Erythromycin and amoxicillin

This procedure can be used for both IgE-and non-IgE–mediated drug allergic reactions to a variety of drugs, including antibiotics, chemotherapeutics and biologic agents (e.g., penicillin, acetylsalicylic acid [ASA] and allopurinol), but it is not used for patients with a history of a severe drug reaction, such as Stevens–Johnson

syndrome

Which common drugs are associated with allergic reactions? About 10% of the population in predominantly developed countries is thought to be penicillin allergic,1 , 27 but 90% or more are able to tolerate penicillin after allergy evaluation.1 , 28 In 2016, a systematic review and meta-analysis of 14 studies reported a low prevalence of IgE-mediated drug allergy to ?-lactam antibiotics of 2.84% (95% confidence interval [CI] 1.77%–3.91%), with a higher prevalence among adults (7.78%, 95% CI 6.53%–9.04%) than among children (1.98%, 95% CI 1.35%–2.

60%

Some studies have suggested that the rate of confirmed penicillin allergy is decreasing.31 , 32 Recent initiatives have suggested the “de-labelling” of

patients

Recent studies have shown that as many as 98% of patients with a history of penicillin allergy are found to have negative penicillin skin tests and will tolerate penicillins.36 Re-evaluation is suggested even in those with confirmed (based on skin testing or oral challenge) penicillin allergy. An evaluation conducted in a pediatric emergency department that involved 100 children with a history of penicillin allergy found that 100% (95% CI 96.4%–100%) of these children with low-risk symptoms had negative results for allergy testing (skin testing and drug provocation test).37 Evaluation is especially useful if the reaction occurred more than 5 to 10 years ago, because there is a high rate of resolution for

penicillin

Although cephalosporins can also cause acute allergic reactions, overall the reaction rate is about 10-fold lower than for penicillin.1 Cross reactivity between cephalosporins and penicillin is thought to be very low.41 The Canadian Pediatric Society’s guideline on otitis media notes that children with a history of reactivity to penicillin or amoxicillin can safely be prescribed second-or third-generation cephalosporins as long as the previous reaction was not life-threatening.42 A 2016 review also reported that avoidance of cephalosporins in patients with amoxicillin or penicillin allergy could result in substantial morbidity, and concluded that there was “ample evidence to allow the safe use of cephalosporins in patients with isolated confirmed penicillin or amoxicillin allergy.”43.

Amoxicillin and cephalosporins contain “R” side chains in addition to the ?-lactam ring, which may be allergenic. Sensitization to the ?-lactam portion of penicillin would result in sensitization to all ?-lactam antibiotics; in contrast, sensitization to the R side chain would lead to tolerance of most ?-lactam antibiotics (except those with a common side chain).

For example, amoxicillin shares an identical R side chain with cefprozil; ampicillin with cefaclor and cephalexin; and ceftriaxone with cefotaxime. For cephalosporins, if an acute allergic reaction does occur, it is often directed at the R-group side chain instead of the common ?-lactam ring.8. Although skin testing has not been validated for ?-lactams other than penicillin, it can still have some utility if there is a history consistent with an IgE-mediated reaction — patients with negative results for penicillin skin tests can safely receive ?-lactam antibiotics, and patients with confirmed penicillin allergy usually tolerate carbapenems and aztreonam.44 Skin testing reagents have been developed for amoxicillin and cephalosporins; however, their negative predictive value has not been validated.1 If patients with a history of a

reaction

The approach to administration of cephalosporins or penicillin in the context of an allergic reaction is outlined in Table 4, as suggested by the Joint Task Force on Practice Parameters.1. Administration of penicillin or cephalosporins in the context of a previous reaction1. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used commonly in North America and can cause different reactions that are either allergic in nature or, more commonly, nonimmune (and related to cyclooxygenase-1 [COX-1] inhibition) (Table 5).

A retrospective review involving all adult patients in an American health care system who were prescribed NSAIDs over an eight-year period reported that 17% of those patients had an adverse drug reaction, of which 18.3% were allergic.46 The common types of NSAID-induced reactions are NSAID-exacerbated respiratory

disease

such

Allergic reactions induced by nonsteroidal anti-inflammatory drugs47.

Nonsteroidal anti-inflammatory drug–exacerbated respiratory disease presents with upper and lower respiratory symptoms within three hours after NSAID ingestion, mostly in adult patients with a history of underlying asthma and rhinosinusitis.47 It is related to COX-1 inhibition and is diagnosed with an oral provocation test. Treatment is avoidance of COX-1 inhibitors (COX-2 inhibitors are usually safe); if asthma or rhinosinusitis is refractory to medical and surgical therapy, ASA induction of tolerance followed by ASA therapy can be considered as well.1.

