Amoxicillin 875 mg potassium clavulanate 125

If the tympanocentesis reveals multidrug-resistant bacteria, seek an infectious disease specialist consultation .

Reprinted with permission from Lieberthal AS, Carroll AE, Chonmaitree T, et al.

The diagnosis and management of acute otitis media .

Oral cephalosporins, such as cefuroxime (Ceftin), may be used in children who are allergic to penicillin.

Recent research indicates that the degree of cross reactivity between penicillin and second- and third-generation cephalosporins is low (less than 10% to 15%), and avoidance is no longer recommended.25 Because of their broad-spectrum coverage, third-generation cephalosporins in particular may have an increased risk of selection of resistant bacteria in the community.26 High-dose azithromycin (Zithromax; 30 mg per kg, single dose) appears to be more effective than the commonly used five-day course, and has a similar cure rate as high-dose amoxicillin/clavulanate.8 , 27 , 28 However, excessive use of azithromycin is associated with increased resistance, and routine use is not recommended.8 Trimethoprim/sulfamethoxazole is no longer effective for the treatment of AOM due to evidence of S.

Intramuscular or intravenous ceftriaxone (Rocephin) should be reserved for episodes of treatment failure or when a serious comorbid bacterial infection is suspected.2 One dose of ceftriaxone may be used in children who cannot tolerate oral antibiotics because it has been shown to have similar effectiveness as high-dose amoxicillin.30 , 31 A three-day course of ceftriaxone is superior to a one-day course in the treatment of nonresponsive AOM caused by penicillin-resistant S.

pneumoniae .31 Although some children will likely benefit from intramuscular ceftriaxone, overuse of this agent may significantly increase high-level penicillin resistance in the community.2 High-level penicillin-resistant pneumococci are also resistant to first- and third-generation cephalosporins. Antibiotic therapy for AOM is often associated with diarrhea.8 , 10 , 32 Probiotics and yogurts containing active cultures reduce the incidence of diarrhea and should be suggested for children receiving antibiotics for AOM.32 There is no compelling evidence to support the use of complementary and alternative treatments in AOM.8. Children with persistent, significant AOM symptoms despite at least 48 to 72 hours of antibiotic therapy should be reexamined.8 If a bulging, inflamed tympanic membrane is observed, therapy should be changed to a second-line agent.2 For children initially on amoxicillin, high-dose amoxicillin/clavulanate is recommended.8 , 10 , 28.

For children with an amoxicillin allergy who do not improve with an oral cephalosporin, intramuscular ceftriaxone, clindamycin, or tympanocentesis may be considered.4 , 8 If symptoms recur more than one month after the initial diagnosis of AOM, a new and unrelated episode of AOM should be assumed.10

For

Check for undiagnosed allergies leading to chronic rhinorrhea.

The Canadian Paediatric Society gives permission to print single copies of this document from our website. For permission to reprint or reproduce multiple copies, please see our copyright policy.

Principal author(s) Tiffany Wong, Adelle Atkinson, Geert t’Jong, Michael J. Abrams; Canadian Paediatric Society, Allergy Section.

Beta-lactam allergy is commonly diagnosed in paediatric patients, but over

90%

than

Most patients can be safely treated with penicillin or amoxicillin if they do not have a history compatible with IgE-mediated or systemic, delayed reactions such as Stevens-Johnson syndrome (SJS), serum sickness-like reactions, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, or acute generalized exanthematous pustulosis (AGEP). Guidance is provided on how to stratify risk of beta-lactam allergy, and on test dosing and monitoring in the outpatient setting for patients deemed low risk.

Guidance for patients at higher risk of beta-lactam allergy includes criteria for appropriate referral to allergists and the use of alternative antimicrobials, such as cephalosporins, while awaiting specialist assessment.

Keywords: Beta-lactam; Challenge; Drug allergy; Penicillin.

Definition and categorization of beta-lactam allergy.

The World Health Organization defines drug allergy as immunologically mediated drug hypersensitivity reactions [1] . Drug allergies have historically been categorized by the Gell and Coombs system of hypersensitivity (Table 1). Clinically, drug allergies are usually classified as immediate (typically occurring within 1 hour) or non-immediate (occurring after 1 hour, but often days or weeks later) after medication initiation. Only IgE-mediated drug allergy falls into the immediate category.

