Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study

Kimberly G Blumenthal, Na Lu, Yuqing Zhang, Yu Li, Rochelle P Walensky, Hyon K Choi, Kimberly G Blumenthal, Na Lu, Yuqing Zhang, Yu Li, Rochelle P Walensky, Hyon K Choi

Abstract

Objective: To evaluate the relation between penicillin allergy and development of meticillin resistant Staphylococcus aureus (MRSA) and C difficile.

Design: Population based matched cohort study.

Setting: United Kingdom general practice (1995-2015).

Participants: 301 399 adults without previous MRSA or C difficile enrolled in the Health Improvement Network database: 64 141 had a penicillin allergy and 237 258 comparators matched on age, sex, and study entry time.

Main outcome measures: The primary outcome was risk of incident MRSA and C difficile. Secondary outcomes were use of β lactam antibiotics and β lactam alternative antibiotics.

Results: Among 64 141 adults with penicillin allergy and 237 258 matched comparators, 1365 developed MRSA (442 participants with penicillin allergy and 923 comparators) and 1688 developed C difficile (442 participants with penicillin allergy and 1246 comparators) during a mean 6.0 years of follow-up. Among patients with penicillin allergy the adjusted hazard ratio for MRSA was 1.69 (95% confidence interval 1.51 to 1.90) and for C difficile was 1.26 (1.12 to 1.40). The adjusted incidence rate ratios for antibiotic use among patients with penicillin allergy were 4.15 (95% confidence interval 4.12 to 4.17) for macrolides, 3.89 (3.66 to 4.12) for clindamycin, and 2.10 (2.08 to 2.13) for fluoroquinolones. Increased use of β lactam alternative antibiotics accounted for 55% of the increased risk of MRSA and 35% of the increased risk of C difficile.

Conclusions: Documented penicillin allergy was associated with an increased risk of MRSA and C difficile that was mediated by the increased use of β lactam alternative antibiotics. Systematically addressing penicillin allergies may be an important public health strategy to reduce the incidence of MRSA and C difficile among patients with a penicillin allergy label.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

References

    1. Zhou L, Dhopeshwarkar N, Blumenthal KG, et al. Drug allergies documented in electronic health records of a large healthcare system. Allergy 2016;71:1305-13. 10.1111/all.12881
    1. Shah NS, Ridgway JP, Pettit N, Fahrenbach J, Robicsek A. Documenting penicillin allergy: The impact of inconsistency. PLoS One 2016;11:e0150514. 10.1371/journal.pone.0150514
    1. van Dijk SM, Gardarsdottir H, Wassenberg MW, Oosterheert JJ, de Groot MC, Rockmann H. The high impact of penicillin allergy registration in hospitalized patients. J Allergy Clin Immunol Pract 2016;4:926-31. 10.1016/j.jaip.2016.03.009
    1. Gomes E, Cardoso MF, Praça F, Gomes L, Mariño E, Demoly P. Self-reported drug allergy in a general adult Portuguese population. Clin Exp Allergy 2004;34:1597-601. 10.1111/j.1365-2222.2004.02070.x
    1. Kerr JR. Penicillin allergy: a study of incidence as reported by patients. Br J Clin Pract 1994;48:5-7.
    1. Lee CE, Zembower TR, Fotis MA, et al. The incidence of antimicrobial allergies in hospitalized patients: implications regarding prescribing patterns and emerging bacterial resistance. Arch Intern Med 2000;160:2819-22. 10.1001/archinte.160.18.2819
    1. Picard M, Bégin P, Bouchard H, et al. Treatment of patients with a history of penicillin allergy in a large tertiary-care academic hospital. J Allergy Clin Immunol Pract 2013;1:252-7. 10.1016/j.jaip.2013.01.006
    1. Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: A cohort study. J Allergy Clin Immunol 2014;133:790-6. 10.1016/j.jaci.2013.09.021
    1. Pépin J, Saheb N, Coulombe MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41:1254-60. 10.1086/496986
    1. Baxter R, Ray GT, Fireman BH. Case-control study of antibiotic use and subsequent Clostridium difficile-associated diarrhea in hospitalized patients. Infect Control Hosp Epidemiol 2008;29:44-50. 10.1086/524320
    1. Palmore TN, Sohn S, Malak SF, Eagan J, Sepkowitz KA. Risk factors for acquisition of Clostridium difficile-associated diarrhea among outpatients at a cancer hospital. Infect Control Hosp Epidemiol 2005;26:680-4. 10.1086/502602
    1. LeBlanc L, Pépin J, Toulouse K, et al. Fluoroquinolones and risk for methicillin-resistant Staphylococcus aureus, Canada. Emerg Infect Dis 2006;12:1398-405. 10.3201/eid1209.060397
    1. Schneider-Lindner V, Delaney JA, Dial S, Dascal A, Suissa S. Antimicrobial drugs and community-acquired methicillin-resistant Staphylococcus aureus, United Kingdom. Emerg Infect Dis 2007;13:994-1000. 10.3201/eid1307.061561
    1. Sacco KA, Bates A, Brigham TJ, Imam JS, Burton MC. Clinical outcomes following inpatient penicillin allergy testing: A systematic review and meta-analysis. Allergy 2017;72:1288-96. 10.1111/all.13168
    1. Solensky R, Khan D, Joint Task Force on Practice Parameters. American Academy of Allergy, Asthma and Immunology. American College of Allergy, Asthma and Immunology. Joint Council of Allergy, Asthma and Immunology Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol 2010;105:259-73. 10.1016/j.anai.2010.08.002
    1. Blanca M, Torres MJ, García JJ, et al. Natural evolution of skin test sensitivity in patients allergic to beta-lactam antibiotics. J Allergy Clin Immunol 1999;103:918-24. 10.1016/S0091-6749(99)70439-2
    1. Simon C. Overview of the GP contract. InnovAit 2008;1:134-9. 10.1093/innovait/inn010.
    1. Chisholm J. The Read clinical classification. BMJ 1990;300:1092. 10.1136/bmj.300.6732.1092
    1. Jick H, Jick SS, Derby LE. Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. BMJ 1991;302:766-8. 10.1136/bmj.302.6779.766
    1. Jick SS, Kaye JA, Vasilakis-Scaramozza C, et al. Validity of the general practice research database. Pharmacotherapy 2003;23:686-9. 10.1592/phco.23.5.686.32205
    1. Cohet C, Haguinet F, Dos Santos G, et al. Effect of the adjuvanted (AS03) A/H1N1 2009 pandemic influenza vaccine on the risk of rejection in solid organ transplant recipients in England: a self-controlled case series. BMJ Open 2016;6:e009264. 10.1136/bmjopen-2015-009264
    1. Schneider-Lindner V, Quach C, Hanley JA, Suissa S. Antibacterial drugs and the risk of community-associated methicillin-resistant Staphylococcus aureus in children. Arch Pediatr Adolesc Med 2011;165:1107-14. 10.1001/archpediatrics.2011.143
    1. Delaney JA, Schneider-Lindner V, Brassard P, Suissa S. Mortality after infection with methicillin-resistant Staphylococcus aureus (MRSA) diagnosed in the community. BMC Med 2008;6:2. 10.1186/1741-7015-6-2
