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Outbreak of methicillin-resistant Staphylococcus aureus in two nursing homes in Central Norway
Journal of Hospital Infection (2005) 60, 312–316
www.elsevierhealth.com/journals/jhin
Outbreak of methicillin-resistant Staphylococcus aureus in two nursing homes in Central Norway K.W. Larssena,*, T. Jacobsena, K. Bergha, P. Tveteb, E. Kvelloc, O. Scheela a
Department of Microbiology, St Olav University Hospital, Olav Kyrresgt 17, N-7006 Trondheim, Norway Overhalla legekontor, N-7386 Overhalla, Norway c Vikna kommunale helsesenter, N-7900 Rørvik, Norway b
Received 12 July 2004; accepted 6 December 2004
KEYWORDS MRSA; Nursing homes; Outbreaks
Summary Until recently, infections with methicillin-resistant Staphylococcus aureus (MRSA) have mainly been associated with hospital outbreaks in Norway. However, increasingly cases are contracted outside hospitals. This paper reports the first two outbreaks of MRSA in two nursing homes in central Norway, affecting 23 residents and five staff members. Pulsed-field gel electrophoresis analysis showed that all strains from nursing home A were identical and that the strains from nursing home B were genotypically similar with one or two band differences. Multi-locus sequence typing (MLST) showed that the strains from the two nursing homes belong to clonal complex 45, with each strain being a single-locus variant of sequence type 45 (ST45), a well-known European epidemic strain. No evident source of the two outbreaks was found, and there was no obvious connection between the two outbreaks. The latter is also supported by the minor differences observed by MLST, suggesting a connection at some time in the past. The outbreaks led to a heavier workload and economic strain on both nursing homes. The outbreak in nursing home A was brought to an end, whereas two residents remained colonized in nursing home B despite several eradication attempts. These outbreaks show the potential for MRSA spread in a nursing home. If the prevalence of MRSA in Norway continues to increase, nursing home staff and residents may have to be included in the groups to be screened for MRSA upon hospital admission. Q 2005 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: C47 73867470; fax: C47 73867765 E-mail address: [email protected] 0195-6701/$ - see front matter Q 2005 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2004.12.021
MRSA outbreaks in nursing homes in Norway
Introduction Methicillin-resistant Staphylococcus aureus (MRSA) emerged as a cause of hospital infection in 1961, only two years after the introduction of methicillin. Like the other Scandinavian countries and the Netherlands, Norway has a low prevalence of MRSA with less than 1% of all staphylococcal infections.1 In the 1970s, there was a large outbreak in a hospital in central Norway.2 Since then, only sporadic cases occurred until the 1990s when several minor outbreaks of MRSA occurred in Norwegian hospitals.3–5 In 2003, 215 cases of MRSA were reported to the Norwegian Notification System for Infectious Diseases. This is a 10-fold increase since registration of MRSA infection was made compulsory in 1995. Prior to 1997, most cases of MRSA were contracted abroad, but since then, most cases have been contracted in Norway and outside hospitals.1 Over the last few years, this increase in MRSA prevalence has proven common to all the Nordic countries.6 More recently, long-term care facilities have been increasingly recognized as reservoirs for this pathogen.7,8 Studies of MRSA colonization in several nursing homes across Europe have reported prevalences from 1 to 27%.9–12 Low-prevalence countries such as Finland and the Netherlands have experienced MRSA outbreaks in nursing homes.13,14 This paper reports two outbreaks of MRSA in 2003 from two different nursing homes in central Norway. To our knowledge, this is the first report of MRSA outbreaks in Scandinavian nursing homes.
Materials and methods The MRSA outbreaks occurred in two different nursing homes in the same region of central Norway. The nursing homes are located 111 km apart and are served by the same hospital. Positive MRSA cultures were sampled between 12 March 2003 and 2 March 2004. This extended period of sampling resulted in a higher number of screened residents than the total number of beds due to turnover of residents.
