ANNUAL REPORT ON STAPHYLOCOCCUS AUREUS BACTERAEMIA CASES IN DENMARK 2012

Transcription

1 ANNUAL REPORT ON STAPHYLOCOCCUS AUREUS BACTERAEMIA CASES IN DENMARK 2012 Aalborg Viborg Herning Aarhus Hillerød Esbjerg Vejle Herlev København Hvidovre Odense Slagelse Sønderborg Nykøbing Falster

2 DEAR COLLEAGUE Please find the annual report on cases of Staphylococcus aureus bacteraemia in Denmark in Staphylococcus aureus bacteraemia (SAB) has been surveyed in Denmark since 1957 by strain characterization and collection of clinical and epidemiological information. This has been performed by the Staphylococcus Laboratory at Statens Serum Institut in collaboration with the Danish Departments of Clinical Microbiology (DCM). Clinical and epidemiological data was extracted from The National Patient Register (NPR, Lynge et al. 2011). Prior to 20 data acquisition was based on reading of discharge notes. This will to some extent make comparisons to earlier results difficult. MEMBERS OF THE DANISH STAPHYLOCOCCUS AUREUS BACTERAEMIA GROUP Paal Skytt Andersen, MSc PhD Thomas Benfield, MD DMSc Niels Frimodt-Møller, Prof. MD DMSc Allan Garlik Jensen, MD DMSc Anders Rhod Larsen, MSc PhD Andreas Petersen, MSc PhD Henrik C. Schønheyder, Prof. MD DMSc Peter Skinhøj, Prof. MD DMSc Robert Skov, MD Henrik Westh, Prof. MD DMSc BEST REGARDS, Andreas Petersen, Anders Rhod Larsen and Robert Skov Acknowledgement The following DCMs have collected and submitted the SAB isolates included in this annual report: Esbjerg Herlev Herning Hillerød Hvidovre Nykøbing F Odense Rigshospitalet Slagelse Vejle Viborg Aalborg Aarhus Sønderborg Lone Ryste Kildevang Hansen, Stine Frese-Madsen and Julie Hindsberg Nielsen are thanked for technical assistance. LIST OF ABBREVIATIONS CC CLSI DCM EUCAST HA hvisa ICD- Clonal complex Clinical and Laboratory Standards Institute Department of Clinical Microbiology The European Committee on Antimicrobial Susceptibility Testing Hospital acquired S. aureus with hetero-resistance to vancomycin International Classification of Diseases lukf/s-pv Genes encoding the Panton-Valentine leukocidin meca mecc MLST MRSA MSSA NPR SAB spa The gene encoding for methicillin resistance The newly described variant of the meca gene Multi locus sequence typing Methicillin-resistant Staphylococcus aureus Methicillin-susceptible Staphylococcus aureus The Danish National Patient Register ( Landspatientregistret ) Staphylococcus aureus bacteraemia The gene encoding the staphylococcal protein A 2

