Rapid detection of methicillin-resistant Staphylococcus aureus directly from clinical samples: methods, effectiveness and cost considerations

GMS German Medical Science — an Interdisciplinary Journal

Enno Stürenburg¹ 

[1] LADR GmbH, MVZ Dr. Kramer & Colleagues, Geesthacht, Germany

关键词: rapid culture;    single-locus PCR;    SCCmec-orfX;    nuc;    mecA;    PCR;    molecular detection;    rapid test;    PBP-2a;    MRSA;    methicillin resistance;    S. aureus;   

Others  :  869136

实施日期：2008-11-04，发布日期：2009-07-02

【 摘 要 】

Methicillin-resistant Staphylococcus aureus (MRSA) isolates is a serious public health problem whose ever-increasing rate is commensurate with the pressure it is exerting on the healthcare system. At present, more than 20% of clinical S. aureus isolates in German hospitals are methicillin resistant. Strategies from low-prevalence countries show that this development is not necessarily inevitable. In the Scandinavian countries and the Netherlands, thanks to a rigorous prevention programme, MRSA prevalence has been kept at an acceptably low level (<1–3%). Central to these ‘search and destroy’ control strategies is an admission screening using several MRSA swabs taken from mucocutaneous colonisation sites of high-risk patients (‘MRSA surveillance’).

It has also been reported that the speed with which MRSA carriage is detected has an important role to play, as it is a key component of any effective strategy to prevent the pathogen from spreading. Since MRSA culturing involves a 2–3 day delay before the final results are available, rapid detection techniques (commonly referred to as ‘MRSA rapid tests’) using PCR methods and, most recently, rapid culturing methods have been developed. The implementation of rapid tests reduces the time of detection of MRSA carriers from 48–72 to 2–5 h. Clinical evaluation data have shown that MRSA can thus be detected with very high sensitivity. Specificity however is sometimes impaired due to false-positive PCR signals occurring in mixed flora specimens. In order to rule out any false-positive PCR results, a culture screen must always be carried out simultaneously.

The data provide preliminary evidence that a PCR assay can reduce nosocomial MRSA transmission in high-risk patients or high-risk areas, whereas an approach that screens all patients admitted to the hospital is probably not effective. Information concerning the cost-effectiveness of rapid MRSA tests is still sparse and thus the issue remains debated.

