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Characteristics of hospital patients colonized with livestock-associated meticillin-resistant Staphylococcus aureus (MRSA) CC398 versus other MRSA clones
Journal of Hospital Infection 79 (2011) 292e296
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Journal of Hospital Infection journal homepage: www.elsevierhealth.com/journals/jhin
Characteristics of hospital patients colonized with livestock-associated meticillin-resistant Staphylococcus aureus (MRSA) CC398 versus other MRSA clones R. Köcka, K. Siamb, S. Al-Malata, J. Christmanna, F. Schaumburgc, K. Beckerc, A.W. Friedrichd, * a
Institute of Hygiene, University Hospital Münster, Münster, Germany Department for Medical Management and Controlling, DRG-Research-Group, University Hospital Münster, Münster, Germany Institute of Medical Microbiology, University Hospital Münster, Münster, Germany d Department of Medical Microbiology, University Hospital Groningen, University of Groningen, Groningen, The Netherlands b c
a r t i c l e i n f o
s u m m a r y
Article history: Received 23 February 2011 Accepted 22 August 2011 by J.A. Child Available online 22 October 2011
Meticillin-resistant Staphylococcus aureus (MRSA) associated with the clonal complex (CC) 398 has emerged among livestock and humans exposed to these animals. MRSA CC398 has so far contributed relatively little to spread of MRSA and the burden of disease in the healthcare setting. This study aimed to assess whether demographic and clinical differences in patients colonized with MRSA CC398 and those carrying other MRSA clones contribute to the observed differences in transmission and infection rates. Age, sex, length of stay (LOS), diagnoses and medical procedures were assessed in all patients with MRSA admitted to a university hospital in 2008 and 2009. S. aureus protein A gene (spa) typing was performed on the first MRSA isolate from each patient. Patients colonized or infected with MRSA that had spa types indicative of CC398 (MRSA CC398) were compared with patients who had other MRSA clones (MRSA non-CC398). Age (53 vs 59 years), mean LOS (8 vs 13 days) and percentage of patients admitted to an intensive care unit (12% vs 17%) differed significantly between MRSA CC398 and MRSA non-CC398 patients, respectively. The mean numbers and types of diagnoses and medical procedures performed for patients in these two groups also differed significantly. The differences in patient characteristics could explain, at least in part, the relatively low rates of transmission and infection associated with MRSA CC398 in the healthcare setting. Ó 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Keywords: CC398 DRG Livestock Meticillin-resistant Staphylococcus aureus ST398 Transmission
Introduction Meticillin-resistant Staphylococcus aureus (MRSA) has emerged in recent years as a colonizer of livestock animals. In a recent survey by the European Food Safety Authority (EFSA), MRSA isolates were found in dust samples from pig holdings in 17 European countries including Germany, where 43% of pig farms were affected.1 The predominant livestock-associated MRSA strains are related to the clonal complex (CC) 398, as determined by multilocus sequence typing (MLST) and S. aureus protein A gene (spa) types t011, t034, t108 and close relatives.1 Several studies have indicated that MRSA * Corresponding author. Address: Department of Medical Microbiology, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Tel.: þ31 50 3613480; fax: þ31 50 3619105. E-mail address: [email protected] (A.W. Friedrich).
CC398 strains are frequently acquired by humans exposed to livestock, resulting in a nasal carriage rate of up to 38% among pig farmers2 and 5% among veterinarians.3 The livestock reservoir of MRSA also has an impact on the prevalence of MRSA in healthcare facilities. For example, we have shown that MRSA CC398 represents 17% of all MRSA isolates found among patients screened on admission to 39 hospitals in a ‘pig-dense’ region in Germany.4 Moreover, we have shown that patients carrying MRSA CC398 at admission usually have contact with pigs or cattle, indicating that these MRSA clones do indeed originate from the livestock reservoir.5 Since it is known that nasal carriage of MRSA at admission increases the risk of healthcare-associated infection (HAI), carriage of MRSA CC398 by patients admitted to hospital could contribute to the spread of these pathogens and to an increase in HAI.6 Indeed, several studies have demonstrated that MRSA CC398 is pathogenic for humans, causing infections including endocarditis, skin and soft
0195-6701/$ e see front matter Ó 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2011.08.011
R. Köck et al. / Journal of Hospital Infection 79 (2011) 292e296
tissue infections, and ventilator-associated pneumonia.7,8 However, in spite of the high proportion of MRSA CC398 in colonized patients in ‘pig-dense’ regions, the overall incidence of human MRSA CC398 infections is comparatively low. Among MRSA isolates from bacteraemic patients in European countries, CC398 accounted for <1% of all strains.9 In Germany, which is an important pig-producing country, the proportion of CC398 among (mostly clinical) human MRSA isolates typed by the national reference laboratory was <1%.7 In The Netherlands, where MRSA CC398 accounted for 33% of all MRSA isolates reported to the national reference centre in 2007 (mostly carrier isolates), the proportion of MRSA CC398 among all MRSA isolates from clinical specimens is smaller (11.9% in 2007).10,11 It is not known why there is such a discrepancy between the high prevalence of MRSA CC398 colonization and its low contribution to the burden of nosocomial infection.12 The observation that MRSA CC398 clones have lower transmission rates than other MRSA clones in the healthcare setting is also unexplained.13,14 We hypothesize that differences in the characteristics of patients carrying MRSA CC398 from those carrying MRSA non-CC398 contribute to the epidemiological differences. We compared demographic and clinical characteristics of inpatients colonized with either MRSA CC398 or MRSA non-CC398 to determine whether differences in these factors could account for the observed differences in infection and transmission rates. Methods The University Hospital Münster (UHM) is a 1300-bedded university hospital situated in a region with the highest density of pig production in Germany.5 Between January 2008 and November 2009 all patients admitted to every department of the UHM were screened for nasopharyngeal MRSA colonization within 48 h of admission using a culture-based approach.15 We included in the study all inpatients in whom MRSA was detected either by admission screening or in clinical specimens. In positive cases, the patients were isolated in single or cohort rooms. For each patient, the first isolate of MRSA obtained from screening specimens and all isolates from clinical specimens were genotyped by S. aureus protein A (spa) sequence-typing.16 We assessed age, sex, hospital length of stay (LOS) and days on medical and surgical intensive care units (ICU days) from automated patient records. Imported cases were defined as those detected within 72 h of hospital admission. All patients from whom MRSA was solely derived from screening specimens (nose, throat, uninfected skin sites) were included in a comparative analysis (MRSA CC398 vs MRSA non-CC398) of colonized patients; patients in whom MRSA was detected in clinical specimens were excluded from this analysis in order to avoid a bias towards invasive strains due to unequal distribution of patients with MRSA infections between the two groups. The assignment of the patients into the two groups (MRSA CC398 or non-CC398) was based upon the spa typing result of their first MRSA isolate and a subsequent clustering of spa types into
293
