- Email: [email protected]
The rise and fall of mandatory surveillance for glycopeptide-resistant enterococcal bacteraemia in England
Letters to the Editor Antimicrobial susceptibility data for Brucella melitensis isolates cultured from UK patients
Dear Editor, For the treatment of brucellosis, the World Health Organisation (WHO) recommends only a limited number of antibiotics with good intracellular penetration and proven clinical efficiency.1 Generally, Brucella species are considered susceptible to the WHO recommended antibiotics through sporadic cases of antimicrobial resistance occur.2,3 Sensitivity testing is infrequently performed due to concerns over laboratory-acquired infection and the need for containment level 3 facilities. However, in-vitro susceptibilities can vary across geographical regions.4,5 Furthermore, until recently invitro susceptibility testing of Brucella spp has not been standardised. Currently, the UK’s British Society of Antimicrobial Chemotherapy and the European Committee on Antimicrobial Susceptibility Testing have not published interpretative breakpoints for brucella antimicrobial sensitivities. As a consequence there are no antimicrobial susceptibility data for Brucella spp cultured from UK patients. We therefore report a prospective study of in-vitro sensitivities to commonly used anti-brucella antibiotic agents. Since 2011, Brucella spp referred to the Brucella Biohazard Facility, Animal Health and Veterinary Agency, for confirmatory identification have routinely undergone antimicrobial sensitivity testing to tetracycline (TET), rifampicin (RIF), ciprofloxacin (CIP), streptomycin (STREP) and gentamicin (GENT) by E-test methodology (Biomerieux, Sweden). The minimum inhibitory concentration (MIC) was interpreted as the value at which the inhibition zone intercepted the scale on the E-strip. MIC90 was defined as the lowest concentration of an antibiotic at which 90% of isolates were inhibited. Clinical Laboratory Standards Institute sensitivity breakpoints (mg/L) were employed for TET (<1), RIF (2) and STREP (8).6 For CIP and GENT, breakpoints were set at 2 based on previously published data.7,8 Seventeen Brucella melitensis isolates were examined. MIC90 values (mg/l) for TET, RIF, CIP, STREP and GENT were 0.064, 1.0, 0.25, 1.0 and 0.25 respectively. Tetracycline was found to be the most active agent followed by CIP/GENT and then RIF/STREP. No antimicrobial resistant strains were identified. Brucellosis is an uncommon infection in the UK and is typically acquired from countries where there is an endemic problem. This is the first UK study that has examined the antimicrobial sensitivity patterns of B. melitensis isolates cultured from UK patients. The WHO considers tetracycline and its derivatives to be one of the most effective antimicrobials against brucellosis. This study confirms that view and should provide reassurance to UK clinicians who manage this infection. Though no antimicrobial resistance in UK strains was identified, continued surveillance for the emergence of antimicrobial resistance in brucellosis is justified and is ongoing.
401
References 1. Corbel MJ. Brucellosis in humans and animals, 5. World Health Organisation in collaboration with the Food and Agriculture Organisation of the United Nations and the World Organisation for Animal Health; 2006. pp. 36e40 (WHO/CDS/EPR/2006.7). 2. Baykam N, Esener H, Ergonul O, Eren S, Celikbas AK, Dokuzoguz B. In vitro antimicrobial susceptibility of Brucella species. Int J Antimicrob Agents 2004;23:405e7. pez-Merino A, Contreras-Rodrıguez A, Migranas-Ortiz R, Or3. Lo ndez-Oliva GM, Gutie rrez-Rubio AT, rantia-Gradın R, Herna et al. Susceptibility of Mexican brucella isolates to moxifloxacin, ciprofloxacin and other antimicrobials used in the treatment of human brucellosis. Scand J Infect Dis 2004;36:636e8. 4. De Reutlin de la Roy YM, Grignon B, Grollier G, Coindreau MF, Becq-Giraudon B. Rifampicin resistance in a strain of Brucella melitensis after treatment with doxycycline and rifampicin. J Antimicrob Chemother 1986;18:648e9. 5. Kinsara A, Al-Mowalled A, Osoba AO. Increasing resistance of Brucellae to co-trimoxazole. Antimicrob Agents Chemother 1999;43:153. 6. Clinical and Laboratory Standards Institute. Performance for antimicrobial susceptibility testing, seventeenth informational supplement, 26. Wayne PA, USA: CLSI; 2007. pp. 1e182. CLSI document M100-517. 7. Falagas ME, Bliziotis IA. Quinolones for treatment of human brucellosis: critical review of the evidence from microbiological and clinical studies. Antimicrob Agents Chemother 2006; 50(1):22e33. 8. Roberts NL, Farrell ID, Hinchcliffe PM. The sensitivity of Brucella abortus to chemotherapeutic agents. J Med Microbiol 1973;6:549e57.
