Alana Arnold

Antibiotic desensitization for the allergic patient: 5 years of experience and practice

Background Antibiotic desensitization is an option for patients with suspected IgE-mediated antibiotic allergy when no other alternative exists for treating life-threatening bacterial infections. However, there are limited data describing the outcomes of this procedure with newer, commonly used antibiotics. Objective To evaluate the safety and utility of antibiotic desensitization. Methods We retrospectively reviewed the medical records of all patients undergoing antibiotic desensitization in our institution between November 1996 and November 2001. Results There were a total of 57 desensitizations performed in 21 patients. The mean age of the patients was 22.8 years (range, 1.9-44.5 years) and 15 (71%) were female. Nineteen (90%) of the 21 patients had been diagnosed as having cystic fibrosis. In 33 (100%) of 33 desensitizations to unique antibiotics that occurred during the study period, the indication for desensitization was a history suggestive of an IgE-mediated reaction to the antibiotic and/or a positive skin test result to the antibiotic or a known cross-reactive antibiotic. Desensitizations were performed to 12 different antibiotics. Successful outcomes were achieved in 43 desensitizations (75%). Of the 11 cases (19%) that were terminated due to an allergic reaction, there were no fatalities, intubations, or other aggressive interventions besides the use of epinephrine, antihistamines, and corticosteroids. In 7 of 11 unsuccessful desensitizations, a non-IgE mechanism appeared to be responsible for the allergic reaction. Conclusions Antibiotic desensitization is a useful option when treating patients with life-threatening infections who must receive antibiotics to which they have an IgE-mediated allergy. These data indicate that in most cases, patients with presumed IgE-mediated antibiotic allergy may safely receive antibiotics after desensitization.

Once-daily Gentamicin Dosing for the Preterm and Term Newborn: Proposal for a Simple Regimen that Achieves Target Levels

OBJECTIVE: Based on recent safety and efficacy data, combined with the known pharmacokinetic parameters of aminoglycosides in the newborn, oncedaily gentamicin should be preferable to the many other dosing regimens currently in use. Although there are growing data to support its use in term newborns, experience with preterm infants is more limited. In our Neonatal Intensive Care Unit, we experienced difficulties regarding complicated dosing regimens, actual dosing errors, and the tendency to check trough and peak levels around the third dose for infants receiving only a 48 hour course. Therefore, we conducted a quality improvement initiative in which we developed and tested a clinical practice guideline for the use of once-daily gentamicin for preterm and term infants that we hoped would yield trough and peak levels in our target range.METHODS: We combined a review of the published English language literature with pharmacokinetic analysis of our own data prior to initiation of this new regimen to design the following dosing regimen: <35 weeks gestation: 3 mg/kg q 24 hours, ≥35 weeks gestation: 4 mg/kg q 24 hours. Our goal serum levels were a trough ≤2 μg/ml and a peak between 6 and 12 μg/ml. We collected and analyzed trough and peak levels from all infants receiving this dosing regimen in the first week of life for at least 72 hours between 3/1/99 and 12/31/00.RESULTS: In total, 214 babies met our inclusion criteria, 75 of whom were <35 weeks gestation. 100% of babies of all gestational ages had a nontoxic trough level. For infants <35 weeks gestation, 79% had a therapeutic peak level, with a mean value of 6.8 μg/ml. For infants of at least 35 weeks gestation, 93% had a therapeutic peak level, with a mean value of 8.4 μg/ml. 92% of nontherapeutic peaks were too low.CONCLUSION: This study of once-daily gentamicin represents the largest sample size of pre-term infants published to date. The proposed regimen is simple and yields a high proportion of desirable levels. We recommend it for use in preterm and term newborns.

Pediatric Heparin-Induced Thrombocytopenia: prevalence, thrombotic risk, and application of the 4Ts scoring system

OBJECTIVE To characterize heparin-induced thrombocytopenia (HIT) at a single pediatric center including the prevalence and the accuracy of the 4Ts scoring system as a predictor of HIT. STUDY DESIGN In this retrospective cohort study, we identified 155 consecutive patients <21 years old with sufficient data for 4Ts scoring. The 4Ts scoring system is a validated pretest tool in adults that predicts the likelihood of HIT using clinical features. Hospital-wide exposure to unfractionated and low molecular weight heparin was determined by querying the hospital pharmacy database. RESULTS The majority of patients with suspected HIT (61.2%) were on surgical services. Prediction of HIT risk using initial 4Ts scoring found 3 (2%) had high risk 4Ts scores, 114 (73%) had intermediate risk 4Ts scores, and the remaining 38 (25%) had low risk 4Ts scores. HIT was confirmed in 0/38 patients with low risk 4Ts scores, 2/114 patients with intermediate-risk 4Ts scores, and all 3 patients with high-risk 4Ts scores presented with HIT with thrombosis. Of 12 positive HIT screening tests, results were falsely positive in 66.6% of patients with intermediate risk 4Ts scores and 100% of patients with low risk 4Ts scores. The prevalence of HIT was 0.058% and HIT with thrombosis was 0.046% in pediatric patients on unfractionated heparin. CONCLUSIONS The prevalence of HIT appears significantly lower in pediatric patients compared with adults. Application of the 4Ts system as a pretest tool may reduce laboratory evaluation for HIT in heparin-exposed children with low risk 4Ts scores, decreasing unnecessary further testing, intervention, and cost.