clonal complexes using the Based Upon Repeat Pattern (BURP) algorithm of the Ridom StaphTypeÒ software (Ridom GmbH, Münster, Germany).17 Patients were included in the MRSA CC398 group if the spa type of their MRSA isolate was either t011, t034, t108 (representing spa types previously detected in regional livestock and confirmed to exhibit MLST ST398) or closely related to these spa types as indicated by being grouped in the same complex by BURP. All other patients were assigned to the non-CC398 group.5 Acute care hospital inpatient stays in Germany are reimbursed according to payment per case by German Diagnosis Related Groups (G-DRGs). All cases are grouped into one of almost 1200 G-DRGs based on several parameters such as diagnoses [using the German Modification of the International Statistical Classification of Diseases and Related Health (ICD-10-GM)], procedures [using the German procedure classification (OPS)] or other patient characteristics (age, sex, discharge status etc.). For all MRSA patients identified during the study period, the procedures, primary and secondary ICD diagnoses were assessed as coded, except the codes Z22.3 (carrier of other specified bacterial diseases), Z22.8 (carrier of other infectious diseases), Z29.0 (isolation) and U80.0 (S. aureus resistant to oxacillin), which are used to code MRSA carriage and isolation measures and are therefore not considered to vary between MRSA CC398 and non-CC398 patients. Data were entered into a Microsoft Access Database (Version 7). Comparisons were performed using chi-squared test (Epi Info; Atlanta, USA) or t-test, where appropriate. P < 0.05 was considered significant. Results During the study period, 167 of 834 MRSA isolates from inpatients (20%) were characterized by spa types belonging to the CC398 group. These MRSA isolates exhibited the following spa types: t011 (N ¼ 87; 10% of all isolates detected during the study period), t034 (N ¼ 55; 7%), t108 (N ¼ 11; 1%), t2582 (N ¼ 3; 0.4%), t567 and t1451 (each N ¼ 2; 0.2%), t1197, t1255, t1457, t1606, t2011, t2346, t2576 (each N ¼ 1; 0.1%). The remaining 667 MRSA isolates were included in the group of MRSA non-CC398 that was made up of a total of 91 spa types, among which t032 (N ¼ 247, 30% of all MRSA isolated), t003 (N ¼ 199, 24%), t008 (N ¼ 17, 2%), t004 (N ¼ 14, 1.7%), t014 (N ¼ 11, 1.3%), t035 (N ¼ 10, 1.2%) and t1227 (N ¼ 10, 1.2%) were the most frequent. All other spa types were found in <1% of all MRSA isolates. In 242 of the 834 cases (29%), MRSA was isolated from clinical specimens; 18 of these (7%) were in the MRSA CC398 group and 224 patients (93%) were in the MRSA non-CC398 group (P < 0.001). The clinical specimens from which MRSA CC398 was isolated were wound swabs (N ¼ 6), respiratory fluids (N ¼ 4), blood cultures (N ¼ 2), urine (N ¼ 1) and others (N ¼ 5; i.e. tissue, cervical swabs, swab from frontal sinus). Seven of these 18 cases (39%) were classified as nosocomial. MRSA was identified by admission screening in 592 of the 834 cases (71%). MRSA CC398 accounted for 149 (25%) of the admission screening isolates.
Table I Characteristics of patients colonized or infected with meticillin-resistant Staphylococcus aureus (MRSA) CC398 and non-CC398 Characteristics Male (%) Mean age (years), (range) Length of hospital stay (days), (range)a Imported cases (%) No. of patients with stay on ICU (%) Length of ICU stay (days), (range) ICU, intensive care unit; NS, non-significant. a Mean (range).
MRSA non-CC398 patients (N ¼ 443)
MRSA CC398 patients (N ¼ 149)
All MRSA patients (N ¼ 592)
P
253 (57%) 59 (0e96) 12.6 (1e196) 392 (88%) 75 (17%) 11 (0.5e74)
104 (70%) 53 (1e88) 7.5 (1e90) 143 (96%) 13 (12%) 8.2 (1e48)
357 57 (0e96) 11.3 (1e196) 535 (90%) 88 (15%) 10.6 (0.5e74)
<0.01 <0.01 <0.01 <0.01 0.023 NS
294
R. Köck et al. / Journal of Hospital Infection 79 (2011) 292e296
Compared with patients colonized by MRSA non-CC398, MRSA CC398 carriers were usually men, significantly younger, had a shorter hospital LOS and were less frequently treated on ICUs (Table I). Complete data sets for comparing the numbers and types of ICD diagnoses were available for 591 patients (Table II). The mean number of diagnoses coded for MRSA CC398 patients was 2.8 (95% CI: 2.5e3.1) compared with 4.1 (95% CI: 3.8e4.3) for MRSA non-CC398 patients (P < 0.001). Significant differences were observed for the diagnoses anaemia, metabolic disorders, diseases of the heart, eye, respiratory or digestive system, renal failure, general symptoms and potential health hazards related to family and personal history. At least one medical procedure was coded for 130 patients with MRSA CC398 and 418 patients with MRSA non-CC398 (Table III). The mean number of medical procedures coded was 6.8 (95% CI: 5.1e8.6) for patients with MRSA CC398 and 11.8 (95% CI: 10.4e13.2) for patients with MRSA non-CC398 (P < 0.001). Significant differences were found for the following procedures: diagnostic endoscopies, surgical interventions of the eyes, immunotherapy, early rehabilitation and physical therapy, access to mechanical ventilation and intubation measures, transfusion of blood cells and therapeutic catheterization.
Discussion Our observation that MRSA CC398 accounted for 25% of all MRSA carriage in patients admitted to the UHM confirms earlier findings of a high proportion of MRSA CC398 among human carriers in an area with a high density of livestock.5 All spa types included in the CC398 group have been described in association with livestock before.18e22 In contrast to this high proportion among admission screening isolates, MRSA CC398 accounted for only 7% of all MRSA from clinical specimens. MRSA CC398 is therefore still under-represented among isolates from infections.7 Whole genome sequencing of a single MRSA CC398 isolate and comparison with the gene content of other MRSA lineages has revealed that it lacked virulence factors such as enterotoxins and phage-encoded toxins.12 If this finding is representative of other CC398 clones, it could explain why they have caused relatively little disease in spite of their wide distribution in many European countries and their frequent introduction into healthcare settings in regions with a high density of livestock farming.5 Another possible explanation is suggested by differences in the nosocomial transmission rates of MRSA CC398 as compared to other MRSA clones. Using a mathematical model, Bootsma et al. have reported that the
Table II Comparison of diagnoses coded for patients colonized with meticillin-resistant Staphylococcus aureus (MRSA) non-CC398 and MRSA CC398 based on chapters and subchapters of the ICD classification Chapter/subchaptera
A00eB99 C00eD48 D50eD90 D50eD53 D60eD64 E00eE90 E70eE90 F00eF99 G00eG99 H00eH59 H49eH52 H60eH95 I00eI99 I30eI52 J00eJ99 J09eJ18 J40eJ47 J60eJ70 K00eK93 K20eK31 K90eK93 L00eL99 M00eM99 N00eN99 N17eN19 O00eO99 P00eP96 Q00eQ99 R00eR99 R50eR69 S00eT98 V01eY84 Z00eZ99b Z80eZ99 U00eU99b
Description
Certain infectious and parasitic diseases Neoplasms Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism Nutritional anaemias Aplastic and other anaemias Endocrine, nutritional and metabolic diseases Metabolic disorders (e.g. hypopotassaemia/hypokalaemia) Mental and behavioural disorders Diseases of the nervous system Diseases of the eye and ocular adnexa Disorders of ocular muscles, binocular movement, accommodation and refraction Diseases of the ear and mastoid process Diseases of the circulatory system Other forms of heart disease Diseases of the respiratory system Influenza and pneumonia Chronic lower respiratory diseases Lung diseases due to external agents Diseases of the digestive system Diseases of oesophagus, stomach and duodenum Other diseases of the digestive system Diseases of the skin and subcutaneous tissue Diseases of the musculoskeletal system and connective tissue Diseases of the genitourinary system Renal failure Pregnancy, childbirth and the puerperium Certain conditions originating in the perinatal period Congenital malformations, deformations and chromosomal abnormalities Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified General symptoms and signs Injury, poisoning and certain other consequences of external causes External causes of morbidity and mortality Factors influencing health status and contact with health services Persons with potential health hazards related to family and personal history and certain conditions influencing health status Codes for special purposes
MRSA non-CC398 (N ¼ 442)
MRSA CC398 (N ¼ 149)
P-value
No.
