Concordance of PCR and culture from nasal swabs for MRSA in

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JCM Accepts, published online ahead of print on 22 January 2014
J. Clin. Microbiol. doi:10.1128/JCM.02972-13
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Concordance of PCR and Culture
1/16/2014
Title: Concordance of PCR and culture from nasal swabs for MRSA in setting of
concurrent anti-staphylococcal antibiotics
Authors:
Erica S. Shenoy, M.D., Ph.D. (#), Farzad Noubary, Ph.D., JiYeon Kim, M.D., M.P.H,
Eric S. Rosenberg, M.D., Jessica A. Cotter, M.P.H., Hang Lee, Ph.D., Rochelle P.
Walensky, M.D., M.P.H., David C. Hooper, M.D.
Affiliations:
Division of Infectious Diseases, Massachusetts General Hospital (ESS, ESR, RPW,
DCH)
Infection Control Unit, Massachusetts General Hospital (ESS, JAC, DCH)
Medical Practice Evaluation Center, Massachusetts General Hospital (ESS, RPW)
Department of Pathology, Massachusetts General Hospital (JK, ESR)
Biostatistics Center, Massachusetts General Hospital (HL)
Division of General Internal Medicine, Massachusetts General Hospital (RPW)
Harvard Medical School (ESS, FN, JK, ESR, HL, RPW, DCH)
The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center,
Boston, Massachusetts (FN)
Tufts Clinical and Translational Science Institute, Tufts University, Boston,
Massachusetts (FN)
Keywords: MRSA, PCR, culture, antibiotics
Running title (33/54 char): Concordance of PCR and culture for MRSA
Word count: 1230 excluding abstract and references:
Contact information (corresponding author): E.S.S. Massachusetts General
Hospital, Infection Control Unit, 55 Fruit Street, Bulfinch 340, Boston, MA, 02114. Tel:
617-643-5637; Fax: 617-724-0267; Pager: 617-726-2000; email: [email protected]
Contact information (alternative corresponding author):D.C.H. Massachusetts
General Hospital, 55 Fruit Street, Gray-Jackson 504, Boston, MA, 02114. Tel: 617-6433856; Fax: 617-726-7416; email: [email protected]
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ABSTRACT
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The effect of concurrent administration of antibiotics on detection of methicillin-resistant
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Staphylococcus aureus (MRSA) remains unresolved. We assessed concordance of
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paired nasal swabs processed using commercial PCR and culture and found high
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concordance in both the absence and presence of antibiotics with activity against MRSA
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[93.7% (95% CI: 88.0%, 97.2%) and 90.9% (95% CI: 84.8%, 94.7%), respectively],
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although PCR was more likely to be positive in the setting of antibiotics.
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TEXT
Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals and
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increasingly in ambulatory settings (1-3). Once patients are designated as having had a
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positive MRSA culture, they require Contact Precautions (CP)(4, 5). Nasal surveillance
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specimens are components of institutional protocols for determination of colonization
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status and, in some cases, for discontinuation of CP; many protocols require such
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specimens to be obtained in the absence of antibiotic exposure(6). Given widespread
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antibiotic use among inpatient populations, the impact of antibiotics on the ability to
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recover MRSA has important implications for infection control and resource utilization(7-
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9)
. To compare the effect of concurrent administration of antibiotics with activity against
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MRSA on detection from nasal surveillance swabs, we assessed the concordance of
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paired samples obtained in a randomized-controlled trial, processed using both
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commercial culture and PCR assays(10). Discordance between PCR and culture could
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be the result of PCR detection of non-viable MRSA, possibly related to antibiotic
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exposure, in contrast to culture dependence on bacterial growth, greater sensitivity of
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PCR to detect viable bacteria compared to culture techniques, or false-positives
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resulting from staphylococcal cassette chromosome (SCC) elements in the absence of
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the mecA gene.
