420
Letters to the Editor / American Journal of Infection Control 43 (2015) 418-21
guidelines for the management of community urinary tract infections advocating trimethoprim or nitrofurantoin,5 it is essential that iterative updates of these policies make reference to the prevailing resistance epidemiology. This must be tempered by the potential for routinely collected microbiology data to overstate resistance.6 First, where resistance prevalence is driving a need for alternative antimicrobial agents for policy inclusion, few options exist; we agree with Solozano et al1 that fosfomycin is a viable alternative, but we also suggest pivmecillinam may be plausible and we found (in a subset of uropathogens tested; that is, those demonstrating resistance to > 4 first-line agents or confirmed extended spectrum b-lactamase production) susceptibility to be 86% in the community (n ¼ 1,779) and 81% in secondary care (n ¼ 2,235). Second, in terms of use of such resistance data as a proxy indicator for antimicrobial stewardship, although comparison of our data to those from Sorlozano et al1 may be confounded by variations in laboratory practice and breakpoints, general intercohort and interyear trends in excess resistance are observed. This provides a foundation for wider analysis of the effect of changes to antimicrobial consumption across international boundaries and over time, potentially also with linkage of resistance data to pharmacy-derived antimicrobial consumption data. Finally, we suggest that perhaps even more fine resolution is needed in these analyses, particularly in secondary care where high levels of antimicrobial resistance with rapid change may exist in specific cohorts (such as critical care).7 This would enable aggregated data to be directed back to frontline clinical staff using innovative ways to display resistance prevalence, such as creation of all-pathogen antibiograms, combined with the potential for integration into decision support systems, which may provide a useful mechanism to help shape empiric antimicrobial choice.
References 1. Sorlozano A, Jimenez-Pacheco A, de Dios Luna Del Castillo J, Sampedro A, Martinez-Brocal A, Miranda-Casas C, et al. Evolution of the resistance to antibiotics of bacteria involved in urinary tract infections: a 7-year surveillance study. Am J Infect Control 2014;42:1033-8. 2. European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2012. Annual report o the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm, Sweden: European Centre for Disease Prevention and Control; 2013. 3. UK Standards for Microbiology Investigations. Investigation of Urine. B41 Issue 7.1. London, England: Public Health England; 2012. 4. British Society of Antimicrobial Chemotherapy. BSAC Methods for Antimicrobial Susceptibility Testing Version 12. Birmingham, England: British Society of Antimicrobial Chemotherapy; 2013. 5. British Infection Association. Management of Infection Guidance for Primary Care for Consultation and Local Adaptation. London, England: Health Protection Agency. Available from: https://www.gov.uk/government/publications/urinarytract-infection-diagnosis; 2010. Accessed November 11, 2014. 6. Smellie W, Clark G, McNulty C. Inequalities of primary care microbiology testing between hospital catchment areas. J Clin Pathol 2003;56: 933-6. 7. Moore LS, Freeman R, Gilchrist MJ, Gharbi M, Brannigan ET, Donaldson H, et al. Homogeneity of antimicrobial policy, yet heterogeneity of antimicrobial resistance: antimicrobial non-susceptibility among 108 717 clinical isolates from primary, secondary and tertiary care patients in London. J Antimicrob Chemother 2014;69:3409-22. Conflicts of interest: PJ has nothing to declare. LM has consulted for bioMérieux, and is in receipt of grant funding from the National Institute of Health Research Imperial Biomedical Research Centre to investigate facets of antimicrobial resistance, and is affiliated with the Centre for Infection Prevention and Management (funded by the UK Clinical Research Collaboration, grant No. G0800777) and the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College London in partnership with Public Health England. HD has received a speaker’s honorarium from Astellas.