%
No.
%
76 75 107
17.2 17.0 24.2
17 20 21
11.4 13.4 14.1
NS NS 0.01
19 78 169 101 73 111 44 1
4.3 17.6 38.2 22.9 16.5 25.1 10.0 0.2
0 14 36 19 18 26 25 5
0.0 9.4 24.2 12.8 12.1 17.5 16.8 3.4
0.004 0.02 0.003 0.01 NS NS 0.04 0.004
15 228 109 111 31 32 11 79 25 14 35 67 109 70 1 7 22 111
3.4 51.6 24.7 25.1 7.0 7.2 2.5 17.9 5.7 3.2 7.9 15.2 24.7 15.8 0.2 1.6 5.0 25.1
6 48 22 19 3.0 4 0 8 2 0 5 19 21 13 2 1 12 23
4.0 32.2 14.8 12.8 2.0 2.7 0.0 5.4 1.3 0.0 3.4 12.8 14.1 8.7 1.3 0.7 8.1 15.4
NS <0.001 0.02 0.002 0.01 0.02 0.04 <0.001 0.01 0.02 NS NS 0.01 0.04 NS NS NS 0.02
47 96 3 242 143
10.6 21.7 0.7 54.8 32.4
6 26 1 64 33
4.0 17.5 0.7 43.0 22.1
0.02 NS NS 0.01 0.02
21
4.8
3
2.0
NS
NS, non-significant. a Chapters of the ICD, German Modification, 10th revision; in case of significant differences in chapters, data for subchapters of the classification are also shown. b Without Z22.3, Z22.8, Z29.0 and U80.0.
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295
Table III Comparison of medical procedures performed for patients colonized with meticillin-resistant Staphylococcus aureus (MRSA) non-CC398 and MRSA CC398 OPSa
1 1-61e1-69 3 5 5-08e5-16 5-18e5-20 6 8 8-03e8-03 8-55e8-60 8-70e8-70 8-80e8-80 8-83e8-83 9
Descriptiona
Diagnostic measures Diagnostic endoscopy Diagnostic imaging techniques Surgical interventions targeting the: Eyes Ears Application of drugs Non-surgical therapeutic interventions Immunotherapy Early rehabilitation and physical therapy Access to mechanical ventilation and intubation measures Transfusion of blood cells Therapeutic catheterization and cannula insertion in blood vessels Complementary measures
MRSA non-CC398 (N ¼ 418)
MRSA CC398 (N ¼ 130)
P-value
No.
%
No.
%
198 95 216 207 26 5 12 320 0 154 22 70 72 83
47.4 22.7 51.7 49.5 6.2 1.2 2.9 76.6 0.0 36.8 5.3 16.8 17.2 19.9
38 14 57 64 20 6 4 93 6 35 2 11 9 22
29.2 10.8 43.9 49.2 15.4 4.6 3.1 71.5 4.6 26.9 1.5 8.5 6.9 16.9
<0.001 0.004 NS NS 0.002 0.04 NS NS <0.001 0.05 0.04 0.03 0.006 NS
NS, non-significant. a Chapters/subchapters of the German procedure classification (OPS), description translated by the authors (no English version of the OPS coding system available); all chapters, but one significant subchapters, are shown.
genotype-specific nosocomial transmission capacity was 5.9 times lower for MRSA CC398 compared to other MRSA clonal lineages prevalent in Dutch hospitals.13 This finding was later confirmed by the same group by analysis of the relative risk of secondary cases after contact to an MRSA index case, which was 0.27 for MRSA CC398 compared to non-CC398 strains.14 The authors concluded that both pathogen- and patient-related factors might contribute to the lower transmission capacity of CC398 strains. Our results provide support for the latter. We found that even when infected patients are excluded from the analysis, there are patient-specific differences between patients carrying MRSA CC398 strains and those carrying other, mostly healthcare-associated MRSA molecular clones (e.g. spa types t032 and t003).9 Patients carrying MRSA CC398 at admission were younger, had a shorter LOS and less frequently required admission to ICUs. Since age, LOS and ICU admission have been associated with the development of nosocomial infections in various other studies, the risk of HAIs is lower for MRSA CC398 patients.23e26 Moreover, we observed significant differences between MRSA CC398 and non-CC398 patients with respect to the mean numbers of ICD diagnoses (N ¼ 2.8 for MRSA CC398 vs N ¼ 4.1 for non-CC398 patients, P < 0.001) and medical procedures (N ¼ 6.8 for MRSA CC398 vs N ¼ 11.8 for non-CC398 patients, P < 0.001). Specifically, the diagnoses anaemia, metabolic disorders (e.g. hypokalaemia), heart or respiratory diseases, diseases of the digestive system and renal failure were significantly less frequent among patients colonized with MRSA CC398 than among MRSA non-CC398 carriers. These results confirm data showing that patients carrying healthcare-associated MRSA clones represent a multi-morbid high risk population.27 Ocular disorders were more frequently coded in the MRSA CC398 group compared to the patients in the MRSA non-CC398 group. This reflects that a larger proportion of patients in the MRSA CC398 group was admitted to hospital for elective surgical interventions of the eye (e.g. refractive eye surgery), mostly associated with a rather low risk for nosocomial infections. We also found that a variety of invasive measures (e.g. endoscopies, mechanical ventilation, transfusion of blood cells and therapeutic catheterization) were more often performed for patients colonized with MRSA non-CC398. These results broadly correspond to the finding that patients with MRSA nonCC398 were more frequently treated on ICUs, and could account for some of the difference in the incidence of nosocomial infections, especially those associated with the use of vascular devices and mechanical ventilation.28,29 The present study cannot answer the questions of whether MRSA CC398 isolates are biologically less transmissible from
human to human or less pathogenic to humans than other MRSA clones. But our data suggest that demographic differences between patients colonized with MRSA CC398 and those colonized with classical healthcare-associated MRSA clones could influence the risk of infection and transmission. The observed differences in transmission and infection rates may disappear over time if MRSA CC398 continues to be introduced into healthcare facilities and spreads to more vulnerable patients. Weaknesses of this study include its retrospective design and the secondary use of DRG data that is normally used for the purpose of hospital reimbursement. All diagnoses and procedures may not have been identified if ICD diagnoses and procedures not considered relevant to payroll were not coded accurately. In summary, we describe demographic and clinical differences between patients carrying MRSA CC398 and MRSA non-CC398 in a hospital located in a region with a high density of pig production. These differences could explain, at least in part, the lower nosocomial infection and transmission rates associated with MRSA CC398. Further research is required to assess whether genotypespecific bacterial factors also contribute to these phenomena. Conflict of interest statement None declared. Funding sources This study has partially been supported by the INTERREG IVa project SafeGuard Workpackage 2.3 ‘MRSA vet-net’ (No. III-2-03 ¼ 025) and by grants from the Bundesministerium für Bildung und Forschung, ‘MedVet-Staph’ (01KI1014A). References 1. European Food Safety Authority. Analysis of the baseline survey on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in holdings with breeding pigs, in the EU, 2008, Part A: MRSA prevalence estimates; on request from the European Commission. EFSA J 2009;7:1376. 2. Denis O, Suetens C, Hallin M, et al. Methicillin-resistant Staphylococcus aureus ST398 in swine farm personnel, Belgium. Emerg Infect Dis 2009;15: 1098e1101. 3. Wulf MW, Sorum M, van Nes A, et al. Prevalence of methicillin-resistant Staphylococcus aureus among veterinarians: an international study. Clin Microbiol Infect 2008;14:29e34. 4. Köck R, Brakensiek L, Mellmann A, et al. Cross-border comparison of the admission prevalence and clonal structure of meticillin-resistant Staphylococcus aureus. J Hosp Infect 2009;71:320e326. 5. Köck R, Harlizius J, Bressan N, et al. Prevalence and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) among pigs on German
296
6. 7.
