By Carol A. Kemper, MD, FACP
Antibiotic Allergy: To Dose or Not to Dose?
Source: Robinson JL, et al. Clin Infect Dis. 2002;35:26-31.
This thoughtful article nicely summarizes the "practical aspects" of choosing an antibiotic in a patient with a reported drug allergy. Although penicillin skin testing is very useful for predicting a serious allergic reaction to the beta-lactam ring of the penicillins, a careful history is probably the most useful tool at the clinician’s disposal. However, I am finding (unfortunately, more often) with the use of computer-based templates and problem lists, that the nature of most allergic reactions is not being well characterized. Often, the important task of collecting this information is left to hospital nursing staff, who cannot be expected to differentiate between mild or more severe reactions, or even simple drug intolerance. The importance of the accuracy of this information is underscored by data suggesting that anywhere from 5-20% of patients believe they are "allergic" to penicillins.
The first challenge is the appropriate characterization of the allergy, as follows: 1) IgE mediated reactions, including diffuse erythema, urticaria, angioedema, bronchospasm, and hypotension; 2) delayed hypersensitivity reactions, including nonurticarial rashes, such as commonly observed with the aminopenicillins; 3) immune-complex mediated reactions or "serum sickness," a rare phenomenon; 4) antibody-mediated reactions, including, most commonly, neutropenia to the cephalosporins, but also hemolysis, thrombocytopenia, and interstitial nephritis; and 5) unknown mechanisms, such as Stevens Johnson Syndrome, erythema multiforme, and toxic epidermal necrolysis, but also fixed drug eruptions, drug fever, and autoimmune phenomenon.
In general, Robinson and colleagues believe that the cross-reactivity between penicillins and the second- and third-generation cephalosporins is significantly less than commonly believed, and probably no greater than reactions to drugs in other classes. Most patients with a history of penicillin allergy can safely be administered penicillins, especially with a negative skin test. In clinical trials, 8.1% of patients with and 4.5% of patients without a reported penicillin allergy had possible allergy to cephalosporins. Most cephalosporin reactions are to the various side-chains and not the beta-lactam ring. Overall, the risk of a serious reaction to cephalosporins is < 0.02% in the population, and may be 3 times more common in patients with a penicillin allergy.
For those in need of a specific antibiotic but with a history of IgE-mediated allergy to that agent, Robinson et al recommend skin testing and desensitization. The one notable exception: skin testing should not be performed in patients with a history of suspected Stevens Johnson Syndrome or toxic epidermal necrolysis and the use of cephalosporins should be avoided. Non-beta-lactam antibiotics seldom cause severe or life-threatening reactions. Most of these antibiotics can safely be administered even in patients with a history of allergy.
Resistance Mutations in HIV: Discordance Between CSF & Plasma
Source: Tashima KT, et al. Clin Infect Dis. 2002;35:82-83.
Although discordance between drug-resistant HIV mutations found in CSF and plasma has been previously reported, this report was interesting because it was the first to describe the presence of K103 resistant virus in CSF but not in plasma. The patient had received a combination of efavirenz and indinavir, with subsequent virologic failure with a plasma viral load of 23, 648, and a CSF viral load of 242 copies/mL. While there was evidence of a protease gene mutation in both CSF and plasma virus (A71V), only the virus found in CSF had evidence of K103N and K70R mutations, which are associated with resistance to the non-nucleoside reverse transcriptase drugs. If the development of drug resistance occurs as the result of exposure of replicating virus to subtherapeutic concentrations of drug, Tashima and colleagues point out that differences in drug levels between CSF and plasma may result in varying risk of drug resistance in the separate compartments. Several antiviral agents, including efavirenz, poorly penetrate the CSF. Virus replicating in CSF would, therefore, be exposed to smaller concentrations of drug, thus increasing the risk of drug resistant mutations.
Dr. Kemper, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, is Associate Editor of Infectious Disease Alert.
The first article summarizes the practical aspects of choosing an antibiotic in a patient with a reported drug allergy. The second describes the presence of K103 resistant virus in CSF but not in plasma.
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