Paul Jones, MSc, BSc Department of Microbiology, Imperial College Healthcare NHS Trust London, United Kingdom
Luke S.P. Moore, FRCPath, MRCP, MPH, MSc, MBChB Department of Microbiology, Imperial College Healthcare NHS Trust London, United Kingdom National Centre for Infection Prevention and Management Imperial College London, London, United Kingdom Hugo Donaldson, FRCPath, MRCP, MBChB* Department of Microbiology, Imperial College Healthcare NHS Trust London, United Kingdom * Address correspondence to Hugo Donaldson, FRCPath, MRCP, MBChB, Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Rd, London W6 8RF United Kingdom. E-mail address: [email protected] (H. Donaldson).
http://dx.doi.org/10.1016/j.ajic.2014.11.028
Risk of zoster in patients on immunosuppressant therapy: Evaluation of current data To the Editor: In the recent years, an increasing use of immunosuppressant drugs, such as biologic drugs, has been noted. Patients who have chronically used these drugs frequently experience severe or complicated primary varicella (also if previously immune) and herpes zoster because of the decline of cellular immunity.1 Furthermore, the clinical presentation of these cases could be very serious. In 2012, Ratchford et al reported a patient with fingolimod-related varicella encephalitis and vasculopathy.2 In 2013, a case of acute encephalomyelitis associated with the reactivation of varicella zoster virus (VZV) was found in a 61year-old woman receiving abatacept therapy for rheumatoid arthritis.3 For the prevention of varicella, some Italian regions, such as Apulia, offer a live attenuated vaccine to all newly born babies, susceptible adolescents, and people at risk. Some studies suggest that the reduction of the circulation of VZV because of universal mass vaccination could increase the incidence of zoster4; then, Apulian immunocompromised patients could be considered at a higher risk of zoster. To evaluate the risk of herpes zoster in patients who received immunosuppressant drugs, we analyzed data available in the Apulian Health Regional Data Warehouse (archive of hospitalization discharge and drug prescription) for 2009-2010. From the regional archive of drugs prescriptions, a cohort of patients who reported 2 prescription drugs of the L04 ATC (Anatomical Therapeutic Chemical) class (immunosuppressants) were selected. Each patient of this group was checked for the use of drugs of JO5 ATC class (antivirals for systemic use) specifically related to herpes zoster (in this case the prescription must report the Italian Drug Authority note no. 84) or for hospitalization because of varicella (first diagnosis: 052 ICD-9-CM code) or herpes zoster (first diagnosis: 053 ICD-9-CM code). The number of Apulian people who reported 2 drug prescriptions of the L04 ATC class was 10.654 in 2009 and 10.562 in 2010. Of these, 398 (3.7%) in 2009 and 375 (3.5%) in 2010 reported the use of antivirals for herpes zoster. Both in 2009 and 2010, 41 (0.38%) people were hospitalized for a diagnosis of varicella or herpes zoster. Then, 3.9% of people
Letters to the Editor / American Journal of Infection Control 43 (2015) 418-21
who used immunosuppressant drugs experienced an infection related to VZV, and 6.9% of them required hospitalization for the disease. Our data show a higher risk of herpes zoster in patients who took immunosuppressants compared with the general population (3-5/1,000 person years). These patients experienced a risk of hospitalization for herpes zoster of 6.9%, which is double the risk for the general population, which accounted for 3%.5 The prevention of the risk of VZV infection and reactivation is quite concerning among these patients. In general, live vaccines are contraindicated in immunocompromised patients because they might be at an increased risk of an adverse reaction owing to uninhibited bacterial or viral replication.6-9 Recent studies, carried out among hematopoietic stem cell transplantation recipients, have shown that live attenuated varicella vaccines appeared generally safe and effective in this population. A review published in 2011 stated that good evidence already supported the administration of the varicella vaccine to healthy susceptible family contacts of children with malignancy, but not to patients themselves.9 Since 2002, a vaccine against herpes zoster has been available, and it has been recommended for people aged >50 years; the safety and effectiveness of herpes zoster vaccination in immunocompromised persons has been assessed only in a few small postlicensure studies. The vaccine has been demonstrated to be generally safe and immunogenic in groups of selected individuals with immunocompromised conditions.9 The use of immunosuppressant drugs for rheumatic, bowel inflammatory or neurologic diseases has increased, and the immunization strategy has changed the epidemiology both of varicella (with an expected increase in the median age of infection) and herpes zoster (with an expected increase in incidence). Then, the risk of VZV infection or reactivation in adults who use immunosuppressant drugs will represent a serious concern. Further data are urgently needed to inform the choice of vaccination against VZV and herpes zoster in immunocompromised patients.
421
References 1. O’Connor MB, Phelan MJ. Herpes zoster infection, vaccination and immunocompromised rheumatology patients. Rheumatol Int 2013;33:239-40. 2. Ratchford JN, Costello K, Reich DS, Calabresi PA. Varicella-zoster virus encephalitis and vasculopathy in a patient treated with fingolimod. Neurology 2013;81: 306. 3. Nakajima H, Takayama A, Ito T, Yoshikawa T. Acute encephalomyelitis with multiple herpes viral reactivations during abatacept therapy. BMJ Case Rep 2013; 2013. pii: bcr2013009731. 4. Brisson M, Melkonyan G, Drolet M, De Serres G, Thibeault R, De Wals P. Modeling the impact of one- and two-dose varicella vaccination on the epidemiology of varicella and zoster. Vaccine 2010;28:3385-97. 5. Harpaz R, Ortega-Sanchez IR, Seward JF, Advisory Committee on ImmunizationPractices (ACIP); Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57:1-30. quiz CE2-4. 6. Davis LE, Bodian D, Price D, Butler IJ, Vickers JH. Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child. N Engl J Med 1977; 297:241-5. 7. Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke DS. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med 1987;316:673-6. 8. Centers for Disease Control and Prevention (CDC). Measles pneumonitis following measles-mumps-rubella vaccination of a patient with HIV infection. MMWR Morb Mortal Wkly Rep 1996;45:603-6. 9. Fisher JP, Bate J, Hambleton S. Preventing varicella in children with malignancies: what is the evidence? Curr Opin Infect Dis 2011;24:203-11. Conflicts of interest: None to report.
Silvio S.T. Tafuri, MD, PhD* Maria M.C. Chironna, PhD Michele M.Q. Quarto, MD Cinzia C.G. Germinario, MD Department of Biomedical Science and Human Oncology Aldo Moro University of Bari, Bari, Italy * Address correspondence to Silvio Tafuri, MD, PhD, Department of Biomedical Science and Human Oncology, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy. E-mail address: [email protected] (S.S.T. Tafuri). http://dx.doi.org/10.1016/j.ajic.2015.01.003
Letters to the Editor / American Journal of Infection Control 43 (2015) 418-21
guidelines for the management of community urinary tract infections advocating trimethoprim or nitrofurantoin,5 it is essential that iterative updates of these policies make reference to the prevailing resistance epidemiology. This must be tempered by the potential for routinely collected microbiology data to overstate resistance.6 First, where resistance prevalence is driving a need for alternative antimicrobial agents for policy inclusion, few options exist; we agree with Solozano et al1 that fosfomycin is a viable alternative, but we also suggest pivmecillinam may be plausible and we found (in a subset of uropathogens tested; that is, those demonstrating resistance to > 4 first-line agents or confirmed extended spectrum b-lactamase production) susceptibility to be 86% in the community (n ¼ 1,779) and 81% in secondary care (n ¼ 2,235). Second, in terms of use of such resistance data as a proxy indicator for antimicrobial stewardship, although comparison of our data to those from Sorlozano et al1 may be confounded by variations in laboratory practice and breakpoints, general intercohort and interyear trends in excess resistance are observed. This provides a foundation for wider analysis of the effect of changes to antimicrobial consumption across international boundaries and over time, potentially also with linkage of resistance data to pharmacy-derived antimicrobial consumption data. Finally, we suggest that perhaps even more fine resolution is needed in these analyses, particularly in secondary care where high levels of antimicrobial resistance with rapid change may exist in specific cohorts (such as critical care).7 This would enable aggregated data to be directed back to frontline clinical staff using innovative ways to display resistance prevalence, such as creation of all-pathogen antibiograms, combined with the potential for integration into decision support systems, which may provide a useful mechanism to help shape empiric antimicrobial choice.
