Determination Of Penicillin Research Articles

Penicillin Therapy in Children with Acute Rheumatic Fever: Side Effects, Malpractice and Anaphylactic Reactions

Acute rheumatic fever ARF is more common in developing countries. ARF is a systemic disorder, which develops in children following group A streptococcal GAS pharyngitis. Rheumatic valvular disease is caused by autoimmune responses. Penicillin is used in the treatment of GAS tonsillopharyngitis and in primary and secondary prophylaxis against ARF. A single intramuscular IM injection of benzathine penicillin or oral penicillin V phenoxymethylpenicillin is administered as primary prophylaxis for 10 days. In the presence of rheumatic valvular disease, secondary prophylaxis with the injection of benzathine penicillin is required for life, or at least until the age of 40. IM injection of penicillin may cause fear and pain in children. Lidocaine or lidocaine-prilocaine EMLA creams can be used to decrease pain associated with IM injections. The most serious side effect of penicillin is, however, the anaphylactic reaction. This reaction can be caused by minor or major determinants of penicillin. Patients should be questioned about the past history of the penicillin allergy, and penicillin skin testing should be performed and interpreted appropriately in order to prevent anaphylactic reaction related to penicillin administration. In the presence of the suspicion of a penicillin allergy, skin testing should be avoided, and the patient should be tested by a pediatric allergy specialist using major and minor determinants to confirm a penicillin allergy. Patients who are allergic to penicillin can undergo desensitization in the absence of an alternative drug. It is a medical and legal obligation to perform and interpret the skin test appropriately, to keep the necessary equipment and drugs available for possible anaphylactic reactions, and to treat the patient appropriately in the case of an anaphylactic reaction. Penicillin is commonly used in pediatrics and pediatric cardiology

Comparison of Single Layer and Bilayer Biosensors Based on Crosslinking of Penicillinase for Potentiometric Detection of Penicillin in Milk and Antibiotics

AbstractThe use of bilayers for fabrication of biosensors is advantageous for increasing enzyme loading. Substantial improvement in sensitivity is often achieved through immobilisation of the enzyme in both layers. In particular, the use of cross linking agents such as glutaraldehyde (GLA), bovine serum albumin (BSA) and polyvinyl alcohol (PVA) are beneficial for enhancing enzyme stability and, hence, for fabricating stable biosensors. The successful fabrication of a single layer BSA‐GLA‐P’nase biosensor for potentiometric detection of penicillin is described. Subsequently, the three crosslinking agents were employed with two polymers, polypyrrole (PPy) and polytyramine (PTy), together with penicillinase (P’nase) for fabrication of PPy‐NO3‐P’nase/BSA‐PVA‐P’nase and PTy‐NO3‐P’nase/BSA‐GLA‐P’nase bilayer biosensors. The analytical performances of the bilayer biosensors were then compared with the single layer BSA‐GLA‐P’nase biosensor for the determination of penicillin in milk and amoxycillin tablets. While the determination of penicillin in milk was somewhat problematic, its determination in amoxicillin tablets proved to be successful, with recoveries of 102±15 % obtained with the PPy‐NO3‐P’nase/BSA‐PVA‐P’nase biosensor, 100±19 % with PTy‐NO3‐P’nase/BSA‐GLA‐P’nase biosensor and 103±5 % with BSA‐GLA‐P’nase biosensor. Notably, the results of the latter agreed favourably with those obtained through a reference titrimetric method.

β-Lactamase-based biosensor for the electrochemical determination of benzylpenicillin in milk

Antibiotics are widely used in dairy cattle production, however this can pose a public health threat, particularly when antibiotic residues remain in the food products like milk. Therefore, new analytical solutions aiming the determination of antibiotics, like the still commonly used penicillin, are welcomed. This work describes a novel electrochemical biosensor, with amperometric and differential pulse voltammetric detection, based on a modified carbon paste with β-lactamase for the determination of penicillin G, a β-lactam antibiotic. It is a ‘second-generation’ biosensor since cobalt phthalocyanine was used as an electron mediator. The proposed biosensor, by differential pulse voltammetry, presented a limit of detection of 0.079μmol/L. Using this biosensor, a value of 43±3μmol/L was determined for the Michaelis–Menten enzymatic constant for penicillinase extracted from Bacillus cereus.