8.
9.
10. 11.
12.
13.
14.
15.
16.
17.
R. Köck et al. / Journal of Hospital Infection 79 (2011) 292e296 farms and import of livestock-related MRSA into hospitals. Eur J Clin Microbiol Infect Dis 2009;28:1375e1382. Bode LG, Kluytmans JA, Wertheim HF, et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med 2010;362:9e17. Witte W, Strommenger B, Stanek C, Cuny C. Methicillin-resistant Staphylococcus aureus ST398 in humans and animals, Central Europe. Emerg Infect Dis 2007;13:255e258. Ekkelenkamp MB, Sekkat M, Carpaij N, Troelstra A, Bonten MJ. Endocarditis due to meticillin-resistant Staphylococcus aureus originating from pigs. Ned Tijdschr Geneeskd 2006;150:2442e2447. Grundmann H, Aanensen DM, van den Wijngaard CC, Spratt BG, Harmsen D, Friedrich AW. Geographic distribution of Staphylococcus aureus causing invasive infections in Europe: a moleculareepidemiological analysis. PLoS Med 2010;7: e1000215. Wulf M, Voss A. MRSA in livestock animals e an epidemic waiting to happen? Clin Microbiol Infect 2008;14:519e521. Van Cleef B, Monnet D, Voss A, et al. Livestock-associated methicillin-resistant Staphylococcus aureus from human samples, Europe, 2007. Emerg Infect Dis 2011;17:502e505. Schijffelen MJ, Boel CH, van Strijp JA, Fluit AC. Whole genome analysis of a livestock-associated methicillin-resistant Staphylococcus aureus ST398 isolate from a case of human endocarditis. BMC Genomics 2010;11:376. Bootsma MC, Wassenberg MW, Trapman P, Bonten MJ. The nosocomial transmission rate of animal-associated ST398 meticillin-resistant Staphylococcus aureus. J R Soc Interface 2011;8:578e584. Wassenberg MW, Bootsma MC, Troelstra A, Kluytmans JA, Bonten MJ. Transmissibility of livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch hospitals. Clin Microbiol Infect 2011;17: 316e319. Becker K, Pagnier I, Schuhen B, et al. Does nasal cocolonization by methicillin-resistant coagulase-negative staphylococci and methicillinsusceptible Staphylococcus aureus strains occur frequently enough to represent a risk of false-positive methicillin-resistant S. aureus determinations by molecular methods? J Clin Microbiol 2006;44:229e231. Mellmann A, Friedrich AW, Rosenkotter N, et al. Automated DNA sequence-based early warning system for the detection of methicillin-resistant Staphylococcus aureus outbreaks. PLoS Med 2006;3:e33. Mellmann A, Weniger T, Berssenbrugge C, et al. Characterization of clonal relatedness among the natural population of Staphylococcus aureus strains by using spa sequence typing and the BURP (based upon repeat patterns) algorithm. J Clin Microbiol 2008;46:2805e2808.
18. Reischl U, Frick J, Hoermansdorfer S, et al. Single-nucleotide polymorphism in the SCCmeceorfX junction distinguishes between livestock-associated MRSA CC398 and human epidemic MRSA strains. Euro Surveill 2009;14: pii: 19436. 19. Huijsdens XW, Bosch T, van Santen-Verheuvel MG, et al. Molecular characterisation of PFGE non-typable methicillin-resistant Staphylococcus aureus in The Netherlands, 2007. Euro Surveill 2009;14: pii: 19335. 20. Gomez-Sanz E, Torres C, Lozano C, et al. Detection, molecular characterization, and clonal diversity of methicillin-resistant Staphylococcus aureus CC398 and CC97 in Spanish slaughter pigs of different age groups. Foodborne Pathogens Dis 2010;7:1269e1277. 21. Argudin MA, Fetsch A, Tenhagen BA, et al. High heterogeneity within methicillin-resistant Staphylococcus aureus ST398 isolates, defined by Cfr9I macrorestriction-pulsed-field gel electrophoresis profiles and spa and SCCmec types. Appl Environ Microbiol 2010;76:652e658. 22. Bundesinstitut für Risikobewertung. Molekularbiologische Charakterisierung und Quantifizierung von Methicillinresistenten Staphylococcus aureus (MRSA) aus landwirtschaftlichen Nutztieren und vom Tier stammenden Lebensmitteln. BLE MRSA Projekt 2808HS032; 2009:1e72. 23. Wang FD, Chen YY, Chen TL, Lin YT, Fung CP. Risk factors and mortality of nosocomial infections of methicillin-resistant Staphylococcus aureus in an intensive care unit. J Crit Care 2011;26:82e88. 24. Hsu MS, Chiu KM, Huang YT, Kao KL, Chu SH, Liao CH. Risk factors for nosocomial infection during extracorporeal membrane oxygenation. J Hosp Infect 2009;73:210e216. 25. Hortal J, Giannella M, Perez MJ, et al. Incidence and risk factors for ventilatorassociated pneumonia after major heart surgery. Intensive Care Med 2009;35:1518e1525. 26. Gastmeier P, Sohr D, Geffers C, Behnke M, Ruden H. Risk factors for death due to nosocomial infection in intensive care unit patients: findings from the Krankenhaus Infektions Surveillance System. Infect Control Hosp Epidemiol 2007;28: 466e472. 27. Fraser S, Brady RR, Graham C, Paterson-Brown S, Gibb AP. Methicillin-resistant Staphylococcus aureus in surgical patients: identification of high-risk populations for the development of targeted screening programmes. Ann R Coll Surg Engl 2010;92:311e315. 28. Chittick P, Sherertz RJ. Recognition and prevention of nosocomial vascular device and related bloodstream infections in the intensive care unit. Crit Care Med 2010;38:S363eS372. 29. Kollef MH. Prevention of nosocomial pneumonia in the intensive care unit: beyond the use of bundles. Surg Infect (Larchmt) 2011;12:211e220.