References 1. Sorlozano A, Jimenez-Pacheco A, de Dios Luna Del Castillo J, Sampedro A, Martinez-Brocal A, Miranda-Casas C, et al. Evolution of the resistance to antibiotics of bacteria involved in urinary tract infections: a 7-year surveillance study. Am J Infect Control 2014;42:1033-8. 2. European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2012. Annual report o the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm, Sweden: European Centre for Disease Prevention and Control; 2013. 3. UK Standards for Microbiology Investigations. Investigation of Urine. B41 Issue 7.1. London, England: Public Health England; 2012. 4. British Society of Antimicrobial Chemotherapy. BSAC Methods for Antimicrobial Susceptibility Testing Version 12. Birmingham, England: British Society of Antimicrobial Chemotherapy; 2013. 5. British Infection Association. Management of Infection Guidance for Primary Care for Consultation and Local Adaptation. London, England: Health Protection Agency. Available from: https://www.gov.uk/government/publications/urinarytract-infection-diagnosis; 2010. Accessed November 11, 2014. 6. Smellie W, Clark G, McNulty C. Inequalities of primary care microbiology testing between hospital catchment areas. J Clin Pathol 2003;56: 933-6. 7. Moore LS, Freeman R, Gilchrist MJ, Gharbi M, Brannigan ET, Donaldson H, et al. Homogeneity of antimicrobial policy, yet heterogeneity of antimicrobial resistance: antimicrobial non-susceptibility among 108 717 clinical isolates from primary, secondary and tertiary care patients in London. J Antimicrob Chemother 2014;69:3409-22. Conflicts of interest: PJ has nothing to declare. LM has consulted for bioMérieux, and is in receipt of grant funding from the National Institute of Health Research Imperial Biomedical Research Centre to investigate facets of antimicrobial resistance, and is affiliated with the Centre for Infection Prevention and Management (funded by the UK Clinical Research Collaboration, grant No. G0800777) and the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College London in partnership with Public Health England. HD has received a speaker’s honorarium from Astellas.
Paul Jones, MSc, BSc Department of Microbiology, Imperial College Healthcare NHS Trust London, United Kingdom
Luke S.P. Moore, FRCPath, MRCP, MPH, MSc, MBChB Department of Microbiology, Imperial College Healthcare NHS Trust London, United Kingdom National Centre for Infection Prevention and Management Imperial College London, London, United Kingdom Hugo Donaldson, FRCPath, MRCP, MBChB* Department of Microbiology, Imperial College Healthcare NHS Trust London, United Kingdom * Address correspondence to Hugo Donaldson, FRCPath, MRCP, MBChB, Charing Cross Hospital, Imperial College Healthcare NHS Trust, Fulham Palace Rd, London W6 8RF United Kingdom. E-mail address: [email protected] (H. Donaldson).
http://dx.doi.org/10.1016/j.ajic.2014.11.028
Risk of zoster in patients on immunosuppressant therapy: Evaluation of current data To the Editor: In the recent years, an increasing use of immunosuppressant drugs, such as biologic drugs, has been noted. Patients who have chronically used these drugs frequently experience severe or complicated primary varicella (also if previously immune) and herpes zoster because of the decline of cellular immunity.1 Furthermore, the clinical presentation of these cases could be very serious. In 2012, Ratchford et al reported a patient with fingolimod-related varicella encephalitis and vasculopathy.2 In 2013, a case of acute encephalomyelitis associated with the reactivation of varicella zoster virus (VZV) was found in a 61year-old woman receiving abatacept therapy for rheumatoid arthritis.3 For the prevention of varicella, some Italian regions, such as Apulia, offer a live attenuated vaccine to all newly born babies, susceptible adolescents, and people at risk. Some studies suggest that the reduction of the circulation of VZV because of universal mass vaccination could increase the incidence of zoster4; then, Apulian immunocompromised patients could be considered at a higher risk of zoster. To evaluate the risk of herpes zoster in patients who received immunosuppressant drugs, we analyzed data available in the Apulian Health Regional Data Warehouse (archive of hospitalization discharge and drug prescription) for 2009-2010. From the regional archive of drugs prescriptions, a cohort of patients who reported 2 prescription drugs of the L04 ATC (Anatomical Therapeutic Chemical) class (immunosuppressants) were selected. Each patient of this group was checked for the use of drugs of JO5 ATC class (antivirals for systemic use) specifically related to herpes zoster (in this case the prescription must report the Italian Drug Authority note no. 84) or for hospitalization because of varicella (first diagnosis: 052 ICD-9-CM code) or herpes zoster (first diagnosis: 053 ICD-9-CM code). The number of Apulian people who reported 2 drug prescriptions of the L04 ATC class was 10.654 in 2009 and 10.562 in 2010. Of these, 398 (3.7%) in 2009 and 375 (3.5%) in 2010 reported the use of antivirals for herpes zoster. Both in 2009 and 2010, 41 (0.38%) people were hospitalized for a diagnosis of varicella or herpes zoster. Then, 3.9% of people