Adverse reactions to vitamin B12 injections due to benzyl alcohol sensitivity: successful treatment with intranasal cyanocobalamin

References 1. Laxenaire MC, Mertes PM. Anaphylaxis during anaesthesia. Results of a two-year survey in France. Br J Anaesth 2001;87:549–558. 2. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245–252. 3. Bernard J, Ittelet D, Christoph A, Potron G, Adjizian JC, Kochman S et al. Adherent-free generation of functional dendritic cells from purified blood monocytes in view of potential clinical use. Hematol Cell Ther 1998;40:17–26. 4. Pichler WJ, Yawalkar N. Allergic reactions to drugs: involvement of T cells. Thorax 2000;55(Suppl. 2): S61–S65. Adverse reactions to vitamin B12 injections due to benzyl alcohol sensitivity: successful treatment with intranasal cyanocobalamin

Practice Guidelines for Lipid-Based Amphotericin B in Stem Cell Transplant Recipients

OBJECTIVE: To provide clinicians who practice in the stem cell transplantation (SCT) setting with practical guidelines for the use of lipid-based amphotericin B (AmB) formulations in SCT patients who have documented or probable invasive fungal infections, are experiencing neutropenic fever, or require secondary prophylaxis for fungal infections. DATA SOURCES: Recommendations are based on the results of a two-day consensus meeting that convened clinicians versed in the management of infectious complications in patients undergoing SCT. This meeting, which was held October 21–23, 1998, in Orlando, Florida, was sponsored by an educational grant from The Liposome Company. In addition, primary articles were identified by MEDLINE search (1980–December 1999) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated, and all information deemed relevant was included in this review. DATA SYNTHESIS: Immunocompromised patients, particularly patients undergoing high-dose chemotherapy with SCT, experience a high degree of morbidity and mortality from invasive fungal infections. Historically, treatment for such infections with conventional AmB had been limited primarily by its associated nephrotoxicity. Lipid-based formulations of AmB have helped to advance the management of invasive fungal infections in the SCT population by offering a treatment alternative that allows for administration of adequate amounts of active drug to produce clinical and mycologic responses, compared with conventional AmB, in a delivery system that is less nephrotoxic. Unfortunately, these agents are relatively expensive. Therefore, patients who are candidates for lipid-based products must be selected carefully. CONCLUSIONS: Practical guidelines are provided for the use of lipid-based AmB formulations in SCT patients who have documented or probable invasive fungal infections, are experiencing neutropenic fever, or require secondary prophylaxis for fungal infections.

Sterile product compounding using an i.v. compounding workflow management system at a pediatric hospital

PURPOSE Patient safety enhancements achieved through the use of an automated i.v. compounding workflow management system are reported. SUMMARY Automated systems integrating barcode verification of ingredients and the capture of serial images of all steps of the admixture process have the potential to improve the accuracy of parenteral i.v. medication dose preparation. About 18 months after the implementation of such a system at a large pediatric hospital, a retrospective analysis of dose preparation outcomes was conducted to evaluate the effectiveness of the i.v. workflow manager in detecting compounding errors and to categorize detected errors. In verifying the accuracy of 425,683 medication doses prepared during the approximately 13-month evaluation period, dispensing pharmacists detected preparation or documentation errors affecting 2,900 doses (0.68%); 1,223 of those doses (0.29%) required reworking, and 1,677 (0.4%) were rejected and destroyed. Roughly 23% of the detected errors were classified as undetectable via the pharmacys previous verification practices, with 167 errors judged to pose the potential for adverse drug events resulting in moderate (n=146) or severe (n=21) harm. Among the reworked and rejected doses, 43.8% and 31.3%, respectively, were due to newly emergent problems not seen with traditional paper-based verification systems; however, most of these errors involved blurry or missing images and were not judged to be clinically significant. CONCLUSION Implementation of an i.v. workflow management system that integrates barcode verification, automated calculations, and image-capture capabilities led to increased detection of errors in the sterile product compounding process.

A randomized controlled trial of a vancomycin loading dose in children.