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Characteristics of hospital patients colonized with livestock-associated meticillin-resistant Staphylococcus aureus (MRSA) CC398 versus other MRSA clones R. Köcka, K. Siamb, S. Al-Malata, J. Christmanna, F. Schaumburgc, K. Beckerc, A.W. Friedrichd, * a
Institute of Hygiene, University Hospital Münster, Münster, Germany Department for Medical Management and Controlling, DRG-Research-Group, University Hospital Münster, Münster, Germany Institute of Medical Microbiology, University Hospital Münster, Münster, Germany d Department of Medical Microbiology, University Hospital Groningen, University of Groningen, Groningen, The Netherlands b c
a r t i c l e i n f o
s u m m a r y
Article history: Received 23 February 2011 Accepted 22 August 2011 by J.A. Child Available online 22 October 2011
Meticillin-resistant Staphylococcus aureus (MRSA) associated with the clonal complex (CC) 398 has emerged among livestock and humans exposed to these animals. MRSA CC398 has so far contributed relatively little to spread of MRSA and the burden of disease in the healthcare setting. This study aimed to assess whether demographic and clinical differences in patients colonized with MRSA CC398 and those carrying other MRSA clones contribute to the observed differences in transmission and infection rates. Age, sex, length of stay (LOS), diagnoses and medical procedures were assessed in all patients with MRSA admitted to a university hospital in 2008 and 2009. S. aureus protein A gene (spa) typing was performed on the first MRSA isolate from each patient. Patients colonized or infected with MRSA that had spa types indicative of CC398 (MRSA CC398) were compared with patients who had other MRSA clones (MRSA non-CC398). Age (53 vs 59 years), mean LOS (8 vs 13 days) and percentage of patients admitted to an intensive care unit (12% vs 17%) differed significantly between MRSA CC398 and MRSA non-CC398 patients, respectively. The mean numbers and types of diagnoses and medical procedures performed for patients in these two groups also differed significantly. The differences in patient characteristics could explain, at least in part, the relatively low rates of transmission and infection associated with MRSA CC398 in the healthcare setting. Ó 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Keywords: CC398 DRG Livestock Meticillin-resistant Staphylococcus aureus ST398 Transmission
Introduction Meticillin-resistant Staphylococcus aureus (MRSA) has emerged in recent years as a colonizer of livestock animals. In a recent survey by the European Food Safety Authority (EFSA), MRSA isolates were found in dust samples from pig holdings in 17 European countries including Germany, where 43% of pig farms were affected.1 The predominant livestock-associated MRSA strains are related to the clonal complex (CC) 398, as determined by multilocus sequence typing (MLST) and S. aureus protein A gene (spa) types t011, t034, t108 and close relatives.1 Several studies have indicated that MRSA * Corresponding author. Address: Department of Medical Microbiology, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Tel.: þ31 50 3613480; fax: þ31 50 3619105. E-mail address: [email protected] (A.W. Friedrich).
CC398 strains are frequently acquired by humans exposed to livestock, resulting in a nasal carriage rate of up to 38% among pig farmers2 and 5% among veterinarians.3 The livestock reservoir of MRSA also has an impact on the prevalence of MRSA in healthcare facilities. For example, we have shown that MRSA CC398 represents 17% of all MRSA isolates found among patients screened on admission to 39 hospitals in a ‘pig-dense’ region in Germany.4 Moreover, we have shown that patients carrying MRSA CC398 at admission usually have contact with pigs or cattle, indicating that these MRSA clones do indeed originate from the livestock reservoir.5 Since it is known that nasal carriage of MRSA at admission increases the risk of healthcare-associated infection (HAI), carriage of MRSA CC398 by patients admitted to hospital could contribute to the spread of these pathogens and to an increase in HAI.6 Indeed, several studies have demonstrated that MRSA CC398 is pathogenic for humans, causing infections including endocarditis, skin and soft
0195-6701/$ e see front matter Ó 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jhin.2011.08.011
R. Köck et al. / Journal of Hospital Infection 79 (2011) 292e296
tissue infections, and ventilator-associated pneumonia.7,8 However, in spite of the high proportion of MRSA CC398 in colonized patients in ‘pig-dense’ regions, the overall incidence of human MRSA CC398 infections is comparatively low. Among MRSA isolates from bacteraemic patients in European countries, CC398 accounted for <1% of all strains.9 In Germany, which is an important pig-producing country, the proportion of CC398 among (mostly clinical) human MRSA isolates typed by the national reference laboratory was <1%.7 In The Netherlands, where MRSA CC398 accounted for 33% of all MRSA isolates reported to the national reference centre in 2007 (mostly carrier isolates), the proportion of MRSA CC398 among all MRSA isolates from clinical specimens is smaller (11.9% in 2007).10,11 It is not known why there is such a discrepancy between the high prevalence of MRSA CC398 colonization and its low contribution to the burden of nosocomial infection.12 The observation that MRSA CC398 clones have lower transmission rates than other MRSA clones in the healthcare setting is also unexplained.13,14 We hypothesize that differences in the characteristics of patients carrying MRSA CC398 from those carrying MRSA non-CC398 contribute to the epidemiological differences. We compared demographic and clinical characteristics of inpatients colonized with either MRSA CC398 or MRSA non-CC398 to determine whether differences in these factors could account for the observed differences in infection and transmission rates. Methods The University Hospital Münster (UHM) is a 1300-bedded university hospital situated in a region with the highest density of pig production in Germany.5 Between January 2008 and November 2009 all patients admitted to every department of the UHM were screened for nasopharyngeal MRSA colonization within 48 h of admission using a culture-based approach.15 We included in the study all inpatients in whom MRSA was detected either by admission screening or in clinical specimens. In positive cases, the patients were isolated in single or cohort rooms. For each patient, the first isolate of MRSA obtained from screening specimens and all isolates from clinical specimens were genotyped by S. aureus protein A (spa) sequence-typing.16 We assessed age, sex, hospital length of stay (LOS) and days on medical and surgical intensive care units (ICU days) from automated patient records. Imported cases were defined as those detected within 72 h of hospital admission. All patients from whom MRSA was solely derived from screening specimens (nose, throat, uninfected skin sites) were included in a comparative analysis (MRSA CC398 vs MRSA non-CC398) of colonized patients; patients in whom MRSA was detected in clinical specimens were excluded from this analysis in order to avoid a bias towards invasive strains due to unequal distribution of patients with MRSA infections between the two groups. The assignment of the patients into the two groups (MRSA CC398 or non-CC398) was based upon the spa typing result of their first MRSA isolate and a subsequent clustering of spa types into