Screening of residents and staff Nursing home A has 39 beds and a total of 114 employees, of whom 70 worked directly with patients. At nursing home A, 50 residents were screened for MRSA. Nursing home B has 39 beds and 65 staff members, 44 of whom have direct patient contact, as well as 10 stand-ins with patient
313 contact. At nursing home B, 55 residents were screened for MRSA. Both nursing homes have screened their residents several times, and all employees have been screened at least once. Staff and residents had their nostrils screened. Residents had additional swabs taken from possible wounds or pus and, if present, from catheters or other foreign bodies. Staff with skin lesions had additional cultures taken. If a person (staff or resident) was identified with MRSA, samples were taken from nose, throat, perineum and possible wounds or catheters in the subsequent screening.
Detection of MRSA Detection of MRSA was mainly performed by the use of a selective phenyl mannitol agar with NaCl 2%, aztreonam (8 mg/L) and oxacillin (4 mg/L).15 A small number of samples were processed by the use of selective phenyl mannitol broth containing aztreonam (75 mg/L) and ceftizoxime (5 mg/L).16 MRSA strains were verified by detection of nuc and mecA genes by polymerase chain reaction (PCR), as described elsewhere.17
Molecular epidemiology Genotyping of all MRSA strains in the study was performed by pulsed-field gel electrophoresis (PFGE). Preparation of chromosomal DNA and SmaI digestion was performed as described by Bannerman et al.18 Electrophoresis was performed with a CHEF XA Mapper (Bio-Rad Laboratories, Hercules, CA, USA) under conditions described elsewhere.5 Criteria for similarities between strains were those proposed by Tenover et al.19 Strains with different PFGE patterns were analysed by multi-locus sequence typing (MLST) by sequencing internal fragments of seven housekeeping genes using primers described by Enright et al.20 The DNA sequences of both strands were determined with a CEQ 8000 DNA sequencer (Beckman Coulter, Inc., Fullerton, CA, USA) with dideoxy NTP fluorescent terminators. The same primers were used for initial PCR amplification and subsequent sequencing. Data were submitted to the MLST database for S. aureus (http://saureus.mlst. net/) to obtain allelic profiles. Characterization of the structural type of the SCCmec element was performed by multiplex PCR as described elsewhere.21
Results Nursing home A had 11 cases of MRSA, all among
314
K.W. Larssen et al.
residents. Nursing home B had 12 cases among residents and five cases among healthcare workers with patient contact. The age distribution of the MRSA-positive residents was 73–95 years for nursing home A (mean 84.1 years) and 70–92 years for nursing home B (mean 81.2 years). The age distribution of the MRSA-positive staff was 24–42 years (mean 33.6 years). MRSA strains were isolated from nostrils and/or wounds. Two strains were also found in purulent discharge from an eye and an ear, respectively (Table I). All 11 strains from nursing home A had an identical PFGE pattern. The 17 strains from nursing home B were mutually similar with one fragment difference. The strains from nursing home B differed by one or two bands from the strain from nursing home A (Figure 1). By the PFGE criteria used, all strains could be part of a common outbreak. MLST of the strains from the two nursing homes showed two new pta alleles. The strain from nursing home A (ST 497) has a mutation in the pta gene at position 227 (G instead of T). The two strains with different PFGE subtypes from nursing home B (ST455) have a new pta allele at position 17 (A instead of C). The strains in question were found to be type IV by PCR of the SCCmec. The strains involved in the outbreaks can therefore be characterized as unique single-locus variants of ST45 belonging to clonal complex 45.22
Figure 1 Representative pulsed-field gel electrophoresis (PFGE) patterns from methicillin-resistant Staphylococcus aureus strains from two nursing homes in central Norway. Lanes 1 and 5 represent molecular weight standards. Lanes 2 and 3 show PFGE patterns from nursing home B, and lane 4 represents all strains from nursing home A.
