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Drug Allergy: Focus on Antibiotics

Jonathan Grey, Pharm.D.Clinical Coordinator/Antibiotic Stewardship Specialist

Morton Plant Mease HealthcareApril 9th, 2016

Disclosure Information I have no actual or potential conflict of interest in relation to this presentation

Objectives By the end of this presentation, you should be able to:

Classify the different types of drug hypersensitivity and explain the various strategies for drug avoidance based on these classifications Describe the risk of cross sensitivity between the antibiotic classes, including the role of R1 side chains in determining β-lactam cross sensitivity Delineate between the different roles of antibiotic desensitization, direct/graded challenges, and antibiotic skin testing in response to a patient with a reported allergy Discuss the significance of some non- β-lactam drug allergies and their impact on patient care

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Predictable Drug Reactions Predictable

Dose dependent Related to pharmacologic action Occur in otherwise healthy individuals i.e. Dizziness with BP meds, hypoglycemia with insulin

Unpredictable Drug ReactionsDrug intolerance

• Undesirable effect• Low doses• Normal metabolism, excretion, bioavailability• i.e. ASA tinnitis

Drug idiosyncrasy• Abnormal, unexpected• Underlying abnormality of metabolism, excretion bioavailability• i.e. Dapsone hemolytic anemia

Drug allergy • Immune mediated• Drug specific antibodies, T cells, or both• i.e. penicillin rash

Pseudoallergy • Mimic anaphylaxis• No sensitization period, can occur with first dose• Not immune mediated• Occur due to direct release of mediators• i.e. Redman with vancomycin, Morphine histamine release

NEJM 2006;354:601-609

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Gell and Combs ClassificationType Classification Onset Clinical Features

I IgE mediated immediate Immediate: 30-60 minAccelerated: 1-72 hrs(T-cell mediated)

Urticaria (Hives)AngioedemaBronchospasmAnaphylaxis

II Cytotoxic 5-12h/>72h Hemolytic anemia, Neutropenia, ThrombocytopeniaIII Immune complex 3-8h/>72h Serum sickness

IV T-Cell mediated or delayed 24-48h/>72h Contact dermatitisMaculopapular/morbilliform rashInterstitial nephritisSJS, TEN

Other Unknown Variable DRESS, eosinophilic pneumonia, drug-induced lupusn

Treatment Alternatives for Allergies- Type II

Avoid the offending agent Cross sensitivity have been noted within the same class for some agents

Neutropenia with vancomycin and teicoplanin β-lactams

Cephalosporin cross sensitivity- related to R1 and R2 side chain similarity Carbapenems an option in patients with piperacillin/tazobactam induced hemolytic anemia?

Single case report of tolerance J Clin Pathol. 1987 Jun;40(6):700-1.J Allergy Clin Immunol Pract. 2015 May-Jun;3(3):452-3.

Treatment Alternatives for Allergies- Type III Possibly agent specific (i.e. cefaclor)

Alternate metabolism results in reactive intermediate compounds Limited data on cross sensitivity of other beta lactams If β-lactam used, use alternate class with different R1/R2 side chains

http://www.aaaai.org/ask-the-expert/reactivity-β-lactams.aspx

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Treatment Alternatives for Allergies- Type IV/Delayed Contact dermatitis

Avoid same beta lactam/antibiotic class Cephalosporin cross sensitivity with occupational contact dermatitis

SJS/TEN Never take any remotely similar antibiotic i.e. lifelong avoidance of all β-lactams

Dermatol Online J. 2011 May 15;17(5):13.

Treatment Alternatives for Allergies-Type IV/Delayed (continued) Maculopapular rash

May tolerate β-lactams with different side chains Aminopenicillins

Childhood rash after exposure often linked to viral syndrome True delayed type reactions can still occur

Can usually tolerate dissimilar cephalosporins, or even penicillin V

Treatment Alternatives for Allergies-Type IV/Delayed (continued) Interstitial nephritis

Only one documentd case of possible cross-reactivity Piperacillin/tazobactam and Meropenem

Reasonable to try a different Beta-lactam class with different side chains

J Antimicrob Chemother. 2007 Jul;60(1):107-11.

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Tolerability of Cefazolin after Non-IgE Hypersensitivity

Reactions to Nafcillin Blumenthal KG, et al. Antimicrob Agents Chemother. 2014 Jun;58(6):3137-43.

