Elizabeth Weber

Impact of Reported Beta-Lactam Allergy on Inpatient Outcomes: A Multicenter Prospective Cohort Study

BACKGROUND Reported allergy to beta-lactam antibiotics is common and often leads to unnecessary avoidance in patients who could tolerate these antibiotics. We prospectively evaluated the impact of these reported allergies on clinical outcomes. METHODS We conducted a trainee-led prospective cohort study to determine the burden and clinical impact of reported beta-lactam allergy on patients seen by infectious diseases consultation services at 3 academic hospitals. The primary outcome was a composite measure of readmission for the same infection, acute kidney injury, Clostridium difficile infection, or drug-related adverse reactions requiring discontinuation. Predictors of interest were history of beta-lactam allergy and receipt of preferred beta-lactam therapy. RESULTS Among 507 patients, 95 (19%) reported beta-lactam allergy; preferred therapy was a beta-lactam in 72 (76%). When beta-lactam therapy was preferred, 25 (35%) did not receive preferred therapy due to their report of allergy even though 13 (52%) reported non-severe prior reactions. After adjustment for confounders, patients who did not receive preferred beta-lactam therapy were at greater risk of adverse events (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.28-7.89) compared with those without reported allergy. In contrast, patients who received preferred beta-lactam therapy had a similar risk of adverse events compared with patients not reporting allergy (aOR, 1.33; 95% CI, .62-2.87). CONCLUSIONS Avoidance of preferred beta-lactam therapy in patients who report allergy is associated with an increased risk of adverse events. Development of inpatient programs aimed at accurately identifying beta-lactam allergies to safely promote beta-lactam administration among these patients is warranted.

Skin reactions associated with bisphosphonates: A report of 3 cases and an approach to management

Allergic reactions or skin reactions of any type or severity associated with bisphosphonates have been rarely described. We report 3 cases of cutaneous reactions associated with bisphosphonates in 3 patients with breast cancer and outline an approach to their management.

Management Options for Patients with Aspirin and Nonsteroidal Antiinflammatory Drug Sensitivity

Objective: To evaluate and provide management strategies for patients with aspirin or nonselective nonsteroidal antiinflammatory drug (NSAID) sensitivity. Data Sources: Literature retrieval was accessed through MEDLINE (1966–March 2007) using the terms acetaminophen, aspirin, antiinflammatory agents nonsteroidal, urticaria, angioedema, asthma, leukotriene antagonists, desensitization, and tacrolimus. Article references retrieved were hand-searched for other relevant articles. Study Selection and Data Extraction: All studies published in English were evaluated. Studies, review articles, and commentaries on aspirin-induced asthma and aspirin- or NSAID-induced urticaria/angioedema were included in the review. Data Synthesis: Aspirin sensitivity is most often manifested as respiratory reactions (eg, bronchospasm, profuse rhinorrhea, conjunctival injection) or urticaria/angioedema. The primary mechanism is believed to be inhibition of the cyclooxygenase 1 (COX-1) enzyme; as such, patients with aspirin sensitivity often display cross-reactions to nonselective NSAIDs that inhibit the COX-1 enzyme. Management strategies include avoidance of aspirin and cross-reacting nonselective NSAIDs. However, desensitization to aspirin is a viable option for patients with aspirin-induced respiratory reactions, especially for those who require aspirin for thromboembolic prophylaxis. Aspirin desensitization is maintained indefinitely with a daily aspirin dose. There is limited evidence of the use of leukotriene modifiers in preventing aspirin-induced asthma. COX-2 selective NSAIDs, especially in patients with aspirin-induced asthma, have not been found to cross-react. However, approximately 4% of patients with a history of aspirin-induced skin reactions may experience a cutaneous reaction following a challenge to a COX-2 selective NSAID. Since acetaminophen is a weak inhibitor of the COX-1 enzyme, patients with aspirin-induced asthma should not take more than 1000 mg of acetaminophen in a single dose. Conclusions: Management of patients with aspirin/NSAID sensitivity includes avoidance of aspirin/nonselective NSAIDs, use of COX-2 selective NSAIDs, acetaminophen in doses less than 1000 mg, and desensitization. The role of leukotriene modifiers requires further study before they can be recommended for patients.

Immediate hypersensitivity to moxifloxacin with tolerance to ciprofloxacin: report of three cases and review of the literature.

Objective To report 3 cases of immediate hypersensitivity reactions to moxifloxacin in patients who tolerated ciprofloxacin. Case summaries A 71-year-old man, a 44-year-old woman, and a 70-year-old woman with a history of a moxifloxacin reaction developed an immediate hypersensitivity reaction upon oral challenge with moxifloxacin in our Drug Safety Clinic. The reaction was mainly characterized by pruritus and urticaria, although dyspnea and hypotension were noted in the first and second patient, respectively. Two of the patients had negative oral challenge tests with ciprofloxacin and all 3 patients tolerated full treatment courses of oral ciprofloxacin. In all 3 cases, use of the Naranjo probability scale indicated a highly probable adverse drug reaction. Discussion Moxiffoxacin, similar to other fluoroquinolones, can cause immediate hypersensitivity reactions. Previous publications have reported both cross-reactivity and a lack of cross-reactivity among various fluoroquinolones. The 3 patients discussed demonstrated a lack of cross-reactivity between moxifloxacin and ciprofloxacin since they tolerated oral challenge tests and full treatment courses of ciprofloxacin. Moxifloxacin has unique side chains at positions 7 and 8 on its bicyclic ring structure. Antigenic specificity to particular side chains at positions 7 and 8 on the bicyclic ring structure of moxifloxacin may explain this lack of cross-reactivity. Higher reporting rates of anaphylaxis to moxifloxacin compared to other fluoroquinolones may also be related to side chain specificity, although definitive evidence for this is lacking. Conclusions Based on our experience, patients who develop immediate hypersensitivity reactions to moxifloxacin may receive ciprofloxacin therapy in an appropriately monitored setting if they have previously tolerated full treatment courses of ciprofloxacin. Research into whether there is a specific side chain reaction unique to moxifloxacin is warranted.