leg amputation, and the only previous contact with the local hospital within the previous six months had been for prosthesis adjustment. MRSA had not been suspected. It is not routine practice in Norway to screen nursing home residents or staff for MRSA unless they have been patients or worked in hospitals/healthcare institutions outside Scandinavia or the Netherlands, or in a healthcare institution with an ongoing MRSA outbreak.23 The index case of nursing home B was diagnosed at the nursing home in March 2003 by testing secretions from a longstanding ulcer after a leg amputation in 2002, where previous cultures had grown methicillin-sensitive S. aureus. MRSA
Discussion No exchange of personnel or residents between the two nursing homes had taken place, and no obvious connection between the two outbreaks nor cause of spread was found. Both nursing homes are served by the same hospital. The index case of nursing home A was initially diagnosed at the nursing home in March 2003 by aerobic culture of wound secretions after a
Table I
Number of cases positive for methicillin-resistant Staphylococcus aureus (MRSA)
MRSAC
Nostrils Wound NostrilsCwound NostrilsCpus (ear) Pus (eye) Total
Nursing home A
Nursing home B
Residents
Staff
Residents
Staff
4 5 0 1 1 11
0 0 0 0 0 0
7 4 1 0 0 12
5 0 0 0 0 5
Number of people identified with at least one positive MRSA culture. The site where the positive culture was taken is indicated. Two people had positive cultures from several screening locations as shown in the table.
MRSA outbreaks in nursing homes in Norway was not suspected in this case either, but the resident had received repeated courses of antimicrobial therapy. This resident had not had any previous contact with the local hospital. However, a resident from the neighbouring room at the same nursing home, who was admitted to the medical ward at the local hospital for reasons unrelated to MRSA, was found to be MRSA positive upon screening. This patient had not been isolated. The screening was performed three days after admission when the hospital was informed about an ongoing MRSA outbreak in the nursing home from which this patient was admitted. The local hospital had not experienced any outbreak of MRSA prior to this finding. Subsequent screening of hospital staff and patients at the ward in question, as well as other staff with known contact with the MRSApositive patient after the positive finding, revealed no carriers. Screening was also performed among staff in the department where the resident from nursing home A had been admitted for prosthesis adjustment, with negative results. The MRSA strains in question have clearly demonstrated their spreading potential. The close relationship between the strains as shown by PFGE might indicate that they were part of an outbreak. However, the strains from each nursing home are unique single-locus variants of ST45, and may be categorized as belonging to clonal complex 45. ST45-MRSA-IV (also known as EMRSA clone Berlin) is an epidemic MRSA clone associated with infections reported from several European countries.22 Due to the minor differences observed by MLST, we suspect that a possible common source of infection may have occurred at some time in the past. If this is the case, it may represent a hitherto unknown spread of MRSA in Norwegian healthcare institutions and/or the community. In this respect, it may be of interest that we have since found an MRSA outbreak at Ulleva ˚l University Hospital5 (the largest hospital in Norway) in 1995–1997 to be caused by ST45. The outbreaks show the potential for MRSA spread within a nursing home, as shown by other authors.9,10 The persistence and spread of MRSA within nursing homes may be explained by several factors: nursing homes have more limited opportunities for isolation procedures than hospital wards with an inadequate number of single rooms, often without separate baths and toilets, high patient to staff ratios and employees less qualified in infection control. Close contact between residents occurs frequently during meals and other social activities. This might facilitate person-to-person transmission.23 Being the home of the resident, it is more difficult to carry out stringent isolation and contact transmission procedures in a nursing home
315 than in a hospital ward. It is also socially unacceptable to maintain strict isolation procedures for a long period of time. The nursing home population is more prone to MRSA than the general population as increasing age and colonization have proven to be connected.7,11 General debility and an increased presence of risk factors such as wounds, indwelling catheters and previous antimicrobial therapy also contribute to MRSA spread within a nursing home.11,23 Colonization with MRSA is often longstanding and eradication may take months to years.24 Prolonged infection control procedures generate a heavier workload and increased costs.25,26 For nursing homes A and B, the estimated extra costs generated to date are approximately 50 000V and 100 000V, respectively. These costs include the screening of residents and staff, eradication, sick leave expenses, stand-ins, inspection visits, gloves, gowns and masks. These figures are only estimates of extra costs; they were calculated on a different basis and cannot be directly compared, e.g. nursing home B included a 30 000V bill of additional laundry costs which was not included in the cost estimate of nursing home A. Medicine costs in nursing home B were also higher than in nursing home A due to a higher number of carriers and the use of more expensive antimicrobial agents. In nursing home A, positive samples were found between March 2003 and February 2004. In September 2004, the nursing home was declared MRSA free. In nursing home B, two residents are still positive and have received another round of eradication therapy. Nursing home B has performed approximately 10 rounds of screening of all staff and patients. Nursing home A has performed seven such screenings. Both nursing homes have put a great deal of effort into staff education and isolation procedures. The low prevalence of MRSA in Norway is unlikely to last forever. Since 1995, infection control in both nursing homes and hospitals has been regulated. The national recommendation for the prevention of MRSA in nursing homes and hospitals outlined in 2002 is currently under revision.27 When the prevalence of MRSA is low, it is probably reasonable to seek to eradicate MRSA from a healthcare facility during an outbreak to avoid spread to the environment and surrounding hospitals.14,26 An organized approach to infection control management in nursing homes as well as in hospitals is essential and may improve patient outcome and reduce expenses.25 To achieve this goal, close co-operation between the laboratory, nursing home and infection control is essential. The finding of these two MRSA outbreaks justifies further investigation of the prevalence of MRSA
316 infection and carriage in Norwegian nursing homes. If the epidemiological situation continues to deteriorate, we suggest that nursing home employees and staff should be included in the groups to be screened upon hospital admission.
References 1. Blix HS, Grave K, Halvorsen DS, et al. NORM/NORM-VET 2002. Consumption of antimicrobial agents and occurrence of antimicrobial resistance in Norway. Lundeblad Media AS: Tromsø/Oslo; 2003. ISSN: 1502-2307. 2. Kvittingen J, Trymer A. Hospital endemic with methicillinresistent staphylococci. Tidsskr Nor Laegeforen 1977;97: 813—816 [in Norwegian]. 3. Christensen A, Scheel O, Urwitz K, Bergh K. Outbreak of methicillin-resistant Staphylococus aureus in a Norwegian hospital. Scand J Infect Dis 2001;33:663—666. 4. Bø K, Rustad L, Harthug S, Akselsen PE, Tveten Y. Infection outbreaks caused by methicillin-resistant Staphylococcus aureus at Haukeland hospital. Tidsskr Nor Laegeforen 2001; 121:204—208 [in Norwegian, English abstract]. 5. Andersen BM, Bergh K, Steinbakk M, et al. A Norwegian nosocomial outbreak of methicillin-resistant Staphylococcus aureus resistant to fucidic acid and susceptible to other antistaphylococcal agents. J Hosp Infect 1999;41:123—132. 6. Iversen B. MSIS report 2004;32:4 [in Norwegian]. Norwegian Notification System for Infectious Diseases, Oslo. ISSN 15031926. 7. Samad A, Banerjee D, Carbarns N, Ghosh S. Prevalence of methicillin-resistant Staphylococcus aureus colonization in surgical patients, on admission to a Welsh hospital. J Hosp Infect 2002;51:43—46. 8. Pacio GA, Visintainer P, Maguire G, Wormser GP, Raffalli J, Montecalvo MA. Natural history of colonization with vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and resistant gram-negative bacilli among long-term-care facility residents. Infect Control Hosp Epidemiol 2003;24:246—250. 9. Cox RA, Bowie PES. Methicillin-resistant Staphylococcus aureus colonization in nursing home residents: a prevalence study in Northamptonshire. J Hosp Infect 1999;43:115—122. 10. O’Sullivan NP, Keane CT. The prevalence of methicillinresistant Staphylococcus aureus among the residents of six nursing homes for the elderly. J Hosp Infect 2000;45:322—329. 11. von Baum H, Schmidt C, Svoboda D, Bock-Hensley O, Wendt C. Risk factors for methicillin-resistant Staphylococcus aureus carriage in residents of German nursing homes. Infect Control Hosp Epidemiol 2002;23:511—515. 12. Hoefnagels-Schuermans A, Niclaes L, Buntinx F, et al. Molecular epidemiology of methicillin-resistant Staphylococcus aureus in nursing homes: a cross-sectional study. Infect Control Hosp Epidemiol 2002;23:546—549. 13. Goettsch W, Geubbels E, Wannet W, Hendrix MGR, Wagenvoort JHT, de Neeling AJ. MRSA in nursing homes in the Netherlands 1989 to 1998: a developing reservoir? Eurosurveillance 2000;5:28—31.