Observational study of 17 OPAT patients switched from nafcillin to cefazolin after non-IgE mediated allergies. Maculopapular rash (n=10), immune mediated nephritis (n=3), isolated eosinophilia (n=2), immune mediated hepatitis (n=1) 16/17 completed course without further reaction 3 patients with maculopapular rash were switched to alternate agent first (daptomycin or vancomycin)

Observational washout period Authors conclude that cefazolin is well tolerated in patients with non-Ige mediated hypersensitivity to nafcillin.

Question 1Ivy Drugabusa is a 26 yo female admitted to Morton Plant Hospital with persistent fever, cough, and malaise. PMH: hypothyroid SH: IVDA, “None in last year”. Ht: 63” Wt 55.5 kg VS: T 38.5, BP 105/60 HR 91 RR 16 BUN/SCR 14/0.9 WBC 15.9 Blood cultures reveal MSSA in 2/2 sets on admission, and again on repeat TEE: Positive for vegetation in tricuspid valve Patient was started on vancomycin in ER, and received this for two days until culture results returned. At thiat time they were switched to nafcillin and received this for several days. WBC normalized, and blood cultures are now negative. On day 7 of admission, patient’s SCr increases to 2.4. Increased eosinophils in serum and urine She is diagnosed by nephrology as having AIN

Question 1 Based on the risk of cross sensitivity of Non-IgEmediated reactions, which of the following is the best therapeutic plan?a) Change therapy to IV vancomycin, to complete a 6 week course.b) Change therapy to IV daptomycin, to complete a 6 week course.c) Continue IV nafcillin as it is the drug of choice. Refer to dialysis.d) Change therapy to IV cefazolin. Monitor carefully for persistent or worsening of renal function. Complete a 6 week course.

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Urticaria Anaphylaxis

IgE Type I Hypersensitivity Reactions

IgE Sensitivity Reaction

Cutaneous Reactions

Cutaneous drug eruptions of all types occur in 1-5% of population PCN compounds are the most common cause

Highest incidence with ampicillin/amoxicillin

Only small percentage are IgE mediated. urticaria versus morbilliform rash

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Urticaria versus Morbilliform RashUrticaria

IgE mediatedMorbilliform eruptions

T-cell mediated

DelayedImmediate

Anaphylaxis Acute systemic allergic reaction 1-4 episodes/10,000 admissions Affects multiple organs

Skin, Resp, GI, CV Symptoms

Urticaria Swelling Difficulty breathing Abdominal cramps Vomiting Diarrhea Circulatory collapse Coma and Death

Penicillin Allergy

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PCN Allergy: Statistics 9% of the US population report a history of penicillin “allergy” Penicillins among most commonly reported “allergies”

Narcotics 13.9 %, NSAIDS 7.7%, ACEIs 2.9%, radiocontrast 2.3%

Most commonly reported antibiotic allergy Sulfas 5.4%, cephalosporins 1.3%, macrolides 1.3%, tetracyclines 0.9%

Am J Med. 2009 Aug;122(8):778.e1-7.

PCN Allergy: correlation with skin testing results Number of patients with reported penicillin allergy and positive penicillin skin tests

Less than 5% Skin test positive patients have been declining steadily over time

Previously ≥ 10%

Perm J. 2009 Spring;13(2):12-8.

Risk Factors for IgE Mediated PCN Allergy

Age 20-49 Route: topical > IV > oral Frequency Multiple drug allergy syndrome Hereditary factors Asthma

Risk of sensitivity not greater, but reactions more severeSpecial Cases HIV infection Cystic Fibrosis

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What are the Penicillin Allergens?

