of the
National Nosocomial Infections Surveillance (NNIS) system
(13). In the face of the increasing incidence of high-level
resistance to penicillin and aminoglycosides, enterococci resistant to
all three antimicrobial agents (penicillin, aminoglycosides, and
vancomycin) with activity against enterococci pose a serious challenge
not only for clinicians but also for health care institutions, because
numerous nosocomial outbreaks have been reported (10, 11).
Moreover, enterococci may be a reservoir for resistance genes for other
gram-positive organisms, including Staphylococcus aureus; in
vitro studies have shown that the vanA gene coding for
vancomycin resistance can be transferred from enterococci to S. aureus (14). Prevention and control of the spread
of vancomycin-resistant enterococci (VRE) are therefore major national
and international public health challenges. Specific guidelines and
recommendations for preventing the spread of VRE were published in 1995 by the Centers for Disease Control and Prevention (CDC) and its
Hospital Infection Control Practices Advisory Committee (3).
Despite this, 40% of hospitals participating in NNIS
reported the detection of one or more isolates of VRE in
1996, and the proportion of enterococci resistant to vancomycin at
hospitals participating in NNIS has continued to increase to 22.6.%
among intensive care unit patients and 16.5% among nonintensive care
patients in 1997 (4). The first step in controlling the
spread of VRE is its early detection. Nevertheless, detection of the
intermediate- and low-level resistance exhibited by strains with the
vanB and vanC phenotypes is not consistently done
by automated commercial methods (15). Different studies in
the United States and Argentina have shown that only 16 to 27% of
these isolates are correctly identified (6, 16).
Little is known about the epidemiology of VRE in Europe. Several
hospital-based reports suggest low prevalence rates of VRE in clinical
specimens (9, 17). In Spain, an annual nationwide point
prevalence study demonstrated a stable prevalence rate of approximately
10% for enterococcal nosocomial infections; however, no data on VRE
were collected (8). During 1994 and 1995, in three hospitals
in Madrid, Spain, vancomycin resistance was found among 8 of 100 (8%)
enterococcal isolates cultured from blood (1). In 1994, the
European Glycopeptide Susceptibility Survey presented unpublished data
suggesting problems in the testing of the susceptibilities of various
gram-positive isolates to glycopeptides (7). However, no
isolates with low-level or intermediate- to low-level vancomycin
resistance were tested, and no final results or information on the
laboratory susceptibility test methods used have been published. To
date, no study of the proficiency of detection of VRE in clinical
laboratories in Spain has been conducted. In the study described here,
we sought to assess the ability of clinical laboratories in Spain to
detect VRE.
| |
MATERIALS AND METHODS |
Bacterial strains.
Five enterococcal isolates were obtained
from the CDC strain collection and were coded as organisms 1 through 5, respectively. The isolates included two Enterococcus faecium
isolates, one Enterococcus faecalis isolate, and one
Enterococcus gallinarium isolate, with each isolate having
one of the four most common vancomycin-resistant phenotypes. In
addition, E. faecalis ATCC 29212, which is susceptible to
vancomycin, penicillin, and ampicillin, was included (Table 1).
The isolates were inoculated onto nutrient agar slants (Becton
Dickinson Microbiology Systems, Cockeysville, Md.), incubated for
24 h, and distributed to the participating clinical laboratories along with standardized susceptibility test result forms. The participating laboratories were blinded as to the species and the
antimicrobial susceptibility patterns of the isolates. Each participant
was instructed to test the five isolates for their susceptibilities to
vancomycin by their routine laboratory procedures and to report the
zone size or MIC. Additionally, the participating laboratories were
asked to provide hospital characteristics, the number and proportion of
enterococci and isolates of VRE detected in the preceding year, the
routine antimicrobial susceptibility method(s) used, and whether the E
test and agar screening tests were routinely used. After completion of
testing, the forms were completed and returned to CDC for data entry
and analysis. Testing at CDC was by National Committee for Clinical
Laboratory Standards (NCCLS) reference methods (12). The MIC
and/or zone size results from participants and CDC were compared.
Testing errors were classified as either very major, major, or minor
errors. A very major error occurred when the CDC method determined that
an organism was resistant to an antimicrobial agent and the method used
by the participant reported that it was susceptible to that agent. A
major error occurred when the CDC method found that an organism was
susceptible and the method used by the participant found that it was
resistant. A minor error occurred when the CDC method determined that
an organism was susceptible or resistant to an antimicrobial agent and
the method used by the participant reported that it was intermediate or
when the CDC method determined that an organism was intermediate and
the participant reported that it was resistant or susceptible.
Reference methods.
Disk diffusion testing at CDC was
performed as described previously (16). Isolates were
defined as susceptible, intermediate, or resistant by using NCCLS
criteria (12). The strains were tested for the presence of
the vanA, vanB, and vanC genes by PCR reaction as described previously (5).
| |
RESULTS |
Participating hospitals' characteristics.
Of 57 hospital
laboratories contacted, 27 (47%) agreed to participate in the study.
Five participants did not provide the MIC or zone size; data from
these laboratories were excluded from the analysis (Table
2). Overall, the participating hospitals were small (<400 beds; n = 10) or medium (400 to
600 beds; n = 7) in size. Of 14 hospitals, 8 (57%)
were not affiliated with a university. All participants routinely
tested enterococcal isolates from blood for vancomycin resistance, and
the majority routinely tested enterococcal isolates from urine for
vancomycin resistance. Participating hospitals used a variety of
vancomycin susceptibility testing methods (Table
3). The 
-lactamase test was routinely performed in 11 of 22 (50%) laboratories. In contrast, agar screening was never used, and the E test was used very infrequently (1 of 22 [4.5%]). In 1994, 7,469 enterococci were isolated at the
participating laboratories. The median prevalence rate of VRE for the
20 participants reporting these data was 0.25% (range, 0 to 9%). In
10 of these 20 (50%) hospitals, no VRE isolates had been detected. VRE
were not significantly more likely to be isolated at hospitals with >600 beds than at hospitals with 
600 beds.
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TABLE 3.
Distribution of concordant rates of participating
laboratories: CDC results by organism and susceptibility testing
method, vancomycin susceptibility tests, 1996
|
|
Vancomycin resistance.
Overall, the participating laboratories
accurately determined vancomycin resistance in 61 of 88 (69.3%)
instances. This rate varied with the level of vancomycin resistance
(Table 3). Organism 1, with high-level resistance (VanA phenotype), was
detected in 20 (90.9%) instances, whereas organism 2, with
low-level resistance (VanB2 phenotype), and organism 4, with
intermediate-level resistance (VanC phenotype), were correctly detected
in only 13 (59.1%) and 11 (50%) instances, respectively. Organism 3, with intermediate- to low-level resistance (VanB phenotype), was
correctly identified in 17 (77.3%) instances. Proficiency was
higher if we considered detection of "at least intermediate
level of resistance" as accurate (21 of 22 [95.4%] instances for
organism 2 and 14 of 22 [63.6%] instances for organism 4).
Categorical errors in the detection of vancomycin resistance occurred
in 27 of 88 (30.7%) categorical errors (Table
4). Minor errors were the most common
categorical error for all enterococcal strains (24 of 27 [88.9%]
instances). For 13 of 24 (54.2%) of these errors, the organism was
misclassified as vancomycin susceptible, for 8 of 24 (33.3%) of these
errors the organism was misclassified as intermediate resistant, and
for 3 of 24 (12.5%) of these errors the organism was misclassified as
resistant. Very major errors occurred among 3 of 27 (11.1%)
errors. Therefore, misclassification of isolates with at least an
intermediate level of resistance as vancomycin susceptible accounted
for 16 of 27 (59.3%) of the errors and occurred in 16 of 88 (18.2%)
instances.