K.W. Larssen et al. 14. Kotilainen P, Routamaa M, Peltonen R, et al. Eradication of methicillin-resistant Staphylococcus aureus from a health center ward and associated nursing home. Arch Intern Med 2001;161:859—863. 15. Perry PL, Coombs GW, Boehm JD, Pearman JW. A rapid (20h) solid screening medium for detecting methicillin-resistant Staphylococcus aureus. J Hosp Infect 1998;40:67—72. 16. Wertheim H, Verbrugh HA, van Pelt C, de Man P, van Belkum A, Vos MC. Improved detection of methicillinresistant Staphylococcus aureus using phenyl mannitol broth containing aztreonam and ceftizoxime. J Clin Microbiol 2001;39:2660—2662. 17. Brakstad OG, Mæland JA, Tveten Y. Multiplex polymerase chain reaction for detection of genes for Staphylococcus aureus thermonuclease and methicillin resistance and correlation with oxacillin resistance. APMIS 1993;101: 681—688. 18. Bannerman TL, Hancock GA, Tenover FC, Miller JM. Pulsedfield gel electrophoresis as a replacement for bacteriophage typing of Staphylococcus aureus. J Clin Microbiol 1995;33: 551—555. 19. Tenover FC, Arbeit RD, Goering RV, et al. Interpreting chromosomal DNA restriction patterns produced by pulsedfield gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 1995;33:2233—2239. 20. Enright MC, Day NPJ, Davies CE, Peacock SJ, Spratt BG. Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol 2000;38:1008—1015. 21. Oliveira DC, Lencastre Hde. Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2002;46:2155—2161. 22. Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc Natl Acad Sci USA 2002; 99:7687—7692. 23. Nicolle LE, Strausbaugh LJ, Garibaldi RA. Infections and antibiotic resistance in nursing homes. Clin Microbiol Rev 1996;9:1—17. 24. Boyce JM. Are the epidemiology and microbiology of methicillin-resistant Staphylococcus aureus changing? JAMA 1998;279:623—624. 25. Capitano B, Leshem OA, Nightingale CH, Nicolau DP. Cost effect of managing methicillin-resistant Staphylococcus aureus in a long-term care facility. Am Geriatr Soc 2003; 51:10—16. 26. Blok HEM, Troelstra A, Kamp-Hopmans TEM, et al. Role of healthcare workers in outbreaks of methicillin-resistant Staphylococcus aureus: a 10-year evolution from a Dutch University Hospital. Infect Control Hosp Epidemiol 2003;24: 679—685. 27. Solberg CO, Bruun JN, Andersen BM, et al. National guidelines for prevention of infections with methicillinresistant Staphylococcus aureus in the health care system. Norwegian Institute of Public Health: Oslo; 2004 [in Norwegian]. ISSN: 500-8479. ISBN: 82-8082-095-7.