Clindamycin skin testing has limited diagnostic potential

We examined the role of clindamycin prick and intradermal skin testing in a tertiary care clinic population. Experience with diagnostic modalities such as prick and intradermal testing has been limited with clindamycin. A retrospective chart review was conducted for patients with immunologic reactions temporally associated with clindamycin who were referred to the Drug Safety Clinic (Toronto, Ontario). A total of 31 patients were identified who had undergone prick and intradermal skin testing. All 31 negative immediate prick and intradermal tests were followed by a 150 mg oral dose of clindamycin. 10/31 (32%) subjects had significant reactions to the oral clindamycin provocation. 2 patients reported delayed reactions at the clindamycin intradermal test sites. Our experience suggests that prick and intradermal skin testing is not adequate in identifying patients with previous allergic reactions associated with clindamycin. Oral provocation tests can be used in patients with histories of clindamycin adverse reactions; however, it should be offered on a risk‐benefit basis.

Evaluation of immediate allergic reactions to cephalosporins in non-penicillin-allergic patients.

Background: Cephalosporins can induce severe or life-threatening IgE-mediated reactions in some individuals. In this study, we wish to describe a group of non-penicillin-allergic patients who were evaluated for immediate allergic reactions to cephalosporins. Methods: The patients were assessed by skin tests with the culprit cephalosporin as well as with other cephalosporins and penicillins. If indicated, oral challenge testing was performed. Results: Six patients were assessed. A total of 42 skin tests and 20 oral challenges were performed. In 4 patients, skin tests included the causative drug; in 2 patients, the diagnosis of a cephalosporin allergy was made by skin test; in 4 patients, the diagnosis of a cephalosporin hypersensitivity was made by oral challenge. In 96.9% of the oral challenges, which were done using medications with no structural side chain similarities to the culprit drug, no adverse reaction occurred. Conclusion: A positive skin test to cephalosporin implies the presence of drug-specific IgE antibodies. Cephalosporins without side chain similarities are suggested to patients with cephalosporin reactions and no β-lactam reactivity.

Ciprofloxacin skin testing: A retrospective study

RATIONALE: Limited information is available regarding the validity of procedures to diagnose allergic adverse drug reactions (ADRs) associated with fluoroquinolones (FQ). A retrospective study was undertaken to examine the clinical utility of ciprofloxacin (CP) skin testing. MATERIALS AND METHODS: A review of 135 charts from patients seen with suspected FQ associated ADRs between 1996-2001 was con- ducted at the Sunnybrook Drug Safety Clinic. Skin testing (prick and intradermal) was performed to CP (0.0001 mg/ml to 0.1 mg/ml) and levofloxacin (0.0001 mg/ml to 0.1 mg/ml) and oral challenge with CP (250 rag) and/or another FQ was administered following the negative skin tests. RESULTS: False positive reactions were associated with concentrations >0.05 mg/ml. 5/135 (4%) tested positive on the skin testing; 2 to levofloxacin and 3 to CP. 20/135 (15%) were positive on the oral challenge; however, only 9 (7%) subjects had reactions consisting of a rash and/or breathing difficulties within the time frame for an immediate or accelerated reaction (between 0 and 72 hours). The other 11 (8%) false negative reactions were potentially non-allergic (eg, pruritus, lightheadedness). There was a significant relationship between the original reaction history (indicative or non-indicative of immediate hypersensitivity) and positive oral challenge outcomes (true false negative or non-specific reactions) (P=0.0014, 95% CI). The negative predictive value for this test was deter- mined to be 93.1%, which is comparable to the negative predictive value for penicillin, the gold standard for skin testing. CONCLUSIONS: Skin testing should be pursued as a diagnostic tool for suspected allergic ADRs associated with FQ antibiotics.

The utility of skin testing in suspected clindamycin allergy

RATIONALE: Skin testing has been validated for lgE-mediated reactions associated with penicillin but little information exists regarding this form of testing for other drugs. We explored the clinical utility of clindamycin prick testing and intradermal testing in patients with immediate or delayed reactions to clindamycin. METHODS: A total of 34 subjects with histories of reactions associated with clindamycin (14 accelerated reactions, 11 delayed, and 8 not documented) underwent prick and intradermal skin testing to clindamycin (0.15 mg/ml to 15 mg/ml) between 1999 and 2001. Subjects with negative skin testing received a single oral dose of clindamycin. RESULTS: Although none of the 34 prick and intradermal tests per- formed were positive, a significant number of patients [11/34 (32%)] had reactions to the oral challenge lie, immediate reactions (n=l) and accelerated reactions (n= 10)]. Sensitivity of the prick and intradermal testing was determined to be 0%, specificity 100%, positive predictive value 0%, and negative predictive value 68%. CONCLUSIONS: Our experience highlights the low clinical utility of prick and intradermal testing for allergic and cutaneous reactions associated with clindamycin. We caution against the use of clindamycin skin testing as a diagnostic tool in this setting. Although a single oral challenge appears to be highly predictive it should be used selectively given the potential for significant morbidity incurred by induced reactions.