    1. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 2005;294:2989-95. 10.1001/jama.294.23.2989
    1. Khan NF, Perera R, Harper S, Rose PW. Adaptation and validation of the Charlson Index for Read/OXMIS coded databases. BMC Fam Pract 2010;11:1. 10.1186/1471-2296-11-1
    1. Lange T, Vansteelandt S, Bekaert M. A simple unified approach for estimating natural direct and indirect effects. Am J Epidemiol 2012;176:190-5. 10.1093/aje/kwr525
    1. Rubin DB. Multiple imputation for nonresponse in surveys. John Wiley & Sons, 1987. 10.1002/9780470316696.
    1. Cluzet VC, Gerber JS, Nachamkin I, et al. CDC PREVENTION EPICENTERS PROGRAM Factors associated with persistent colonisation with methicillin-resistant Staphylococcus aureus . Epidemiol Infect 2017;145:1409-17. 10.1017/S0950268817000012
    1. Graffunder EM, Venezia RA. Risk factors associated with nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection including previous use of antimicrobials. J Antimicrob Chemother 2002;49:999-1005. 10.1093/jac/dkf009
    1. Hill DA, Herford T, Parratt D. Antibiotic usage and methicillin-resistant Staphylococcus aureus: an analysis of causality. J Antimicrob Chemother 1998;42:676-7. 10.1093/jac/42.5.676
    1. Høiby N, Jarløv JO, Kemp M, et al. Excretion of ciprofloxacin in sweat and multiresistant Staphylococcus epidermidis . Lancet 1997;349:167-9. 10.1016/S0140-6736(96)09229-X
    1. Urgent Threats (online). United States Centers for Disease Control and Prevention, 2017. . Accessed 27/2, 2018.
    1. Khanafer N, Vanhems P, Barbut F, Luxemburger C, CDI01 Study group Factors associated with Clostridium difficile infection: A nested case-control study in a three year prospective cohort. Anaerobe 2017;44:117-23. 10.1016/j.anaerobe.2017.03.003
    1. Garey KW, Dao-Tran TK, Jiang ZD, Price MP, Gentry LO, Dupont HL. A clinical risk index for Clostridium difficile infection in hospitalised patients receiving broad-spectrum antibiotics. J Hosp Infect 2008;70:142-7. 10.1016/j.jhin.2008.06.026
    1. Cohen SH, Gerding DN, Johnson S, et al. Society for Healthcare Epidemiology of America. Infectious Diseases Society of America Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431-55. 10.1086/651706
    1. Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis 2001;1:101-14. 10.1016/S1473-3099(01)00066-4
    1. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:825-34. 10.1056/NEJMoa1408913
    1. Barlam TF, Cosgrove SE, Abbo LM, et al. Executive Summary: Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62:1197-202. 10.1093/cid/ciw217
    1. Global action plan on antimicrobial resistance (online). World Health Organization, 2015. . Accessed 27/2, 2018.
    1. Blumenthal KG, Wickner PG, Hurwitz S, et al. Tackling inpatient penicillin allergies: Assessing tools for antimicrobial stewardship. J Allergy Clin Immunol 2017;140:154-161.e6. 10.1016/j.jaci.2017.02.005
    1. NQF launches antibiotic stewardship initiative. National Quality Forum, 2015. . Accessed 27/2, 2018.
    1. Penicillin Allergy in Antibiotic Resistance Workgroup Asthma & Immunology. Penicillin allergy testing should be performed routinely in patients with self-reported penicillin allergy. J Allergy Clin Immunol Pract 2017;5:333-4. 10.1016/j.jaip.2016.12.010
    1. Blumenthal KG, Li Y, Banerji A, Yun B, Long AA, Walensky RP. The cost of penicillin allergy evaluation. J Allergy Clin Immunol Pract 2018;6:1019-1027.e2.
    1. Khan NF, Harrison SE, Rose PW. Validity of diagnostic coding within the General Practice Research Database: a systematic review. Br J Gen Pract 2010;60:e128-36. 10.3399/bjgp10X483562
    1. Freedberg DE, Lamousé-Smith ES, Lightdale JR, Jin Z, Yang YX, Abrams JA. Use of acid suppression medication is associated with risk for C. difficile infection in infants and children: A population-based study. Clin Infect Dis 2015;61:912-7. 10.1093/cid/civ432
    1. Davis KA, Stewart JJ, Crouch HK, Florez CE, Hospenthal DR. Methicillin-resistant Staphylococcus aureus (MRSA) nares colonization at hospital admission and its effect on subsequent MRSA infection. Clin Infect Dis 2004;39:776-82. 10.1086/422997
    1. National action plan for combating antibiotic-resistant bacteria. House TW, 2015. . Accessed 27/2, 2018.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren