Butler, David F

Goldman, Jennifer L

Harte, Lory

Lee, Brian R

Newland, Jason G

Sandritter, Tracy

Suppes, Sarah

English

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Washington University School of MedicineDigital Commons@BeckerOpen Access Publications2018Variability of surgical prophylaxis in penicillin-allergic childrenDavid F. ButlerChildren’s Mercy Hospital, Kansas City, MissouriBrian R. LeeChildren’s Mercy Hospital, Kansas City, MissouriSarah SuppesChildren’s Mercy Hospital, Kansas City, MissouriTracy SandritterChildren’s Mercy Hospital, Kansas City, MissouriJason G. NewlandWashington University School of Medicine in St. LouisSee next page for additional authorsFollow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubsThis Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in OpenAccess Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact engeszer@wustl.edu.Recommended CitationButler, David F.; Lee, Brian R.; Suppes, Sarah; Sandritter, Tracy; Newland, Jason G.; Harte, Lory; and Goldman, Jennifer L.,,"Variability of surgical prophylaxis in penicillin-allergic children." Infection Control & Hospital Epidemiology.39,12. 1480-1483.(2018).https://digitalcommons.wustl.edu/open_access_pubs/7374AuthorsDavid F. Butler, Brian R. Lee, Sarah Suppes, Tracy Sandritter, Jason G. Newland, Lory Harte, and Jennifer L.GoldmanThis open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/open_access_pubs/7374Infection Control & Hospital Epidemiology (2018), 39, 1480–1483doi:10.1017/ice.2018.244Concise CommunicationVariability of surgical prophylaxis in penicillin-allergic childrenDavid F. Butler MD1,†, Brian R. Lee MPH, PhD1, Sarah Suppes PharmD2, Tracy Sandritter PharmD2,Jason G. Newland MD, M.Ed3, Lory Harte PharmD2 and Jennifer L. Goldman MD, MS11Department of Pediatrics, Children’s Mercy Hospital, Kansas City, Missouri, 2Department of Pharmacy, Children’s Mercy Hospital, Kansas City, Missouri and3Department of Pediatrics, Washington University School of Medicine, St Louis, MissouriAbstractWe retrospectively evaluated the effect of penicillin adverse drug reaction (ADR) labeling on surgical antibiotic prophylaxis. Cefazolin wasadministered in 86% of penicillin ADR-negative (− ) and 28% penicillin ADR-positive ( + ) cases. Broad-spectrum antibiotic use was morecommon in ADR( + ) cases and was more commonly associated with perioperative adverse drug events.(Received 21 March 2018; accepted 19 August 2018)Approximately 10% of patients have a documented penicillinallergy, although the incidence of a true allergic reaction is muchless frequent.1 A penicillin adverse drug reaction (ADR) label isassociated with the unnecessary use of broad-spectrum anti-biotics, prolonged hospitalization, increased prevalence ofmultidrug-resistant infections, and increased risk of death com-pared to those without a penicillin ADR label.2–4 ADRs may referto allergic reactions (eg, rash or anaphylaxis) or side effects (eg,diarrhea). Unfortunately, clinicians often fail to obtain a thoroughADR history or to clarify the type of reported reaction prior toprescribing medication.2,3Antibiotic prophylaxis is utilized routinely to reduce the risk ofsurgical site infections (SSIs) in high-risk pediatric procedures.5,6Cefazolin is the drug of choice for many procedures because it isbactericidal, rapidly infused/distributed, and covers skin patho-gens such as Staphylococcus aureus associated with SSIs.5,6 Whilestructurally similar to penicillin due to the β-lactam ring, differentside chains result in minimal cross reactivity. Only patients whoexperience an IgE-mediated response (eg, anaphylaxis) or a severecutaneous reaction (eg, Stevens-Johnson syndrome) to penicillinshould avoid future cephalosporins.5 The primary objective of ourstudy was to determine antibiotic prophylaxis selection inpediatric surgical patients with a documented penicillin ADR.Secondarily, we aimed to determine the antibiotic prophylaxismost commonly associated with perioperative adverse drugevents (ADEs).Materials and methodsPopulation and settingA retrospective study was performed extracting data from a surgicalbundle reliability report for the period from January 1, 2011, toDecember 31, 2013. The surgical bundle reliability report is gener-ated from the hospital electronic medical records as a part of anational quality improvement collaborative. All operating roomprocedures lasting >5 minutes are included in the report. For thisstudy, only patients who received at least 1 dose of an intraoperativeantibiotic were included. The data collected included age, race,gender, surgery month/year, surgical procedure, isolation status (ie,evidence of methicillin-resistant S. aureus (MRSA) carrier status),wound class (ie, clean, clean/contaminated, contaminated, dirty/infected), and antibiotic(s) administered during surgery. The Chil-dren’s Mercy Institutional Review Board approved this protocol.Penicillin ADR labelPenicillin ADR type was defined as allergy or hypersensitivity orside effect, and severity was defined as follows: mild, implicateddrug continued; moderate, implicated drug discontinued and/orADR treatment required; and severe, life-threatening or need forhospitalization. ADR type and severity data were available in theelectronic medical record (EMR) at the time of surgery. Thesedata are readily available to prescribers; however, attention to thisqualifier is user dependent and likely variable. Documentation ofpenicillin ADRs included any of the following antibiotics:amoxicillin, oxacillin, penicillin, amoxicillin-clavulanate, ampi-cillin, ampicillin-sulbactam, piperacillin-tazobactam. Patientswith a penicillin allergy or hypersensitivity but undocumentedseverity were included as ‘unknown’ severity. Patients with adocumented cephalosporin ADR were excluded.Potential perioperative adverse drug event (ADE)Potential perioperative ADEs were based on International Clas-sification of Diseases, Ninth Revision, Clinical ModificationCite this article: Butler DF et al. (2018). Variability of surgical prophylaxis inpenicillin-allergic children. Infection Control & Hospital Epidemiology 2018, 39, 1480–1483. doi: 10.1017/ice.2018.244Authors for correspondence: David F. Butler, MD, Division of Pediatric Critical CareMedicine, Department of Pediatrics, Seattle Children’s Hospital, University ofWashington School of Medicine, FA.2.112, 4800 Sand Point Way NE, Seattle WA 98105.E-mail: david.butler@seattlechildrens.org. Also, Jennifer Goldman MD, MS Divisionsof Pediatric Infectious Diseases & Clinical Pharmacology, Department of Pediatrics,Children’s Mercy Hospital, 2401 Gillham Rd, Kansas City, MO 64108. E-mail:jlgoldman@cmh.edu† Present affiliation: Division of Pediatric Critical Care, University of Washington,Seattle Children’s Hospital, Seattle, Washington.© 2018 by The Society for Healthcare Epidemiology of America. All rights reserved.(ICD-9-CM) diagnostic codes (Table 1). ADE codes were selectedfrom an extensive list of the National Expert Panel of the ICD-9-CM Adverse Event Classification, Utah/Missouri Patient SafetyConsortium and from codes used by our active hospital phar-macovigilance program to identify ADEs.7,8 Those codes con-sidered pertinent to antibiotic-associated ADEs were included.Patients who had an ADE-associated ICD-9 code or E-code ateither the point of discharge following the initial surgical proce-dure or during a subsequent hospitalization (if readmissionoccurred within 48 hours of the initial surgical procedure) wereconsidered to have potentially experienced a perioperative ADE.Data analysisThe association of penicillin ADR status with intraoperativeantibiotic selection and perioperative ADEs was determined usingcategorical analysis; the Fisher exact test was used to determinestatistical significance. A multivariable logit model was developedto determine the odds of receiving a drug other than cefazolin,adjusting for MRSA isolation and surgical wound class. All ana-lyses were completed using Stata version 14 software (StataCorp,College Station, TX).ResultsIn total, 17,741 operations with intraoperative AP were identified.We excluded 382 operations (2.2%) due to a documentedcephalosporin allergy. These patients were predominatelymale (56%) and white (69%), with a median age of 7.6 years(interquartile range [IQR], 2.3–13.4). Most wounds were classifiedas clean (66%) or clean-contaminated (28%). The most commonprocedures were closed reduction of the elbow with percutaneouspinning, removal of hardware, and laparoscopic-assisted gastro-stomy. A penicillin ADR label (allergy or hypersensitivity or sideeffect) was documented in 1,150 cases (6.6%). The prevalence ofcefazolin administration in ADR negative (− ) cases was sig-nificantly higher (86%) compared to ADR positive ( + ) allergy orhypersensitivity cases (28%; P < .001) or ADR( + ) side-effectcases (48%; P < .001). After adjusting for MRSA isolation andwound class, the odds of receiving an alternative agent comparedto ADR(− ) cases, was significantly higher in ADR( + ) allergy orhypersensitivity cases (25.4; 95% confidence interval [CI], 21.8–29.6) and ADR( + ) side-effect cases (6.4; 95% CI, 3.8–11.0).Penicillin ADR severity had no effect on the likelihood ofreceiving an alternative to cefazolin.Clindamycin was the most commonly prescribed alternativeantibiotic prophylaxis among ADR( + ) patients at 58.4%. Thiswas significantly higher compared to ADR(− ) patients (5.3%;P < .001). Penicillin ADR( + ) patients also received gentamicin(4% vs 0.1%; P < .001) and vancomycin more frequently (2.8% vs0.7%; P < .001) compared to ADR(− ) patients (Fig. 1).In total, 137 perioperative ADEs were identified, the mostcommon were skin eruption, documented in 59 cases (43%),allergic urticaria (N= 10; 7.3%), and drug dermatitis (N= 9;6.6%). When cefazolin was administered, there was no differencein the perioperative ADE rate between penicillin ADR( + ) allergyor hypersensitivity and ADR(− ) patients (1.04% vs 0.75%,respectively; P= 0.485). Overall, vancomycin was the antibioticmost commonly associated with a perioperative ADE, occurringin 3.3% of all cases. Penicillin ADR( + ) patients experiencedperioperative ADEs to vancomycin (9.7%), noncefazolin cepha-losporins (5.1%), and clindamycin (0.77%).DiscussionSurgical antibiotic prophylaxis results in significant antibioticexposure among children.6,9 Despite evidence that cefazolin issafe to use in children with a non–life-threatening penicillin ADRhistory, many clinicians remain reluctant. Ideally, cefazolin wouldbe selected when indicated because it is narrow-spectrum andwell tolerated and has been extensively studied. Our resultsdemonstrate that prescribers avoid cefazolin in children labeledwith a penicillin ADR, regardless of the severity of the reaction.Additionally, alternative antibiotics such as vancomycin wereassociated with higher rates of perioperative ADRs compared tocefazolin.In this study, penicillin ADR( + ) patients received an alter-native agent instead of cefazolin in 72% of cases. This is consistentwith Beltran et al9 who reported that ADR( + ) children receivedcefazolin in only 20% of cases. We observed that penicillin ADRclassification and severity did not influence antibiotic choice,suggesting that providers are not relying on ADR history to guideantibiotic selection. Clindamycin was the most common cefazolinalternative selected. Unfortunately, clindamycin has limitationsdue to rising resistance, making it potentially ineffective againstmethicillin-susceptible S. aureus for which cefazolin would be100% effective.10Only 1% of penicillin ADR( + ) patients who received cefazolinexperienced a perioperative ADE, which is consistent with pre-vious findings.9 Our data reveal that perioperative ADEs occurredTable 1. International Classification of Diseases, Ninth Revision, Clinical Mod-ification (ICD-9-CM) Codes Used to Identify Perioperative Adverse Drug EffectsICD-9-CM Description283.9 Acquired hemolytic anemia288.03 Drug induced neutropenia693.0 Drug dermatitis695.1 Erythema multiforme708.0 Allergic urticaria708.9 Urticaria nosa782.1 Nonspecific skin eruption995 Other anaphylactic reaction995.1 Angioneurotic edema995.2 Unspecified adverse effect of unspecified drug, medicinaland biological substance995.27 Other drug allergy995.3 Allergy, unspecifiede94.60 Local anti-infectives and anti-inflammatory drugs causingadverse effects in therapeutic use960–961,E856–857Poisoning by antibiotics and other anti-infectivesE930–E931 Adverse effects of antibiotics and other anti-infectivesaNot otherwise specified.Infection Control & Hospital Epidemiology 1481more frequently in ADR( + ) patients who received vancomycinor alternative cephalosporins. Thus, data also highlight the find-ing that cefazolin alternatives are associated with a potentialincreased risk for perioperative ADEs.Our study has several limitations. The findings are limited to asingle pediatric institution and therefore may not be generalizable.This study was retrospective in nature, and perioperative ADEswere documented based on ICD-9-CM and E codes. Conversely,ICD-9-CM and E codes have proven effective in identifying ADEsin hospitalized patients, including surgical patients.11,12 Theselected codes were likely not all-inclusive for antibiotic-associatedADEs and could have resulted in an underrepresentation ofADEs. Attributing a perioperative ADE specifically to an anti-biotic is difficult without subsequent drug rechallenge or skintesting. Most of the documented penicillin ADRs were unknownin severity, which made it challenging to determine whethercefazolin would be indicated using ADR label alone. Notably, areview of the surgical procedures included in our study’s patientpopulation revealed that many do not routinely require antibioticprophylaxis (ie, circumcision, tympanoplasty). This findinghighlights the lack of standardization for routine antibiotic pro-phylaxis and demonstrates that additional work is needed to limitantibiotic exposure and ADE risk for procedures without pro-phylaxis indications. Regardless, our data strongly indicate thatperioperative antibiotic prescribing is highly variable amongchildren with a documented penicillin ADR. Further research isneeded to optimize clarification and interpretation of an ADRhistory to safely standardize care, to provide the antibiotic ofchoice when possible, and to utilize a safe alternative when trulyneeded.In conclusion, our study demonstrates that surgical AP variessignificantly in children with documented penicillin ADRsresulting in the unnecessary use of alternative antibiotics thatresult in higher rates of perioperative ADEs. Further work isneeded to standardize AP selection in those labeled penicillinallergic and minimize the avoidance of cefazolin in cases when itcan be safely administered.Acknowledgments.Financial support. All authors report no financial support relevant to thisarticle to disclose.Conflicts of interest. All authors report no conflicts of relevant to this articleto disclose.References1. Kerr JR. Penicillin allergy: a study of incidence as reported by patients.Brit J Clin Pract 1994;48:5–7.2. Attia MS, Stringer MD, McClean P, Prasad KR. The reduced left lateralsegment in pediatric liver transplantation: an alternative to themonosegment graft. Pediatr Transplant 2008;12:696–700.3. MacLaughlin EJ, Saseen JJ, Malone DC. Costs of beta-lactam allergies:selection and costs of antibiotics for patients with a reported beta-lactamallergy. Arch Fam Med 2000;9:722–726.4. Alsultan A, Peloquin CA. Therapeutic drug monitoring in the treatmentof tuberculosis: an update. Drugs 2014;74:839–854.5. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelinesfor antimicrobial prophylaxis in surgery. Am J Health Syst Pharm2013;70:195–283.6. Sandora TJ, Fung M, Melvin P, Graham DA, Rangel SJ. Nationalvariability and appropriateness of surgical antibiotic prophylaxis in USchildren’s hospitals. JAMA Pediatr 2016;170:570–576.7. National Expert Panel of the ICD-9-CM Adverse Event Classification,Utah/Missouri Patient Safety Consortium. The ICD-9-CM adverse eventclassification. Utah Department of Health website. health.utah.gov/psi/icd9.htm. Accessed June 25, 2018.8. Goldman JL, Sandritter TL, Sullins A, Leeder JS, Lowry JA. Pediatricpharmacovigilance: enhancing adverse drug reaction reporting in atertiary care children’s hospital. Ther Innov Regulat Sci 2013;47:566–571.Fig. 1. Antibiotic prophylaxis exposure based on penicillin allergy classification and associated perioperative adverse drug reactions (ADR).1482 David F. Butler et al9. Beltran RJ, Kako H, Chovanec T, Ramesh A, Bissonnette B, Tobias JD.Penicillin allergy and surgical prophylaxis: cephalosporin cross-reactivityrisk in a pediatric tertiary care center. J Pediatr Surg 2015;50:856–859.10. Albertson TE, Chenoweth JA, Colby DK, Sutter ME. The changingdrug culture: use and misuse of appearance- and performance-enhancing drugs. FP Essent 2016;441:30–43.11. Hougland P, Nebeker J, Pickard S, et al. Using ICD-9-CM codes inhospital claims data to detect adverse events in patient safetysurveillance. In: Henriksen K, Battles JB, Keyes MA, et al., editors.Advances in Patient Safety: New Directions and Alternative Approaches,Vol. 1: Assessment. Rockville, MD: Agency for Healthcare Research andQuality; 2008.12. Hougland P, Xu W, Pickard S, Masheter C, Williams SD. Performance ofInternational Classification of Diseases, 9th Revision, Clinical Modificationcodes as an adverse drug event surveillance system. Med Care2006;44:629–636.Infection Control & Hospital Epidemiology 1483

Variability of surgical prophylaxis in penicillin-allergic children

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Variability of surgical prophylaxis in penicillin-allergic children

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