Fabrication of a Single Layer and Bilayer Potentiometric Biosensors for Penicillin by Galvanostatic Entrapment of Penicillinase into Polypyrrole Films

AbstractA single layer and bilayer potentiometric biosensors for the detection of penicillin have been developed. The favourable conditions that were established for the polypyrrole‐penicillinase ((PPy‐P’nase) single layer biosensor were 0.03 M pyrrole, 50 U/mL P’nase, 0.01 M penicillin, applied current density of 0.9 mA/cm2 and a polymerisation time of 40 s. The optimum conditions for the formation of the outer layer of the bilayer were: (a) 0.1 M Py, 19 U/mL P’nase, 0.01 M pen, current density of 0.9 mA/cm2 and a polymerisation time of 40 s. The minimum detectable penicillin concentration with the bilayer potentiometric biosensor was 0.3 µM and the linear concentration range was 7.5–146 µM. The average percentage recovery of penicillin that was found in amoxycillin 500 mg was 113±24 %. The determination of penicillin in milk was fraught with problems of non‐specific binding of penicillin to the milk.

Fluorescent immunoassay for determination of penicillin and sulphonamide residues in milk using carboxylic magnetic nanoparticles

A fluorescent immunoassay for separate and simultaneous determination of penicillin (PEN) and sulphadimethoxine (SDM) in milk was developed. Monoclonal antibodies immobilised on carboxylic magnetic nanoparticles (MNPs) were used. It was proved that the protein A‐oriented immobilisation method (OI) provided a 1.5‐times more sensitive assay than the random immobilisation one (RI). The activation of MNPs with a mixture of N‐(3‐dimethylaminopropyl)‐N‐ethylcarbodiimide (EDC) and N‐hydroxysuccinimide (NHS) ensured a five‐times higher sensitivity of immunoassay than the activation using EDC. The linearity of standard curves in milk was: 3/10 ng/mL PEN (OI and RI), 50/250 ng/mL SDM (OI), and 50/500 ng/mL SDM (RI).

Simultaneous determination and toxicological assessment of penicillins in different water matrices.

A multi-residue analysis method was developed for the determination of penicillins in wastewater of WWTP, surface water and groundwater in Spain. The procedure involves a solid phase extraction (SPE) and the subsequent analysis by liquid chromatography coupled to tandem mass spectrometry detection (LC-QqQ-MS/MS). The SPE processes were optimized by test of cartridges, sample pH and elution solvents. ENV+ cartridge was chosen for the extraction of penicillins from different environmental samples. The best conditions for the extraction efficiency of the targets were observed at sample pH 6, by eluting solvents of methanol and acetonitrile respectively. The method has been validated by calibration curve, corresponding regression coefficient, limit of quantification and recoveries. The results showed that the recoveries of more than 90% were presented in all the compounds, except AMOX and AMPI, which had special amino-group in the molecular structure different with others. The matrix effect was also considered in the experiment and it was concluded that different matrix effect could be found between three kinds of waters, and the low retention of AMOX and AMPI on the cartridges was attributed to the matrices interference. The real sample detection showed that the penicillins degraded fast and only AMOX appeared in the studied environmental samples. The results of toxicology test on two compounds (AMOX and AMPI) showed that bacteria V. fischeri was proved to be relatively insensitive to both targets. The decreasing order of toxicity in three environmental waters for AMOX and AMPI was: wastewater > groundwater > surface water.

Electronic Nose Application for the Determination of Penicillin G in Saanen Goat Milk with Fisher Discriminate and Multilayer Perceptron Neural Network Analyses

Antibiotics are routinely added to milk products and pose potential harm to public health. The objective of this study was to use an innovative and nondestructive application of an electronic nose instrument for rapid detection of penicillin G in goat milk. The PEN3 electronic nose system was utilized to detect volatile substances in goat milk after the addition of penicillin G sodium salt at concentrations of 0, 50, 100 and 200 μg/L. The data were extracted at 60 s to carry out a linear discriminant analysis. Additional statistical analysis was conducted using neural networks to predict the penicillin G concentration in goat milk samples. Accuracy rates for the two methods were 98.0 and 96.7% for training samples, and 97.0 and 94.9% for testing samples, respectively. The results from this study show that the electronic nose system can be utilized to predict the penicillin G concentrations in goat milk samples. Practical Applications Antibiotics are routinely added to animal-derived food products and have been reported to cause potential harm to human health. However, traditional analytical chemical methods (i.e., gas, liquid and high-performance liquid chromatography) can detect trace amounts of additives and have some drawbacks, such as complicated operation, high costs of implementation and lengthy analysis time. This research has examined the feasibility, accuracy and effectiveness of a metal oxide semiconductor gas sensor type electronic nose device (the PEN3 e-nose) to detect and discriminate among different concentrations of penicillin G in goat milk. Data from this study show that the electronic nose system can be used to predict the penicillin G concentration in goat milk samples.