【 授权许可】

   
© 2009 Stürenburg.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

【 参考文献 】

• [1]Geffers C, Gastmeier P, Rüden H. Gesundheitsberichterstattung des Bundes: Nosokomiale Infektionen. Berlin: Robert Koch-Institut und Statistisches Bundesamt; 2002. (Themenheft; 8). Available from: http://infomed.mds-ev.de/sindbad.nsf/44eb5931ca44b6c9c12571e700442be5/7a2868e0855f85e580256bf20067a880/$FILE/GBE_NosokomInf.pdf 
• [2]Kresken M, Hafner D, Schmitz FJ, Wichelhaus TA. Resistenzsituation bei klinisch wichtigen Infektionserregern gegenüber Antibiotika in Deutschland und im mitteleuropäischen Raum: Bericht über die Ergebnisse einer multizentrischen Studie der Arbeitsgemeinschaft Empfindlichkeitsprüfungen & Resistenz der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. aus dem Jahre 2007. Rheinbach: Antiinfective Intelligence; 2009.
• [3]Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis. 2003;36(1):53-9. DOI: 10.1086/345476 
• [4]Cosgrove SE, Qi Y, Kaye KS, Harbarth S, Karchmer AW, Carmeli Y. The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges. Infect Control Hosp Epidemiol. 2005;26(2):166-74. DOI: 10.1086/502522 
• [5]Wertheim HF, Vos MC, Boelens HA, Voss A, Vandenbroucke-Grauls CM, Meester MH, Kluytmans JAJW, van Keulen PHJ, Verbrugh HA. Low prevalence of methicillin resistant Staphylococcus aureus (MRSA) at hospital admission in the Netherlands: the value of search and destroy and restrictive antibiotic use. J Hosp Infect. 2004;56(4):321-5. DOI: 10.1016/j.jhin.2004.01.026 
• [6]Styers D, Sheehan DJ, Hogan P, Sahm DF. Laboratory-based surveillance of current antimicrobial resistance patterns and trends among Staphylococcus aureus: 2005 status in the United States. Ann Clin Microbiol Antimicrob. 2006;5:2. DOI: 10.1186/1476-0711-5-2 
• [7]Kommission für Krankenhaushygiene und Infektionsprävention. Kommentar zu den "Empfehlungen zur Prävention und Kontrolle von Methicillin-resistenten Staphylococcus aureus-Stämmen in Krankenhäusern und anderen medizinischen Einrichtungen". Epidemiol Bull 2004;46:396.
• [8]Girou E, Pujade G, Legrand P, Cizeau F, Brun-Buisson C. Selective screening of carriers for control of methicillin-resistant Staphylococcus aureus (MRSA) in high-risk hospital areas with a high level of endemic MRSA. Clin Infect Dis. 1998;27(3):543-50. DOI: 10.1086/514695 
• [9]Jernigan JA, Pullen AL, Flowers L, Bell M, Jarvis WR. Prevalence of and risk factors for colonization with methicillin-resistant Staphylococcus aureus at the time of hospital admission. Infect Control Hosp Epidemiol. 2003;24(6):409-14. DOI: 10.1086/502230 
• [10]Lucet JC, Grenet K, Armand-Lefevre L, Harnal M, Bouvet E, Regnier B, Andremont A. High prevalence of carriage of methicillin-resistant Staphylococcus aureus at hospital admission in elderly patients: implications for infection control strategies. Infect Control Hosp Epidemiol. 2005;26(2):121-6. DOI: 10.1086/502514 
• [11]Jernigan JA, Titus MG, Groschel DH, Getchell-White S, Farr BM. Effectiveness of contact isolation during a hospital outbreak of methicillin-resistant Staphylococcus aureus. Am J Epidemiol. 1996;143(5):496-504.
• [12]Bootsma MC, Diekmann O, Bonten MJ. Controlling methicillin-resistant Staphylococcus aureus: quantifying the effect of interventions and rapid diagnostic testing. Proc Natl Acad Sci U S A. 2006;103(14):5620-5. DOI: 10.1073/pnas.0510077103 
• [13]Harbarth S, Masuet-Aumatell C, Schrenzel J, Francois P, Akakpo C, Renzi G, Pugin J, Ricou B, Pittet D. Evaluation of rapid screening and pre-emptive contact isolation for detecting and controlling methicillin-resistant Staphylococcus aureus in critical care: an interventional cohort study. Critical Care 2006;10(1):R25. DOI: 10.1186/cc3982 
• [14]Geiss HK, Mack D, Seifert H. Identifizierung von speziellen Resistenzmechanismen und Interpretation von Ergebnissen der Antibiotika-Empfindlichkeitstestung bei grampositiven und gramnegativen Erregern. Chemother J. 2004;13:1-16.
• [15]Kniehl E. Nachweis methicillin-resistenter Staphylococcus aureus (MRSA) im Routinelabor. Chemother J. 2006;15(5):152-61.
• [16]Cuny C, Werner G, Braulke C, Witte W. Diagnostics of staphylococci with special reference to MRSA. J Lab Med. 2002;26:165-173.
• [17]Hoc S. MRSA-Infektionen. Diagnose liegt nach nur fünf Stunden vor. Dtsch Arztebl. 2007;104(23):A1679.
• [18]O'Hara S, Gregory S, Taylor D, et al. Evaluation of the 3M™ BacLite™ Rapid MRSA; Test for the direct detection of MRSA from nasal and groin surveillance specimens (Abstract 540). In: Abstracts of the Annual Meeting of the Infectious Diseases Society of America, San Diego, CA, 2007. . Arlington, VA, USA. p. 162-3.