R.P.D. Cooke* Brucella Reference Unit, University Hospital Aintree, Liverpool, UK *Corresponding author. Tel.: þ44 0151 529 4916; fax: þ44 0151 529 4918. L. Perrett Brucella Biohazard Faculty, Animal Health and Veterinary Agency, Surrey, UK E-mail address: [email protected] Accepted 11 January 2014 ª 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jinf.2014.01.002
The rise and fall of mandatory surveillance for glycopeptide-resistant enterococcal bacteraemia in England
Dear Editor, We read with interest the report by Mikulska and colleagues revealing a heterogeneous but rising incidence
402 of enterococci as a cause of bacteraemia in haematooncology patients in Europe.1 Over the last three decades, enterococci have emerged as a leading cause of nosocomial infection in some immunocompromised patient groups, and currently rank as the 3rd commonest cause of healthcare-associated infections in Europe and the United States, and 5th in England.2e4 The vast majority are caused by two species (Enterococcus faecalis and Enterococcus faecium). Their success as nosocomial pathogens follows the worldwide spread of hospital-adapted lineages, which have acquired resistance to multiple antibiotics.5 Glycopeptide-resistant enterococci (GRE) were first isolated in the UK in 1986, and by the late 1990s were a cause for concern for several reasons. The rate of glycopeptide resistance rose sharply following its emergence and by 1998, 24% of E. faecium associated with bacteraemia were glycopeptide-resistant.6 At that time, there were no antimicrobial drugs with reliable activity to treat GRE E. faecium bacteraemia, which was associated with a higher crude and attributable mortality, longer hospital stay, and increased costs compared with bacteraemia caused by glycopeptide-susceptible enterococci (GSE).7 It was also feared that the mobile genetic elements encoding glycopeptide resistance would be readily transferred to Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). In 2002, the Chief Medical Officer formally identified GRE as a threat for UK hospitals and GRE bacteraemia reporting became mandatory for all acute NHS Trusts in England in September 2003.8 The process for GRE mandatory surveillance differed from concurrent systems for reporting MRSA bacteraemia and Clostridium difficile infections (CDI).8 Surveillance for MRSA and CDI is ‘enhanced’, and includes collection of risk factor and epidemiological data, the expression of infection rates based on hospital activity (100,000 bed days) to allow comparison between individual Trusts, and is linked to annual target setting for each Trust. By comparison, GRE surveillance was more limited and only collected the number (rather than rate) of GRE bacteraemias each year in 161 acute NHS Trusts in England.8 Despite recommendations made by the National GRE Bacteraemia Surveillance Working Group Report to the Department of Health in 2004 to collect additional data,9 surveillance did not become enhanced. Consequently, reports lacked information on rates, risk factors, hospital specialty of affected patients, and the distinction between the two main species of enterococci. A total of 6246 GRE bacteraemias were recorded in England between 2003 and 12 through the mandatory reporting mechanism.8 Incidence peaked in 2006e7 with 911 cases followed by a decrease to 541 in 2009e10 (a 40% reduction), but this decline has not been sustained and there were 651 cases in 2011e12. This pattern contrasts with the sustained and dramatic decrease in numbers of CDI and MRSA bacteraemia over the same period (Fig. 1).8 Infection prevention and control initiatives introduced over the last decade to reduce MRSA bacteraemia and CDI have included antimicrobial stewardship, intravascular catheter care bundles, improved hand hygiene and environmental cleaning. Understanding why these have not had a comparable impact on GRE bacteraemia rates over time is important for further initiatives to reduce rates
Letters to the Editor
Figure 1 Trends in glycopeptide-resistant enterococcus (GRE) bacteraemia (OcteSept), and methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and Clostridium difficile infections (CDI) in patients aged 2 years and over (AprileMarch), adapted from mandatory surveillance data reported by Public Health England.8