Determination of penicillin G in milk samples using its effect on cloud point extraction of triiodide ion.

A cloud point extraction (CPE) method for determination of trace amounts of penicillin G by spectrophotometry based on its effect on the triiodide ion (I3(-)) has been developed. Penicillin G is converted to the corresponding penicilloic acid by carrying out hydrolysis with sodium hydroxide solution, and treatment with acid yields D-penicillamine that is oxidized quantitatively by iodine to give rise to a disulfide. The 13- remaining in the solution is extracted into the surfactant Triton X-100, and the difference between absorbance of the working solution in the presence and absence of penicillin G is proportional to the amount of penicillin G. The effects of different variables, such as concentrations of sodium hydroxide, hydrochloric acid, surfactant, and I3(-) and the temperature and incubation time on the CPE were studied. The calibration graph was linear in the range of 50-1250 microg/L, and the LOD was 38 microg/L (n = 10). The RSD for 10 replicate determinations of 1000 microg/L of penicillin G was 1.0%. The method was applied to the determination of penicillin G in milk samples.

Selective determination of penicillin G from tap water and milk samples using surface molecularly imprinted polymers as solid-phase extraction sorbent

AbstractIn this study, a selective sample preparation method coupling surface molecularly imprinting polymers (SMIPs) with solid-phase extraction (SPE) was developed for the determination of penicillin G from tap water and milk samples. SMIPs for penicillin G were synthesized by using silica gel as supporting matrix, methacrylic acid (MAA) as the functional monomer, ethylene glycol dimethacrylate (EDMA) as the cross-linker, methanolacetonitrile (1:1,v/v) as the solvents and 2,2′-azo-bisisobutyronitrile (AIBN) as the initiator. Characterization and adsorption experiments revealed that SMIPs exhibited large adsorption capacity, high recognition ability and high rate of mass transfer. Application of SMIPs in SPE followed by HPLC was done to selectively determine penicillin G from tap water and milk samples. Under the optimal conditions, the proposed method demonstrated high linearity with the concentration of penicillin G ranging from 0.12 to 200 μg mL

Beta-Lactam Allergy and Cross-Reactivity

Penicillins and cephalosporins are commonly prescribed beta-lactam antibiotics that are able to induce severe and sometimes even life-threatening hypersensitivity reactions. These reactions can be broadly classified as immediate or non immediate/delayed depending on the onset of the reaction after the last drug administration. A definitive diagnosis of beta-lactam hypersensitivity is required to carry out the proper preventive measures. The diagnostic approach to beta-lactam allergy should be considered if the risk/possible benefit ratio is positive. In Korea, however, the diagnostic approach to beta-lactam allergy remains a major challenge. Major and minor determinants of penicillin for skin testing are unavailable, making skin testing appear to be less sensitive. Drug allergy work-ups that include standardized skin tests, reliable in vitro tests, and drug provocation tests are rarely carried out in clinical practice. However, screening patients without a prior history of beta-lactam allergy is routinely recommended. In this review, we discuss practical evaluation of beta-lactam allergy and cross-reactivity between penicillins and cephalosporins. (Korean J Med 2014,87:652-658)

Amperometric immunosensor based on covalent immobilization of new methylene blue and penicillin polyclonal antibody for determination of penicillin G in milk

A novel amperometric immunosensor for the detection of penicillin G (PeG) in milk was developed by covalent immobilization of new methylene blue (NMB) and Horseradish peroxidase-labeled penicillin polyclonal antibody (HRP-PePAb) on a glassy carbon electrode (GCE). The results of cyclic voltammetry and impedance spectroscopy showed that the NMB on the GCE exhibited excellent electrochemical activity and enhanced electron transfer. HRP labeled on PePAb shows remarkable electrocatalytic activity and good reproducibility towards the reduction of hydrogen peroxide due to the advantages of high electron transfer kinetics. Based on the specificity of the immunoreaction of antigen and antibody, the presented immunosensor exhibits high sensitivity, long-term stability, wide linear range, and low detection limit for the detection of PeG in milk. The linear response to PeG in the range of 5.20–41.6 nmol L−1 was obtained with the detection limit of 1.82 nmol L−1. Therefore, the proposed immunosensor can well be used to determine PeG residues in milk.