β-lactam ring Antimicrobial metabolite/s Chemical side chain

β-lactam Antibiotics

NEJM 2006;354:601-609

75% of PCNallergic patients react to the Major determinant

Metabolites

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Reaction to Side Chain

More common in Southern Europe

Penicillin Skin Testing Preferred method for the evaluation of possible IgE mediated PCN allergy Performed in setting prepared to treat a possible allergic reaction. Test for PCN major and minor determinants Useful if want to use penicillin drug, but there is a questionable IgE mediated allergy Not useful in ruling out allergies to other β-lactam classes

Penicillin Skin Test ReagentsMajor determinant Penicilloyl-polylysine (Pre-Pen)

US: Up to 75% of PCN skin test + patients reactMinor determinants Penicillin G- Commercially available Penicilloate Penilloate Ampicillin/amoxicillin Pencilloyl-polylysine/Pen G skin testing

Amoxicillin 250 mg oral challenge if negative 0.2% of patients will react, and not to Pencilloyl-polylysine/Pen G

Safely identifies patients with penicillin allergies NPV > 95%

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Pencillin Skin Test Process at Morton Plant Mease

Inclusion Criteria Documented infection where PCN agent is drug of choice Histamine antagonits held for 24 hours Amenable skin surface (usually right and left forearms)

Exclusion Non IgE mediated reaction Adverse effect, not allergy Anaphylaxis in last four weeks Hemodynamic instability Age < 18

Current part of protocol, but not a true exclusion for PST Pregnancy

Current part of protocol, but PST is option in these patients if risk outweighs benefits

Pencillin Skin Test Process at Morton Plant Mease

It’s a TEAM effort!

Administration of Penicillin Skin Test Step 1: Scratch test

Place one drop of solution onto patient arm and use lancet to make shallow puncture Histamine: positive control Saline: negative control Pre-Pen®: major determinant Penicillin G: minor determinant

Wait 15 minutes and observe for wheal (> 5 mm) and erythema reaction

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Administration of Penicillin Skin Test

Step 2: Intradermal test Intradermally inject a small bleb of each component on opposite arm

Saline: negative control (one bleb) Pre-Pen®: major determinant (two blebs) Penicillin G: minor determinant (two blebs)

Observe for 15 minutes and then read skin testNegative test: sites produce no wheal or wheal is < 3 mm larger than saline control (or < 5 mm total)

Positive Test

Remove PCN Allergy From Profile

Document Negative Penicillin Skin Test

Penicillin skin testing at Morton Plant Measeo Protocol in place since end of 2014o 12 patients received PCN skin testing

11 negative skin test switched to a β-lactam antibiotics PCN allergy removed from their profiles

1 patient who was anergic and not able to proceed with intradermal test

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Question 2 Alma Mycins is an 86 year old female admitted to MeaseCountryside with altered mental status and dysuria. Allergies: Penicillin (swelling as child), Keflex (swelling), Ciprofloxacin (dizziness), SULFA (unknown), doxycycline (N/V), Vancomycin (unknown), ALL MYCINS PMH: overactive bladder, depression Medications: Ditropan, Sertraline UA: WBC TNTC, LE 3+ CBC, BMP: WNL Patient is admitted with complicated UTI Reflex Urine Cultures are positive for Vancomycin Resistant Enterococcus faecalis, sensitive to ampicillin Currently on IV daptomycin (which she is amazingly able to tolerate despite her ALL MYCINS allergy) She has improved after 3 days of therapy, and is no longer confused Physician is looking for an oral option to facilitate discharge

Question 2 The physician asks if penicillin skin testing is an option for Alma. Which of the following is correct?a. Penicillin skin testing is not an option for this patient since she has a history of reported IgE mediated reaction. It is not worth the risk of anaphylaxis.b. There is no need for penicillin skin testing. Proceed with a graded challenge of amoxicillin.c. Given her history, penicillin skin testing may be of value. If negative, may skip the oral challenge if treatment will begin with amoxicillind. This patient requires a full ampicillin desensitization. Immediately transfer to the ICU to begin the process.

Graded Challenge and

Desensitization

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Direct/Graded Challenge Appropriate when likelihood of being allergic is low

i.e. different β-lactam class with dissimilar side chains Does not desensitize patient Cautious way of administering drug Performed in setting prepared to treat a possible allergic reaction Does not require admission to ICU

Direct/Graded Challenge Dosing

1/100- 1/10 of the full dose Increase 10 fold every 30-60 min until full therapeutic dose is reached

Example with Ceftriaxone Ceftriaxone 1 mg over 15 minutes, observe 15 minutes Ceftriaxone 10 mg over 15 minutes, observe 15 minutes Ceftriaxone 889 mg over 30 minutes, observe for 30 minutes Breath sounds and VS at baseline, then q30 minutes throughout procedure and 30 minutes after the last infusion

May want to wait longer between oral challenge doses to allow for absorption Patients who tolerate a graded challenge prove that they are not allergic Nursing education