of preventable infection. Possible reasons include lack of screening for VRE carriage,9 and infection that arises from the patient’s pre-existing flora rather than as a result of acquisition through transmission in hospital. The marked decrease in MRSA bacteraemias in England means that in some acute NHS Trusts, the GRE bacteraemia rate is now higher than that for MRSA bacteraemias. Using the latest available data, the number of GRE bacteraemias (Oct 2011eSep 2012) was higher than MRSA bacteraemias (Apr 2012eMar 2013) in 35/161 (21.7%) acute NHS Trusts. It is unclear whether this percentage is stable or whether GRE will overtake MRSA in an increasing number of hospitals over time, since rates of GRE bacteraemia are very heterogeneous in different centres across England. For example, 124/161 (77%) acute NHS Trusts reported less than 5 cases in the period from Oct 2011eSep 2012, with 50/124 (40%) recording none. By contrast, from 2003 to 2012, just 15 (9.3%) Trusts accounted for 48% of the national total and reported on average more than 10 cases per year, with the five most-affected Trusts accounting for 28% of all cases. Such heterogeneity can be explained in part by a concentration of highly immunocompromised patients in specialist centres, but this is probably an oversimplification since there is also considerable variation in both the annual incidence and the trend in rates over time between the most-affected Trusts. Accurate comparisons between Trusts are hampered by lack of denominator data for the size and nature of at-risk populations, but the possibility of differences in local factors merits investigation. The increased mortality of GRE versus GSE bacteraemia observed in meta-analyses published in the early 2000s7 has not been replicated in newer studies,10 which may be related to improved study methodology and/or the introduction of antimicrobial drugs with greater activity against GRE; these include linezolid, quinupristinedalfopristin (active against E. faecium but not E. faecalis) and daptomycin (although no European breakpoints exist). However,
Letters to the Editor GRE bacteraemia remains associated with increased healthcare costs and longer length of stay compared with GSE.10 Furthermore, enterococcal bacteraemia as a whole is associated with increased mortality compared with no bacteraemia in high-risk group patients such as those receiving an allogeneic stem cell transplantation.11 The recognition that hospital-adapted GSE E. faecium can acquire glycopeptide resistance genes merits further investigation to understand the dynamics and spread of these organisms in the hospital environment.12 The discontinuation of mandatory surveillance for GRE bacteraemia was announced by Public Health England (PHE) in July 2013,8 following a recommendation of the Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infections (ARHAI). Many of the concerns that led to mandatory surveillance of GRE bacteraemia have been outdated by advancements in antimicrobial treatment or have proved unjustified, but a watching brief is required. PHE continue to collect data on GRE and GSE bacteraemia in England, Wales and Northern Ireland via LabBase2 through the voluntary surveillance scheme.8
Funding This work was supported by grants from the UKCRC Translational Infection Research (TIR) Initiative, and the Medical Research Council (Grant Number G1000803) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate; Public Health England; and the NIHR Cambridge Biomedical Research Centre.
Transparency declaration None of the authors have conflicts of interest to declare.
Acknowledgements The authors wish to thank Prof. Neil Woodford and Prof. Alan P. Johnson for reviewing the manuscript.
References 1. Mikulska M, Viscoli C, Orasch C, Livermore DM, Averbuch D, Cordonnier C, et al. Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. J Infect 2014;68:321e31. 2. Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, et al. NHSN annual update: antimicrobialresistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006e2007. Infect Control Hosp Epidemiol 2008;29:996e1011. 3. European Centre for Disease Prevention and Control. Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals 2011e2012. Stockholm: ECDC; 2013. Available at: http://
403
4.
5.
6.
7.
8.
9.
10.
11.