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clonal complexes using the Based Upon Repeat Pattern (BURP) algorithm of the Ridom StaphTypeÒ software (Ridom GmbH, Münster, Germany).17 Patients were included in the MRSA CC398 group if the spa type of their MRSA isolate was either t011, t034, t108 (representing spa types previously detected in regional livestock and confirmed to exhibit MLST ST398) or closely related to these spa types as indicated by being grouped in the same complex by BURP. All other patients were assigned to the non-CC398 group.5 Acute care hospital inpatient stays in Germany are reimbursed according to payment per case by German Diagnosis Related Groups (G-DRGs). All cases are grouped into one of almost 1200 G-DRGs based on several parameters such as diagnoses [using the German Modification of the International Statistical Classification of Diseases and Related Health (ICD-10-GM)], procedures [using the German procedure classification (OPS)] or other patient characteristics (age, sex, discharge status etc.). For all MRSA patients identified during the study period, the procedures, primary and secondary ICD diagnoses were assessed as coded, except the codes Z22.3 (carrier of other specified bacterial diseases), Z22.8 (carrier of other infectious diseases), Z29.0 (isolation) and U80.0 (S. aureus resistant to oxacillin), which are used to code MRSA carriage and isolation measures and are therefore not considered to vary between MRSA CC398 and non-CC398 patients. Data were entered into a Microsoft Access Database (Version 7). Comparisons were performed using chi-squared test (Epi Info; Atlanta, USA) or t-test, where appropriate. P < 0.05 was considered significant. Results During the study period, 167 of 834 MRSA isolates from inpatients (20%) were characterized by spa types belonging to the CC398 group. These MRSA isolates exhibited the following spa types: t011 (N ¼ 87; 10% of all isolates detected during the study period), t034 (N ¼ 55; 7%), t108 (N ¼ 11; 1%), t2582 (N ¼ 3; 0.4%), t567 and t1451 (each N ¼ 2; 0.2%), t1197, t1255, t1457, t1606, t2011, t2346, t2576 (each N ¼ 1; 0.1%). The remaining 667 MRSA isolates were included in the group of MRSA non-CC398 that was made up of a total of 91 spa types, among which t032 (N ¼ 247, 30% of all MRSA isolated), t003 (N ¼ 199, 24%), t008 (N ¼ 17, 2%), t004 (N ¼ 14, 1.7%), t014 (N ¼ 11, 1.3%), t035 (N ¼ 10, 1.2%) and t1227 (N ¼ 10, 1.2%) were the most frequent. All other spa types were found in <1% of all MRSA isolates. In 242 of the 834 cases (29%), MRSA was isolated from clinical specimens; 18 of these (7%) were in the MRSA CC398 group and 224 patients (93%) were in the MRSA non-CC398 group (P < 0.001). The clinical specimens from which MRSA CC398 was isolated were wound swabs (N ¼ 6), respiratory fluids (N ¼ 4), blood cultures (N ¼ 2), urine (N ¼ 1) and others (N ¼ 5; i.e. tissue, cervical swabs, swab from frontal sinus). Seven of these 18 cases (39%) were classified as nosocomial. MRSA was identified by admission screening in 592 of the 834 cases (71%). MRSA CC398 accounted for 149 (25%) of the admission screening isolates.
Table I Characteristics of patients colonized or infected with meticillin-resistant Staphylococcus aureus (MRSA) CC398 and non-CC398 Characteristics Male (%) Mean age (years), (range) Length of hospital stay (days), (range)a Imported cases (%) No. of patients with stay on ICU (%) Length of ICU stay (days), (range) ICU, intensive care unit; NS, non-significant. a Mean (range).
MRSA non-CC398 patients (N ¼ 443)
MRSA CC398 patients (N ¼ 149)
All MRSA patients (N ¼ 592)
P
253 (57%) 59 (0e96) 12.6 (1e196) 392 (88%) 75 (17%) 11 (0.5e74)
104 (70%) 53 (1e88) 7.5 (1e90) 143 (96%) 13 (12%) 8.2 (1e48)
357 57 (0e96) 11.3 (1e196) 535 (90%) 88 (15%) 10.6 (0.5e74)
<0.01 <0.01 <0.01 <0.01 0.023 NS
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Compared with patients colonized by MRSA non-CC398, MRSA CC398 carriers were usually men, significantly younger, had a shorter hospital LOS and were less frequently treated on ICUs (Table I). Complete data sets for comparing the numbers and types of ICD diagnoses were available for 591 patients (Table II). The mean number of diagnoses coded for MRSA CC398 patients was 2.8 (95% CI: 2.5e3.1) compared with 4.1 (95% CI: 3.8e4.3) for MRSA non-CC398 patients (P < 0.001). Significant differences were observed for the diagnoses anaemia, metabolic disorders, diseases of the heart, eye, respiratory or digestive system, renal failure, general symptoms and potential health hazards related to family and personal history. At least one medical procedure was coded for 130 patients with MRSA CC398 and 418 patients with MRSA non-CC398 (Table III). The mean number of medical procedures coded was 6.8 (95% CI: 5.1e8.6) for patients with MRSA CC398 and 11.8 (95% CI: 10.4e13.2) for patients with MRSA non-CC398 (P < 0.001). Significant differences were found for the following procedures: diagnostic endoscopies, surgical interventions of the eyes, immunotherapy, early rehabilitation and physical therapy, access to mechanical ventilation and intubation measures, transfusion of blood cells and therapeutic catheterization.
Discussion Our observation that MRSA CC398 accounted for 25% of all MRSA carriage in patients admitted to the UHM confirms earlier findings of a high proportion of MRSA CC398 among human carriers in an area with a high density of livestock.5 All spa types included in the CC398 group have been described in association with livestock before.18e22 In contrast to this high proportion among admission screening isolates, MRSA CC398 accounted for only 7% of all MRSA from clinical specimens. MRSA CC398 is therefore still under-represented among isolates from infections.7 Whole genome sequencing of a single MRSA CC398 isolate and comparison with the gene content of other MRSA lineages has revealed that it lacked virulence factors such as enterotoxins and phage-encoded toxins.12 If this finding is representative of other CC398 clones, it could explain why they have caused relatively little disease in spite of their wide distribution in many European countries and their frequent introduction into healthcare settings in regions with a high density of livestock farming.5 Another possible explanation is suggested by differences in the nosocomial transmission rates of MRSA CC398 as compared to other MRSA clones. Using a mathematical model, Bootsma et al. have reported that the
Table II Comparison of diagnoses coded for patients colonized with meticillin-resistant Staphylococcus aureus (MRSA) non-CC398 and MRSA CC398 based on chapters and subchapters of the ICD classification Chapter/subchaptera
A00eB99 C00eD48 D50eD90 D50eD53 D60eD64 E00eE90 E70eE90 F00eF99 G00eG99 H00eH59 H49eH52 H60eH95 I00eI99 I30eI52 J00eJ99 J09eJ18 J40eJ47 J60eJ70 K00eK93 K20eK31 K90eK93 L00eL99 M00eM99 N00eN99 N17eN19 O00eO99 P00eP96 Q00eQ99 R00eR99 R50eR69 S00eT98 V01eY84 Z00eZ99b Z80eZ99 U00eU99b
Description
Certain infectious and parasitic diseases Neoplasms Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism Nutritional anaemias Aplastic and other anaemias Endocrine, nutritional and metabolic diseases Metabolic disorders (e.g. hypopotassaemia/hypokalaemia) Mental and behavioural disorders Diseases of the nervous system Diseases of the eye and ocular adnexa Disorders of ocular muscles, binocular movement, accommodation and refraction Diseases of the ear and mastoid process Diseases of the circulatory system Other forms of heart disease Diseases of the respiratory system Influenza and pneumonia Chronic lower respiratory diseases Lung diseases due to external agents Diseases of the digestive system Diseases of oesophagus, stomach and duodenum Other diseases of the digestive system Diseases of the skin and subcutaneous tissue Diseases of the musculoskeletal system and connective tissue Diseases of the genitourinary system Renal failure Pregnancy, childbirth and the puerperium Certain conditions originating in the perinatal period Congenital malformations, deformations and chromosomal abnormalities Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified General symptoms and signs Injury, poisoning and certain other consequences of external causes External causes of morbidity and mortality Factors influencing health status and contact with health services Persons with potential health hazards related to family and personal history and certain conditions influencing health status Codes for special purposes
MRSA non-CC398 (N ¼ 442)
MRSA CC398 (N ¼ 149)
P-value
No.
%
No.
%
76 75 107
17.2 17.0 24.2
17 20 21
11.4 13.4 14.1
NS NS 0.01
19 78 169 101 73 111 44 1
4.3 17.6 38.2 22.9 16.5 25.1 10.0 0.2
0 14 36 19 18 26 25 5
0.0 9.4 24.2 12.8 12.1 17.5 16.8 3.4
0.004 0.02 0.003 0.01 NS NS 0.04 0.004
15 228 109 111 31 32 11 79 25 14 35 67 109 70 1 7 22 111
3.4 51.6 24.7 25.1 7.0 7.2 2.5 17.9 5.7 3.2 7.9 15.2 24.7 15.8 0.2 1.6 5.0 25.1
6 48 22 19 3.0 4 0 8 2 0 5 19 21 13 2 1 12 23
4.0 32.2 14.8 12.8 2.0 2.7 0.0 5.4 1.3 0.0 3.4 12.8 14.1 8.7 1.3 0.7 8.1 15.4
NS <0.001 0.02 0.002 0.01 0.02 0.04 <0.001 0.01 0.02 NS NS 0.01 0.04 NS NS NS 0.02
47 96 3 242 143
10.6 21.7 0.7 54.8 32.4
6 26 1 64 33
4.0 17.5 0.7 43.0 22.1
0.02 NS NS 0.01 0.02
21
4.8
3
2.0
NS
NS, non-significant. a Chapters of the ICD, German Modification, 10th revision; in case of significant differences in chapters, data for subchapters of the classification are also shown. b Without Z22.3, Z22.8, Z29.0 and U80.0.
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Table III Comparison of medical procedures performed for patients colonized with meticillin-resistant Staphylococcus aureus (MRSA) non-CC398 and MRSA CC398 OPSa
1 1-61e1-69 3 5 5-08e5-16 5-18e5-20 6 8 8-03e8-03 8-55e8-60 8-70e8-70 8-80e8-80 8-83e8-83 9
Descriptiona
Diagnostic measures Diagnostic endoscopy Diagnostic imaging techniques Surgical interventions targeting the: Eyes Ears Application of drugs Non-surgical therapeutic interventions Immunotherapy Early rehabilitation and physical therapy Access to mechanical ventilation and intubation measures Transfusion of blood cells Therapeutic catheterization and cannula insertion in blood vessels Complementary measures
MRSA non-CC398 (N ¼ 418)
MRSA CC398 (N ¼ 130)
P-value
No.
%
No.
%
198 95 216 207 26 5 12 320 0 154 22 70 72 83
47.4 22.7 51.7 49.5 6.2 1.2 2.9 76.6 0.0 36.8 5.3 16.8 17.2 19.9
38 14 57 64 20 6 4 93 6 35 2 11 9 22
29.2 10.8 43.9 49.2 15.4 4.6 3.1 71.5 4.6 26.9 1.5 8.5 6.9 16.9
<0.001 0.004 NS NS 0.002 0.04 NS NS <0.001 0.05 0.04 0.03 0.006 NS
NS, non-significant. a Chapters/subchapters of the German procedure classification (OPS), description translated by the authors (no English version of the OPS coding system available); all chapters, but one significant subchapters, are shown.
genotype-specific nosocomial transmission capacity was 5.9 times lower for MRSA CC398 compared to other MRSA clonal lineages prevalent in Dutch hospitals.13 This finding was later confirmed by the same group by analysis of the relative risk of secondary cases after contact to an MRSA index case, which was 0.27 for MRSA CC398 compared to non-CC398 strains.14 The authors concluded that both pathogen- and patient-related factors might contribute to the lower transmission capacity of CC398 strains. Our results provide support for the latter. We found that even when infected patients are excluded from the analysis, there are patient-specific differences between patients carrying MRSA CC398 strains and those carrying other, mostly healthcare-associated MRSA molecular clones (e.g. spa types t032 and t003).9 Patients carrying MRSA CC398 at admission were younger, had a shorter LOS and less frequently required admission to ICUs. Since age, LOS and ICU admission have been associated with the development of nosocomial infections in various other studies, the risk of HAIs is lower for MRSA CC398 patients.23e26 Moreover, we observed significant differences between MRSA CC398 and non-CC398 patients with respect to the mean numbers of ICD diagnoses (N ¼ 2.8 for MRSA CC398 vs N ¼ 4.1 for non-CC398 patients, P < 0.001) and medical procedures (N ¼ 6.8 for MRSA CC398 vs N ¼ 11.8 for non-CC398 patients, P < 0.001). Specifically, the diagnoses anaemia, metabolic disorders (e.g. hypokalaemia), heart or respiratory diseases, diseases of the digestive system and renal failure were significantly less frequent among patients colonized with MRSA CC398 than among MRSA non-CC398 carriers. These results confirm data showing that patients carrying healthcare-associated MRSA clones represent a multi-morbid high risk population.27 Ocular disorders were more frequently coded in the MRSA CC398 group compared to the patients in the MRSA non-CC398 group. This reflects that a larger proportion of patients in the MRSA CC398 group was admitted to hospital for elective surgical interventions of the eye (e.g. refractive eye surgery), mostly associated with a rather low risk for nosocomial infections. We also found that a variety of invasive measures (e.g. endoscopies, mechanical ventilation, transfusion of blood cells and therapeutic catheterization) were more often performed for patients colonized with MRSA non-CC398. These results broadly correspond to the finding that patients with MRSA nonCC398 were more frequently treated on ICUs, and could account for some of the difference in the incidence of nosocomial infections, especially those associated with the use of vascular devices and mechanical ventilation.28,29 The present study cannot answer the questions of whether MRSA CC398 isolates are biologically less transmissible from
human to human or less pathogenic to humans than other MRSA clones. But our data suggest that demographic differences between patients colonized with MRSA CC398 and those colonized with classical healthcare-associated MRSA clones could influence the risk of infection and transmission. The observed differences in transmission and infection rates may disappear over time if MRSA CC398 continues to be introduced into healthcare facilities and spreads to more vulnerable patients. Weaknesses of this study include its retrospective design and the secondary use of DRG data that is normally used for the purpose of hospital reimbursement. All diagnoses and procedures may not have been identified if ICD diagnoses and procedures not considered relevant to payroll were not coded accurately. In summary, we describe demographic and clinical differences between patients carrying MRSA CC398 and MRSA non-CC398 in a hospital located in a region with a high density of pig production. These differences could explain, at least in part, the lower nosocomial infection and transmission rates associated with MRSA CC398. Further research is required to assess whether genotypespecific bacterial factors also contribute to these phenomena. Conflict of interest statement None declared. Funding sources This study has partially been supported by the INTERREG IVa project SafeGuard Workpackage 2.3 ‘MRSA vet-net’ (No. III-2-03 ¼ 025) and by grants from the Bundesministerium für Bildung und Forschung, ‘MedVet-Staph’ (01KI1014A). References 1. European Food Safety Authority. Analysis of the baseline survey on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in holdings with breeding pigs, in the EU, 2008, Part A: MRSA prevalence estimates; on request from the European Commission. EFSA J 2009;7:1376. 2. Denis O, Suetens C, Hallin M, et al. Methicillin-resistant Staphylococcus aureus ST398 in swine farm personnel, Belgium. Emerg Infect Dis 2009;15: 1098e1101. 3. Wulf MW, Sorum M, van Nes A, et al. Prevalence of methicillin-resistant Staphylococcus aureus among veterinarians: an international study. Clin Microbiol Infect 2008;14:29e34. 4. Köck R, Brakensiek L, Mellmann A, et al. Cross-border comparison of the admission prevalence and clonal structure of meticillin-resistant Staphylococcus aureus. J Hosp Infect 2009;71:320e326. 5. Köck R, Harlizius J, Bressan N, et al. Prevalence and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) among pigs on German
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6. 7.
8.
9.
10. 11.
12.
13.
14.
15.
16.
17.
R. Köck et al. / Journal of Hospital Infection 79 (2011) 292e296 farms and import of livestock-related MRSA into hospitals. Eur J Clin Microbiol Infect Dis 2009;28:1375e1382. Bode LG, Kluytmans JA, Wertheim HF, et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med 2010;362:9e17. Witte W, Strommenger B, Stanek C, Cuny C. Methicillin-resistant Staphylococcus aureus ST398 in humans and animals, Central Europe. Emerg Infect Dis 2007;13:255e258. Ekkelenkamp MB, Sekkat M, Carpaij N, Troelstra A, Bonten MJ. Endocarditis due to meticillin-resistant Staphylococcus aureus originating from pigs. Ned Tijdschr Geneeskd 2006;150:2442e2447. Grundmann H, Aanensen DM, van den Wijngaard CC, Spratt BG, Harmsen D, Friedrich AW. Geographic distribution of Staphylococcus aureus causing invasive infections in Europe: a moleculareepidemiological analysis. PLoS Med 2010;7: e1000215. Wulf M, Voss A. MRSA in livestock animals e an epidemic waiting to happen? Clin Microbiol Infect 2008;14:519e521. Van Cleef B, Monnet D, Voss A, et al. Livestock-associated methicillin-resistant Staphylococcus aureus from human samples, Europe, 2007. Emerg Infect Dis 2011;17:502e505. Schijffelen MJ, Boel CH, van Strijp JA, Fluit AC. Whole genome analysis of a livestock-associated methicillin-resistant Staphylococcus aureus ST398 isolate from a case of human endocarditis. BMC Genomics 2010;11:376. Bootsma MC, Wassenberg MW, Trapman P, Bonten MJ. The nosocomial transmission rate of animal-associated ST398 meticillin-resistant Staphylococcus aureus. J R Soc Interface 2011;8:578e584. Wassenberg MW, Bootsma MC, Troelstra A, Kluytmans JA, Bonten MJ. Transmissibility of livestock-associated methicillin-resistant Staphylococcus aureus (ST398) in Dutch hospitals. Clin Microbiol Infect 2011;17: 316e319. Becker K, Pagnier I, Schuhen B, et al. Does nasal cocolonization by methicillin-resistant coagulase-negative staphylococci and methicillinsusceptible Staphylococcus aureus strains occur frequently enough to represent a risk of false-positive methicillin-resistant S. aureus determinations by molecular methods? J Clin Microbiol 2006;44:229e231. Mellmann A, Friedrich AW, Rosenkotter N, et al. Automated DNA sequence-based early warning system for the detection of methicillin-resistant Staphylococcus aureus outbreaks. PLoS Med 2006;3:e33. Mellmann A, Weniger T, Berssenbrugge C, et al. Characterization of clonal relatedness among the natural population of Staphylococcus aureus strains by using spa sequence typing and the BURP (based upon repeat patterns) algorithm. J Clin Microbiol 2008;46:2805e2808.
18. Reischl U, Frick J, Hoermansdorfer S, et al. Single-nucleotide polymorphism in the SCCmeceorfX junction distinguishes between livestock-associated MRSA CC398 and human epidemic MRSA strains. Euro Surveill 2009;14: pii: 19436. 19. Huijsdens XW, Bosch T, van Santen-Verheuvel MG, et al. Molecular characterisation of PFGE non-typable methicillin-resistant Staphylococcus aureus in The Netherlands, 2007. Euro Surveill 2009;14: pii: 19335. 20. Gomez-Sanz E, Torres C, Lozano C, et al. Detection, molecular characterization, and clonal diversity of methicillin-resistant Staphylococcus aureus CC398 and CC97 in Spanish slaughter pigs of different age groups. Foodborne Pathogens Dis 2010;7:1269e1277. 21. Argudin MA, Fetsch A, Tenhagen BA, et al. High heterogeneity within methicillin-resistant Staphylococcus aureus ST398 isolates, defined by Cfr9I macrorestriction-pulsed-field gel electrophoresis profiles and spa and SCCmec types. Appl Environ Microbiol 2010;76:652e658. 22. Bundesinstitut für Risikobewertung. Molekularbiologische Charakterisierung und Quantifizierung von Methicillinresistenten Staphylococcus aureus (MRSA) aus landwirtschaftlichen Nutztieren und vom Tier stammenden Lebensmitteln. BLE MRSA Projekt 2808HS032; 2009:1e72. 23. Wang FD, Chen YY, Chen TL, Lin YT, Fung CP. Risk factors and mortality of nosocomial infections of methicillin-resistant Staphylococcus aureus in an intensive care unit. J Crit Care 2011;26:82e88. 24. Hsu MS, Chiu KM, Huang YT, Kao KL, Chu SH, Liao CH. Risk factors for nosocomial infection during extracorporeal membrane oxygenation. J Hosp Infect 2009;73:210e216. 25. Hortal J, Giannella M, Perez MJ, et al. Incidence and risk factors for ventilatorassociated pneumonia after major heart surgery. Intensive Care Med 2009;35:1518e1525. 26. Gastmeier P, Sohr D, Geffers C, Behnke M, Ruden H. Risk factors for death due to nosocomial infection in intensive care unit patients: findings from the Krankenhaus Infektions Surveillance System. Infect Control Hosp Epidemiol 2007;28: 466e472. 27. Fraser S, Brady RR, Graham C, Paterson-Brown S, Gibb AP. Methicillin-resistant Staphylococcus aureus in surgical patients: identification of high-risk populations for the development of targeted screening programmes. Ann R Coll Surg Engl 2010;92:311e315. 28. Chittick P, Sherertz RJ. Recognition and prevention of nosocomial vascular device and related bloodstream infections in the intensive care unit. Crit Care Med 2010;38:S363eS372. 29. Kollef MH. Prevention of nosocomial pneumonia in the intensive care unit: beyond the use of bundles. Surg Infect (Larchmt) 2011;12:211e220.