Letters to the Editor / American Journal of Infection Control 43 (2015) 418-21
who used immunosuppressant drugs experienced an infection related to VZV, and 6.9% of them required hospitalization for the disease. Our data show a higher risk of herpes zoster in patients who took immunosuppressants compared with the general population (3-5/1,000 person years). These patients experienced a risk of hospitalization for herpes zoster of 6.9%, which is double the risk for the general population, which accounted for 3%.5 The prevention of the risk of VZV infection and reactivation is quite concerning among these patients. In general, live vaccines are contraindicated in immunocompromised patients because they might be at an increased risk of an adverse reaction owing to uninhibited bacterial or viral replication.6-9 Recent studies, carried out among hematopoietic stem cell transplantation recipients, have shown that live attenuated varicella vaccines appeared generally safe and effective in this population. A review published in 2011 stated that good evidence already supported the administration of the varicella vaccine to healthy susceptible family contacts of children with malignancy, but not to patients themselves.9 Since 2002, a vaccine against herpes zoster has been available, and it has been recommended for people aged >50 years; the safety and effectiveness of herpes zoster vaccination in immunocompromised persons has been assessed only in a few small postlicensure studies. The vaccine has been demonstrated to be generally safe and immunogenic in groups of selected individuals with immunocompromised conditions.9 The use of immunosuppressant drugs for rheumatic, bowel inflammatory or neurologic diseases has increased, and the immunization strategy has changed the epidemiology both of varicella (with an expected increase in the median age of infection) and herpes zoster (with an expected increase in incidence). Then, the risk of VZV infection or reactivation in adults who use immunosuppressant drugs will represent a serious concern. Further data are urgently needed to inform the choice of vaccination against VZV and herpes zoster in immunocompromised patients.
421
References 1. O’Connor MB, Phelan MJ. Herpes zoster infection, vaccination and immunocompromised rheumatology patients. Rheumatol Int 2013;33:239-40. 2. Ratchford JN, Costello K, Reich DS, Calabresi PA. Varicella-zoster virus encephalitis and vasculopathy in a patient treated with fingolimod. Neurology 2013;81: 306. 3. Nakajima H, Takayama A, Ito T, Yoshikawa T. Acute encephalomyelitis with multiple herpes viral reactivations during abatacept therapy. BMJ Case Rep 2013; 2013. pii: bcr2013009731. 4. Brisson M, Melkonyan G, Drolet M, De Serres G, Thibeault R, De Wals P. Modeling the impact of one- and two-dose varicella vaccination on the epidemiology of varicella and zoster. Vaccine 2010;28:3385-97. 5. Harpaz R, Ortega-Sanchez IR, Seward JF, Advisory Committee on ImmunizationPractices (ACIP); Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008;57:1-30. quiz CE2-4. 6. Davis LE, Bodian D, Price D, Butler IJ, Vickers JH. Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child. N Engl J Med 1977; 297:241-5. 7. Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke DS. Disseminated vaccinia in a military recruit with human immunodeficiency virus (HIV) disease. N Engl J Med 1987;316:673-6. 8. Centers for Disease Control and Prevention (CDC). Measles pneumonitis following measles-mumps-rubella vaccination of a patient with HIV infection. MMWR Morb Mortal Wkly Rep 1996;45:603-6. 9. Fisher JP, Bate J, Hambleton S. Preventing varicella in children with malignancies: what is the evidence? Curr Opin Infect Dis 2011;24:203-11. Conflicts of interest: None to report.
Silvio S.T. Tafuri, MD, PhD* Maria M.C. Chironna, PhD Michele M.Q. Quarto, MD Cinzia C.G. Germinario, MD Department of Biomedical Science and Human Oncology Aldo Moro University of Bari, Bari, Italy * Address correspondence to Silvio Tafuri, MD, PhD, Department of Biomedical Science and Human Oncology, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy. E-mail address: [email protected] (S.S.T. Tafuri). http://dx.doi.org/10.1016/j.ajic.2015.01.003