12.
www.ecdc.europa.eu/en/publications/Publications/ healthcare-associated-infections-antimicrobial-use-PPS.pdf [last accessed 22.11.13]. Health Protection Agency. English national point prevalence survey on healthcare-associated infections and antimicrobial use, 2011. London: Health Protection Agency; 2012. Available at: http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/ 1317134304594 [last accessed 22.11.13]. Lebreton F, van Schaik W, McGuire AM, Godfrey P, Griggs A, Mazumdar V, et al. Emergence of epidemic multidrugresistant Enterococcus faecium. MBio 2013;4. e00534e13. Reacher MH, Shah A, Livermore DM, Wale MC, Graham C, Johnson AP, et al. Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998: trend analysis. Br Med J 2000;320:213e6. Salgado CD, Farr BM. Outcomes associated with vancomycinresistant enterococci: a meta-analysis. Infect Control Hosp Epidemiol 2003;24:690e8. Public Health England. Mandatory and voluntary surveillance data. Available at: http://www.hpa.org.uk/ [last accessed 22.11.13]. Brown DFJ, Brown NM, Cookson BD, Duckworth G, Farrington M, French GL, et al. National glycopeptide-resistant enterococcal bacteraemia surveillance Working Group report to the Department of Health e August 2004. J Hosp Infect 2006;62(Suppl. 1):S1e27. http://dx.doi.org/10.1016/j.jhin.2005.04.011. Cheah ALY, Spelman T, Liew D, Peel T, Howden BP, Spelman D, et al. Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization. Clin Microbiol Infect 2013;19:E181e9. Vydra J, Shanley RM, George I, Ustun C, Smith AR, Weisdorf DJ, et al. Enterococcal bacteremia is associated with increased risk of mortality in recipients of allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2012;55:764e70. Howden BP, Holt KE, Lam MMC, Seemann T, Ballard S, Coombs GW, et al. Genomic insights to control the emergence of vancomycin-resistant enterococci. MBio 2013;4. e00412e13.
T. Gouliouris S.J. Peacock University of Cambridge, Department of Medicine, Box 157, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom Cambridge Public Health England Microbiology and Public Health Laboratory, Box 236, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, United Kingdom *Corresponding author. Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, United Kingdom. Tel.: þ44 01223 336867; fax: þ44 01223 336846. E-mail address: [email protected] (T. Gouliouris) Accepted 26 January 2014 ª 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jinf.2014.01.009
Dear Editor, For the treatment of brucellosis, the World Health Organisation (WHO) recommends only a limited number of antibiotics with good intracellular penetration and proven clinical efficiency.1 Generally, Brucella species are considered susceptible to the WHO recommended antibiotics through sporadic cases of antimicrobial resistance occur.2,3 Sensitivity testing is infrequently performed due to concerns over laboratory-acquired infection and the need for containment level 3 facilities. However, in-vitro susceptibilities can vary across geographical regions.4,5 Furthermore, until recently invitro susceptibility testing of Brucella spp has not been standardised. Currently, the UK’s British Society of Antimicrobial Chemotherapy and the European Committee on Antimicrobial Susceptibility Testing have not published interpretative breakpoints for brucella antimicrobial sensitivities. As a consequence there are no antimicrobial susceptibility data for Brucella spp cultured from UK patients. We therefore report a prospective study of in-vitro sensitivities to commonly used anti-brucella antibiotic agents. Since 2011, Brucella spp referred to the Brucella Biohazard Facility, Animal Health and Veterinary Agency, for confirmatory identification have routinely undergone antimicrobial sensitivity testing to tetracycline (TET), rifampicin (RIF), ciprofloxacin (CIP), streptomycin (STREP) and gentamicin (GENT) by E-test methodology (Biomerieux, Sweden). The minimum inhibitory concentration (MIC) was interpreted as the value at which the inhibition zone intercepted the scale on the E-strip. MIC90 was defined as the lowest concentration of an antibiotic at which 90% of isolates were inhibited. Clinical Laboratory Standards Institute sensitivity breakpoints (mg/L) were employed for TET (<1), RIF (2) and STREP (8).6 For CIP and GENT, breakpoints were set at 2 based on previously published data.7,8 Seventeen Brucella melitensis isolates were examined. MIC90 values (mg/l) for TET, RIF, CIP, STREP and GENT were 0.064, 1.0, 0.25, 1.0 and 0.25 respectively. Tetracycline was found to be the most active agent followed by CIP/GENT and then RIF/STREP. No antimicrobial resistant strains were identified. Brucellosis is an uncommon infection in the UK and is typically acquired from countries where there is an endemic problem. This is the first UK study that has examined the antimicrobial sensitivity patterns of B. melitensis isolates cultured from UK patients. The WHO considers tetracycline and its derivatives to be one of the most effective antimicrobials against brucellosis. This study confirms that view and should provide reassurance to UK clinicians who manage this infection. Though no antimicrobial resistance in UK strains was identified, continued surveillance for the emergence of antimicrobial resistance in brucellosis is justified and is ongoing.
