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    Penicillin skin testing in patients with a history of beta-lactam allergy. del Real Gonzalo Alvarez,Rose Mark E,Ramirez-Atamoros Maria T,Hammel Jeffrey,Gordon Steven M,Arroliga Alejandro C,Arroliga Mercedes E Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology BACKGROUND:Vancomycin and fluoroquinolones are commonly used in patients with a history of penicillin allergy. OBJECTIVE:To determine the safety and utility of penicillin skin testing (PST). METHODS:Retrospective study of patients with a history of penicillin allergy between April 1, 1999, and September 30, 2004. Penicillin skin testing was performed by means of standard methods using benzylpenicilloyl-polysine, penicillin G, and histamine and saline controls. RESULTS:Of 596 patients studied, 25.3% were outpatients, 50.3% were inpatients, and 24.3% were intensive care unit patients. The most common antibiotics used during the time of PST were vancomycin and fluoroquinolones. Results of PST were negative in 88.4% of patients, positive in 8.2%, and indeterminate in 3.4%. One patient (0.17%) developed urticaria immediately after PST. Fifty-five percent of patients with negative PST results were changed to a beta-lactam drug, more frequently in the intensive care unit vs the outpatient setting (70.3% vs 8.6%; P < .001) and in adults vs patients younger than 18 years (58.6% vs 8.1%; P < .001). A beta-lactam antibiotic was used in 290 patients with negative PST results. Of the patients given beta-lactam antibiotics, 5 (1.7%) had adverse reactions: 2 had hives after 16 and 20 days of therapy, 1 had a nonspecific rash after 17 days of therapy, 1 had flushing and urticaria 3 hours after a test dose of piperacillin-tazobactam, and 1 had a pruritic rash after 12 hours of therapy. CONCLUSIONS:Patients with a history of penicillin allergy can safely use beta-lactam drugs if negative PST results. 10.1016/S1081-1206(10)60882-4
    Determination of antibiotic dosage adjustments in patients with renal impairment: elements for success. Patel Nimish,Scheetz Marc H,Drusano George L,Lodise Thomas P The Journal of antimicrobial chemotherapy This report reviews a contemporary methodology for determining antibiotic dosage modifications among patients with renal impairment. Historically, the approach to identifying renal dosage adjustments has focused on achieving comparable concentration-time profiles between patients with renal impairment and those with normal kidney function. While this approach is intuitive, it fails to incorporate the relationship between antibiotic exposure and effect in the renal dose selection process. A candidate renal dosing scheme that is worthy of incorporation into clinical practice should balance the probability of achieving the exposure target associated with success against the risks of toxicity and the emergence of resistance. This review describes a methodology for optimally identifying dosage adjustments in patients with impaired renal function using extended-infusion piperacillin/tazobactam as an illustrative example. 10.1093/jac/dkq323
    Allergy test outcomes in patients self-reported as having penicillin allergy: Two-year experience. Meng Juan,Thursfield David,Lukawska Joanna J Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology BACKGROUND:Penicillin allergy is associated with increased antibiotic resistance and health care costs. However, most patients with self-reported penicillin allergy are not truly allergic. OBJECTIVE:To summarize our experience with allergy tests in patients with a history of penicillin allergy and to compare them with the results of other groups. METHODS:We retrospectively reviewed all patients with a suspected clinical history of penicillin allergy referred to the Drug Allergy Unit at University College London Hospital between March 2013 and June 2015. RESULTS:In total, 84 patients were reviewed. The index drugs included: unidentified penicillin (n = 44), amoxicillin (n = 17), amoxicillin-clavulanic acid (n = 13), flucloxacillin (n = 4), and other penicillins (ampicillin, benzylpenicillin, piperacillin-tazobactam; n = 7). Allergy diagnoses were confirmed in 24 patients (28.6%) (16 to penicillin, 3 to flucloxacillin, 5 to clavulanic acid). Twenty-two patients (91.7%) had allergy diagnosed