Background: Despite its frequent use, the optimal dosing regimen of intravenous vancomycin remains controversial. Achievement of therapeutic trough early in the course of illness may be beneficial. Our objective was to assess whether a loading dose of vancomycin would increase the proportion of children reaching target trough concentrations 8 hours after initiation of therapy. Methods: We enrolled hospitalized children aged 2–18 years prescribed vancomycin at Boston Children’s Hospital between February 2011 and January 2012. Participants were randomized to receive a loading dose (30 mg/kg) or a conventional initial dose (20 mg/kg). These were followed by a 20 mg/kg/dose every 8 hours in both groups. Serum vancomycin concentrations were measured before the second and third doses. Pharmacokinetic parameters were calculated using individual and population pharmacokinetic models. Results: Two of nineteen (11%) loading dose recipients had a trough 15–20 mg/L before the second dose, compared with 0 of 27 in the conventional dose group (P = 0.17). However, the median area under the curve/minimum inhibitory concentration estimates (for a hypothetical minimum inhibitory concentration = 1 mg/L) were above 400 in both groups. Red man syndrome incidence was higher in loading dose recipients (48% vs. 24%, P = 0.06). Conclusions: A vancomycin loading dose did not result in earlier achievement of therapeutic trough concentrations in this study. However, the systemic exposure to vancomycin in children administered 60 mg/kg/day was adequate, despite lower than recommended measured trough levels. Therefore, the need for higher target trough concentrations should be questioned.

Production Standard and Stability of Compounded Del Nido Cardioplegia Solution

Background: The del Nido cardioplegia solution (dNCS) was originally developed for pediatric cardiac surgery, being now also used for adult patients. Hospital pharmacies frequently resort to internal dNCS production which has led to an increase in the need for validated parameters for compounding and storage. Objective: This report defines in-house production standards, as well as the stability of dNCS under optimal storage conditions. Methods: All ingredients were sterile and United States Pharmacopeia (USP)/National Formulary (NF) certified. All final bags were quarantined at 4°C for quality control, when 3 of 33 weekly bags were randomly assayed for potassium content. Each lot was only released if all 3 samples were within ±5% of target. Stability testing was performed per USP 797 guidance. Over a 6-month period, 4 different lots and 4 bags from each lot of dNCS were assayed. Each bag was assessed for physical and chemical stability while refrigerated at 4°C, at 35°C in an incubator, and at 70°C under 80% relative humidity. A light exposure arm was also set up at 25°C under 150 lumens. Calibrators of lidocaine, mannitol, and gluconate were freshly prepared and assayed with the samples by Liquid chromatography/Mass spectrometry (LC/MS). Results: Lidocaine concentrations averaged 0.117 mg/mL (95.8% of theoretical) at 4°C for 30 days. At 35°C, they decayed by 67% in 30 days, while at 70°C nearly 50% was lost after the first day. A first-order kinetics was observed with an Arrhenius activation energy of 25 kcal/mol. Degradation products identified under stress conditions were absent in the stable product. Conclusions: The dNCS is stable for at least 30 days under 4°C refrigeration in ethylene vinyl acetate (EVA) bags.

Antibiotic desensitization for the allergic patient: 5 Years of experience and practice

BACKGROUND Antibiotic desensitization is an option for patients with suspected IgE-mediated antibiotic allergy when no other alternative exists for treating life-threatening bacterial infections. However, there are limited data describing the outcomes of this procedure with newer, commonly used antibiotics. OBJECTIVE To evaluate the safety and utility of antibiotic desensitization. METHODS We retrospectively reviewed the medical records of all patients undergoing antibiotic desensitization in our institution between November 1996 and November 2001. RESULTS There were a total of 57 desensitizations performed in 21 patients. The mean age of the patients was 22.8 years (range, 1.9-44.5 years) and 15 (71%) were female. Nineteen (90%) of the 21 patients had been diagnosed as having cystic fibrosis. In 33 (100%) of 33 desensitizations to unique antibiotics that occurred during the study period, the indication for desensitization was a history suggestive of an IgE-mediated reaction to the antibiotic and/or a positive skin test result to the antibiotic or a known cross-reactive antibiotic. Desensitizations were performed to 12 different antibiotics. Successful outcomes were achieved in 43 desensitizations (75%). Of the 11 cases (19%) that were terminated due to an allergic reaction, there were no fatalities, intubations, or other aggressive interventions besides the use of epinephrine, antihistamines, and corticosteroids. In 7 of 11 unsuccessful desensitizations, a non-IgE mechanism appeared to be responsible for the allergic reaction. CONCLUSIONS Antibiotic desensitization is a useful option when treating patients with life-threatening infections who must receive antibiotics to which they have an IgE-mediated allergy. These data indicate that in most cases, patients with presumed IgE-mediated antibiotic allergy may safely receive antibiotics after desensitization.