• [19]Cohen D, Almeida M, Bagoole B, et al. Evaluation of the 3M BacLite Rapid MRSA test for the direct detection of MRSA. In: Abstracts of the Institute of Biomedical Science International Congress, Birmingham, UK, 2007.
• [20]von Eiff C, Maas D, Sander G, Friedrich AW, Peters G, Becker K. Microbiological evaluation of a new growth-based approach for rapid detection of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 2008;61(6):1277-80. DOI: 10.1093/jac/dkn122 
• [21]Reischl U, Holzmann T. Aktuelle Verfahren zum Nukleinsäure gestützten Direktnachweis von MRSA. J Lab Med. 2008;32:253-65.
• [22]Becker K, Pagnier I, Schuhen B, Wenzelburger F, Friedrich AW, Kipp F, Peters G, von Eiff C. Does nasal cocolonization by methicillin-resistant coagulase-negative staphylococci and methicillin-susceptible Staphylococcus aureus occurs frequently enough to present a risk of false-positive methicillin-resistant Staphylococcus aureus determinations by molecular methods. J Clin Microbiol. 2006;44(1):229-31. DOI: 10.1128/JCM.44.1.229-231.2006 
• [23]Hoffmann I. MRSA-Screening mit dem hyplex StaphyloResist Multiplex-PCR-System. Mikrobiologe. 2007;17:30-2.
• [24]Eigner U, Holfelder M, Wild U, Peters B, Fahr AM. Direct detection of MRSA from clinical swabs with nucleic acid amplification assays. In: 56th Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM) Congress; 2004; Münster, Germany (Abstract no. DVV09).
• [25]Kola A, Mattner F, Reischl U, Vonberg R, et al. Workshop zum MRSA-Screening am 25.05.2005 in Hannover. Mikrobiologe. 2005;15:175-81.
• [26]Koelemann J, te Witt R, de Man P. Evaluation of the hyplex Staphyloresist multiplex PCR system for the detection of methicillin-resistant Staphylococcus aureus from clinical samples. In: European meeting of molecular diagnostics (EMMD); 2005 Oct 13-14; Scheveningen.
• [27]Ieven M, Michiels M, Jansens H, Goossens H. Evaluation of a real-time PCR assay and an multiplex-reverse hybridisation system for the detection of methicillin-resistant Staphylococcus aureus. In: 17th European Congress of Clinical Microbiology and Infectious Diseases ICC; 2007 Mar-Apr 31-4; Munich, Germany. (Abstract number: 1733_393).
• [28]Huletsky A, Giroux R, Rossbach V, Gagnon M, Vaillancourt, Bernier M, Gagnon F, Truchon K, Bastien M, Picard FJ, van Belkum A, Oulette M, Roy PH, Bergeron MG . New real-time PCR assay for rapid detection of methicillin-resistant Staphylococcus aureus directly from specimens containing a mixture of staphylococci. J Clin Microbiol. 2004;42(5):1875-84. DOI: 10.1128/JCM.42.5.1875-1884.2004 
• [29]Cuny C, Witte W. PCR for the identification of methicillin-resistant Staphylococcus aureus (MRSA) strains using a single primer pair specific for SCCmec elements and the neighbouring chromosome-borne orfX. Clin Microbiol Infect. 2005;11(10):834-7. DOI: 10.1111/j.1469-0691.2005.01236.x 
• [30]Holfelder M, Eigner U, Turnwald AM, Witte W, Weizenegger M, Fahr A. Direct detection of methicillin-resistant Staphylococcus aureus in clinical specimens by a nucleic acid-based hybridisation assay. Clin Microbiol Infect. 2006;12(12):1163-7. DOI: 10.1111/j.1469-0691.2006.01547.x 
• [31]Oberdorfer K, Wendt C. MRSA - rationale und rationelle Diagnostik. Mikrobiologe. 2008;18:97-106.
• [32]Boyce JM, Havill NL. Comparison of BD GeneOhm methicillin-resistant Staphylococcus aureus (MRSA) PCR versus the CHROMagar MRSA assay for screening patients for the presence of MRSA strains. J Clin Microbiol. 2008;46:350-1. DOI: 10.1128/JCM.02130-07 
• [33]de San N, Denis O, Gasasira MF, De Mendonça R, Nonhoff C, Struelens MJ. Controlled evaluation of the IDI-MRSA assay for detection of colonization by methicillin-resistant Staphylococcus aureus in diverse mucocutaneous specimens. J Clin Microbiol. 2007;45(4):1098-101. DOI: 10.1128/JCM.02208-06 
• [34]Desjardins M, Guibord C, Lalonde B, Toye B, Ramotar K. Evaluation of the IDI-MRSA assay for detection of methicillin-resistant staphylococcus aureus from nasal and rectal specimens pooled in a selective broth. J Clin Microbiol. 2006;44(4):1219-23. DOI: 10.1128/JCM.44.4.1219-1223.2006 
• [35]Francois P, Bento M, Renzi G, Harbarth S, Pittet D, Schrenzel J. Evaluation of three molecular assays for rapid identification of methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2007;45(6):2011-3. DOI: 10.1128/JCM.00232-07 
• [36]Deplano A, Tassios PT, Glupczynski Y, Godfroid E, Struelens MJ. In vivo deletion of the methicillin resistance mec region from the chromosome of Staphylococcus aureus strains. J Antimicrob Chemother. 2000;46(4):617-20. DOI: 10.1093/jac/46.4.617 
• [37]Corkill JE, Anson JJ, Griffiths P, Hart CA. Detection of elements of the staphylococcal cassette chromosome (SCC) in a methicillin-susceptible (mecA gene negative) homlogue of a fucidin-resistant MRSA. J Antimicrob Chemother. 2004;54(1):229-31. DOI: 10.1093/jac/dkh284 
• [38]Cepheid. Xpert™MRSA. Redefining Active MRSA Surveillance Testing [product brochure]. Available from: http://www.cepheid.com/media/files/brochures/Xpert%20MRSA%20US%20Brochure_v1A.pdf [last accessed 2009-06-03]. 
• [39]Rossney AS, Herra CM, Brennan GI, Morgan PM, O'Connell B. Evaluation of the Xpert methicillin-resistant Staphylococcus aureus (MRSA) assay on the GeneXpert real-time PCR platform for rapid detection of MRSA from screening specimens. J Clin Microbiol. 2008;46(10):3285-90. DOI: 10.1128/JCM.02487-07 
• [40]Kunori T, Cookson B, Roberts JA, Stone S, Kibbler C. Cost-effectiveness of different MRSA screening methods. J Hosp Infect. 2002;51(3):189-200. DOI: 10.1053/jhin.2002.1247 
• [41]Raboud J, Saskin R, Simor A, Loeb M, Green K, Low DE, McGeer A. Modeling transmission of methicillin-resistant Staphylococcus aureus among patients admitted to a hospital. Infect Control Hosp Epidemiol. 2005;26(7):607-15. DOI: 10.1086/502589 
• [42]Tomic V, Svetina Sorli P, Trinkaus D, Sorli J, Widmer AF, Trampuz A. Comprehensive strategy to prevent nosocomial spread of methicillin-resistant Staphylococcus aureus in a highly endemic setting. Arch Intern Med. 2004;164(18):2038-43. DOI: 10.1001/archinte.164.18.2038 
• [43]Wernitz MH, Swidsinki S, Weist K, Sohr D, Witte W, Franke KP , Roloff D, Rüden H, Veit SK. Effectiveness of a hospital-wide selective screening programme for methicillin-resistant Staphylococcus aureus (MRSA) carriers at hospital admission to prevent hospital-acquired MRSA infections. Clin Micobiol Infect. 2005;11(6):457-65. DOI: 10.1111/j.1469-0691.2005.01152.x 
• [44]Bühlmann M, Bögli-Stuber K, Droz S, Mühlemann K. Rapid screening for carriage of methicillin-resistant Staphylococcus aureus by PCR and associated costs. J Clin Microbiol. 2008;46(7):2151-4. DOI: 10.1128/JCM.01957-07 
• [45]Harbarth S, Fankhauser C, Schrenzel J, Christenson J, Gervaz P, Bandiera-Clerc C, Renzi G, Vernaz N, Sax H, Pittet D. Universal screening of methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients. JAMA. 2008;299(10):1149-57. DOI: 10.1001/jama.299.10.1149 
• [46]Jeyaratnam D, Whitty CJ, Phillips K, Liu D, Orezzi C, Ajoku U, French GL. Impact of rapid screening tests on acquisition of meticillin resistant Staphylococcus aureus: cluster randomised crossover trial. BMJ. 2008;336(7650):927-30. DOI: 10.1136/bmj.39525.579063.BE 
• [47]Jog S, Cunningham R, Cooper S, Wallis M, Marchbank A, Vasco-Knight P, Jenks PJ. Impact of preoperative screening for meticillin-resistant Staphylococcus aureus by real-time polymerase chain reaction in patients undergoing cardiac surgery. J Hosp Infect. 2008;69(2):124-30. DOI: 10.1016/j.jhin.2008.02.008 
• [48]Cunningham R, Jenks P, Nortwood J, Wallis M, Ferguson S, Hunt S. Effect on MRSA transmission of rapid PCR testing of patients admitted to critical care. J Hosp Infect. 2007;65(1):24-8. DOI: 10.1016/j.jhin.2006.09.019 
• [49]Linde H, Mistlbeck G, Wolf H, Lehn N. Schnellnachweis von Methicillin-resistentem Staphylococcus aureus - Ökonomische Aspekte von Screening bei Aufnahme des Patienten. Mikrobiologe. 2007;17:141-7.
• [50]Safdar N, Marx J, Meyer NA, Maki DG. Effectiveness of preemptive barrier precautions in controlling nosocomial colonization and infection by methicillin-resistant Staphylococcus aureus in a burn unit. Am J Infect Control. 2006;34(8):476-83. DOI: 10.1016/j.ajic.2006.01.011 
• [51]Wernitz MH, Keck S, Swidsinki S, Schulz S, Veit SK. Cost analysis of a hospital-wide selective screening programme for methicillin-resistant Staphylococcus aureus (MRSA) carriers in the context of diagnosis related group (DRG) payment. Clin Microbiol Infect. 2005;11(6):466-71. DOI: 10.1111/j.1469-0691.2005.01153.x 
• [52]Vriens M, Blok H, Fluit A, Troelstra A, Van Der Werken C, Verhoef J. Costs associated with a strict policy to eradicate methicillin-resistant Staphylococcus aureus in a Dutch University Medical Center: a 10-year survey. Eur J Clin Microbiol Infect Dis. 2002; 21(11):782-6. DOI: 10.1007/s10096-002-0811-4 
• [53]Papia G, Louie M, Tralla A, Johnson C, Collins V, Simor AE. Screening high-risk patients for methicillin-resistant Staphylococcus aureus on admission to the hospital: is it cost effective? Infect Control Hosp Epidemiol. 1999;20(7):473-7. DOI: 10.1086/501655