Desensitization Alters the immune response to the antibody and results in TEMPORARY tolerance Indication: known or strongly suspected IgE allergy and there are no acceptable alternatives Contraindication: Non-IgE mediated reactions such as SJS or TEN At MPM, performed in ICU

Patients need 1:1 nursing Protocols

Rapid versus Slow protocols Oral and intravenous protocols

*MUST be repeated with each exposure*

Do not give•Glucocorticoids•Antihistamines•Beta-Blockers

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Desensitizations at Morton Plant Mease

Established protocols for 12 different antibiotics Order sets created for each desensitization protocol with antibiotics and rescue medications For IV antibiotics, use continuous IV infusion, and double rate for each dose increase

Example-Ampicillin IV desensitization Step Ampicillin

(mg/mL)Flow rate

(mL/hour) Dose (mg) Cumulative dose (mg) Bag

1 0.04 6 0.06 0.06 2 mg / 50 mL NS2 0.04 12 0.12 0.18

3 0.04 24 0.24 0.424 0.4 5 0.50 0.92

400 mg / 100 mL NS

5 0.4 10 1 1.926 0.4 20 2 3.927 0.4 40 4 7.928 0.4 80 8 15.929 0.4 160 16 31.92

10 40 3 30 61.92

4,000 mg / 100 mL NS

11 40 6 60 121.9212 40 12 120 241.9213 40 25 250 491.9214 40 50 500 991.9215 40 100 1000 1991.9216 40 200 2000 3991.92

Question 3 Coughy McHackerson is a 58 year old male admitted with short of breath and fever for the last several days. A chest X-ray in the ER reveals bilateral infiltrates. He is diagnosed with community acquired pneumonia. Allergies: Penicillin (unknown reaction), Ciprofloxacin (hives), Shellfish The physician starts the patient on aztreonam 2 g q8h and azithromycin 500 mg daily.

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Question 3 Which of the following is true regarding treatment options for Mr. McHackerson?a. A graded challenge with ceftriaxone is a good option given the low rate of cross sensitivity between penicillin and dissimilar cephalosporins.b. A graded challenge with ceftriaxone requires an admission to the ICU, and may not be possible based on bed availability.c. Given the unknown reaction for penicillin, it is best to avoid cephalosporins at this time. Continue aztreonam.d. Penicillin “allergies” are rarely accurate. Initiate IV ampicillin/sulbactam.

Example-Ampicillin IV desensitization (order set)

In PCN allergy, can you safely administer structurally related

antibiotics?CephalosporinsCarbapenemsMonobactams

If PCN allergy = No β-lactams Significant Reduction in antibiotic options

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Cephalosporin AllergyCephalosporin allergy Reported in 1.3% of patients Anaphylaxis is rare

1:1000 to 1:1,000,000 Cross-reactivity related to R1 and R2 side chains

Can be cephalosporin allergic and not PCN allergic May be allergic to certain cephalosporins and still be able to tolerate others

J Allergy Clin Immunol 2015 Mar;135(3):745-52.e5.

CephalosporinPotential for Cross Reactivity Source of cross reactivity

R-group side chain shared by specific drugs β-lactam ring

Less important Metabolites/haptens– Unknown #

Cephalosporin skin testing is of limited value Negative predictive value uncertain Possibly could be considered for specific cephalosporins in emergency situations

2 mg/mL (0.005 M) However, could also just perform a desensitization in these cases

Clin Rev Allergy Immunol. 2014 Aug;47(1):46-55.

Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273.

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Cephalosporin Cross reactivity with Ampicillin/Amoxicillin

Amoxicillin AmpicillinCefadroxil (Duricef)Cefprozil (Cefzil)

Cefaclor (Ceclor)Cephalexin (Keflex)Cephradine (Velosef)Loracarbef (Lorabid)

Potential for Cephalosporin Cross-reactivity with Penicillins- BackgroundCross reactivity with PCN Older data suggested as high as 18% Incidence confounded by non-immunologic ADRs Up until 1985 the manufacturing process of PCN used a cephalosporin mold Current Product labeling

"Cross hypersensitivity among the β-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with penicillin allergy.“ Based on retrospective, open studies Lacked control group PCN allergy not confirmed by skin testing

Cephalosporin Cross Reactivity: LiteratureStudy Design Cross sensitivityDePestel, et al. 2008

• Metaanalysis of skin testing cross sensitivity studies, N=5420• 2.3%, mostly in 1st

generation cephalosporinsApter, et al. 2006 • Large retrospective cohort using UK General Practice Database

• N= 534,810• Determined “allergic type reaction” from diagnostic codes for possible type I reactions• Not confirmed by skin testing

• 43/3920 (1%) in patients with priorreaction to penicillin.0.1% in patients without prior reaction to penicillin (RR=10.0)• RR for SULFA reaction was similar (RR=7.2)

Park MA, et al. • Retrospective chart review. 85PCN skin test positive patients from 1991 to 2005.• 726 PCN skin test negative.

• 2/85 (2%) in PCNskin test positive patient (both with 1stgeneration cephalosporins).

• 0.1% in PCN skin test negative patients. (p=0.0304)

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Cephalosporin Cross Reactivity: Literature ContinuedStudy Design Cross sensitivityMacy E, et al. 2011 • Retrospective cohort.

• 54 PCN skin test positive patients with 169 courses of cephalosporins• 819 PCN skin test negative patients with 2485 courses of cephalosporins

• PCN skin test positive:• 1/169 (0.6%) courses of cephalosporins• 4/81 (4.9%) courses of SULFA

• PCN skin test negative: 29/2485 (1.2%) courses of cephalosporins.• Concluded patients with PCN allergy can safely receive cephalsporins.

Martinez TadeoJA, et al. 2015 • Series of 22 PCN skin test positive patients • All tested negative to cephalosporins with dissimilar side chains via skin testing/oral challenge(Cefuroxime, cefixime).• Concluded cephalosporins with dissimilar side chains to penicillins may be used safely in patient with penicillin allergy.

Cephalosporin Cross Reactivity: Literature ContinuedStudy Design Cross sensitivityMacy E, et al. 2015 • Large Retrospectivecohort.

• Total study population of 3,999,290 (1% of U.S)• 65,915 patients with penicillin allergy who received 127,125 courses of cephalosporins

• Physician documented cephalosporin associated anaphylaxis was 2.9-fold more likely in patients with history of penicillin allergy, but still very rare.• 0.0024% if history penicillin allergy vs. 0.00082% if no history of penicillin allergy

• Again concluded that patients with historyof PCN allergy may safely receive cephalosporins

Romano, et al. 2010 • 98 patients with IgEmediated reactions to cephalosporins• Underwent skin tests and serum IgEassays to other β-lactams

• Cross reactivity• PCN-25%, 3.1% aztreonam, 2% imipenem/cilastatin, 1% meropenem

• Critique-• IgE levels do not correlate with skin tests and oral challenge• Threshold for reaction with scratch test was only 3 mm instead of 5 mm

Cephalosporin Cross Reactivity: Summary

Rate of cross reactivity with PCN is only 1 to 2% This is comparable to other agents (i.e. SULFA)

Cross reactivity rates are highest in first generation cephalosporins with similar side chains to penicillins Even if patient does end up having cross reactivity, risk of anaphylaxis is very low (<1:10,000) In patient with a history of “penicillin allergy”, graded challenges with a cephalosporin with dissimilar side chains are unlikely to cause a serious adverse event

Remember, <5% of penicillin “allergies” can be confirmed by skin testing

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Carbapenems Potential for Cross Reactivity

Incidence of hypersensitivity 0.3-2.3% (rash, pruritus, urticaria)

Structural similarity Agents

Imipenem (Primaxin®) Meropenem (Merrem®) Ertapenem (Invanz®) Doripenem (Doribax®)

Ann Pharmacotherapy 2009;43:304

Why is this important? Carbapenems are broad spectrum, β-lactamase stable agents Often used for the treatment of infections caused by multi-drug resistant pathogens:

Extended Spectrum β-lactamase producing organisms (ESBLs) Acinetobacter species Pseudomonas aeruginosa

Carbapenems Potential for Cross Reactivity

Cross Sensitivity Studies range from 0.9% to 47.4%

Early prospective studies Saxon et al. – 47.4% cross reactivity by imipenem skin testing in patients with + PCN skin test

Ann Pharmacotherapy 2009;43:304

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Carbapenem Cross Sensitivity Prospective StudiesAuthor PCN skin test positive

(N)Carbapenemverification Result of Cross reactivity between PCN and carbapenemSkin Test

Romano(2006)

112 Imipenem skin test, then IM challenge • 1/112 (0.9%), to imipenem skin testNo skin test neg patients reacted to Carbapenem challenge

Romano(2007)

104 Meropenem skin test, then IV challenge • 1/104 (1%), to meropenem test• No skin test neg patients reacted to Carbapenemchallenge

Atanaskovic-Markovic(2008)

108Children 3-14YO

Meropenem skin test, then IV challenge • 1/108 (0.9%), to meropenemtest• No skin test neg patients reacted to Carbapenem

Romano(2015)

212 Skin test and IV challenge to aztreonam, imipenem-cilastatin, meropenem, ertapenem

• No patients reacted to skin test to any agent, or subsequent IV challenge

Ann Pharmacotherapy 2009;43:304J Allergy Clin Immunol. 2015 Apr;135(4):972-6

Carbapenem and Cross SensitivityRecommendations

Clinical cross reactivity between PCN and carbapenems appears to be lower than would be expected Carbapenems are a reasonable option in patients with a history of IgE mediated PCN allergy Should still proceed with caution- i.e., graded challenge Based on the fact that <5% of individuals with a history of PCN allergy will be skin test positive, and of those over 99% are able to tolerate carbapenems

Clin Infect Dis. 2014 Oct 15;59(8):1113-22.

Monobactam Cross ReactivityAztreonam Weakly immunogenic

Allergic reaction directed to the side chain No cross reactivity with PCN or Cephalosporins

except ceftazidime- share similar side chain Indication: Treatment of infection caused by Gram negative aerobic organisms in patients with an IgE mediated allergy to PCN compounds

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Cross-reactivity: Ceftazidime and AztreonamAztreonam Ceftazidime

Similar spectrum of activity- aerobic gram negative bacilli

Allergy Assessment

Allergy ValidationAllergies are poorly reported in the medical record!!!! 68% of allergies lack information about the nature and severity Allergic patients- 2 X more likely to receive Vancomycin and 3 X more likely to receive FQ 416 reported allergic reactions, only 36.3% had a description of allergic reaction in the medical records The cost of antimicrobials increased 63% for inpatients and 38% for discharged patients with penicillin allergies compared with non-allergic patients History of β-lactam allergy is a barrier to the effective delivery of preoperative prophylaxis

Arch Int Med. 2000;160:2819, Pharmacotherapy. 2008;28:1348, Clin Exp Allergy. 2003;33:501, Infec Control Hosp Epidemiol 2005;26:478-85

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Allergy AssessmentAntibiotic allergies influences antibiotic selection

Use of expensive alternative agents Use of ineffective agentsAffect institutional resistant patternsAdversely affect the patientIncrease in health care cost

Allergy Assessment Name of the agent/s Nature of the event, symptoms and severity How long ago did reaction occur? Timing, onset of reaction Course of the reaction Any prior exposure to agents in the same class and presence or absence of any reactions Previous ADRs and outcomes

Allergy HistoryVery important question to answer

When did the reaction occur? Gradual loss of penicillin IgE over time

50% lost sensitivity after 5 years 80% lost the sensitivity after 10 years

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Take Home MessageAllergy verification and documentation is critical

<5% OF REPORTED PCN ALLERGIES ARE IgE MEDIATEDβ-lactam ANTIBIOTICS ARE DRUGS OF FIRST CHOICE FOR SEVERAL INFECTIONS

Sulfonamide Allergy

Sulfonamide Allergy (S02NH2) Second most common antibiotic associated allergy Many patients labeled with a sulfonamide allergy may receive a sulfonamide antimicrobial

“SULFA” Allergy

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Sulfonamide Allergy Immunologic and non-immunologic

Detailed allergy history is critical No useful in-vitro or in-vivo test for allergy Desensitization protocols availableHypersensitivity

Delayed onset Fever & pruritic, maculopapular or morbilliform rash Organ involvement Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

SJS and TEN

Sulfonamide AllergyFacts

Cross reactivity between sulfonamide antimicrobials and non-antimicrobials sulfonamides is not seen (furosemide, bumetanide, HCTZ, acetazolamide, diazoxide, sumatriptan, glyburide, celecoxib) Sulfonamide ≠ Sulfone ≠ Sulfyl ≠ Sulfate ≠ Sulfite

Dapsone

Captopril,OmeprazoleRanitidine

albuterol

Foodsbeverages

SulfamethoxazoleSulfisoxazoleSulfadiazineSulfamerazineSulfamethizoleSulfapyridineSulfamoxaoleSulfamethazine

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“Sulfa” Allergy Label TMP/SMX (Bactrim, Septra) is the drug of choice for infections caused by the following pathogens:

Stenotrophomonas maltophilia Burkholderia cepacia (formerly Pseudomonas cepacia) Nocardia spp. Pneumocystis jiroveci (PCP)

VERY FEW THERAPEUTIC ALTERNATIVES

Summary MANY PATIENTS LABELED WITH ALLERGY TO ANTIBIOTICS ARE NOT ALLERGIC <5% OF REPORTED PCN ALLERGIES ARE IgEMEDIATED

1-2% CROSS REACTIVITY TO CEPHALOSPORINS 1% CROSS REACTIVITY TO CARBAPENEMS

CHOICE OF ANTIMICROBIAL IS BASED ON: IF KNOWN IgE MEDIATED SKIN TEST RESULTS SEVERITY OF REACTION

Summary THERE IS LESS DATA FOR NON-IgE MEDIATED ANTIBIOTIC HYPERSENSITIVITY

CAUTIOUS USE OF DIFFERENT β-LACTAM CLASS WITH DISSIMILAR SIDE CHAINS MAY BE APPROPRIATE SJS, TEN- NEVER USE β-LACTAMS AGAIN

MOST IMPORTANT OBTAIN A DETAILED ALLERGY HISTORY DOCUMENT REACTION IN THE MEDICAL RECORDS PATIENT EDUCATION

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Questions ?

References1. Gruchalla RS, Pirmohamed M. Clinical practice. Antibiotic allergy. N Engl J Med. 2006 Feb 9;354(6):601-9.2. Lown JA, Barr AL. Immune thrombocytopenia induced by cephalosporins specific for thiomethyltetrazoleside chain. J Clin Pathol. 1987 Jun;40(6):700-1.3. Prince BT, McMahon BJ, Jain M, Peters AT. Meropenem tolerance in a patient with probable fulminant piperacillin-induced immune hemolytic anemia. J Allergy Clin Immunol Pract. 2015 May-Jun;3(3):452-3.4. Antunes J, Silva R, Pacheco D, Travassos R, Filipe P. Occupational contact allergy to cephalosporins. Dermatol Online J. 2011 May 15;17(5):13.5. Trcka J, Seitz CS, Bröcker EB, Gross GE, Trautmann A. Aminopenicillin-induced exanthema allows treatment with certain cephalosporins or phenoxymethyl penicillin. J Antimicrob Chemother. 2007 Jul;60(1):107-11.6. Blumenthal KG, Youngster I, Shenoy ES, Banerji A, Nelson SB. Tolerability of cefazolin after immune-mediated hypersensitivity reactions to nafcillin in the outpatient setting. Antimicrob Agents Chemother. 2014 Jun;58(6):3137-43.7. Macy E, Poon K-Y T. Self-reported antibiotic allergy incidence and prevalence: age and sex effects. Am J Med. 2009 Aug;122(8):778.e1-7.8. Macy E, Schatz M, Lin C, Poon KY. The falling rate of positive penicillin skin tests from 1995 to 2007. Perm J. 2009 Spring;13(2):12-8.9. Gruchalla RS, Pirmohamed M. Clinical practice. Antibiotic allergy. N Engl J Med. 2006 Feb 9;354(6):601-9.10. Macy E, Contreras R. Adverse reactions associated with oral and parenteral use of cephalosporins: A retrospective population-based analysis. J Allergy Clin Immunol. 2015 Mar;135(3):745-52.e5.11. Macy E, Ngor E. Recommendations for the management of β-lactam intolerance. Clin Rev Allergy Immunol. 2014 Aug;47(1):46-55.12. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273.13. DePestel DD, Benninger MS, Danziger L, LaPlante KL, May C, Luskin A, Pichichero M, Hadley JA. Cephalosporin use in treatment of patients with penicillin allergies. J Am Pharm Assoc (2003). 2008 Jul-Aug;48(4):530-40.

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