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We performed an analysis of subjects enrolled in an investigator-initiated randomized
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controlled trial (NCT01234831). Eligible subjects for that trial included those patients
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admitted to the Massachusetts General Hospital (MGH) between 12/6/2010 and
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9/16/2011 with a history of MRSA infection or colonization > 90 days from the day of
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admission. Subjects were approached and attempts were made to screen on Days 1, 2,
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and 3 of hospitalization. Subjects who were enrolled and had at least one set of
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surveillance screens performed were included in this analysis. Subjects were screened
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simultaneously by study staff with both BBLTM CultureSwabTM Collection and Transport
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System and inoculated onto BBLTM CHROMagarTM MRSA media plates (“CA”, Becton,
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Dickinson and Company) and commercial polymerase chain reaction using the Xpert
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MRSA® real-time PCR assay on the GeneXpert platform (“PCR”, Cepheid). Samples
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obtained within the 48 hours after administration of one or more doses of select
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antibiotics were considered to be obtained in the presence of “concurrent antibiotics.”
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These antibiotics included: trimethoprim/sulfamethoxazole, mupirocin, ciprofloxacin,
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clindamycin, daptomycin, doxycycline, levofloxacin, linezolid, nitrofurantoin,
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quinupristin/dalfopristin, rifampin, tetracycline, tigecycline; or vancomycin (IV only). The
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first paired sample was analyzed due to the policy implications of using a single PCR for
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infection control purposes.
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A total of 259 subjects were simultaneously tested using CA and PCR. The t-test was
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used to compare age, length of hospital stay (LOS), hospitalizations in the month and
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year prior to admission to MGH, and MRSA history (time since last positive MRSA
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culture and time since original MRSA culture). An equality of variance test was
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performed to determine the appropriate t-test. If the F-test result was <0.05 then an
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unequal variance t-test was performed; and if the F-test result was >0.05, the equal
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variance t-test was performed. The chi-squared test was used to compare gender, race,
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admission source, admitting site and admitting service. The concordance between CA
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and PCR of single paired nasal swabs in the presence and absence of antibiotics as
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defined by the study with known activity against MRSA was assessed, and the data
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were analyzed using the exact McNemar’s test for marginal homogeneity.
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Antibiotic exposure was identified in 51% (132/259) screened patients, while 49%
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(127/259) were sampled in the absence of antibiotics, forming the two comparison
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groups. There were no observed statistically significant differences in the antibiotics
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receipt or non-receipt groups in age, gender, admission source, admitting site, admitting
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service, number of hospitalizations at our institution in the prior month or year.
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Compared to the off antibiotics group, the group with concurrent antibiotic exposure had
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a longer mean length of stay (8 days vs 6 days; P=0.03) and a greater median number
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of inpatient hospitalizations at MGH in the prior year (1 vs 0, P=0.03). The group with
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concurrent antibiotic exposure had a more recent history of MRSA infection or
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colonization compared to the non-receipt group, with a significantly lower mean number
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of days since last positive MRSA isolate (586 days vs 872 days, P<0.01) and mean
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number of days since their original MRSA isolate (951 days vs 1225 days, P=0.02).
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(See Supplementary Material, Table A)
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There was high concordance between culture and PCR assays across all subjects
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tested (Table 1). Among 127 paired samples that were obtained in the absence of
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antibiotics, 119 (93.7%; 95% CI: 88.0%, 97.2%) were concordant. For those without
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exposure to MRSA-active antibiotics, the exact McNemar’s test revealed no significant
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difference in the proportion of positive test results between CA and PCR (33.1%
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[42/127] vs. 36.2% [46/127]), respectively; P=0.29). Of the 132 paired samples obtained
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in the presence of antibiotics, 120 (90.9%; 95% CI: 84.8%, 94.7%) were concordant.
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For those with exposure to MRSA-active antibiotics, however, there was a greater
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tendency for PCR to give positive results (34.1% [45/132] positive for CA, 41.7%
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[55/132] positive for PCR; P<0.01). Of the twelve patients with discordant results, the
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single patient with culture positive/PCR negative discordance had received a single
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dose each of vancomycin and a fluorquinolone; while the eleven patients with culture
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negative/PCR positive discordance in the presence of MRSA-active antibiotics, eight
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had received at least one dose of vancomycin during the 48 hour time window and three
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had received at least one dose of a fluoroquinolone.
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Regardless of the assay employed, efficient strategies for discontinuation of CP are
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needed in order to improve patient care and resource utilization. This study
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demonstrates high concordance in both the absence and presence of concurrent
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antibiotic use, however, PCR was significantly more likely to give positive results in the
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presence of concurrent antibiotic administration. The latter may reflect the higher
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sensitivity of PCR compared to culture for detection of viable organisms, the detection
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of DNA from non-viable organisms, or false-positives resulting from staphylococcal
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cassette chromosome (SCC) elements in the absence of the mecA gene. This study
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has limitations, most notably that the current MRSA status of subjects with history of
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MRSA was not known with certainty. As such, it was not possible to evaluate standard
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test characteristics, such as sensitivity and specificity. Broth enrichment techniques
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would attenuate this limitation. In addition, it was not possible to randomize subjects in
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the study to receipt or non-receipt of antibiotics and there were differences observed
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between the groups, notably the length of stay and timing of the most recent MRSA
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isolate.
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In conclusion, PCR and culture surveillance swabs for MRSA had a high concordance
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rate, though PCR was more likely to be positive in the setting of concurrent antibiotic
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administration. Others have compared molecular methods with culture methods and
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found discordance between samples, although not in the context of assessing for
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clearance of colonization and discontinuation of CP(11, 12). Given our findings,
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discontinuation policies should carefully consider the interpretation of assays obtained
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in the presence of antibiotics with activity against MRSA. A conservative interpretation
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would use any positive PCR result as evidence of continued colonization with viable
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MRSA. Infection Control programs will need to make individual judgments as to
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whether a negative PCR is sufficient to proceed with discontinuing precautions in
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patients with negative results obtained while on antibiotics.
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Table 1. Concordance of Paired Nasal Swabs
1A. Test Results: Off-Antibiotics (N=127)
CA+
CA─
Total
PCR+
40
6
46
PCR─
2
79
81
Total
42
85
127
CA+
CA─
Total
PCR+
44
11
55
PCR─
1
76
77
Total
45
87
132
1B. Test Results: On-Antibiotics (N=132)
Shaded cells represent concordant paired results and total subjects. Abbreviations: CA,
chromogenic agar; PCR, polymerase chain reaction; antibiotics defined by Study
Protocol
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ACKNOWLEDGEMENTS
This work was conducted with support from the Harvard Catalyst, National Center for
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Research Resources and the National Center for Advanced Translational Sciences
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(8UL1TR000170-05, 1UL1RR025758), and financial contributions from Harvard
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University and its affiliated academic health centers; by the MGH 2010-2011 Clinical
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Innovation Award; the National Institutes of Health (T32A107061); MGH Departmental
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Funds; and the Harvard Center for AIDS Research (P30A1060354). PCR reagents and
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testing equipment were provided without charge by Cepheid.
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CONFLICTS OF INTEREST
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ESR reports consultancy with T2 Biosystems, Microphage, and royalties from Up to
Date, all outside the scope of the work herein. JAC reports receiving grant support from
Pfizer, Inc., unrelated to the scope of work herein. RPW reports receiving consultancy
fees from LeClair Ryan, unrelated to the scope of work herein. DCH reports receiving
grant support from Pfizer, Inc., unrelated to the scope of work herein. All other authors
report no potential conflicts of interest.
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REFERENCES
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1. Jarvis, W. R., A. A. Jarvis, and R. Y. Chinn. 2012. National prevalence of methicillinresistantStaphylococcus aureusin inpatients at United States health care facilities, 2010. Am. J.
Infect. Control. 40:194-200.
183
184
185
186
187
2. Pallin, D. J., D. J. Egan, A. J. Pelletier, J. A. Espinola, D. C. Hooper, and C. A. Camargo
Jr. 2008. Increased US emergency department visits for skin and soft tissue infections, and
changes in antibiotic choices, during the emergence of community-associated methicillinresistantStaphylococcus aureus. Ann. Emerg. Med. 51:291-298. doi:
10.1016/j.annemergmed.2007.12.004.
188
189
190
191
3. Landrum, M. L., C. Neumann, C. Cook, U. Chukwuma, M. W. Ellis, D. R. Hospenthal, and
C. K. Murray. 2012. Epidemiology of Staphylococcus aureus blood and skin and soft tissue
infections in the US military health system, 2005-2010. JAMA. 308:50-59. doi:
10.1001/jama.2012.7139.