401
References 1. Corbel MJ. Brucellosis in humans and animals, 5. World Health Organisation in collaboration with the Food and Agriculture Organisation of the United Nations and the World Organisation for Animal Health; 2006. pp. 36e40 (WHO/CDS/EPR/2006.7). 2. Baykam N, Esener H, Ergonul O, Eren S, Celikbas AK, Dokuzoguz B. In vitro antimicrobial susceptibility of Brucella species. Int J Antimicrob Agents 2004;23:405e7. pez-Merino A, Contreras-Rodrıguez A, Migranas-Ortiz R, Or3. Lo ndez-Oliva GM, Gutie rrez-Rubio AT, rantia-Gradın R, Herna et al. Susceptibility of Mexican brucella isolates to moxifloxacin, ciprofloxacin and other antimicrobials used in the treatment of human brucellosis. Scand J Infect Dis 2004;36:636e8. 4. De Reutlin de la Roy YM, Grignon B, Grollier G, Coindreau MF, Becq-Giraudon B. Rifampicin resistance in a strain of Brucella melitensis after treatment with doxycycline and rifampicin. J Antimicrob Chemother 1986;18:648e9. 5. Kinsara A, Al-Mowalled A, Osoba AO. Increasing resistance of Brucellae to co-trimoxazole. Antimicrob Agents Chemother 1999;43:153. 6. Clinical and Laboratory Standards Institute. Performance for antimicrobial susceptibility testing, seventeenth informational supplement, 26. Wayne PA, USA: CLSI; 2007. pp. 1e182. CLSI document M100-517. 7. Falagas ME, Bliziotis IA. Quinolones for treatment of human brucellosis: critical review of the evidence from microbiological and clinical studies. Antimicrob Agents Chemother 2006; 50(1):22e33. 8. Roberts NL, Farrell ID, Hinchcliffe PM. The sensitivity of Brucella abortus to chemotherapeutic agents. J Med Microbiol 1973;6:549e57.
R.P.D. Cooke* Brucella Reference Unit, University Hospital Aintree, Liverpool, UK *Corresponding author. Tel.: þ44 0151 529 4916; fax: þ44 0151 529 4918. L. Perrett Brucella Biohazard Faculty, Animal Health and Veterinary Agency, Surrey, UK E-mail address: [email protected] Accepted 11 January 2014 ª 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jinf.2014.01.002
The rise and fall of mandatory surveillance for glycopeptide-resistant enterococcal bacteraemia in England
Dear Editor, We read with interest the report by Mikulska and colleagues revealing a heterogeneous but rising incidence
402 of enterococci as a cause of bacteraemia in haematooncology patients in Europe.1 Over the last three decades, enterococci have emerged as a leading cause of nosocomial infection in some immunocompromised patient groups, and currently rank as the 3rd commonest cause of healthcare-associated infections in Europe and the United States, and 5th in England.2e4 The vast majority are caused by two species (Enterococcus faecalis and Enterococcus faecium). Their success as nosocomial pathogens follows the worldwide spread of hospital-adapted lineages, which have acquired resistance to multiple antibiotics.5 Glycopeptide-resistant enterococci (GRE) were first isolated in the UK in 1986, and by the late 1990s were a cause for concern for several reasons. The rate of glycopeptide resistance rose sharply following its emergence and by 1998, 24% of E. faecium associated with bacteraemia were glycopeptide-resistant.6 At that time, there were no antimicrobial drugs with reliable activity to treat GRE E. faecium bacteraemia, which was associated with a higher crude and attributable mortality, longer hospital stay, and increased costs compared with bacteraemia caused by glycopeptide-susceptible enterococci (GSE).7 It was also feared that the mobile genetic elements encoding glycopeptide resistance would be readily transferred to Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). In 2002, the Chief Medical Officer formally identified GRE as a threat for UK hospitals and GRE bacteraemia reporting became mandatory for all acute NHS Trusts in England in September 2003.8 The process for GRE mandatory surveillance differed from concurrent systems for reporting MRSA bacteraemia and Clostridium difficile infections (CDI).8 Surveillance for MRSA and CDI is ‘enhanced’, and includes collection of risk factor and epidemiological data, the expression of infection rates based on hospital activity (100,000 bed days) to allow comparison between individual Trusts, and is linked to annual target setting for each Trust. By comparison, GRE surveillance was more limited and only collected the number (rather than rate) of GRE bacteraemias each year in 161 acute NHS Trusts in England.8 Despite recommendations made by the National GRE Bacteraemia Surveillance Working Group Report to the Department of Health in 2004 to collect additional data,9 surveillance did not become enhanced. Consequently, reports lacked information on rates, risk factors, hospital specialty of affected patients, and the