by positive skin test results. Two patients (8.3%) developed IgE-mediated allergic symptoms during oral challenge (although the skin test results were negative). In vitro specific IgE test results for penicilloyl V, penicilloyl G, and amoxicilloyl were positive in 3 of 16 patients (18.8%). Moreover, reactions to cefuroxime were observed in 3 of 15 patients with penicillin allergy (20%). Selective clavulanic acid and flucloxacillin responders tolerated amoxicillin challenge. The interval between the index reaction and evaluation was shorter (P < .001), and the proportion of patients who could recall the name of the culprit drug was higher (P = .009) in the allergic group. Furthermore, histories of anaphylaxis (33.3%), urticaria, and/or angioedema (58.3%) were more common in the allergic group. Unspecified rashes (35.0%) and nonspecific symptoms (28.3%) predominated in the nonallergic group. CONCLUSION:Only 28.6% of patients with self-reported penicillin allergy were confirmed to be allergic. Importantly, when the index drug is amoxicillin-clavulanic acid or flucloxacillin, the patients may tolerate amoxicillin. 10.1016/j.anai.2016.07.009
    Evaluation of a pharmacist-led penicillin allergy de-labelling ward round: a novel antimicrobial stewardship intervention. Devchand M,Kirkpatrick C M J,Stevenson W,Garrett K,Perera D,Khumra S,Urbancic K,Grayson M L,Trubiano J A The Journal of antimicrobial chemotherapy BACKGROUND:Antibiotic allergy labels (AALs), reported by up to 25% of hospitalized patients, are a significant barrier to appropriate prescribing and a focus of antimicrobial stewardship (AMS) programmes. METHODS:A prospective audit of a pharmacist-led AMS penicillin allergy de-labelling ward round at Austin Health (Melbourne, Australia) was evaluated. Eligible inpatients with a documented penicillin allergy receiving an antibiotic were identified via an electronic medical report and then reviewed by a pharmacist-led AMS team. The audit outcomes evaluated were: (i) AMS post-prescription review recommendations; (ii) direct de-labelling; (iii) inpatient oral rechallenge referral; (iv) skin prick testing/intradermal testing referral; and (v) outpatient antibiotic allergy clinic assessment. RESULTS:Across a 5 month period, 106 patients were identified from a real-time electronic prescribing antibiotic allergy report. The highest rate of penicillin allergy de-labelling was demonstrated in patients who were referred for an inpatient oral rechallenge with 95.2% (n = 21) successfully having their penicillin AAL removed. From the 22 patients with Type A reactions, 63.6% had their penicillin AAL removed. We demonstrated a significant decrease in the prescribing of restricted antibiotics (defined as third- or fourth-generation cephalosporins, fluoroquinolones, glycopeptides, carbapenems, piperacillin/tazobactam, lincosamides, linezolid or daptomycin) in patients reviewed (pre 42.5% versus post 17.9%, P = 0.0002). CONCLUSIONS:A pharmacist-led AMS penicillin allergy de-labelling ward round reduced penicillin AALs and the prescribing of restricted antibiotics. This model could be implemented at other hospitals with existing AMS programmes. 10.1093/jac/dkz082
    Evaluation of Pharmacy-Developed Antibiotic Desensitization Protocols. Chen Xian Jie Cindy,Fong Karen,Altshuler Diana,Dubrovskaya Yanina,Louie Eddie,Amoroso Nancy,Goldenberg Ronald,Papadopoulos John The Annals of pharmacotherapy BACKGROUND:Parameters within reconstitution, storage, stability, and administration may be optimized according to the unique pharmacokinetics of each antibiotic to ensure a successful desensitization. OBJECTIVE:The study aims to evaluate the successfulness and safety of antibiotic desensitization protocols developed by the pharmacy department at our institution. METHODS:A retrospective study was conducted at an 800-bed, urban, tertiary care, academic medical center. A total of 36 patients 18 years of age or older, admitted to our intensive care units between March 2013 and July 2017, who underwent antibiotic desensitization utilizing our pharmacy developed protocols were included. RESULTS:In 36 patients, 61 desensitization cases were identified and included; 17 (47%) were male, 27 (75%) were Caucasian, and the median age was 55 years (range 19-94). In all, 15 different antibiotics were administered for desensitization, with meropenem (n = 12, 20%), ampicillin (n = 7, 11%), piperacillin/tazobactam (n = 7, 11%), and penicillin (n = 7, 11%) being the most common; 59 (97%) of 61 desensitizations were completed successfully with or without experiencing reactions, and 53 (89%) of the successful desensitization cases were completed without reactions. Two cases were categorized as anaphylaxis, which was severe enough to terminate the desensitization process. Of the 59 cases successfully completed, the 6 (10%) cases that experienced reactions were managed successfully during desensitization with completion of the process. Conclusion and Relevance: The findings suggest that our pharmacy-developed antibiotic desensitization protocols are successful and safe and may be adapted by other institutions. 10.1177/1060028018801959
    Drug-induced tubulointerstitial nephritis in a retrospective study using spontaneous reporting system database. Oyama Saki,Hosohata Keiko,Inada Ayaka,Niinomi Iku,Mori Yasuhiro,Yamaguchi Yuki,Uchida Mayako,Iwanaga Kazunori Therapeutics and clinical risk management Introduction:Tubulointerstitial nephritis (TIN) is a problem in clinical settings because drug therapy is the cause in most cases. Patients often present with nonspecific symptoms, which can lead to delays in the diagnosis and treatment of the disease. The purpose of this study was to clarify the rank-order of the association of TIN with the causative drugs using a spontaneous reporting system database. Materials and methods:Data were extracted from the Japanese Adverse Drug Event Report database of the Pharmaceuticals and Medical Devices Agency (Japan). Based on 5,195,890 reports of all adverse reactions, we obtained 3,088 reports of TIN caused by all drugs and calculated the reporting odds ratio (ROR) and 95% CI for TIN. Results:The 5 drugs with the highest RORs were gliclazide (ROR, 30.5; 95% CI, 17.4-53.2), tosufloxacin tosilate hydrate (ROR, 29.5; 95% CI, 21.3-41.0), piperacillin-tazobactam (ROR, 24.3; 95% CI, 19.4-30.5), cefteram pivoxil (ROR, 23.5; 95% CI, 12.5-44.2), and mefenamic acid (ROR, 22.5; 95% CI, 13.4-37.7). No sex-related difference was observed in drug-induced TIN. Most of the reports about TIN onset following the administration of culprit drugs were recorded within 12 weeks. Conclusion:Based on the results, a comprehensive study using a pharmacovigilance database enabled us to identify the dugs that most frequently induced TIN, so these drugs should be used carefully in clinical practice to avoid TIN. 10.2147/TCRM.S168696
    Surveillance of drugs that most frequently induce acute kidney injury: A pharmacovigilance approach. Hosohata Keiko,Inada Ayaka,Oyama Saki,Furushima Daisuke,Yamada Hiroshi,Iwanaga Kazunori Journal of clinical pharmacy and therapeutics WHAT IS KNOWN AND OBJECTIVE:Acute kidney injury (AKI) often occurs in hospitalized patients, and it is an increasing problem worldwide. Recently, clinical studies have shown that there is a strong association between drug-induced AKI and poor outcomes, including the progression of chronic kidney disease and end-stage renal disease; however, limited data are available on drug-induced AKI. The purpose of this study was to clarify the rank-order of the association of all drugs with AKI using a spontaneous reporting system database. METHODS:We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to Pharmaceuticals and Medical Devices Agency between April 2004 and January 2017 were analysed. RESULTS AND DISCUSSION:Based on 5 195 890 reports of all adverse events, we obtained 12 964 reports of AKI caused by all drugs and calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for AKI. The most frequently reported drugs were valaciclovir hydrochloride (ROR, 24.88; 95% CI: 23.1-26.8), eldecalcitol (ROR, 14.23; 95% CI, 11.68-17.33), edaravone (ROR, 14.03; 95% CI, 11.76-16.75), acyclovir (ROR, 11.17; 95% CI, 9.55-13.1), piperacillin-tazobactam (ROR, 9.23; 95% CI, 7.72-11.0), and spironolactone (ROR, 7.36; 95% CI, 6.12-8.86). WHAT IS NEW AND CONCLUSION:A comprehensive study using a pharmacovigilance database enabled us to identify the drugs that most frequently induce AKI, raising physicians' awareness of the drugs in use for patients with potentially decreased renal function. 10.1111/jcpt.12748