Multi-analyte quantification in bioprocesses by Fourier-transform-infrared spectroscopy by partial least squares regression and multivariate curve resolution

This paper presents the quantification of Penicillin V and phenoxyacetic acid, a precursor, inline during Pencillium chrysogenum fermentations by FTIR spectroscopy and partial least squares (PLS) regression and multivariate curve resolution – alternating least squares (MCR-ALS). First, the applicability of an attenuated total reflection FTIR fiber optic probe was assessed offline by measuring standards of the analytes of interest and investigating matrix effects of the fermentation broth. Then measurements were performed inline during four fed-batch fermentations with online HPLC for the determination of Penicillin V and phenoxyacetic acid as reference analysis. PLS and MCR-ALS models were built using these data and validated by comparison of single analyte spectra with the selectivity ratio of the PLS models and the extracted spectral traces of the MCR-ALS models, respectively. The achieved root mean square errors of cross-validation for the PLS regressions were 0.22gL−1 for Penicillin V and 0.32gL−1 for phenoxyacetic acid and the root mean square errors of prediction for MCR-ALS were 0.23gL−1 for Penicillin V and 0.15gL−1 for phenoxyacetic acid. A general work-flow for building and assessing chemometric regression models for the quantification of multiple analytes in bioprocesses by FTIR spectroscopy is given.

Determination of penicillins in milk of animal origin by capillary electrophoresis: Is sample treatment the bottleneck for routine laboratories?

Capillary electrophoresis (CE) is increasingly being used not only for research purposes but also for routine analyses. The latter, however, are especially difficult when the analytes are present at very low concentrations in complex food samples (e.g. penicillins in milk of animal origin). No study of the difficulties encountered in daily practice in sample treatments for the determination of penicillins (PENs) in milk by CE has to our knowledge been reported. Rather than reviewing the main uses of CE for determining PENs in different types of samples, this paper focuses on the weaknesses of available methods for this purpose, which originate in sample treatment rather than in a lack of robustness of the CE technique. Some problems which, based on our own experience, often confront sample treatment and method development in this context are discussed here. Clearly, the greatest source of error in this context is sample processing, which must provide optimal extraction and preconcentration of analytes, and extracts compatible with the separation technique to be used. In this respect, using time-consuming procedures can cause the loss of variable amounts of analytes in different steps. Interestingly, dramatically simplifying the sample preparation process can detract from sensitivity but lead to increased recoveries. As with any methodological development in routine analysis, acceptable results can only be obtained by considering all potentially influential factors.

Simultaneous determination of penicillin G and its major metabolites in blood using ultra performance liquid chromatography-tandem mass spectrometry

A fast method for the quantitative determination of penicillin G (PEN G) , penicilloic acid and penilloic acid in blood with ultra performance liquid chromatography-electrospray tandem mass spectrometry was developed. A simple deproteinization of the blood was used with a mixed solution of acetonitrile and water (4:1, v/v) as extraction solvent. The blood extract was directly injected onto an LC column. The chromatographic separation of the components was performed on a BEH C18 column (50 mm x 2.1 mm, 1.7 microm) using acetonitrile and water containing 0.1% formic acid. The mass spectrometer was operated in positive electrospray ion mode. Finally, the analysis was carried out with multiple reaction monitoring (MRM) mode. The limits of detection (LODs) for these three compounds were in the range of 0.1 to 2.0 ng/mL and the limits of quantification (LOQs) in the range of 0.5 to 5.0 ng/mL. Within the linear range, the correlation coefficients (r) of PEN G and its metabolites were all more than 0.9974. Accuracies for these targeted compounds were ranged from 92.3% to 105.5%, and the within-day precisions were less than 10%. The stabilities of the components were evaluated in the temperature range from 18 to 80 degrees C, and the mass concentration of penicillin G was decreased significantly with the extensions of storage temperature and storage time. Biological samples of the rats medicated with PEN G were analyzed using the developed method. The results show that PEN G can just be detected at 0.5 h after administration. However, the detection time limitation of penicilloic acid can be extended to 36 h. The established method has been further expanded for the applicability of forensic identification, and has a reference value for the detection of penicillin G residue in food.

Diagnosis of penicillin allergy revisited: the value of case history, skin testing, specific IgE and prolonged challenge

Skin testing in duplicate, correlation between case history of immediate and nonimmediate reactions and challenge outcome and prolonged oral treatment with penicillin in the diagnostic evaluation of allergic reactions to β-lactam antibiotics, mimicking real-life situations, have only been addressed in few studies. A total of 342 patients suspected of having β-lactam allergy were investigated according to the European Network for Drug Allergy (ENDA) guidelines and patients found to be negative in the ENDA program were supplemented with a 7-day oral treatment with penicillin. Skin testing with penicillins was performed in duplicate. Patients with case histories of reactions to other β-lactams were also subsequently challenged with the culprit drug. Nineteen patients were IgE-sensitized to penicillin. Then, intracutaneous tests (ICTs) were performed, in which 35 patients tested positive for allergy, 21 with delayed and 14 with immediate reactions. Only three patients tested positive for the major (PPL) and/or minor (MDM) penicillin determinants, all being positive for penicillin G in ICT. The remaining 291 patients were challenged with penicillin: 10 tested positive in single-dose challenge and 23 tested positive in the 7-day challenge. A total of 17 of 78 patients with a negative penicillin challenge tested positive during challenges with other β-lactams. We found no correlation between case histories of immediate and nonimmediate reactions and reaction time during challenge. The data suggest that case history is often insufficient to discriminate between immediate reactors and nonimmediate reactors. A 7-day challenge with the culprit β-lactam may yield more positive reactions than the accepted one- or 2-day challenge. Interpretation of skin testing should be made with caution.

Immunofluorescent Analysis with Magnetic Nanoparticles for Simultaneous Determination of Antibiotic Residues in Milk

An analytical system for simultaneous detection of three antibiotic residues in milk (penicillin, tetracycline, and sulfadimethoxine sodium salt) was developed. The method was based on a fluorescence immunoassay. Magnetic nanoparticles (MNPs) were prepared and then coated with 3-(aminopropyl) triethoxysilane (APTES). Antibodies, against penicillin, tetracycline, and sulfadimethoxine, were immobilized on APTES-MNPs. Two immobilization methods were used: a random and an oriented method by protein A. The fluorochrome-antigen conjugates, containing FITC, ATTO 590, and ATTO 630 were obtained. Three separate immunofluorescent analyses were investigated for penicillin, tetracycline, and sulfadimethoxine, first in buffer and then in milk. Linearity values of standard curves in milk were: for penicillin 4–15 ng mL−1, for tetracycline 50–500 ng mL−1 (using random immobilization) and 100–500 ng mL−1(using oriented immobilization), and for sulfadimethoxine 100–500 ng mL−1. The linearity and sensitivity of calibration curves of determination of penicillin, tetracycline and sulfadimethoxine in milk were very close to the obtained results for separate determination of three antibiotics. It was shown that the multiple immunofluorescence analysis for antibiotic residues in milk without preliminary treatment is effective and rapid.

Utility of penicillin allergy testing in patients presenting with a history of penicillin allergy

BackgroundCurrent statistics show that approximately 10% of patients claim to be allergic to penicillin yet only 10% of these have demonstrable allergy. The most appropriate and cost-effective antibiotics are sometimes withheld on the basis of patient history of drug allergy.ObjectiveInvestigation of IgE hypersensitivity and delayed hypersensitivity in patients with a history of penicillin allergy to a teaching hospital allergy clinic.MethodsPatients underwent skin prick and intradermal testing (IDT) with major and minor penicillin determinants. Those with negative skin tests were administered a three-day oral challenge. Demographic and clinical details about the reactions were noted.ResultsOne hundred twenty eight patients underwent testing, of these, one hundred and ten had self-reported histories of penicillin allergy and eighteen were referred because of other antibiotic allergies. Seventeen patients with self-reported penicillin allergy had either positive skin tests or oral challenge results, corresponding to 15% of patients having proven allergy. None reacted on skin prick testing, four reacted to IDT, thirteen reacted to oral challenge (five immediate and eight delayed). Analysis of clinical histories showed that patients with a well-defined history of allergy and a history of anaphylaxis were more likely to have a positive test compared to patients with vague histories. Skin testing proved to be less sensitive than oral challenge.ConclusionA minority of patients presenting with a history of penicillin allergy have evidence of immune-mediated hypersensitivity (17/110, 15%) in this study. Of these, eight out of seventeen (47%) had delayed reactions, demonstrating the usefulness and discriminating power of objective testing, which must include three-day oral challenge. Discriminating factors for immune-mediated allergy from patient history were a clear description of the original reaction and a history of anaphylaxis. Negative allergy testing enables the use of penicillin as first-line treatment when necessary and this can significantly reduce costs of antibiotics.