Proficiency in determination of vancomycin resistance also varied with
the antimicrobial susceptibility testing method used (Tables 3 and
5). However, only three methods (Pasco
[Difco Laboratories, Detroit, Mich.] and Microscan Walkaway and
Microscan Autoscan [Dade International, Inc., Microscan
Division, Haywood, Calif.]) were used by at least three
laboratories. All methods had difficulties detecting low and
intermediate levels of resistance. However, Microscan users had
consistently better results for every isolate. For organisms 2 through
4, Microscan Walkaway users accurately determined the MIC in 22 of 27 (81.5%) instances, Microscan Autoscan users accurately determined the
MIC in 7 of 9 (77.7%) instances, and Pasco users accurately determined
the MIC in 6 of 15 (40%) instances. In addition, errors were
consistently distributed among Pasco users but not among Microscan
users. Only one of five (20%) Pasco users had no errors at all,
whereas seven of nine (77.7%) Microscan Walkaway users and two of
three (66.6%) Microscan Autoscan users had no errors at all. Moreover,
errors within only onefold dilution were more common among Microscan
users than among Pasco users (Microscan Walkaway, two of five [40%]
of the errors; Microscan Autoscan, one of two [50%] of the errors;
and Pasco, three of nine [33.3%] of the errors). Finally, we
examined the distribution of errors among the 10 of 20 (50%) hospitals
from which no VRE were reported in 1996. The clinical laboratories from
these hospitals misclassified enterococcal isolates with at least an
intermediate level of vancomycin resistance as vancomycin susceptible
in 8 of 40 (20%) instances; in only 2 of the 8 (25%) errors was the Microscan system used. In contrast, in the clinical laboratories from
the 10 hospitals that reported the detection of VRE in 1996, misclassification of the organisms as vancomycin susceptible occurred in 6 of 40 (15%) instances. This difference, however, was not statistically significant. Of these 10 hospitals, 8 (80%) used the
Microscan system.
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TABLE 5.
Distribution of reported result rates and
categorical errors by susceptibility testing method,
vancomycin susceptibility tests, 1996
|
|
| |
DISCUSSION |
The laboratory serves as the first step in the prevention and
control of the spread of antimicrobial resistance. To accurately detect
antimicrobial agent-resistant strains, proficiency is essential. Previous studies have documented difficulties in detecting in the
clinical setting strains of enterococci with low or intermediate levels
of vancomycin resistance (6, 7, 16). Misclassification of an
isolate as susceptible (minor errors for intermediate
vancomycin-resistant strains and very major errors) has serious
implications for both the clinical management of patients and the
adequacy of any antimicrobial resistance surveillance system. On the
other hand, misclassification of an isolate as at least intermediate
resistant (major errors and minor errors for resistant isolates) has
less serious consequences for the clinical management of patients but
overestimates the number of isolates with at least an intermediate
level of resistance. The control of the spread of VRE will be more
difficult if more isolates are misclassified as vancomycin susceptible.
However, overestimation of the number of VRE isolates adds expenses for unnecessary prevention and control measures.
Overall, the Spanish clinical laboratories participating in this study
correctly identified VRE in 61 of 88 (69.3%) instances. These results
are better than those obtained in the New Jersey (58.5%) or
Argentine-U.S. (60%) studies (6, 16). Similar to those
studies, proficiency varied by level of vancomycin resistance, and most
participating laboratories had difficulty in detecting isolates with
low and intermediate levels of resistance. Improvement was noted,
however, in the detection of vancomycin resistance in isolates with the
VanB2 and VanB phenotypes. Previously reported rates of detection of
these organisms have ranged from 29 to 50 and 38 to 50%, respectively.
These rates are lower than the rates of 59.19 and 77.3%, respectively,
in the present study. Results with the organism of the VanB phenotype
are particularly reassuring, because the proportion of these clinical
isolates is increasing (2). Misclassification of
vancomycin-resistant isolates as vancomycin susceptible occurred in 16 of 88 (18.2%) instances, which represents a definitive improvement
compared to the rates in former studies performed in the United States
and Argentina (approximately 30% rate of misclassification as
vancomycin susceptible in both countries). Our results are even better,
if we consider only the results of methods used by at least three
participants (8 of 68 [11.8%] instances). Misclassification to
vancomycin susceptible accounted for the majority of errors (16 of 27 [59.3%] errors). However, half of these occurred with organism 3 (E. gallinarum phenotype VanC), which accounts for only 5 to
10% of clinical isolates and which, to date, has not been implicated
in nosocomial outbreaks (2, 5). Thus, the impact of
these misclassification errors on the total number of VRE missed is
minimal. Very major errors are worrisome. In this study, they were seen
in 3.4% of the instances. They tended to occur by methods used by a
very small number of laboratories.
All comparisons between methods must be made with caution. This study
was designed to evaluate proficiency in the detection of vancomycin
resistance by participating clinical laboratories and not to evaluate
the proficiencies of the diagnostic methods. Therefore, we did not
collect information on innoculum size, incubation time, or the controls
used at these facilities to standardize the test procedures, but
rather, we asked the participants to test the isolates by their routine
laboratory techniques. Differences in those factors might explain
differences in performance.
Automated MIC determination methods were most commonly used by
participating Spanish clinical laboratories (20 of 22 [90.9%]). All
methods had difficulty in detecting intermediate or low levels of
resistance. However, the accuracy varied by the method. When the
analysis was limited to methods used by at least three laboratories, the Microscan Walkaway and Microscan Autoscan systems yielded the most
accurate and consistent results. For tests with isolates with at least
an intermediate level of resistance, their overall error rates were 5 of 36 (13.9%) and 2 of 12 (16.7%) instances, respectively. Half of
their errors were within onefold dilution, and no isolate with
vancomycin resistance mediated by vanA and vanB
was misclassified as susceptible. Moreover, of 10 participating laboratories with no errors, 9 (90%) used these methods. Finally, errors by Microscan users were clustered among 5 of 12 (41.6%) participants, which suggests some differences in local factors not
related to the method. When compared with the study performed in New
Jersey (16), our results for Microscan users were much better (Walkaway error rate, 13.9 versus 50.5%; Autoscan error rate,
16.7 versus 51.9%). Improvements in the software may explain this
improved proficiency. In contrast, the broth-based method, i.e.,
the Pasco system, performed poorly at the five participating laboratories that used this method. The Pasco system has previously been reported to be highly accurate, and as stated above, this difference in performance might be partly explained by differences in
local factors such as innoculum size, incubation time, or the controls
used at these facilities.
The rates of incidence or prevalence of VRE in Spain and most countries
in Europe are unknown. The very few published studies suggest low VRE
prevalence rates. In our study, the participating laboratories reported
very low annual prevalence rates (median, 0.25%; range, 0 to 9%),
with 10 of 20 (50%) participants reporting no VRE isolates. However,
those hospitals reporting no VRE isolates misclassified enterococcal
isolates with at least an intermediate level of vancomycin resistance
as vancomycin susceptible in 8 of 40 (20%) instances. Therefore, VRE
prevalence rates may be underestimated at the participating laboratories.
There are several limitations to our study. First, the participating
laboratories are not a representative sample of all clinical laboratories in Spain. Therefore, we cannot estimate the magnitude of
underreporting of the prevalence of VRE related to inadequate proficiency in laboratory detection in Spain. Second, because some
methods were used by only a small number of participants, any
comparison between methods must be made with great caution.
In conclusion, the Spanish laboratories that participated in this study
showed an overall acceptable proficiency in detecting VRE and provided
more accurate results than those provided by other laboratories in
similar studies in other countries (6, 16). However, our
results suggest the possibility of a substantial underestimation
of VRE prevalence rates as a result of an inability to detect low and
intermediate levels of vancomycin resistance. As in previous studies,
all antimicrobial susceptibility testing methods demonstrated
difficulties in detecting isolates with intermediate and low levels of
vancomycin resistance. However, the current Microscan Walkaway
and Microscan Autoscan methods demonstrated improved proficiency
compared to those demonstrated in former studies and to those of the
other methods used in this study. Moreover, our study documented that a
substantial proportion of the errors clustered in a few laboratories;
it is hoped that feedback of our results will enhance the proficiencies
of those laboratories. It is encouraging that most errors were those
with limited clinical significance. We recommend that studies be
conducted to validate laboratory proficiency testing as an important
step in the prevention and control of antimicrobial resistance.
| |
APPENDIX |
The following investigators constitute the Spanish VRE Study
Group (all cities listed are in Spain): M. J. Arbesu Vallina, Atencion Primaria, Gijon; J. Cañon Campos, Ministerio Sanidad y
Consumo, Madrid; T. Perez Pomata, J. Bisquet Santiago, and R. Sanchez Blanque, Hospital General y Universitario, Guadalajara; F. Baquero and R. Canton, Hospital Ramon y Cajal, Madrid; A. Tinajas Puertas and P. Vidal, Complejo Hospitalario Cristal Piñor,
Orense; S. Perez Ramos, Hospital Universitario de Puerto Real, Puerto Real; M. Garcia Gonzalez, Hospital Universitario Arnau de Vilanova, Lleida; P. Carrero Gonzalez and S. Garcia Carbajosa, Complejo Hospitalario H. G. Segovia, Segovia; G. Esteban, Hospital Sta. Maria "Madre Cabaleiro Goas," Orense; H. Villar Perez, N. Ruiz Palma, and P. Perez Pelaez, Hospital San Agustin, Aviles; F. J. Mendez, Hospital Central de Asturias, Oviedo; D. Damaso Glez, Clinica
Puerta de Hierro, Madrid; R. Villanueva Glez, Complejo Hospitalario
Juan Canalejo Maritimo de Oza, La Coruña; E. Sanchez Yangüela, Hospital Insalud de Barbastro, Barbastro; L. Lopez Yepes, Hospital Virgen del Castillo, Murcia; R. Garcia Saavedra, Hospital Alvarez Buylla, Mieres; M. M. Lopez Perezagua, and C. Martinez Peinado, Hospital Marina Baixa, Villajoyosa; A. Torreblanca Gil, Hospital Carmen y Severo Ochoa, Cangas del Narcea; P. Teno Sanchez, Hospital S. Pedro de Alcantara, Caceres; P. Garcia Hierro, Hospital Universitario de Getafe, Getafe; J. Plazas Ruiz, Hospital General Universitario Alicante, Alicante; L. Calvo Torrecillas, Hospital del SAS de Jerez de la Frontera, Jerez de la Frontera; I. Dorronsoro, Hospital de Navarra, Navarra; A. Garcia del Busto, Hospital
General de Castellon, Castellon; R. Carranza Gonzalez, Hospital General
La Mancha-Centro, Ciudad Real; A. Lopez Paredes, Hospital Comarcal
Noroeste, Caravaca de la Cruz; P. Alonso Alonso, Hospital Comarcal
Monforte de Lemos, Monforte de Lemos, T. Nebreda and A. Campos,
Hospital General del Insalud, Soria; and R. M. Ferreruela Vicente
and D. Glez Grandas, Hospital Lluis Alcanyis, Xativa.
| |
ACKNOWLEDGMENTS |
We thank Fred Tenover and Christine Steward of the Nosocomial
Pathogens Laboratory Branch, Hospital Infections Program, CDC, for
providing the enterococcal isolates and the Hospital General y
Universitario, Guadalajara, Spain, for inoculating and sending the
isolates to all participating laboratories.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Hospital
Infections Program, Centers for Disease Control and Prevention MS E69,
1600 Clifton Rd., Atlanta, GA 30333. Phone: (404) 639-6413. Fax: (404) 639-6459. E-mail: wrj1{at}cdc.gov.
The investigators participating in The Spanish VRE Study Group are
listed in the Appendix.
| |
REFERENCES |
| 1.
|
Balas, D.,
B. Perea,
I. Wilhelmi,
J. Romanyk,
J. I. Alos, and J. L. Gomez-Garces.
1997.
Prevalence of antimicrobial resistance in enterococci isolated from blood in Madrid.
Enferm. Infecc. Microbiol. Clin.
15:22-23[Medline].
|
| 2.
|
Boyce, J. M.,
S. M. Opal,
J. W. Chow,
M. J. Zervos,
G. Patter-Bynoe,
C. B. Sherman,
R. L. C. Romulo,
S. Fortna, and A. A. Medeiros.
1994.
Outbreak of multidrug-resistant Enterococcus faecium with transferable vanB class vancomycin resistance.
J. Clin. Microbiol.
32:1148-1153[Abstract/Free Full Text].
|
| 3.
| Centers for Disease Control and Prevention. 1995. Recommendations of the Hospital Infection Control Practices Advisory
Committee for preventing the spread of vancomycin resistance. Morbid.
