Amoxiclav 500mg

NOTE : Cefdinir, cefuroxime, cefpodoxime, and ceftriaxone are highly unlikely to be associated with cross-reactivity with penicillin allergy on the basis of their distinct chemical structures . *— May be considered in patients who have received amoxicillin in the previous 30 d or who have the otitis-conjunctivitis syndrome .

†— Perform tympanocentesis/drainage if skilled in the procedure, or seek a consultation from an otolaryngologist for tympanocentesis/drainage.

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

Intramuscular or intravenous ceftriaxone (Rocephin) should be reserved for episodes of

treatment

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 children with recurrent AOM (i.e., three or more episodes in six months, or four episodes within 12 months with at least one episode during the preceding six months) with middle ear effusion, tympanostomy tubes may be considered to reduce the need for systemic antibiotics in favor of observation, or topical antibiotics for tube otorrhea.8 , 10 However, tympanostomy tubes may increase the risk of long-term tympanic membrane abnormalities and reduced hearing compared with medical therapy.33 Other strategies may help prevent recurrence (Table 4) .34 – 37.

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% of individuals reporting this allergy are able to tolerate the medications prescribed after evaluation by an allergist.

Beta-lactam allergy labels are associated with negative clinical and administrative outcomes, including use of less desirable alternative antibiotics, longer hospitalizations, increasing antibiotic-resistant infections, and greater medical costs.

Also, children with true IgE-mediated allergy to penicillin medications are often advised to avoid all beta-lactam antibiotics, including cephalosporins, which is likely unnecessary in greater than 97% of those reporting penicillin allergies. Most patients can be safely treated with penicillin or amoxicillin if

they

not

eosinophilia

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

and

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

with

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

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

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 medications. Pre-1980 cephalosporins were found to be contaminated with penicillin, and these early reactions are now known to have been caused primarily by structurally similar side chains (Tables 2 and 3).

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

cefmetazole

Detailed history-taking is critical to the evaluation of possible beta-lactam allergy, the level of patient risk, and for deciding whether skin testing or an oral challenge is indicated. Individuals should be assessed and examined by a physician while they are experiencing a suspected reaction, if possible. Investigations

will

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 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

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 of increased alternative, broad-spectrum

antibiotic

antibiotic

Rising health care costs around the world are due in part to

higher

Penicillin allergy de-labelling programs have become a key strategy of antimicrobial stewardship programs in North America. 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 to be non-allergic by an allergist on the same day as their clinic appointment

could

Figure 3: Algorithm to identify paediatric patients at low risk for penicillin allergy is available as a supplementary file . Guiding principles for beta-lactam allergy in the paediatric population. Individuals with a history of suspected penicillin reaction but who have since tolerated one course of the medication are not allergic.

These antibiotics can be prescribed again without monitoring dose administration.

Individuals at low risk for penicillin allergy can safely have the medication

prescribed

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, avoid prescribing cephalosporins with similar side chains. Cephalosporin medications with dissimilar side chains can be prescribed.

When necessary (e.g., for patients who require frequent antibiotics for a chronic disease), or when a certain cephalosporin is desirable, a provocative challenge to the specific cephalosporin a treatment team would like to use, can be conducted. Individuals who have experienced severe systemic or cutaneous delayed adverse reactions following a dose of penicillin, should not be prescribed this antibiotic in the future. 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

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.