distinction between the two main species of enterococci. A total of 6246 GRE bacteraemias were recorded in England between 2003 and 12 through the mandatory reporting mechanism.8 Incidence peaked in 2006e7 with 911 cases followed by a decrease to 541 in 2009e10 (a 40% reduction), but this decline has not been sustained and there were 651 cases in 2011e12. This pattern contrasts with the sustained and dramatic decrease in numbers of CDI and MRSA bacteraemia over the same period (Fig. 1).8 Infection prevention and control initiatives introduced over the last decade to reduce MRSA bacteraemia and CDI have included antimicrobial stewardship, intravascular catheter care bundles, improved hand hygiene and environmental cleaning. Understanding why these have not had a comparable impact on GRE bacteraemia rates over time is important for further initiatives to reduce rates
Letters to the Editor
Figure 1 Trends in glycopeptide-resistant enterococcus (GRE) bacteraemia (OcteSept), and methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and Clostridium difficile infections (CDI) in patients aged 2 years and over (AprileMarch), adapted from mandatory surveillance data reported by Public Health England.8
of preventable infection. Possible reasons include lack of screening for VRE carriage,9 and infection that arises from the patient’s pre-existing flora rather than as a result of acquisition through transmission in hospital. The marked decrease in MRSA bacteraemias in England means that in some acute NHS Trusts, the GRE bacteraemia rate is now higher than that for MRSA bacteraemias. Using the latest available data, the number of GRE bacteraemias (Oct 2011eSep 2012) was higher than MRSA bacteraemias (Apr 2012eMar 2013) in 35/161 (21.7%) acute NHS Trusts. It is unclear whether this percentage is stable or whether GRE will overtake MRSA in an increasing number of hospitals over time, since rates of GRE bacteraemia are very heterogeneous in different centres across England. For example, 124/161 (77%) acute NHS Trusts reported less than 5 cases in the period from Oct 2011eSep 2012, with 50/124 (40%) recording none. By contrast, from 2003 to 2012, just 15 (9.3%) Trusts accounted for 48% of the national total and reported on average more than 10 cases per year, with the five most-affected Trusts accounting for 28% of all cases. Such heterogeneity can be explained in part by a concentration of highly immunocompromised patients in specialist centres, but this is probably an oversimplification since there is also considerable variation in both the annual incidence and the trend in rates over time between the most-affected Trusts. Accurate comparisons between Trusts are hampered by lack of denominator data for the size and nature of at-risk populations, but the possibility of differences in local factors merits investigation. The increased mortality of GRE versus GSE bacteraemia observed in meta-analyses published in the early 2000s7 has not been replicated in newer studies,10 which may be related to improved study methodology and/or the introduction of antimicrobial drugs with greater activity against GRE; these include linezolid, quinupristinedalfopristin (active against E. faecium but not E. faecalis) and daptomycin (although no European breakpoints exist). However,
Letters to the Editor GRE bacteraemia remains associated with increased healthcare costs and longer length of stay compared with GSE.10 Furthermore, enterococcal bacteraemia as a whole is associated with increased mortality compared with no bacteraemia in high-risk group patients such as those receiving an allogeneic stem cell transplantation.11 The recognition that hospital-adapted GSE E. faecium can acquire glycopeptide resistance genes merits further investigation to understand the dynamics and spread of these organisms in the hospital environment.12 The discontinuation of mandatory surveillance for GRE bacteraemia was announced by Public Health England (PHE) in July 2013,8 following a recommendation of the Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infections (ARHAI). Many of the concerns that led to mandatory surveillance of GRE bacteraemia have been outdated by advancements in antimicrobial treatment or have proved unjustified, but a watching brief is required. PHE continue to collect data on GRE and GSE bacteraemia in England, Wales and Northern Ireland via LabBase2 through the voluntary surveillance scheme.8
Funding This work was supported by grants from the UKCRC Translational Infection Research (TIR) Initiative, and the Medical Research Council (Grant Number G1000803) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate; Public Health England; and the NIHR Cambridge Biomedical Research Centre.
Transparency declaration None of the authors have conflicts of interest to declare.
Acknowledgements The authors wish to thank Prof. Neil Woodford and Prof. Alan P. Johnson for reviewing the manuscript.
References 1. Mikulska M, Viscoli C, Orasch C, Livermore DM, Averbuch D, Cordonnier C, et al. Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. J Infect 2014;68:321e31. 2. Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, et al. NHSN annual update: antimicrobialresistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006e2007. Infect Control Hosp Epidemiol 2008;29:996e1011. 3. European Centre for Disease Prevention and Control. Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals 2011e2012. Stockholm: ECDC; 2013. Available at: http://
403
4.
5.
6.
7.
8.
9.
10.
11.
12.
www.ecdc.europa.eu/en/publications/Publications/ healthcare-associated-infections-antimicrobial-use-PPS.pdf [last accessed 22.11.13]. Health Protection Agency. English national point prevalence survey on healthcare-associated infections and antimicrobial use, 2011. London: Health Protection Agency; 2012. Available at: http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/ 1317134304594 [last accessed 22.11.13]. Lebreton F, van Schaik W, McGuire AM, Godfrey P, Griggs A, Mazumdar V, et al. Emergence of epidemic multidrugresistant Enterococcus faecium. MBio 2013;4. e00534e13. Reacher MH, Shah A, Livermore DM, Wale MC, Graham C, Johnson AP, et al. Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998: trend analysis. Br Med J 2000;320:213e6. Salgado CD, Farr BM. Outcomes associated with vancomycinresistant enterococci: a meta-analysis. Infect Control Hosp Epidemiol 2003;24:690e8. Public Health England. Mandatory and voluntary surveillance data. Available at: http://www.hpa.org.uk/ [last accessed 22.11.13]. Brown DFJ, Brown NM, Cookson BD, Duckworth G, Farrington M, French GL, et al. National glycopeptide-resistant enterococcal bacteraemia surveillance Working Group report to the Department of Health e August 2004. J Hosp Infect 2006;62(Suppl. 1):S1e27. http://dx.doi.org/10.1016/j.jhin.2005.04.011. Cheah ALY, Spelman T, Liew D, Peel T, Howden BP, Spelman D, et al. Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization. Clin Microbiol Infect 2013;19:E181e9. Vydra J, Shanley RM, George I, Ustun C, Smith AR, Weisdorf DJ, et al. Enterococcal bacteremia is associated with increased risk of mortality in recipients of allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2012;55:764e70. Howden BP, Holt KE, Lam MMC, Seemann T, Ballard S, Coombs GW, et al. Genomic insights to control the emergence of vancomycin-resistant enterococci. MBio 2013;4. e00412e13.
T. Gouliouris S.J. Peacock University of Cambridge, Department of Medicine, Box 157, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom Cambridge Public Health England Microbiology and Public Health Laboratory, Box 236, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, United Kingdom *Corresponding author. Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, United Kingdom. Tel.: þ44 01223 336867; fax: þ44 01223 336846. E-mail address: [email protected] (T. Gouliouris) Accepted 26 January 2014 ª 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jinf.2014.01.009