Mortal. Weekly Rep. 44(RR-12).
|
| 4.
| Centers for Disease Control and Prevention.
Unpublished data.
|
| 5.
|
Clarke, N. C.,
R. C. Cooksey,
B. C. Hill,
J. M. Swenson, and F. C. Tenover.
1993.
Characterization of glycopeptide-resistant enterococci from U.S. hospitals.
Antimicrob. Agents Chemother.
37:2311-2317[Abstract/Free Full Text].
|
| 6.
|
Cookson, S. T.,
H. Lopardo,
M. Marin,
R. Arduino,
M. J. Rial,
M. Altschuler,
L. Galanternik,
J. M. Swenson,
F. C. Tenover,
J. I. Tokars, and W. R. Jarvis.
1997.
An Argentine-United States study to determine the ability of clinical laboratories to detect antimicrobial-resistant enterococcus isolates.
Diagn. Microbiol. Infect. Dis.
29:107-109[Medline].
|
| 7.
|
Felmingham, D.,
D. Brown,
P. Courvalin, and Members of the European Workshop on Glycopeptide Resistance.
1995.
European Glycopeptide Susceptibility Survey: quality assessment using five reference strains, abstr. E34, p. 91.
In
Program and abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, Washington, D.C.
|
| 8.
|
Grupo de Trabajo EPINE.
1997.
Informe de la evolucion de la prevalencia de las infecciones nosocomiales segun las encuestas EPINE 1991-1996.
Sociedad Española de Higiene y Medicina Preventiva Hospitalarias, Madrid, Spain.
|
| 9.
|
Guiney, M., and G. Urwin.
1993.
Frequency and antimicrobial susceptibility of clinical isolates of enterococci.
Eur. J. Clin. Microbiol. Infect. Dis.
12:362-366[Medline].
|
| 10.
|
Handwerger, S.,
B. Raucher,
D. Altarac,
J. Monka,
S. Marchione,
K. V. Singh,
B. E. Murray,
J. Wolff, and B. Walters.
1993.
Nosocomial outbreak due to Enterococcus faecium highly resistant to vancomycin, penicillin and gentamicin.
Clin. Infect. Dis.
16:750-755[Medline].
|
| 11.
|
Montecalvo, M. A.,
H. Horowitz,
C. Gedris,
C. Carbonaro,
F. C. Tenover,
A. Issah,
P. Cook, and G. P. Wormser.
1994.
Outbreak of vancomycin-, ampicillin-, and aminoglycoside-resistant Enterococcus faecium bacteremia in an adult oncology unit.
Antimicrob. Agents Chemother.
38:1363-1367[Abstract/Free Full Text].
|
| 12.
|
National Committee for Clinical Laboratory Standards.
1997.
Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A4.
National Committee for Clinical Laboratory Standards, Wayne, Pa.
|
| 13.
|
National Nosocomial Infections Surveillance System.
1996.
National Nosocomial Infections Surveillance System report, data summary from October 1986-April 1996.
Am. J. Infect. Control
24:380-388[Medline].
|
| 14.
|
Noble, W. C.,
Z. Virani, and R. G. A. Cree.
1992.
Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus.
FEMS Microbiol. Lett.
93:195-198.
|
| 15.
|
Tenover, F. C.,
J. M. Swenson,
C. M. O'Hara, and S. A. Stocker.
1995.
Ability of commercial and reference antimicrobial susceptibility testing methods to detect vancomycin resistance in enterococci.
J. Clin. Microbiol.
33:1524-1527[Abstract].
|
| 16.
|
Tenover, F. C.,
J. Tokars,
J. Swenson,
S. Paul,
K. Spitalny, and W. Jarvis.
1993.
Ability of clinical laboratories to detect antimicrobial agent-resistant enterococci.
J. Clin. Microbiol.
31:1695-1699[Abstract/Free Full Text].
|
| 17.
|
Venditti, M., and A. Goglio.
1996.
Vancomycin susceptibility in enterococcal blood isolates in Italy: a multicenter retrospective analysis.
J. Chemother.
8:33-36[Medline].
|
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Abstract
Introduction