Clinical presentation of beta-lactam allergy Immune reaction Timing post-exposure Clinical presentation Type I (IgE-mediated) ?1 to 2 hours Urticaria/angioedema, respiratory distress, GI symptoms, hypotension, anaphylaxis Type II (cytotoxic) 10 hours to weeks Anemia, thrombocytopenia Type III (immune complex) 1 to 3 weeks Serum sickness-like reaction: fever, urticaria, vasculitis, arthritis/arthralgia Type IV (T cell-mediated) 2 to 14 days Maculopapular rash, Stevens-Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, acute generalized exanthematous pustulosis (AGEP) Adapted from reference 8. Type I reactions, though rare, are concerning for many patients and practitioners.

They are unlikely to occur with the first course because exposure is required before sensitization can occur [2] . Anaphylactic reactions to penicillin medications are rare, having been reported in [2] . Although maculopapular exanthems associated with beta-lactams are believed to be true type IV allergy in about 5% of adults, they are far less common—and have been estimated to affect less than 2%—of children.

Most maculopapular exanthems in children are caused by infection and do not contraindicate further use of antibiotics [2] [3] . Beta-lactam allergy is reported in 5% to 8% of children in North America and Europe [4] . In paediatric patients labelled with beta-lactam allergy and referred to an allergist, 94% to 96% tolerate beta-lactam challenges upon further evaluation [3] [5] .

Paediatric patients labelled as having a beta-lactam allergy are often misdiagnosed due to misclassification of symptoms of illness or common side effects of antibiotic medications. An interaction between the antibiotic and a pathogen can sometimes mimic an allergic reaction [6] . Circulating beta-lactam-specific IgE antibodies can decrease naturally over time [7] . However, many patients are never reassessed and continue to carry this label. Beta-lactam antibiotics (penicillins and cephalosporins) share a beta-lactam ring. Medications differ based on the different R groups on the acyl side chain (Figure 1). Beta-lactam antibiotics develop allergenic potential when the beta-lactam ring opens and links with nearby proteins in the blood. Penicillins, slide 13: www.slideshare.net/seetaram443/penicillins-53561419.

Cross-reactivity among beta-lactam antibiotics in allergic individuals. Cross-reactivity among the penicillins is caused primarily by similarities in their core ring structure and their side chains.

Cross-reactivity cannot be determined by side-chain similarities alone.

When a patient has a true allergy to a penicillin, all penicillins should be avoided. It was previously believed that cephalosporin allergy occurred in 10% to 20% of penicillin-allergic individuals, and that they should avoid all cephalosporins.

However, it is now understood that this occurrence rate was an overestimation, and that associated precautions were overly restrictive.

Although these medications share a common beta-lactam ring (Figure 2), evidence has shown that it is rarely the structure implicated in allergy [2] . All early cases reported were in patients who received

first-generation

For example, when an individual has a confirmed allergy to amoxicillin, they are likely to react to cephalexin as well because of the group 2 side chain at position 7.

The true rate of cross-reactivity is thought to be about 2% [2] .

With the true incidence of penicillin allergy among patients who report a history being at or under 10%, the rate of cross-reactivity is now estimated to be less than 1% in patients with self-reported, but unconfirmed, allergy.

Chemical structures of 7-position side chains of penicillins and cephalosporins Similar side-chain cross-reactivity within group Group 1 Group 2 Group 3 cefoxitin cephalothin cephaloridine penicillin g cefaclor cephradine cephalexin cefadroxil cefatrizine cefprozil amoxicillin ampicillin cefepime ceftizoxime cefpirome cefotaxime cefpodoxime ceftriaxone cefetamet cefteram Adapted from reference 8.

Chemical structures of 3-position side chains of cephalosporins Similar side-chain cross-reactivity within group Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 cefadroxil cephalexin cephradine cefmetazole cefoperazone cefotetan cefamandole cefotaxime cephalothin cephapirin ceftibuten ceftizoxime cefuroxime cefoxitin cefdinir

cefixime

Individuals should be assessed and examined by a physician while they are experiencing a suspected reaction, if possible.

Investigations will depend on the nature of the suspected reaction.

Important questions on history after a suspected reaction.

Epicutaneous and intradermal testing with validated and standardized penicillin reagents is recommended by international guidelines for the assessment of suspected IgE-mediated allergy.

Although the negative predictive value of skin testing for penicillin allergy in adults approaches 100% , one recent Canadian study showed the predictive value of penicillin skin testing in children to be poor, with a negative test in 94% of children who had a positive amoxicillin and clavulanate potassium 625mg oral challenge [5] .

Thus, skin testing is less likely to be useful in children than in adults.

Skin testing is not a useful test for screening of allergy where there is no history of a convincing reaction because the positive predictive value for penicillin allergy has been reported to be as low as 40% [2] . The gold standard test to rule out an IgE-mediated allergy is a drug challenge test, conducted when, after thorough history taking +/- skin testing, an individual is deemed unlikely to be allergic.

Skin testing with standardized reagents is specific to penicillin and does not necessarily rule out allergy to other penicillin group members with different side chains (e.g., amoxicillin).

Thus, oral drug challenge to the specific medication is preferred.

There is no international consensus on how challenge tests are to be conducted.

Many Canadian centres provide a single dose challenge, whereas others provide graded dosing in two steps (i.e., 10% of the dose, followed by the remaining 90% 30 minutes later).

Drug challenge tests in appropriately selected individuals are safe and effective,

and

Drug challenge tests can be dangerous and are contraindicated if when a child’s history is consistent with recent anaphylaxis or systemic, non-immediate immunologic reaction (e.g., serum sickness-like

reaction

Clinical implications of erroneous beta-lactam allergy labelling. A diagnosis of drug allergy in children should be made with special care because inaccurate penicillin allergy labelling is associated with negative clinical and administrative outcomes. Second-line non-beta-lactam antimicrobials are generally inferior for infection management and have been associated with prolonging hospital stays, higher admission rates for intensive care, readmissions, and mortality. As a

result

Rising health care costs around the world are due in part to higher antibiotic costs per hospitalization and prolonged hospital stays.

Removal of erroneous

penicillin

Figure 3 has been evaluated by paediatric allergists, an antimicrobial stewardship pharmacist, a general paediatrician, and paediatric infectious disease specialists.

Just over 60% of subjects found potassium clavulanate uses to be non-allergic by an allergist on the same day as their clinic appointment could have been identified as low-risk based on history alone, using the questionnaire and following this algorithm.

No patient

identified

allergic

Individuals at low risk for penicillin allergy can safely have the medication prescribed again. Mild, delayed exanthems do not contraindicate further use of these antibiotics.

Administration of a single test dose of amoxicillin (15 mg/kg) with a 1-hour observation period can provide reassurance and confirm that no allergy is present.

These individuals can be prescribed cephalosporins (with similar and dissimilar side chains), carbapenems, and monobactams, without monitoring dose administration. Individuals with suspected IgE-mediated allergy should not be prescribed penicillin.

They must be referred to a paediatric allergist for assessment.

For individuals with suspected IgE-mediated

allergy

Individuals who have experienced severe systemic or cutaneous delayed adverse reactions

following

They must be referred to a paediatric allergist for assessment and counselling. There is no robust evidence to indicate cross-reactivity between specific penicillins or penicillins and cephalosporins with similar side chains in severe delayed allergic reactions. Future decisions for penicillin use other than the ones implicated should be based on benefit versus risk assessment on a case-by-case basis.

Some organizations recommend avoiding cephalosporins with similar side chains in such cases [11] .

Individuals who have been diagnosed with penicillin allergy by an allergist should be re-assessed by a paediatric allergist after 5 years.

This allergy can be outgrown and avoiding penicillin for life may not be necessary.

This practice point was reviewed by the Community Paediatrics and Infectious Disease and Immunization Committees of the Canadian Paediatric Society, and co-authored by two members of the CPS

Drug

Chan MD (Secretary-Treasurer) Principal authors: Tiffany Wong MD, Adelle Atkinson MD, Geert t’Jong MD, Michael J.