192
193
194
195
4. Siegel, J. D., E. Rhinehart, M. Jackson, L. Chiarello, and Health Care Infection Control
Practices Advisory Committee. 2007. 2007 Guideline for Isolation Precautions: Preventing
Transmission of Infectious Agents in Health Care Settings. Am. J. Infect. Control. 35:S65-164.
doi: 10.1016/j.ajic.2007.10.007.
196
197
198
5. Siegel, J. D., E. Rhinehart, M. Jackson, L. Chiarello, and Healthcare Infection Control
Practices Advisory Committee. 2007. Management of multidrug-resistant organisms in health
care settings, 2006. Am. J. Infect. Control. 35:S165-93. doi: 10.1016/j.ajic.2007.10.006.
199
200
201
202
6. Shenoy, E. S., H. Hsu, F. Noubary, D. C. Hooper, and R. P. Walensky. 2012. National
Survey of Infection Preventionists: Policies for Discontinuation of Contact Precautions for
Methicillin-ResistantStaphylococcus aureusand Vancomycin-Resistant Enterococcus. Infect.
Control Hosp. Epidemiol. 33:1272-1275. doi: 10.1086/668427; 10.1086/668427.
203
204
205
7. Yu, V. L., A. Goetz, M. Wagener, P. B. Smith, J. D. Rihs, J. Hanchett, and J. J. Zuravleff.
1986. Staphylococcus aureusnasal carriage and infection in patients on hemodialysis. Efficacy
of antibiotic prophylaxis. N. Engl. J. Med. 315:91-96. doi: 10.1056/NEJM198607103150204.
206
207
208
209
8. Keene, A., P. Vavagiakis, M. H. Lee, K. Finnerty, D. Nicolls, C. Cespedes, B.
Quagliarello, M. A. Chiasson, D. Chong, and F. D. Lowy. 2005. Staphylococcus
aureuscolonization and the risk of infection in critically ill patients. Infect. Control Hosp.
Epidemiol. 26:622-628. doi: 10.1086/502591.
210
211
212
213
214
215
9. Ellis, M. W., M. E. Griffith, D. P. Dooley, J. C. McLean, J. H. Jorgensen, J. E. Patterson,
K. A. Davis, J. S. Hawley, J. A. Regules, R. G. Rivard, P. J. Gray, J. M. Ceremuga, M. A.
Dejoseph, and D. R. Hospenthal. 2007. Targeted intranasal mupirocin to prevent colonization
and infection by community-associated methicillin-resistantStaphylococcus aureusstrains in
soldiers: a cluster randomized controlled trial. Antimicrob. Agents Chemother. 51:3591-3598.
doi: 10.1128/AAC.01086-06.
11
Shenoy et al
Concordance of PCR and Culture
1/16/2014
216
217
218
219
10. Shenoy, E., J. Kim, E. Rosenberg, J. Cotter, H. Lee, R. Walensky, and D. Hooper. 2013.
Discontinuation of Contact Precautions for Methicillin-ResistantStaphylococcus aureus(MRSA):
A Randomized Controlled Trial Comparing Passive and Active Screening with Culture and
Polymerase Chain Reaction. Clin. Infect. Dis. . doi: 10.1093/cid/cit206.
220
221
222
223
11. Paule, S. M., M. Mehta, D. M. Hacek, T. M. Gonzalzles, A. Robicsek, and L. R. Peterson.
2009. Chromogenic media vs real-time PCR for nasal surveillance of methicillinresistantStaphylococcus aureus: impact on detection of MRSA-positive persons. Am. J. Clin.
Path. 131:532-539.
224
225
226
227
228
12. Wolk, D. M., E. Picton, D. Johnson, T. Davis, P. Pancholi, C. C. Ginocchio, S. Finegold,
D. F. Welch, M. de Boer, D. Fuller, M. C. Solomon, B. Rogers, M. S. Mehta, and L. R.
Peterson. 2009. Multicenter evaluation of the Cepheid Xpert methicillinresistantStaphylococcus aureus(MRSA) test as a rapid screening method for detection of MRSA
in nares. J. Clin. Microbiol. 47:758-764. doi: 10.1128/JCM.01714-08.
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