Patients who present with cutaneous symptoms after NSAID exposure may have one of three conditions: NSAID-exacerbated cutaneous disease, NSAID-induced urticaria/angioedema or single-NSAID–induced urticaria/angioedema or

anaphalaxis

presents

Distinguishing between these conditions by drug provocation testing (to both the implicated NSAID and a chemically unrelated NSAID) is beneficial as a means of differentiating the conditions and predicting the extent of necessary NSAID avoidance according to a 2013 review.47 For NSAID-exacerbated cutaneous disease and NSAID-induced urticaria/angioedema, all COX-1 inhibitors should be avoided (COX-2 inhibitors are usually safe). For single-NSAID–induced urticaria/angioedema or anaphalaxis, only the implicated NSAID and chemically related NSAIDs must be avoided.1 , 47 For all of these conditions, COX-2 inhibitors are largely well tolerated.1 , 47.

Although adverse drug reactions are common, allergic reactions are uncommon. Cutaneous manifestations are the most common clinical manifestation of an allergic drug reaction. Diagnosis largely relies on medical history, because there are few standardized tests in the diagnosis of drug allergy, with the exception amoxicillin and sore throat of skin testing for penicillin.

However, evaluation of patients labelled as allergic remains an important public health goal because mislabelling can have health consequences, such as increased morbidity and public health costs. Competing interests: Elissa Abrams has received an unrestricted educational grant from Novartis, outside the submitted work.

Adverse effects of amoxicillin may be potentially under-reported.

the Oncology Nurse Advisor take: Amoxicillin is a widely used antibiotic in the penicillin group of

drugs

In a systematic review, researchers conducted a review of controlled trials to assess potential harms related to amoxicillin use.

The review included a total of 45 trials, featuring a total of 10,519 participants. The researchers found that almost twice as many patients receiving amoxicillin had diarrhea compared with patients receiving placebo, and diarrhea was more than three times more likely among participants receiving amoxicillin-clavulanate. An association between candidiasis and amoxicillin-clavulanic acid use was also observed. However, the authors acknowledge a limitation to their study. All the trials measured efficacy rather than harm as their primary outcome, and only 25 of the study included information on harms.

Therefore, the number of harms reported was lower than expected, which contributed to a conclusion that harms may be under-reported in clinical trials.

In a related commentary, clinicians are advised to be wary of the lack of information on potential adverse effects from amoxicillin.

Researchers have found that taking the common antibiotics amoxicillin and amoxicillin-clavulanic acid can result in symptoms of diarrhea and candidiasis, also known as thrush. Not only that, but these adverse effects could also be under-reported, leading to a high prevalence of prescriptions. When are Oral Antibiotics a Safe and Effective Choice for Bacterial Bloodstream Infections? Hale, MD, University of Vermont Medical Center, Infectious Disease Unit, 111 Colchester Avenue, Mailstop 115 SM2. Burlington, VT 05401; Telephone: 802-847-2264; Fax: 802-847-5322; E-mail: [email protected] Abstract. Bacterial bloodstream infections (BSIs) are a major cause of morbidity and mortality in the United States.

Traditionally, BSIs have been managed with intravenous antimicrobials.

However, whether intravenous antimicrobials are necessary for the entirety of the treatment course in BSIs, especially for uncomplicated episodes, is a more controversial matter. Patients that are clinically stable, without signs of shock, or have been stabilized after an initial septic presentation, may be appropriate candidates for treatment of BSIs with oral antimicrobials. There are risks and costs associated with extended courses of intravenous agents, such as the necessity for long-term intravenous catheters, which entail risks for procedural complications, secondary infections, and thrombosis. Oral antimicrobial therapy for bacterial BSIs offers several potential benefits.

When selected appropriately, oral antibiotics offer lower cost, fewer side effects, promote antimicrobial stewardship, and are easier for patients.

The decision to use oral versus intravenous antibiotics must consider the characteristics of the pathogen, the patient, and the drug.

In this narrative review, the authors highlight areas where oral therapy is a safe and effective choice to treat bloodstream infection, and offer guidance and cautions to clinicians managing patients experiencing BSI.

Bacterial bloodstream infections (BSIs) are a major cause of morbidity and mortality in the United States. Approximately 600,000 BSI cases occur annually, resulting in 85,000 deaths, 1 at a cost exceeding $1 billion.

2 Traditionally, BSIs have been managed with intravenous antimicrobials, which rapidly achieve therapeutic blood concentrations, and are viewed as more potent than oral alternatives.

Indeed, for acutely ill patients with bacteremia and sepsis, timely intravenous antimicrobials are lifesaving. However, whether intravenous antimicrobials are essential for the entire treatment course in BSIs, particularly for uncomplicated episodes, is controversial.