3 MATERIALS AND METHODS STAPHYLOCOCCUS AUREUS BACTERAEMIA (SAB) EPISODES One S. aureus isolated from blood per bacteraemia episode was referred to the Staphylococcus Laboratory from the Departments of Clinical Microbiology in Denmark. Subsequent isolates from the same patient were only included if the period between two received isolates was more than one month (new episode). Medical records from NPR were extracted for each patient with SAB. The registry contains information for every time a citizen is in contact with the health system. The following data were extracted: onset of infection in relation to hospital admission, comorbidities, secondary foci (assessed during admission, after 3 months of onset of SAB and after 6 months). Onset of infection was classified as hospital acquired (HA) if S. aureus was found by blood culture more than two days after admission. Charlson comorbidities (1987) were extracted based on the ICD- codes by Quan et al. (2005); for intravenous drug use the definition of Elixhauser et al. (1998) was used. A comorbidity index score was calculated based on the revised weights by Quan et al. (2005). ICD- codes used to identify secondary infections were listed in the 20 SAB report ( bakteriaemirapport20). 30 day mortality was calculated based on data extracted from the Danish Civil Registration System ( CPR-registret, Pedersen et al. (2006)). TYPING All isolates were typed by sequencing of the spa gene, which encodes the staphylococcal protein A. The spa gene is present in almost all S. aureus isolates and offers a high level of discrimination (Harmsen et al., 2003). The used method simultaneously detects the meca, mecc and lukf/s-pv genes (PVL) (Stegger et al. 2012). The sequences were analysed and spa types were annotated using Bionumerics 6.1 (Applied Maths, Sint-Martens-Latem, Belgium) and RidomStaphType 1.4 (Ridom GmbH, Würzburg, Germany). spa types were approximated to multi locus sequence typing (MLST) clonal complexes (CC), using the MLST homepage and eburst ( ANTIBIOTIC SUSCEPTIBILITY TESTING Susceptibility testing was performed by disc diffusion according to EUCAST methodology using discs from Oxoid (Ballerup, DK) on Mueller Hinton Agar (SSI Diagnostica, Hillerød, DK). The following antibiotics were tested: Erythromycin, clindamycin, kanamycin, rifampicin, penicillin, cefoxitin, fusidic acid, norfloxacin, linezolid, tetracycline, mupirocin, and trimethoprim-sulfamethoxazole. EUCAST breakpoints were used for interpretation of antimicrobial resistance. For kanamycin the breakpoints of CLSI were used. Intermediate zone diameters were interpreted as susceptible. S. aureus ATCC was included as quality control for each batch of resistance determination. In order to demonstrate geographic differences, SAB per participating DCM is presented. The location of the DCMs can be seen on the front page. Demographic data from Denmark were obtained through the homepage of Statistics Denmark ( 3

4 PATIENT INFORMATION 1,528 SAB cases were submitted in 2012 (Figure 1). This corresponds to an incidence rate of SAB of 28.6/0,000 inhabitants/year (Figure 2). Please note that Sønderborg DCM is underrepresented in 2012 but this has been corrected for in calculating the incidence. The number of bacteraemia cases has been at the same level during the last decade (Figure 1). There was an excess of men (62% vs. 38% women) among the cases of SAB in This proportion has been relatively constant comprising 60%-64% during the last 20 years. Figure 1. Number of S. aureus bacteraemia cases The moving average demonstrates increasing numbers throughout the period Figure 2. Incidence rate of SAB per 0,000 inhabitants during The rate has been relatively constant during the last decade Number of SAB moving average (5 years) No of SAB/0,000 incidence rate moving average (5 years) 4

5 GEOGRAPHIC VARIATION The incidence of SAB varied from 9 to 37 cases/0,000 in the catchment population for the DCMs (Table 1). The highest incidence was observed in Greater Copenhagen. Incidences for Viborg, Herning and Nykøbing were lower in 2012 than in previous years. In 2012 isolates were only submitted sporadically from Sønderborg. Table 1. Number of SAB and SAB/0,000 inhabitants in each area covered by the Department of Clinical Microbiology Number of SAB SAB/0,000 inhabitants DCM Aalborg Aarhus Viborg Herning Vejle 68 NA Esbjerg Sønderborg (2) (3) (<1) (<1) Odense Hillerød Greater Copenhagen Slagelse 180 (25) (30) Nykøbing Note: The catchment population for Slagelse DCM changed in 20 and the incidence for DCM Slagelse after 20 reflects this. The incidence from previous years from Slagelse is not directly comparable. NA: Not applicable. 5

6 AGE More than 80% of the SAB patients were older than 50 years and more than 23% were older than 80 years (Figure 3). In 2012 the general Danish population only included 3.6% persons older than 80 years and the incidence of SAB among people above 80 years of age (176.4/0,000 inhabitants/year) was more than six times higher than for the whole population. Figure 3. Age distribution of SAB 2012 and the general Danish population (%). SAB was primarily affecting people over 60 years of age Percentage SAB 2012 Population Mortality (discharge summaries) Mortality NPR Moving average (5 years) 6

7 MORTALITY The 30 day mortality was 22.4% in 2012 (Table 2) and did not differ from mortality rates from the previous -15 years where the information was extracted from discharge summaries and doctors notes (Figure 4). Patients in age groups 0-1 and years had higher 30 day mortality compared with age group years. The 30-day mortality increased with age from the age group of years and patients above 80 years had a mortality rate of 39.8% (Table 2). Table 2. Mortality among Danish SAB 2012 by age group and in total. The highest mortality was recorded among the eldest patients. Age group TOTAL No of SAB day mortality (N) day mortality (%) Figure 4. Mortality of Danish SAB patients The mortality has been 20-25% the last 20 years Percentage Mortality (discharge summaries) Mortality NPR Moving average (5 years) 7