www.elsevierhealth.com/journals/jhin
Outbreak of methicillin-resistant Staphylococcus aureus in two nursing homes in Central Norway K.W. Larssena,*, T. Jacobsena, K. Bergha, P. Tveteb, E. Kvelloc, O. Scheela a
Department of Microbiology, St Olav University Hospital, Olav Kyrresgt 17, N-7006 Trondheim, Norway Overhalla legekontor, N-7386 Overhalla, Norway c Vikna kommunale helsesenter, N-7900 Rørvik, Norway b
Received 12 July 2004; accepted 6 December 2004
KEYWORDS MRSA; Nursing homes; Outbreaks
Summary Until recently, infections with methicillin-resistant Staphylococcus aureus (MRSA) have mainly been associated with hospital outbreaks in Norway. However, increasingly cases are contracted outside hospitals. This paper reports the first two outbreaks of MRSA in two nursing homes in central Norway, affecting 23 residents and five staff members. Pulsed-field gel electrophoresis analysis showed that all strains from nursing home A were identical and that the strains from nursing home B were genotypically similar with one or two band differences. Multi-locus sequence typing (MLST) showed that the strains from the two nursing homes belong to clonal complex 45, with each strain being a single-locus variant of sequence type 45 (ST45), a well-known European epidemic strain. No evident source of the two outbreaks was found, and there was no obvious connection between the two outbreaks. The latter is also supported by the minor differences observed by MLST, suggesting a connection at some time in the past. The outbreaks led to a heavier workload and economic strain on both nursing homes. The outbreak in nursing home A was brought to an end, whereas two residents remained colonized in nursing home B despite several eradication attempts. These outbreaks show the potential for MRSA spread in a nursing home. If the prevalence of MRSA in Norway continues to increase, nursing home staff and residents may have to be included in the groups to be screened for MRSA upon hospital admission. Q 2005 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: C47 73867470; fax: C47 73867765 E-mail address: [email protected] 0195-6701/$ - see front matter Q 2005 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2004.12.021
MRSA outbreaks in nursing homes in Norway
Introduction Methicillin-resistant Staphylococcus aureus (MRSA) emerged as a cause of hospital infection in 1961, only two years after the introduction of methicillin. Like the other Scandinavian countries and the Netherlands, Norway has a low prevalence of MRSA with less than 1% of all staphylococcal infections.1 In the 1970s, there was a large outbreak in a hospital in central Norway.2 Since then, only sporadic cases occurred until the 1990s when several minor outbreaks of MRSA occurred in Norwegian hospitals.3–5 In 2003, 215 cases of MRSA were reported to the Norwegian Notification System for Infectious Diseases. This is a 10-fold increase since registration of MRSA infection was made compulsory in 1995. Prior to 1997, most cases of MRSA were contracted abroad, but since then, most cases have been contracted in Norway and outside hospitals.1 Over the last few years, this increase in MRSA prevalence has proven common to all the Nordic countries.6 More recently, long-term care facilities have been increasingly recognized as reservoirs for this pathogen.7,8 Studies of MRSA colonization in several nursing homes across Europe have reported prevalences from 1 to 27%.9–12 Low-prevalence countries such as Finland and the Netherlands have experienced MRSA outbreaks in nursing homes.13,14 This paper reports two outbreaks of MRSA in 2003 from two different nursing homes in central Norway. To our knowledge, this is the first report of MRSA outbreaks in Scandinavian nursing homes.
Materials and methods The MRSA outbreaks occurred in two different nursing homes in the same region of central Norway. The nursing homes are located 111 km apart and are served by the same hospital. Positive MRSA cultures were sampled between 12 March 2003 and 2 March 2004. This extended period of sampling resulted in a higher number of screened residents than the total number of beds due to turnover of residents.
Screening of residents and staff Nursing home A has 39 beds and a total of 114 employees, of whom 70 worked directly with patients. At nursing home A, 50 residents were screened for MRSA. Nursing home B has 39 beds and 65 staff members, 44 of whom have direct patient contact, as well as 10 stand-ins with patient
313 contact. At nursing home B, 55 residents were screened for MRSA. Both nursing homes have screened their residents several times, and all employees have been screened at least once. Staff and residents had their nostrils screened. Residents had additional swabs taken from possible wounds or pus and, if present, from catheters or other foreign bodies. Staff with skin lesions had additional cultures taken. If a person (staff or resident) was identified with MRSA, samples were taken from nose, throat, perineum and possible wounds or catheters in the subsequent screening.
Detection of MRSA Detection of MRSA was mainly performed by the use of a selective phenyl mannitol agar with NaCl 2%, aztreonam (8 mg/L) and oxacillin (4 mg/L).15 A small number of samples were processed by the use of selective phenyl mannitol broth containing aztreonam (75 mg/L) and ceftizoxime (5 mg/L).16 MRSA strains were verified by detection of nuc and mecA genes by polymerase chain reaction (PCR), as described elsewhere.17
Molecular epidemiology Genotyping of all MRSA strains in the study was performed by pulsed-field gel electrophoresis (PFGE). Preparation of chromosomal DNA and SmaI digestion was performed as described by Bannerman et al.18 Electrophoresis was performed with a CHEF XA Mapper (Bio-Rad Laboratories, Hercules, CA, USA) under conditions described elsewhere.5 Criteria for similarities between strains were those proposed by Tenover et al.19 Strains with different PFGE patterns were analysed by multi-locus sequence typing (MLST) by sequencing internal fragments of seven housekeeping genes using primers described by Enright et al.20 The DNA sequences of both strands were determined with a CEQ 8000 DNA sequencer (Beckman Coulter, Inc., Fullerton, CA, USA) with dideoxy NTP fluorescent terminators. The same primers were used for initial PCR amplification and subsequent sequencing. Data were submitted to the MLST database for S. aureus (http://saureus.mlst. net/) to obtain allelic profiles. Characterization of the structural type of the SCCmec element was performed by multiplex PCR as described elsewhere.21
Results Nursing home A had 11 cases of MRSA, all among
314
K.W. Larssen et al.
residents. Nursing home B had 12 cases among residents and five cases among healthcare workers with patient contact. The age distribution of the MRSA-positive residents was 73–95 years for nursing home A (mean 84.1 years) and 70–92 years for nursing home B (mean 81.2 years). The age distribution of the MRSA-positive staff was 24–42 years (mean 33.6 years). MRSA strains were isolated from nostrils and/or wounds. Two strains were also found in purulent discharge from an eye and an ear, respectively (Table I). All 11 strains from nursing home A had an identical PFGE pattern. The 17 strains from nursing home B were mutually similar with one fragment difference. The strains from nursing home B differed by one or two bands from the strain from nursing home A (Figure 1). By the PFGE criteria used, all strains could be part of a common outbreak. MLST of the strains from the two nursing homes showed two new pta alleles. The strain from nursing home A (ST 497) has a mutation in the pta gene at position 227 (G instead of T). The two strains with different PFGE subtypes from nursing home B (ST455) have a new pta allele at position 17 (A instead of C). The strains in question were found to be type IV by PCR of the SCCmec. The strains involved in the outbreaks can therefore be characterized as unique single-locus variants of ST45 belonging to clonal complex 45.22
Figure 1 Representative pulsed-field gel electrophoresis (PFGE) patterns from methicillin-resistant Staphylococcus aureus strains from two nursing homes in central Norway. Lanes 1 and 5 represent molecular weight standards. Lanes 2 and 3 show PFGE patterns from nursing home B, and lane 4 represents all strains from nursing home A.
leg amputation, and the only previous contact with the local hospital within the previous six months had been for prosthesis adjustment. MRSA had not been suspected. It is not routine practice in Norway to screen nursing home residents or staff for MRSA unless they have been patients or worked in hospitals/healthcare institutions outside Scandinavia or the Netherlands, or in a healthcare institution with an ongoing MRSA outbreak.23 The index case of nursing home B was diagnosed at the nursing home in March 2003 by testing secretions from a longstanding ulcer after a leg amputation in 2002, where previous cultures had grown methicillin-sensitive S. aureus. MRSA
Discussion No exchange of personnel or residents between the two nursing homes had taken place, and no obvious connection between the two outbreaks nor cause of spread was found. Both nursing homes are served by the same hospital. The index case of nursing home A was initially diagnosed at the nursing home in March 2003 by aerobic culture of wound secretions after a
Table I
Number of cases positive for methicillin-resistant Staphylococcus aureus (MRSA)
MRSAC
Nostrils Wound NostrilsCwound NostrilsCpus (ear) Pus (eye) Total
Nursing home A
Nursing home B
Residents
Staff
Residents
Staff
4 5 0 1 1 11
0 0 0 0 0 0
7 4 1 0 0 12
5 0 0 0 0 5
Number of people identified with at least one positive MRSA culture. The site where the positive culture was taken is indicated. Two people had positive cultures from several screening locations as shown in the table.
MRSA outbreaks in nursing homes in Norway was not suspected in this case either, but the resident had received repeated courses of antimicrobial therapy. This resident had not had any previous contact with the local hospital. However, a resident from the neighbouring room at the same nursing home, who was admitted to the medical ward at the local hospital for reasons unrelated to MRSA, was found to be MRSA positive upon screening. This patient had not been isolated. The screening was performed three days after admission when the hospital was informed about an ongoing MRSA outbreak in the nursing home from which this patient was admitted. The local hospital had not experienced any outbreak of MRSA prior to this finding. Subsequent screening of hospital staff and patients at the ward in question, as well as other staff with known contact with the MRSApositive patient after the positive finding, revealed no carriers. Screening was also performed among staff in the department where the resident from nursing home A had been admitted for prosthesis adjustment, with negative results. The MRSA strains in question have clearly demonstrated their spreading potential. The close relationship between the strains as shown by PFGE might indicate that they were part of an outbreak. However, the strains from each nursing home are unique single-locus variants of ST45, and may be categorized as belonging to clonal complex 45. ST45-MRSA-IV (also known as EMRSA clone Berlin) is an epidemic MRSA clone associated with infections reported from several European countries.22 Due to the minor differences observed by MLST, we suspect that a possible common source of infection may have occurred at some time in the past. If this is the case, it may represent a hitherto unknown spread of MRSA in Norwegian healthcare institutions and/or the community. In this respect, it may be of interest that we have since found an MRSA outbreak at Ulleva ˚l University Hospital5 (the largest hospital in Norway) in 1995–1997 to be caused by ST45. The outbreaks show the potential for MRSA spread within a nursing home, as shown by other authors.9,10 The persistence and spread of MRSA within nursing homes may be explained by several factors: nursing homes have more limited opportunities for isolation procedures than hospital wards with an inadequate number of single rooms, often without separate baths and toilets, high patient to staff ratios and employees less qualified in infection control. Close contact between residents occurs frequently during meals and other social activities. This might facilitate person-to-person transmission.23 Being the home of the resident, it is more difficult to carry out stringent isolation and contact transmission procedures in a nursing home
315 than in a hospital ward. It is also socially unacceptable to maintain strict isolation procedures for a long period of time. The nursing home population is more prone to MRSA than the general population as increasing age and colonization have proven to be connected.7,11 General debility and an increased presence of risk factors such as wounds, indwelling catheters and previous antimicrobial therapy also contribute to MRSA spread within a nursing home.11,23 Colonization with MRSA is often longstanding and eradication may take months to years.24 Prolonged infection control procedures generate a heavier workload and increased costs.25,26 For nursing homes A and B, the estimated extra costs generated to date are approximately 50 000V and 100 000V, respectively. These costs include the screening of residents and staff, eradication, sick leave expenses, stand-ins, inspection visits, gloves, gowns and masks. These figures are only estimates of extra costs; they were calculated on a different basis and cannot be directly compared, e.g. nursing home B included a 30 000V bill of additional laundry costs which was not included in the cost estimate of nursing home A. Medicine costs in nursing home B were also higher than in nursing home A due to a higher number of carriers and the use of more expensive antimicrobial agents. In nursing home A, positive samples were found between March 2003 and February 2004. In September 2004, the nursing home was declared MRSA free. In nursing home B, two residents are still positive and have received another round of eradication therapy. Nursing home B has performed approximately 10 rounds of screening of all staff and patients. Nursing home A has performed seven such screenings. Both nursing homes have put a great deal of effort into staff education and isolation procedures. The low prevalence of MRSA in Norway is unlikely to last forever. Since 1995, infection control in both nursing homes and hospitals has been regulated. The national recommendation for the prevention of MRSA in nursing homes and hospitals outlined in 2002 is currently under revision.27 When the prevalence of MRSA is low, it is probably reasonable to seek to eradicate MRSA from a healthcare facility during an outbreak to avoid spread to the environment and surrounding hospitals.14,26 An organized approach to infection control management in nursing homes as well as in hospitals is essential and may improve patient outcome and reduce expenses.25 To achieve this goal, close co-operation between the laboratory, nursing home and infection control is essential. The finding of these two MRSA outbreaks justifies further investigation of the prevalence of MRSA
316 infection and carriage in Norwegian nursing homes. If the epidemiological situation continues to deteriorate, we suggest that nursing home employees and staff should be included in the groups to be screened upon hospital admission.
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