Benzathine penicillin G: a model for long-term pharmacokinetic comparison of parenteral long-acting formulations

Long-acting intramuscular penicillin G injection is an important product for the management of some severe infections. However, testing the bioequivalence of such long-acting formulations is difficult. Our aim was to undertake such a test using a generic formulation containing 1 200 000 IU of benzathine penicillin G powder and an innovator's product (Retarpen(®) 1·2 million units; Sandoz, Switzerland). In an open, double-blind, randomized, two-periods, two-group crossover study, 12 healthy male volunteers received both formulations of benzathine penicillin G on two different days with a 5-month washout period between the doses and a sampling period of over 500 h. A simple, sensitive and rapid high-performance liquid chromatography (HPLC)-UV method was developed and validated for determination of penicillin G plasma concentrations and other pharmacokinetic (PK) parameters. The analytical method used produced linear responses within a wide analyte concentration range with average within-run and between-run variations of below 15% with acceptable recovery, accuracy and sensitivity. The primary PK parameters we used were maximum plasma concentration (Cmax ), time to reach the maximal concentration (Tmax ) and the area under the plasma concentration vs. time curve from time zero to the last sampling time (AUC0→t ) using a standard non-compartmental approach. Based on these parameters, the two formulations were bioequivalent. We illustrate the bioequivalence testing of a very long-acting product. The data indicate that the generic test formulation and the branded reference formulation were bioequivalent in fasting healthy Iranian male volunteers.

Simultaneous determination of penicillin and their major enzymatic metabolites in milk and milk powder by high performance liquid chromatography-tandem mass spectrometry

A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS) method has been developed for the determination of eight compounds in milk and milk powder. They are four penicillins (penicillin G, penicillin V, amoxicillin and ampicillin) and four major beta-lactamase enzymatic metabolites of them (penilloic acid G, penilloic acid V, amoxiilloic acid and ampilloic acid). The compounds were extracted from the samples with acetonitrile and water, cleaned-up by HLB solid-phase extraction cartridges, and then detected by HPLC-MS/MS and quantified by external standard method. The linearities were satisfactory with the correlation coefficients > 0.99 at the mass concentrations ranging from 4 microg/L to 200 microg/L for penicillins and from 10 microg/L to 500 microg/L for enzymatic metabolites. The limits of detection and the limits of quantification were 5-50 microg/kg (S/N > or = 3) and 8-100 microg/kg (S/N > or = 10), respectively. The average recoveries of the eight compounds were 83.48%-96.97% in milk and 82.70%-95.14% in milk powder. The relative standard deviations (RSDs) in milk and milk powder were 3.86%-10.87% and 3.02%-9.81%, respectively. In conclusion, the established method is convenient, accurate and sensitive so that it can be applied to the determination of penicillin residues and enzymatic metabolites in milk and milk powder.

Chapter 30: Drug allergy

Drug allergy describes clinical adverse reactions that are proved or presumed to be immunologically based. Allergic drug reactions do not resemble pharmacologic actions of the incriminated drug and may occur at fractions of what would be the therapeutic dosage. Allergic drug reactions are unpredictable; nevertheless, there is increased risk of drug hypersensitivity in (1) patients with cystic fibrosis who receive antibiotics; (2) patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) who receive trimethoprim/sulfamethoxazole of if HLA-B*5701(+) and receive the antiretroviral agent, abacavir; (3) other genetically susceptible populations such as Han-Chinese who are HLA-B*1502(+) who develop Stevens-Johnson syndrome and toxic epidermal necrolysis from carbamazepine or if HLA-B*5801(+) are at increased risk for such reactions from allopurinol; and (4) patients with a history of previous compatible allergic reaction to the same medication, similar class, or potentially unrelated medication. Specific patient groups at higher risk for drug allergy include those with Ebstein-Barr virus infection, chronic lymphatic leukemia, HIV/AIDS, cystic fibrosis, patients with seizures being treated with antiepileptic medications, and patients with asthma (especially severe asthma) who are at increased risk of anaphylaxis from any cause including drugs compared with patients without asthma. In patients with a history of penicillin allergy, skin testing helps clarify the current level of risk for anaphylaxis by using the major (penicilloyl-polylysine) and minor penicillin determinants where sensitivity is 99%. If penicilloyl-polylysine and penicillin G are used for skin testing, the sensitivity is ∼85%. When skin tests are negative, graded challenges are performed to administer optimal or truly essential antibiotics.