8 Table 3. Secondary infections (%) among Danish SAB cases in 2012, recorded during admission and 3 and 6 months after. Endocarditis was the most frequent secondary infection. CNS Endocarditis Arthritis Spondylytis Osteomyelitis Prosthesis During admission months after SAB onset months after SAB onset Table 4. Number and percentage of comorbidities among SAB cases Diabetes without chronic complication was the most frequently registered comorbidity. Comorbidity Number Percentage AIDS/HIV Any malignancy Metastatic solid tumour Diabetes without chronic complication Diabetes with chronic complication Dementia Hemiplegia or paraplegia Cerebrovascular disease Myocardial infarction Congestive heart failure Chronic pulmonary disease Peptic ulcer disease Mild liver disease Moderate or severe liver disease Renal disease Rheumatic disease Peripheral vascular disease Drug abuse ACQUISITION Data from NPR allowed the acquisition of SAB to be divided into hospital acquired (HA) and non-hospital acquired. 451 (29.5%) cases had an onset of infection 2 or more days after admission (HA). The corresponding number was 29.0% in 2011 and has been steadily decreasing since 2002 (from 41%). SECONDARY INFECTIONS In Table 3 secondary infections are given during admission, three and six months after SAB onset. Initially the incidence of secondary infections were low but increased up to 3-fold after three months (spondylitis). No further increase was registered after six months. Endocarditis was the most prevalent secondary infection, followed by spondylitis, prosthesis and arthritis (Table 3). Tenosynovitis, myositis, and abdominal abscesses were all registered in less than 1%. COMORBIDITIES A comorbidity index is presented in Table 4. Diabetes without chronic complication (23.6%), malignancy (23.4%), and renal disease (20.0%) were the most frequently registered comorbidities. 305 cases (20%) had no comorbidities registered, while 571 cases (37%) had a comorbidity index score of 1-2 and 478 cases (31%) had a score of more than 2. In the period comorbidities were categorised differently and thus comparisons to previous results are difficult to make, but data acquisition from NPR seems to increase the number of registered comorbidities. 8

9 TYPING spa types were obtained from 1,498 isolates (98.0%). In total, 483 different spa types were identified, with ten spa types accounting for 34% of the isolates. A total of 327 spa types were only encountered once. Putative assignment to MLST CC was possible for 1,276 isolates (84%). In the remaining cases assignment was not possible due to low number of repeats in the spa type or otherwise unresolved relationship with MLST typing. A total of 26 MLST CC groups were assigned. The three most prevalent CC groups constituted 42% of the SAB isolates in 2012 while the most prevalent constituted 73% (Table 5). PVL was demonstrated among 12 SAB isolates (0.8%), of these were 3 methicillin-resistant S. aureus (MRSA; two spa type t044 and one t019). Among MSSAs, PVL was demonstrated in 6 spa types, (t005 (2), t021 (2), t 645 (2) and one each for spa types t5, t355 and t433). Table 5: Predominant CC groups and frequent spa type(s) within each CC group among Danish S. aureus bacteraemia isolates in , based on putative assignment to multi locus sequence typing (MLST) clonal complexes (CC) from the spa type. CC45 has been the most frequent CC group during the last five years. CC group/ Predominant spa type(s) Number of isolates (% of total) CC (21.2) 326 (22.0) 309 (21.7) 338 (22.2) 271 (17.7) t t CC (15.6) 244 (16.5) 232 (16.3) 200 (13.2) 215 (14.1) t t CC (11.9) 151 (.2) 164 (11.5) 177 (11.6) 157 (.3) t CC5 96 (7.2) 8 (7.3) 7 (7.5) 2 (6.7) 112 (7.3) t CC1 86 (6.4) 96 (6.5) 118 (8.3) 1 (7.2) 2 (6.7) t CC8 84 (6.3) 7 (7.2) 84 (5.9) 92 (6.1) 1 (6.6) t t CC22 48 (3.6) 45 (3.0) 41 (2.9) 54 (3.6) 51 (3.3) t CC7 39 (2.9) 29 (2.0) 39 (2.7) 47 (3.1) 44 (2.9) t CC59 36 (2.7) 36 (2.4) 25 (1.8) 36 (2.4) 30 (2.0) t CC97 20 (1.5) 33 (2.2) 28 (2.0) 28 (1.8) 29 (1.9) t CC1 18 (1.3) 22 (1.5) 16 (1.1) 14 (0.9) 22 (1.4) t

10 Figure 5: Resistance patterns ( ). Resistance to penicillin is not shown Percentage (%) 5 Meth/Oxa/Fox Erythromycin Clindamycin Tetracycline Streptomycin Gentamicin Kanamycin Rifampicin Fusidic Fusidic acid acid Flouroquinolone Trim/sulfa Sensitive Sensitive to all to all Percentage (%) Year Year Table 6: Resistance prevalences The increase in resistance towards fusidic acid continued. Resistance to 2008 (%) 2009 (%) 20 (%) 2011 (%) 2012 (%) Penicillin Tetracycline Erythromycin Methicillin Fusidic acid Norfloxacin Rifampicin Linezolid Kanamycin Clindamycin Mupirocin Trimethoprim/sulfamethoxazole Sensitive to all antibiotics Multi-resistance Penicillin Penicillin Penicillin

11 ANTIMICROBIAL SUSCEPTIBILITY TESTING The prevalence of resistance to the tested antimicrobials is shown in Table 6. Results from are provided for comparison. The number of MRSA cases was 20 (1.3%). This proportion is comparable to proportions in recent years, with the exception of 2007 (0.6%). Two of the MRSAs contained the new meca homologue mecc All SAB isolates were susceptible to linezolid in 2011 and none of the 20 MRSA was positive when screened for hvisa (macro Etest). The proportion of isolates that was susceptible to all antibiotics (20.3%) was at the same level as in previous years. Resistance towards single antimicrobials were also at the same levels as previous years. Multi-resistance, defined as resistance to at least one, two or three antimicrobials in addition to penicillin is also shown in Table 5. Resistance to one antimicrobial in addition to penicillin was 19.5% and resistance to 2 and 3 additional antimicrobials was 7.1% and 1.8%, respectively (Table 5). In Figure 5 resistance prevalences are shown from 1980 to Table 7. Resistance prevalences (%) for the most frequent spa types in Resistance varied considerably between spa types. spa type t230 t127 t084 t002 t015 t012 t008 t021 t091 t701 No of isolates Penicillin Erythromycin Clindamycin Tetracycline Fusidic acid Rifampicin Norfloxacin Kanamycin Mupirocin Trimethoprim/ sulfamethoxazole REFERENCES Charlson ME, Pompei P, Ales KL, MacKenzie CR A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 40(5): Elixhauser A, Steiner C, Harris DR, Coffey RM Comorbidity measures for use with administrative data. Med Care. 36(1):8-27. Harmsen D, Claus H, Witte W, Rothgänger J, Claus H, Turnwald D, Vogel U Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novel software for spa repeat determination and database management. J Clin Microbiol. 41(12): Lynge E, Sandegaard JL, Rebolj M The Danish National Patient Register. Scand J Public Health. 39(7 Suppl):30-3. Pedersen CB, Gøtzsche H, Møller JØ Mortensen PB The Danish Civil Registration System. Dan Med Bull 53:441-9 Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, Januel JM, Sundararajan V Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 173(6): Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, Saunders LD, Beck CA, Feasby TE, Ghali WA Coding algorithms for defining comorbidities in ICD-9-CM and ICD- administrative data. Med Care. 43(11): Stegger M, Andersen PS, Kearns A, Pichon B, Holmes MA, Edwards G, Laurent F, Teale C, Skov R, Larsen AR Rapid detection, differentiation and typing of methicillinresistant Staphylococcus aureus harbouring either meca or the new meca homologue meca(lga251). Clin Microbiol Infect. 18(4):

12 ANNUAL REPORT ON STAPHYLOCOCCUS AUREUS BACTERAEMIA CASES IN DENMARK 2012 STATENS SERUM INSTITUT Staphylococcus Laboratory Artillerivej Copenhagen S Denmark Web: